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1), 21110
Oral Session
Saturday, 28 May
Autonomic nervous system disorders
and Clinical neurophysiology
O1101
Intravascular electroencephalography: a
pilot study in patients undergoing neuro-
interventional surgery
V. Keereman1, P. vanMierlo2, L. Defreyne3, P.A. Boon1
1LCEN3, Department of Neurology, Ghent University
Hospital, 2MEDISIP, Department of Electronics and
Epoch demonstrating the EEG signal recorded on the intravascular
Information Systems, Ghent University, 3Vascular and (IV) and scalp channels. The intravascular electrode was placed in the
Interventional Radiology, Ghent University Hospital, Ghent, M2 segment of the right medial cerebral artery. A high-frequency
Belgium discharge is observed on the intravascular channel as well as on the
nearest scalp electrode (T4).
Background and aims: Invasive electroencephalography
(EEG) is used in the presurgical evaluation of patients with
refractory epilepsy. Although it yields high quality
recordings, electrode implantation is associated with a risk
of complications. Therefore, a less invasive alternative
would be of interest. In this study we demonstrate the
feasibility of recording intravascular EEG from an electrode
inside the cerebral vasculature.
Methods: Intra-arterial EEG was recorded in 5 patients
undergoing a neuro-interventional procedure. Before the
start of the procedure, 9 EEG recording electrodes were
attached using the standard 10-20 system (Fp1-Fp2-C3-C4-
T3-T4-O1-O2-Cz). A microcatheter was placed over a Signal standard deviation on all channels, demonstrating the higher
0.010 guidewire in the M2 segment of the medial cerebral amplitude of the intravascular channel compared to the scalp EEG
artery. The micro-catheter was withdrawn so that the distal channels.
end of the guidewire was 5mm outside the catheter. The
proximal end of the guidewire was connected to the EEG Conclusion: We have demonstrated the feasibility of
recording amplifier. EEG was recorded for 15 minutes. recording intra-arterial EEG using a guidewire and micro-
Results: There were no artefacts that significantly affected catheter. Our results indicate that intra-arterial EEG could
signal quality on the intra-arterial EEG channel. Fig. 1 be a less invasive alternative to invasive EEG.
shows an EEG epoch, recorded in a patient in whom the Disclosure: Nothing to disclose
guidewire was placed in the right M2 segment. A high-
frequency discharge is detected on the intra-arterial channel
which was also detected on the nearest scalp electrode (T4).
Fig. 2 depicts the standard deviation on each channel,
demonstrating that the amplitude of the intra-arterial
channel is approximately 3 times higher than the scalp
channels.
2016 EAN 21
22 Oral Sessions
O1102
Fatigue of forearm extensor muscles
induced by repetitive peripheral magnetic
stimulation in healthy subjects
C. Cabib1, M. Garcia-Magaa2, M. Morales1,
L. Izquierdo-Robert1, P. Pereira3, P. Arias4, J. Valls-Sole5
1Neurology, EMG Unit, Hospital Clinic of Barcelona,
facilitation. Combining these PP TMS paradigm with the Background and aims: Transthyretin familial amyloid
TST may improve the accuracy which could be useful for polyneuropathy (TTR-FAP) is a rare, progressive, adult-
clinical practice. onset, hereditary disorder. Its neurological hallmark is an
Disclosure: Nothing to disclose axonal sensory-motor and autonomic neuropathy. Reliable
quantification of sudomotor function could prove essential
O1104 in the diagnosis and management of the disease. Sudoscan
is a fairly recent technique that provides a quick, non-
Autonomic dysfunction in Wilson's invasive and quantitative assessment of the sudomotor
disease: a comprehensive evaluation function. Our aim was to assess the diagnostic value of
K. Li1, C. Lindauer1, R. Haase1, H. Reichmann2, Sudoscan for the detection of symptoms, particularly
U. Reuner2, T. Ziemssen2 dysautonomia, in TTR-FAP.
1Center of Clinical Neuroscience, 2Department of Neurology, Methods: 133 TTR-FAP Val30Met carriers, divided in
University Hospital Carl Gustav Carus, Dresden, Germany asymptomatic and symptomatic in stage 1 of the disease,
were compared with thirty-seven healthy controls. We
Background and aims: Wilsons disease is reported to
analysed the right sural sensory nerve action potential
have autonomic dysfunction, but comprehensive autonomic
(SNAP), the feet sympathetic skin response (SSR) and the
function evaluation, especially with Baroreflex sensitivity
electrochemical skin conductance (ESC) for both hands and
(BRS) and spectral analyses is lacking. We aimed to
feet measured by Sudoscan.
comprehensively assess autonomic function in Wilsons
Results: All neurophysiological measures were significantly
disease.
worse (all p<0.05) in the symptomatic subjects. Subjects
Methods: 26 patients with Wilsons disease and 26 healthy
with autonomic complaints presented the lowest feet ESC
controls were recruited. 20 patients in the Wilsons disease
values (all p<0.001). Moreover, those with non-autonomic
group were examined again in a three-year follow-up. All the
symptoms had significantly lower feet ESC measurements
participants were evaluated by a questionnaire on dysautonomia
than both asymptomatic TTR-FAP group and controls (both
symptoms, sympathetic skin response, pupillography with
p<0.001; Fig1). On multiple logistic regression, both sural
pupil diameter in darkness (PDD) and pupil light reflex, 24
SNAP and feet ESC were significant independent predictors
hour blood pressure monitoring, and cardiovascular autonomic
for the presence of symptoms as well as for autonomic
function examination in various conditions including at rest,
dysfunction (all p<0.05; Table1). Feet ESC (cut-off: 66S)
deep breathing, Valsalva manoeuvre, isometric handgrip and
had 76% sensitivity and 85% specificity in detecting
passive tilting. BRS and spectral analyses were performed via
dysautonomia (Fig2).
trigonometric regressive spectral analysis.
Results: Patients with Wilsons disease showed autonomic
dysfunction mainly in the following aspects: 1. the heart
rate was higher than the control group, both at rest and
during 24h monitoring. 2. The BRS was lower in all the
cardiovascular autonomic function examinations. When
tested three years later, BRS did not decrease further under
different tests except BRS at rest. 3. The pupillography
demonstrated that patients with Wilsons disease had a
smaller PDD and larger relative reflex amplitude at three-
Fig. 1. Boxplots for each subjects group of the neurophysiological
year follow-up compared with the control group. There was evaluations: A) electrochemical skin conductance (ESC); B) sural
a significant correlation between PDD and clinical severity, sensory nerve action potential (SNAP) amplitude; C) sympathetic skin
disability and cirrhosis. response (SSR) amplitude. Mean (line), 95% CI (darker gray), and 1SD
Conclusion: The present study suggests that patients with (lighter gray). *p<0.05, **p<0.001 on ANOVA Tukeys HSD post-hoc
Wilsons disease have autonomic dysfunction in heart rate, comparisons.
BRS, PDD, and pupil light reflex. Furthermore, some of the
impairments progress with disease duration.
Disclosure: Nothing to disclose
O1105
The diagnostic accuracy of Sudoscan in
transthyretin familial amyloid
polyneuropathy
J. Castro1, B. Miranda2, I. Castro1, M. Carvalho1,
I. Conceicao1
1CHLN, Hospital de Santa Maria and Clinical and Table 1. Multiple logistic regression analysis for the presence of
autonomic complaints.
Translational Physiology Unit, Physiology Institute, Faculty
of Medicine, IMM, Lisbon, Portugal, 2Lisbon, Portugal
O1106
Combined CV and sudomotor autonomic
testing to differentiate multiple system
atrophy from Parkinsons disease
A. Pavy-LeTraon1, C. Brefel-Courbon1, F. Ory-Magne1,
O. Rascol2, J.-H. Calvet3, J.-M. Senard4
1University hospital of Toulouse, 2U825, Inserm, Toulouse,
France, 3Paris, France, 4Toulouse, France
Background and aims: In usual practice, it is sometimes
difficult to differentiate Multiple System Atrophy (MSA)
with predominant Parkinsonism (MSA-P) from Parkinson
disease (PD). Autonomic dysfunction, including cardiac
autonomic neuropathy (CAN) and sudomotor dysfunction,
Fig. 2. Receiver Operating Characteristic Curve of the feet ESC is classically more pronounced in MSA as compared to PD.
measurements for the presence of autonomic symptoms (AUC = 0.80). Autonomic impairment is considered to be post-ganglionic
in PD and mostly pre-ganglionic in MSA. We investigated
Conclusion: Feet ESC showed good diagnostic accuracy if CAN and sudomotor dysfunction assessment using a new
for autonomic involvement in TTR-FAP subjects. This simple device is useful to differentiate patients with MSA
technique should be considered for routine assessment in from PD.
this population and could useful in future clinical trials. Methods: 162 patients (63 with MSA-P and 99 with PD),
Disclosure: Nothing to disclose comparable for age, BMI and sex ratio with disease duration
of 5.35.2 years for MSA vs. 11.75.4 years for PD
(p<0.0001) underwent CAN testing using Ewing tests
(score from 0 to 5) and sudomotor function using
SUDOSCAN.
Results: 67% of patients with MSA-P vs. 47% with PD
(p=0.017) had sudomotor dysfunction according to
threshold values defined in previous studies (60 S for
hands and 70 S for feet conductances). Using a multivariate
model adjusted for sex, BMI, age and treatment the Odds
Ratio for having MSA vs. PD was 4.60 (2.24-9.43,
p<0.0001) for abnormal Ewing tests and 2.51 (1.23-5.13,
p=0.001) for sudomotor dysfunction. The OR was 5.97
(2.31-15.45, p<0.0001) when combining the 2 explorations.
Conclusion: These preliminary results suggest that Ewing
tests for CAN and SUDOSCAN allowing quick, non-
invasive and quantitative assessment of sudomotor function
could be helpful in combination to differentiate MSA and
PD patients
Disclosure: Nothing to disclose
Epilepsy 1 O1108
Long-term prognosis of epilepsy and
O1107 drug-resistance
Localizing value of electrical source E. Beghi1, G. Giussani1, V. Canelli1, E. Bianchi1,
imaging as compared to SEEG: which G. Erba2, C. Franchi1, A. Nobili1, L.J. Sander3
1Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche
patients are the best candidates?
"Mario Negri", Milan, Italy, 2Neurology, University of
C. Abdallah1, L. Koessler2, E. Rikir3, J.P. Vignal4, Rochester, Rochester, NY, United States, Rochester, USA,
S. Colnat-Coulbois5, M. Gavaret6, L. Maillard7 3NIHR University College London Hospitals Biomedical
1Nancy, France, 2CRAN UMR 7039, CNRS, Universit de Research Centre, UCL Institute of Neurology, London,
Lorraine , Nancy, France, 3Neurology, Neurology United Kingdom
Department, University Hospital of Sart-Tilman, Liege,,
Liege, Belgium, 4Neurology, Neurology Department, Background and aims: There is little information on the
University Hospital of Nancy, Nancy, France, 5Neurosurgery, long-term outcome of people who fail to achieve seizure
Neurology Department, University Hospital of Nancy, Nancy, control despite the use of two antiepileptic drugs (drug
France, 6Neurology, Marseilles, France, 7Neurology, CHU resistance, ILAE definition).
Nancy, Nancy, France Methods: People with epilepsy and drug-resistant epilepsy
(i.e., failure of two antiepileptic drugs) during the period
Background and aims: Prospectively evaluating
2000-2008 were identified from 123 family physicians in an
anatomical concordance of source localizations derived
area of Northern Italy. We determined the cumulative time-
from 64-channel scalp EEG recordings of inter-ictal
dependent probability to achieve 2-year and 5-year
discharges (IID) with the epileptogenic zone (EZ) estimated
remission in patients followed for at least two years and five
by stereo-electroencephalography (SEEG) according to the
years respectively.
type of epilepsy, the presence of a structural MRI lesion, the
Results: 657 individuals were followed for at least two
aetiology and the depth of the EZ categorized in medial,
years, 540 for at least five years. As of December 31st 2008,
lateral or medio-lateral.
428 people (57%) had been seizure-free for at least 2 years,
Methods: In a prospective multicentric observational study,
110 of them off-treatment. The probability of achieving
we enrolled 85 consecutive patients undergoing pre-surgical
2-year remission was 18% at treatment start and increased
investigation for focal drug-resistant epilepsy between
to 67% at 20 years. The probability of starting 5-year
2009-2013. Electric source imaging (ESI) derived from IID
remission was 14.5% at treatment start and increased to
and individual realistic head modelling.The results of ESI
50.2% at 20 years. The corresponding probability of 2-year
were interpreted blinded to and subsequently compared
and 5-year sustained remission (i.e., being in remission at
with SEEG estimated EZ.
last follow-up) at 20 years were lower (59.7% and 46.2%).
Results: 51% of patients had temporal and 49% extra-
The number of patients achieving 2-year and 5-year
temporal lobe epilepsy. MRI was positive in 70%. 55% of
remission varied with epilepsy syndrome and treatment
patients had malformation of cortical development (MCD).
response. However, patients with drug-resistant epilepsy
EZ was medial in 36%, lateral in 18%, and medio-lateral in
had 24.9% and 11.5% chance of 2-year and 5-year remission
46%. In the overall cohort, ESI completely or partly
at 20 years.
localized the EZ in 85%.The rate of ESI full concordance
Conclusion: The long-term prognosis of epilepsy is
with EZ was significantly higher in (i) frontal lobe epilepsy
favorable in most cases. Prolonged seizure remission can be
than in temporal, posterior, operculo-insular and multilobar
predicted by syndromic category and failure of two
epilepsies (p=0.05) (ii) cases of negative than positive MRI
antiepileptic drugs. However, drug-resistance is still
(p=0.01) and (iii) MCD than in other aetiologies (p=0.03).
compatible with long-term remission.
The rate of ESI full concordance with EZ was not
Disclosure: The study was supported by an unrestricted
statistically different according to the depth of the EZ.
educational grant from UCB-Pharma.
Conclusion: For the first time, we prospectively
demonstrated in the same study that ESI more accurately
estimate the EZ in patients with frontal lobe epilepsy,
negative MRI, MCD who represent the most difficult cases
for epilepsy surgery.
Disclosure: Nothing to disclose
Results: Of 779 patients analyzed, 244 (31.3%) suffered al. 2015). This study revisited the SUDEP rate in patients
from epilepsy before surgery and 204 (26.6%) had epilepsy with VNS Therapy in a 100-fold larger population.
after surgery. Of the 244 patients with preoperative epilepsy, Methods: This retrospective study included all US patients
144 (59.0%) became seizure-free after surgery; of the 535 with drug-resistant epilepsy (DRE) implanted with VNS
patients without preoperative seizures, 104 (19.4%) suffered from 19882012 with known social security numbers. VNS
from epilepsy after surgery. Risk factors for postoperative exposure was calculated from date of implant until death,
epilepsy were preoperative epilepsy (odds ratio [OR]: 3.46 device explant, known date at which the device was disabled
[95% confidence interval {CI}: 2.325.16]), major surgical or the last followup date of December 31, 2012. Date and
complications including CNS infections (OR: 5.89 [95% cause of death were obtained from the Social Security
CI: 1.5322.61]), hydrocephalus (OR: 3.27 [95% CI: 1.35 Death Index Master File and the National Death Index
7.95]), recraniotomy (OR: 2.91 [95% CI: 1.256.78]), and (NDI) which provides ICD-9 or ICD-10 codes. An algorithm
symptomatic intracranial hemorrhage (OR: 2.60 [95% CI: was developed for SUDEP case ascertainment according to
1.175.76]) as well as epileptiform EEG potentials (OR: Annegers SUDEP classification leveraging the NDI cause-
2.52 [95% CI: 1.364.67]), younger age (OR: 1.74 [(95% of-death codes along with any additional patient
CI: 1.182.58]), and tumor progression (OR: 1.92 [95% CI: information.
1.163.18]). Results: 40,443 patients were included with 3,689 deaths
recorded. 953 (26%) corresponded to cause-of death codes
that potentially include SUDEP. The algorithm identified
660 as possible/probable/definite SUDEP. Crude SUDEP
rate was 2.28/1000 patient years (PY) and age adjusted rate
was 2.04/1000 PY with a statistically significant 32%
reduction after the first two years (Table 1).
Figure 1. Consort.
O1120 O1121
Cross-modal plasticity among sensory Age and disability drive cognitive
networks in neuromyelitis optica impairment in multiple sclerosis
spectrum disorders independent of disease subtype: insights
M.A. Rocca1, F. Savoldi1, P. Valsasina2, A. D'ambrosio3, from an Italian multicentre study
M. Radaelli4, P. Preziosa1, G. Comi4, A. Falini5, L. Ruano1, E. Portaccio2, B. Goretti2, C. Niccolai2,
M. Filippi1 F. Patti3, S. Cilia4, P. Gallo5, P. Grossi6, A. Ghezzi7,
1Neuroimaging Research Unit, Institute of Experimental
M. Roscio8, F. Mattioli9, C. Stampatori10, M. Trojano11,
Neurology, DIvision of Neuroscience, San Raffaele Scientific R.G. Viterbo12, M.P. Amato13
Institute, Milan, Italy, 21Neuroimaging Research Unit, San 1EPIUnit, Institute of Public Health, University of Porto,
Raffaele Scientific Institute, Vita-Salute San Raffaele Porto, Portugal, 2University of Florence, Florence, Italy,
University, Milan, Italy, 3Naples, Italy, 4Department of 3Catania, Italy, 4University of Catania, Catania, Italy,
Neurology, San Raffaele Scientific Institute, Vita-Salute San 5Padua, Italy, 6University of Padova, Padua, Italy,
Raffaele University, Milan, Italy, 5Neuroradiology, 7Gallarate, Italy, 8Gallarate Hospital, Gallarate, Italy,
Universit Vita-Salute San Raffaele, Milan, Italy 9Brescia, Italy, 10Spedali Civili of Brescia, Brescia, Italy,
Background and aims: We compared resting state (RS) 11Bari, Italy, 12Department of Basic Medical Sciences,
functional connectivity (FC) within and among RS networks Neurosciences and Sense Organs, University of Bari, Bari,
between patients with neuromyelitis optica spectrum Italy, 13Florence, Italy
disorder (NMOSD, 2015 criteria), isolated recurrent optic Background and aims: There is limited and inconsistent
neuritis (ON) and recurrent myelitis. information on the clinical determinants of cognitive
Methods: RS fMRI was acquired from 30 NMOSD, 11 impairment (CI) in multiple sclerosis (MS). The aim of this
ON, 12 myelitis patients and 30 healthy controls (HC). RS work is to describe the prevalence and profile of CI in a
FC within and between the main sensory and motor large sample of patients with MS and assess the relationship
networks as well as correlations with motor performance of CI with the main demographic and clinical characteristics.
were assessed using SPM12. Methods: Six Italian MS centres participated in the study.
Results: Compared with HC, NMOSD patients showed Cognitive performance was assessed through the Brief
decreased RS FC of the secondary visual network. They Repeatable Battery and the Stroop Test, using as reference
also showed increased RS FC of the visual and auditory values the Italian norms. CI was defined as impairment in
networks vs HC, ON and myelitis. No sensorimotor RS FC two or more cognitive domains.
abnormalities were detected. ON patients experienced Results: 1040 patients where included: 167 clinically
decreased RS FC of the visual and auditory networks and isolated syndromes (CIS), 759 relapsing remitting (RR), 74
increased RS FC of primary visual regions. Myelitis patients secondary progressive (SP) and 44 primary progressive
had reduced RS FC of the sensorimotor, visual and auditory (PP). The prevalence of CI was 46.3% in the whole sample;
networks vs HC, NMOSD and ON. They also showed 34.5% in CIS, 44.5% in RR, 79.4% in SP and 91.3% in PP
increased RS FC of the precuneus (sensorimotor network) patients (p<0.05). Information processing speed and
and cerebellum (visual network). In all groups, decreased executive function were the most frequently affected
RS FC correlated with poor motor performance. In myelitis domains in CIS and RRMS subjects, whereas a wider range
increased precuneus RS FC correlated with better motor of domains were involved in the SP and PP forms. In a
performance. FNC between motor and visual RSNs was logistic regression model for overall CI the main correlates
increased in NMOSD, while FNC was markedly decreased were higher EDSS and older patient age. These variables
between primary and secondary visual RSNs in ON. remained significant when considering impairment in
Conclusion: In recurrent ON and myelitis, abnormal RS FC distinct cognitive domains.
was observed in networks primarily affected by the Conclusion: The frequency and severity of CI tends to
pathological process. NMOSD showed decreased visual increase over the disease course and is mainly driven by
system RS FC and increased RS FC in other sensory disease severity and aging rather than disease subtype.
networks, suggesting cross-modal plasticity among different Disclosure: Nothing to disclose
sensory modalities.
Disclosure: Nothing to disclose
O1123 O1124
Systematic review of ganglion cell layer Cerebellar contribution to motor and
changes measured by optical coherence cognitive impairment in multiple sclerosis
tomography in multiple sclerosis and patients: an MRI sub-regional structural
optic neuritis analysis
J. Britze1, J.L. Frederiksen2 A. D'ambrosio1, M.A. Rocca1, E. Pagani1,
Medical Sciences, Copenhagen University, Copenhagen,
1
G.C. Riccitelli1, B. Colombo2, M. Rodegher2, A. Falini3,
Denmark, 2Neurology, Glostrup Hospital, Copenhagen G. Comi2, M. Filippi1
University Teaching Hospital, Glostrup, Denmark 1Neuroimaging Research Unit, San Raffaele Scientific
Introduction: The aim of this study was to summarise Institute, Vita-Salute San Raffaele University, Milan, Italy,
2Department of Neurology, San Raffaele Scientific Institute,
existing findings regarding optical coherence tomography
(OCT) measurements of ganglion cell layer (GCL) Vita-Salute San Raffaele University, Milan, Italy,
3Neuroradiology, Universit Vita-Salute San Raffaele, Milan,
alterations in relation to multiple sclerosis (MS) and optic
neuritis (ON). Italy
Methods: Peer-reviewed studies published prior to Background and aims: The cerebellum plays a role in a
February 2016 were searched using PubMed and EMBASE. wide variety of complex behaviors. Many evidences support
Studies were included if they (a) included data on GCL a topographic division into motor and non-motor
measured using OCT (b) in patients with either MS, regions localized in the anterior and posterior cerebellum,
clinically isolated syndrome or ON and (c) were in English. respectively. Our aim is to assess the role of cerebellar sub-
Results: 35/218 studies involving 4745 subjects were regions in determining motor and cognitive impairment in
reviewed. Studies showed that GCL thickness decreased multiple sclerosis (MS) patients.
significantly over the first weeks-12 months after acute ON Methods: Cerebellar analysis was performed on the 3D-T1
(n=3). GCL thinning may present before retinal nerve fiber brain images from 95 MS patients and 32 healthy controls
layer (RNFL) thinning (n=5). (HC) using the SUIT tool from SPM12. For all subjects, we
The GCL was significantly reduced in eyes of MS patients also obtained normalized cerebral volumes and scores of
with (n=15) and without (n=15) previous ON (n=5). motor performance (Nine Hole Peg Test [9-HPT]). MS
GCL thinning showed some association with visual patients also underwent a cognitive evaluation (Symbol
function, particularly low contrast letter acuity (LCVA) Digit Modalities Test [SDMT], Paced Auditory Serial
(n=8). GCL thickness could be a better estimate of visual Addition Test [PASAT]). Bivariate Spearmans correlation
function than RNFL thickness (n=3). was applied to brain volumes (cerebral and cerebellar) and
GCL and expanded disability status scale (EDSS) scores motor and cognitive scores.
were correlated (n=8), and more strongly than with RNFL Results: No significant differences in the cerebellar
thinning (n=4). GCL thinning at 1-2 months after acute ON volumes were found between MS patients and HC. In MS
predicted visual function at 6 months (n=2). patients, better 9-HPT performance correlated with higher
Conclusion: GCL thinning occurs in ON and MS with and cerebellar volumes, mostly in the anterior region (lobules
without ON. GCL thickness may provide a better estimate I-V) (p=0.0003), whereas better cognitive performance
of neurodegeneration and may be of prognostic value with correlated with higher cerebellar volumes, mostly
regards to visual function, at least in short term. Longitudinal (p<0.0001) in the posterior-inferior region (lobules VI-X).
studies are warranted to determine whether GCL No correlations were found between clinical/cognitive
measurements can be used to predict long-term visual parameters and normalized cerebral (total brain, white and
function and MS. grey matter) volumes.
Disclosure: Nothing to disclose Conclusion: Motor and cognitive performances in MS
seem to be more influenced by cerebellar than cerebral
volumes. Cerebellar posterior-inferior volume accounted
for variance in cognitive measures, whereas anterior
cerebellar volume accounted for variance in motor
performance, supporting a critical contribution of regional
cerebellar damage to the clinical manifestations of MS.
Disclosure: This study was partially supported by a grant
from FISM 2011/R/19 and Italian Ministry of Health (GR-
2009-1529671).
Neuroepidemiology O1126
Diagnosing hereditary neuropathies in the
O1125 clinic with next-generation sequencing
The burden of neurological diseases in technology, the Norwegian experience
Hungary. The initial database of the H. Hyer1, .L. Busk1, .L. Holla1, L. Strand1,
NEUROHUN-20042017 project C.F. Skjelbred1, M.B. Russell2, G.J. Braathen1
1Department of Laboratory Medicine, Section of Medical
D. Bereczki1, A. Ajtay1, F. Oberfrank2
1Department of Neurology, Semmelweis University, Genetics, Telemark Hospital, Skien, Norway, 2Head and
Budapest, Hungary, 2Institute of Experimental Medicine , Neck Research group, Research Centre, Akershus University
Hungarian Academy of Sciences, Budapest, Hungary Hospital, Lrenskog, Norway
Background and aims: Hungary is a Central-European Background and aims: Next-generation sequencing
country with 10 million inhabitants and a single-payer (NGS) or massively parallel sequencing detects the precise
health insurance system. We aim to monitor the national order of nucleotides within a DNA molecule. NGS is more
burden of neurological diseases using the database of the effective than traditional sequencing methods, such as
National Health Insurance Fund. Sanger sequencing, when several genes are involved.
Methods: In the framework of the Hungarian Brain Targeted NGS is starting to be used in diagnostics for
Research Program we created the anonymized NEUROHUN disorders caused by several genes.
database from medical reports submitted for reimbursement We wanted to investigate the diagnostic yield of targeted
purposes to the National Health Insurance Fund from all NGS compared to traditional Sanger sequencing studying
hospitals and outpatient services throughout the country for clinic patients suspicious of hereditary neuropathy.
the ten-year period between 2004 and 2013. ICD-10 codes Methods: This retrospective study includes 103 patients
for neurological diseases (G00 G99) and cerebrovascular investigated for hereditary neuropathy at Telemark Hospital,
diseases (I60 I69) given by neurologists any time during Norway from March 1, 2012 to May 1, 2014. After
the 10-year period either in the inpatient or the outpatient exclusion of PMP22 duplication /deletion, the remaining 96
setting are used for patient selection into the database. samples were examined with targeted NGS for 52 hereditary
Record linkage is possible by anonymized individual codes neuropathy genes looking for sequence variants / mutations.
created specifically for the database. Medication use is Results: A genetic hereditary neuropathy cause was
estimated by pharmacy reports for prescription drugs. identified in 35 patients (34%), of which 28 patients (27%)
Demographic and socioeconomic data are obtained from had point mutations identified by NGS.
the Central Statistical Bureau of Hungary. Conclusion: 12 pathogenic sequence variants/mutations
Results: 184 hospitals and 457 outpatient services reported were identified in genes previously Sanger sequenced in our
2.9 million patients with at least one neurological diagnosis department while 16 sequence variants were identified in
over the 10-year period. Further data will be entered to the genes that previously would not have been investigated.
database for 2014 2017. The initial set of the NEUROHUN Disclosure: Nothing to disclose
database contains over 1 billion records. The reconstruction
of patient history and follow-up of each patient is possible
using data linkage.
Conclusion: The NEUROHUN database is appropriate to
evaluate clinical, epidemiological, organisational and health
economic features of neurological disorders at a nationwide
level to provide accurate information for health care
decision makers to plan neurological services in upcoming
years.
Disclosure: Nothing to disclose
O1127 O1128
Temporal trends in transthyretin familial Epidemiology of Listeria monocytogenes
amyloid polyneuropathy survival over the meningitis in the Netherlands, 1985-2014
last 100 years M. Koopmans1, M. Bijlsma1, M. Brouwer1,
M. Ines1, T. Coelho2, I. Conceicao3, P. Saramago4, A. vanderEnde2, D. vandeBeek1
1Neurology, Academic Medical Centre, Amsterdam,
M. Carvalho1, J. Costa5
1Instituto de Medicina Molecular, Faculty of Medicine, Netherlands, 2Medical Microbiology department and the
University of Lisbon, Lisbon, Portugal, 2Corino de Andrade Netherlands Reference Laboratory for Bacterial Meningitis,
Unit, Hospital de Santo Antnio, Centro Hospitalar do Academic Medical Centre, Amsterdam, Netherlands
Porto, Porto, Portugal, 3Department of Neurosciences, Background and aims: Listeria monocytogenes is the third
Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, most common cause of bacterial meningitis. A recent study
Lisbon, Portugal, 4CHE, University of York, York, United showed unfavourable outcome has increased in the past
Kingdom, 5University of Lisbon, Faculty of Medicine, decade from 27% to 61%, that was associated with a shift
Lisbon, Portugal in listeria genotype in listeria meningitis.
Background and aims: Comprehensive long-term data on Methods: National surveillance data from the Netherlands
transthyretin familial amyloid polyneuropathy (TTR-FAP) Reference Laboratory of Bacterial Meningitis (NRLBM)
survival are scarce. We estimate disease natural long-term were examined for cases of L.monocytogenes from 1985-
survival using data from the largest and oldest international 2014. Multi Locus Sequence Typing was performed to
patients' cluster. identify changes in serotypes and sequence types. Patients
Methods: Registry data from the Portuguese referral were divided into age-groups: neonates, <50years old and
centres were merged until Dec 2015 integrating 1,667 50years old. Differences between proportions were tested
Val30Met untreated patients. Kaplan-Meier survival with the Pearson test.
estimates were obtained and Cox proportional hazards Results: Between 1985 and 2014 a total of 1077 L.
model used to estimate hazard ratios (HR) and 95% monocytogenes isolates have been collected. 375 (35%)
confidence intervals (CI). We analysed survival trends using were isolates from cerebrospinal fluid. Incidence of listeria
five cohorts: born before 1934, 193443, 194453, 1954 meningitis fluctuates over the years. In neonates incidence
63 and after 1963, adjusted by gender and late-onset. was highest (0.61 per 100,000 live births) followed by
Results: Natural long-term median survival since disease elderly (peak at 82 years of age; 0.52 per 100,000 same-age
onset is 11.05 years (95%CI: 11.01-11.49) and has increased population). Of 374 (99%) serotyped isolates main groups
from 10.01 years (95%CI: 9.01-11.01) to 11.42 years were serotype 4b (213 [57%]) and 1/2a (95 [25%]). MLST
(95%CI: 9.80-12.19). Being male (HR 1.25, 95%CI: 1.12 showed that the proportion of sequence type (ST) 1, 2 and
1.40) and late-onset (HR 1.40, 95%CI: 1.191.64) were 3 are decreasing and the proportion of ST6 increased
found to be important risk factors associated with increased significantly (2.5% in 1985-1989 to 36% in 2010-2014, p
mortality. The 193443, 194453, 195463 cohorts are <0.001).
associated with increased survival (p<0.05) as compared
with the first cohort. The cohort born after 1963 also present
a positive trend however without statistical difference,
possibly due to higher selection into disease modifying
interventions that impacted the number and characteristics
of untreated patients.
Conclusion: If untreated, long-term survival since TTR-
FAP disease onset is very poor, particularly in males and
late-onset patients. Surveillance enhancement and
multidisciplinary care provided by FAP referral centres can
underscore the observed survival increase. Improvement in
TTR-FAP early diagnosis is warranted. This may be
achieved through better disease awareness and more Figure 1. Proportion of sequence types in listeria meningitis
efficient referral to FAP centres.
Disclosure: No funding or sponsorship was received for Conclusion: There has been a shift in the past 30 years of
this study. This research was conducted under the doctoral L.monocytogenes sequence types that cause listeria
programme of the Lisbon Academic Medical Centre meningitis. ST6 has emerged as the dominant sequence
(CAML). Mnica Ins is a Pfizer employee at the time this type. A recent study showed an association between ST6
study was conducted. and unfavourable outcome therefore further studies on
virulence factors of L.monocytogenes sequence types are
needed.
Disclosure: Nothing to disclose
O1129 O1130
Seasonal changes in the incidence of Epidemiologic aspects of the Charcot-
transient global amnesia Marie-Tooth diagnosis in Denmark: a
N. Lev, O. Keret, I. Steiner nationwide study
Department of Neurology, Rabin Medical Center, Beilinson S. Vth1, M. Vth2, H. Andersen3, R. Christensen1,
Hospital, Petach Tikva, Israel U.B. Jensen1
Background and aims: Transient global amnesia (TGA) is 1Department of Clinical Genetics, Aarhus University
a stereotypic condition, characterized by anterograde and Hospital, Aarhus, Denmark, 2Department of Public Health,
retrograde amnesia that typically resolves within 24 hours. Section for Biostatistics, Aarhus University, Aarhus,
The pathophysiology of TGA is still unclear. We noted that Denmark, 3Department of Neurology, Aarhus University
patients hospitalized with TGA tend to appear in seasonal Hospital, Aarhus, Denmark
clusters. Background and aims: Charcot-Marie-Tooth Disease
Methods: In our medical center every patient with acute (CMT) is the most common inherited neurologic disease,
presentation of amnesia is hospitalized for observation and but little is known about its epidemiology. Prevalence
evaluation. We reviewed the monthly occurrence of TGA in estimates in the literature vary considerably, and only a few
our patient population between the years 2000 and 2014. nationwide studies have been conducted.
Results: During this period 154 patients who met the Methods: Using The Danish National Patient Registry we
criteria for TGA were hospitalized. Annual incidence retrieved all records with CMT diagnostic codes (ICD8 and
ranged from 5 to 16. There were 91TGA events in women ICD10) from 1977 to 2012 given at a neurologic,
and 63 in men, with a mean age of 62.810.6 years. Two neurophysiologic, paediatric or clinical genetic clinic. The
significant incidence peaks were noted within the months of positive predictive value (PPV) of the CMT diagnosis was
December (OR 2.8 95% CI 1.2-6.6) and March (OR 2.8 assessed in a validation study. We calculated prevalence by
95% CI 1.2-6.5. Incidence was decreased during April December 31, 2012 and based on data from 1985-2012, we
through August. A monthly rate climb and descent was obtained an incidence rate and computed a Standardized
noted from September to February. A seasonal trend was Mortality Ratio (SMR).
observed as well, with winter (OR 1.8, 95% CI 1.1-2.9) and Results: A total of 1539 patients (892 males and 647
spring (OR 1.8, 95% CI 1.1-2.9) showing peaks of females) were identified. PPV was 88.5% (95%CI
incidence. 80.4%;94.1%). The average age at first diagnosis was 42.5
Conclusion: Our findings suggest that TGA has seasonal years. The incidence rate was 0.76 (95%CI 0.70; 0.84) per
incidence variations. This result should be examined and 100,000 persons per year. By December 31, 2012 1271
verified in other cohorts. patients with a CMT diagnosis were alive corresponding to
Disclosure: Nothing to disclose a prevalence proportion of 20.0 per 100,000 (95%CI 18.4;
21.9). The average age at death was 70 years. SMR relative
to the general Danish population was 1.51 (95%CI 1.34;
1.70); 1.57 (95%CI 1.36; 1.81) for males and 1.40 (95%CI
1.14;1.72) for females.
Conclusion: We found a reduced lifespan among patients
diagnosed with CMT. To our knowledge, this study is the
first nationwide register-based study of CMT, and the first
to report estimates of incidence and mortality.
Disclosure: Nothing to disclose
Neurogenetics O1132
Variants in four genes on chromosome 12
O1131 is associated with intermediate Charcot
MarieTooth disease
Quantitative MRI of the spinal cord and
G. J. Braathen1, H. Hyer2, .L. Busk2, K. Tveten2,
brain in adrenomyeloneuropathy: cross- C.F. Skjelbred2, M.B. Russell3
sectional and preliminary longitudinal 1Skien, Norway, 2Department of Laboratory Medicine,
O1133 O1134
Low cancer prevalence in polyglutamine An SPG2/PLP1 mutation mimicking
expansion diseases multiple sclerosis in a family identified
G. Coarelli1, A. Diallo2, F. Calvas3, P. Charles4, through targeted next generation
C. TosiMarelli5, C. Ewenczyk4, C. Tranchant6, sequencing
M. Tchikviladz4, M.-L. Monin4, B. Carlander5, A. Rubegni1, A. Tessa1, C. Battisti2, E. Storti1, A. Cerase3,
M. Anheim6, F. Mochel1, A. Brice1, A. Malandrini2, F.M. Santorelli1, A. Federico2
S. TezenasDuMontcel2, S. Humbert7, A. Drr1 1IRCCS Stella Maris, Unit of Molecular Medicine, Pisa,
1INSERM U 1127, Centre National de la Recherche Italy, 2Department of Medicine, Surgery and Neurosciences,
Scientifique UMR 7225, UMRS 1127, Universit Pierre et Unit of Neurology and Neurometabolic Disorders, Sienna,
Marie Curie, Sorbonne Universits, France; Institut du Italy, 3Azienda ospedaliera universitaria senese, SIena Italy,
Cerveau et de la Moelle pi, Paris, France, 2Sorbonne Neuroimaging and neurointervention unit, Sienna, Italy
Universits, UPMC Univ UMR_S1136, and INSERM UMR_S
1136, Institut Pierre Louis dEpidmiologie et de Sant Background and aims: Several single gene disorders have
Publique, Paris, France, 3CIC, CHRU Pierre-Paul Riquet the potential to be overlooked in the differential diagnostic
Hospital, Toulouse, France, 4Department of Genetics, evaluation of patients with multiple sclerosis. Pelizaeus-
Assistance Publique-Hpitaux de Paris, Groupe Hospitalier Merzbacher disease and spastic paraplegia type 2 (SPG2)
Piti-Salptrire Charles-Foix, Paris, France, 5Service de are allelic X-linked disorders associated with defective
Neurologie, CHRU Gui de Chauliac, Montpellier, France, myelination of the central nervous system and mutations in
6CHU de Strasbourg-Hpital de Hautepierre, Strasbourg, PLP1. Neurological symptoms are occasionally observed in
France, 7Univ. Grenoble Alpes, Grenoble Institut des women
Neurosciences, GIN, INSERM, U1216, Grenoble, France Methods: P1, a 29-year-old woman and her 52-year-old
Background and aims: Polyglutamine (PolyQ) diseases mother (P2) referred walking difficulties since adolescence
are dominantly transmitted neurological disorders, caused and progressive cognitive decline. In both cases,
by coding and expanded CAG trinucleotide repeats. Given neurological examination revealed spastic gait, pyramidal
the broad expression and basic cellular functions of wild- tract involvement, distal muscle atrophy in the legs, and hip
type proteins, it seems likely that the mutant forms may adductor and tibialis anterior muscle weakness. Axonal
affect the etiology of other diseases. Cancer was reported to peripheral neuropathy and diffuse white matter changes
be rare in patients with polyQ diseases and we aimed to (WMC) at brain MRI were observed. In P1 cerebrospinal
investigate its prevalence in French polyQ diseases. oligoclonal bands were identified and the patient was
Methods: Consecutive patients with Huntington disease diagnosed with primary progressive multiple sclerosis
(HD) and spinocerebellar ataxias (SCAs) were questioned (PPMS).
about cancer, cardiovascular diseases and related risk Results: Using a targeted method in next generation
factors in 4 University Hospital through France (Paris, sequencing (NGS), we identified in P2 the novel
Toulouse, Strasbourg and Montpellier). Standardized heterozygous c.210T>G/p.Y70* in PLP1. The mutation was
Incidence ratios (SIRs), based on age and sex-adjusted rate also found in P1 but not in a healthy daughter. A moderately
of French population were assessed for different types of and extremely skewed chromosome X inactivation pattern
cancer. Tumor samples were collected for wild type and was observed in P1 and P2, respectively. We also observed
mutated protein distributions. 60% reduction of PLP1 mRNA expression in skin cells
Results: We identified 372 HD and 134 SCAs patients, compared to controls.
reporting 36 cancers (6.13%). SIRs showed significantly Conclusion: SPG2 and other single gene disorders share
reduced risk of cancer in HD (SIR=0.22, 95% CI 0.14-0.32) clinical and radiologic features with PPMS and definition of
and SCAs (SIR=0.20, 95% CI 0.08-0.42). In contrast, skin the molecular defect require a more comprehensive NGS-
cancers were more frequent than expected in HD (SIR= based approach. In this family mother and daughter
5.12, 95% CI 1.65-11.95). Prevalence of cardiovascular presented a X-linked dominant disorder with skewed X
diseases was 15%. In our sample, incidence of cancer or inactivation suggesting that PLP1 should be tested in
cardiovascular disease was not influenced by the CAG women with spastic paraparesis, cognitive decline and
repeat size. No difference between HD and SCAs were WMC.
observed, except for tobacco and alcohol consumption that Disclosure: Nothing to disclose
were more frequent in HD (p<.0056).
Conclusion: There was decreased cancer rate in polyQ
diseases despite high risk factors. Analyses of tumor tissues
are ongoing.
Disclosure: Nothing to disclose
O1135 O1136
Idebenone is effective and well tolerated Patients carrying a loss-of-function
in Lebers Hereditary Optic Neuropathy mutation in ABCA7 exhibit a classical
(LHON): results of a 3-year Expanded late-onset Alzheimers disease phenotype
Access Program (EAP) T. vanDenBossche1, K. Sleegers1, S. Engelborghs2,
T. Klopstock1, G. Metz2, C. Galllenmller1, A. Sieben1, A. deRoeck1, M. Vandenbulcke3,
B. Livonius-FreifrauvonEyb3, F. Lob3, T. Meier2, R. Vandenberghe4, J.-J. Martin2, P.P. deDeyn2, P. Cras2,
C. Catarino1 C. vanBroeckhoven1
1Neurology, University of Munich, Munich, Germany, 1Department of Molecular Genetics, VIB, Antwerp, Belgium,
2Santhera Pharmaceuticals, Liestal, Switzerland, 2Institute Born-Bunge, University of Antwerp, Antwerp,
3Ophthalmology, University of Munich, Munich, Germany Belgium, 3Department of Old Age Psychiatry and Memory
Clinic, University Hospitals Leuven, Leuven, Belgium,
Background and aims: LHON is an inherited mitochondrial 4Department of Neurology, University Hospitals Leuven,
disorder leading to severe bilateral vision loss from which
Leuven, Belgium
recovery is rare. Increasing evidence from a randomized
placebo-controlled study and retrospective cohort studies Background and aims: Rare loss-of-function (LOF)
indicates that idebenone has therapeutic potential for the mutations were reported in ABCA7, a gene associated with
treatment of LHON. Alzheimer disease (AD) risk in genome wide association
Methods: To evaluate the efficacy and safety of idebenone studies. Through targeted resequencing of the full ABCA7
(Raxone), 93 patients with a recent diagnosis of LHON locus, we identified seven different LOF mutations in
were given idebenone 900 mg/day in an EAP involving 36 Belgian AD patients. Moreover, one frameshift mutation
medical centres worldwide. Visual acuity (VA) was assessed (p.E709fs) segregated with disease in an extended Belgian
at baseline and every 3 months thereafter. Clinically relevant autosomal dominant AD family, and was also present in 14
recovery (CRR) was defined as (i) improvement by at least apparently unrelated AD patients. All p.E709fs carriers
10 letters on the ETDRS chart or (ii) improvement from shared the mutation on the same haplotype, suggestive of a
off-chart to on-chart. Prevention of VA loss was assessed founder effect in the Belgian population. We aimed to
in the subgroup of patients with VA<1.0 logMAR at generate a clinicopathological phenotype of the ABCA7
baseline. LOF carriers.
Results: Of 69 patients with post baseline data and carrying Methods: Available demographic, clinical and
one of the 3 major mutations, 34 (49%) showed CRR upon neuropathological data were reviewed.
treatment with idebenone. The mean duration from start of Results: The mutation carriers (n=22) had a mean onset age
treatment to first objective improvement of VA was 6 of 73.48.4 years, with a wide age range of 36 (54-90)
months. The proportion of CRR is higher than expected for years, which was independent of APOE genotype and
spontaneous recoveries as reported in the literature and in a cerebrovascular disease. The mean disease duration was
Case Record Survey from a comparable untreated patient 5.73.0 years (range 2-12 years). A positive family history
cohort. At the start of treatment, 21 patients had their best was noted in 10 carriers (45.5%). All patient carriers, except
VA below 1.0 logMAR. 12 patients in this subgroup (57%) one, had an amnestic presentation. Further progression of
kept that level of VA at the last assessment, at a mean disease was compatible with AD. Signs of frontal
follow-up time of 15 months. dysfunction in the neurocognitive profile were present in
Conclusion: Idebenone is well tolerated and effective in seven patients. Four patients developed mild parkinsonism,
LHON in both prevention of VA loss and recovery. and four patients showed delusions and/or hallucinations. In
Disclosure: Santhera Pharmaceuticals provided idebenone four carriers autopsy was performed, showing typical
free of costs for this Expanded Access Program. immunohistochemical changes of late-onset AD.
Conclusion: The patients carrying a LOF mutation in
ABCA7 manifested a typical Alzheimer's disease
phenotype, although the wide range in onset age suggests
the influence of yet unknown modifying factors.
Disclosure: Nothing to disclose
O1203 O1204
Non-infectious complications of acute Does the proportion of single-chain rtPA
stroke and their impact on hospital influence outcomes in patients with
mortality in an urban Polish stroke unit: cerebral ischemia?
changes from 1995 to 2013 D. Leys1, I. Sibon2, J.-L. Mas3, T. Moulin4, M. Giroud5,
M. Karlinski, J. Bembenek, A. Baranowska, R. Bordet6, D. Vivien7
I. Kurkowska-Jastrzebska, A. Czlonkowska
1Lille, France, 2CHU Pellegrin, Bordeaux, France,
2nd Department of Neurology, Institute of Psychiatry and
3Neurology, Ste Anne Hospital, Paris, France, 4Besanon,
Neurology, Warsaw, Poland France, 5Neurology, University of Burgundi, Dijon, France,
6U1171-Laboratoire de pharmacologie mdicale, Lille,
Background and aims: Our aim was to investigate changes
France, 7INSERM, Caen, France
in the occurrence of non-infectious complications of acute
stroke and their impact on hospital mortality over the last Background and aims: The 2 forms of tissue plasminogen
two decades in a single urban stroke centre. activator (tPA), single- (sc-tPA) and 2-chain (tctPA) have
Methods: It is a retrospective registry-based analysis of similar thrombolytic activities, but neurotoxicity is specific
consecutive acute stroke patients from a highly urbanized to sc-tPA. The proportion of sc- and tc-forms of recombinant
area (Warsaw, Poland) admitted to a single stroke centre tPA (rtPA) being different between blisters, patients who
between 1995 and 2013. A total of 4770 patients were receive higher proportions of the sc-form might have worse
divided to four time periods: 1995-1999 (n=637), 2000- outcomes.
2004 (n=1501), 2005-2009 (n=1575) and 2010-2013 Objective: To determine whether the sc/(sc+tc) rtPA ratio
(n=1057). Odds ratios for hospital death were adjusted for influences the proportion of patients without handicap 3
pre-existing disability, stroke type, age and baseline months after cerebral ischemia, and to identify its influence
neurological deficit. on (i) dependency, (ii) survival, and (iii) symptomatic
Results: Over time there was a significant decrease in intracerebral hemorrhage (s-ICH).
occurrence of myocardial infarction (2.1%, 1.7%, 1.0% and Methods: We prospectively included consecutive stroke
0.6%, respectively) and exacerbated congestive heart failure patients treated with i.v. rtPA in 13 French centers, and
(4.4%, 5.5%, 3.1%, 1.7%). The proportions of patients determined the sc/(sc+tc) ratio in the treatment administered
experiencing pulmonary embolism (1.3%, 1.3%, 1.3%, for each patient. Samples were frozen at -20C and analyzed
1.5%), recurrent stroke (1.3%, 1.5%, 2.0%, 1.9%) and by densitometry. We studied the association between sc/
seizures (0.3%, 0.4%, 0.3%, 0.7%) remained stable. (sc+tc) ratios and the 4 outcome measures. OPHELIE was
Occurrence of gastrointestinal bleeding was fluctuating registered under ClinicalTrials.gov Identifier n
with an increasing tendency (0.0%, 1.1%, 2.0%, 1.2%). All NCT01614080.
investigated complications, apart from seizures, increased Results: We recruited 1,004 patients (515 men, median age
odds for hospital death. However, there were individual 75 years, median onset-to-needle time 170 minutes, median
exceptions for gastrointestinal bleeding (years 2000-04) or national institutes of health stroke scale score 10). The sc/
myocardial infarction, heart failure and recurrent stroke (sc+tc) ratios ranged from 51% to 91% (median 71%).
(years 2010-13). There was no statistical association between sc/(sc+tc)
Conclusion: All non-infectious complications of acute ratios and handicap, dependency or death at 3 months.
stroke but seizures increase odds for hospital death. The Patients with s-ICH had significantly lower ratios (median
occurrence of myocardial infarction and exacerbation of 69%, IQR 67%-72% vs. 72%, 68%-76%; adjusted p=0.003).
congestive heart failure decreased over the years, whilst the Conclusion: The neurotoxicity of rtPA does not influence
negative effect of cardiac conditions and recurrent stroke functional outcomes and mortality in patients with cerebral
has been recently attenuated. It may reflect positive changes ischemia. Higher proportions of sc-rtPA are even associated
in Polish urban stroke care. with lower risks of s-ICH.
Disclosure: Nothing to disclose Disclosure: Nothing to disclose
O1205 O1206
Early start of NOAC after an acute The rs12041331G alleles are associated
cerebrovascular event: risk of intracranial with aspirin response in ischemic stroke
hemorrhage and recurrent events patients in China
D. Seiffge1, C. Traenka1, A. Polymeris1, L. Hert1, Y. Xu, X. Zhang, Y. Shao
R. Sutter2, N. Peters1, P. Lyrer1, L. Bonati1, S. Engelter1, Department of Neurology, Nanjing Drum Tower Hospital ,
G.M. deMarchis1 Nanjing, China
1Stroke Center and Neurology, University Hospital Basel,
Background and aims: Little research regarding genotypes
Basel, Switzerland, 2Basel, Switzerland and aspirin response related to acute ischemic stroke has
Background and aims: Randomized clinical trials (RCT) been published. This study was conducted to investigate
on non-vitamin K antagonist oral anticoagulants (NOACs) whether the polymorphisms affect aspirin response and
for atrial fibrillation (AF) excluded patients up to 6 months prognosis related to acute stroke.
after acute stroke (AIS) to minimize the risk of intracerebral Methods: A total of 752 patients with acute ischemic stroke
hemorrhage (ICH). In clinical practice, NOACs are were enrolled in this study; all received follow-up
administered before the time frames studied in RCTs (early evaluations 3, 6 and 12 months after aspirin treatment.
NOAC-starts). We sought to assess (i) the frequency of rs1045642, rs868853, rs1330344, rs20417, rs12041331,
early NOAC-starts, (ii) the rate of ICH and (iii) recurrent rs2768759 were screened. The arachidonic acid (AA)-
AIS/TIA. induced and adenosine diphosphate-induced(ADP) platelet
Methods: aggregation test, the National Institutes of Health Stroke
Analysis from the prospective NOACISP registry. We Scale (NIHSS), and the modified Rankin Scale (mRS) were
included consecutive patients with nonvalvular AF, used, and blood vascular events were evaluated.
hospitalized for AIS/TIA (= index event), and who received Results: The difference before and after aspirin treatment
NOAC (NOACafter) or Vitamin K antagonists (VKAafter) on AA-induced platelet aggregation was significantly
for secondary prophylaxis. Patients were followed-up for smaller in patients carrying rs12041331G alleles compared
3-6 months after the index event for ICH, recurrent AIS/ with patients carrying none. Patients with none had better
TIA. NOACafter vs. VKAafter groups were compared, and outcomes demonstrated by NIHSS and mRS scores after
the early vs. RCT-conform NOAC-starts. treatment.
Results: Conclusion: rs12041331 genotypes had significant impact
204 patients were included, for a total follow-up time of on aspirin response and prognosis of patients with stroke.
78.25 patient-years. In the NOACafter cohort (n=155), Disclosure: Nothing to disclose
median delay between index event and OAC-start was 5 Motor neurone disease
days (IQR 3-11), in the VKAafter cohort (n=49) 4 days
(IQR 2-8). Early NOAC-starts occurred in 81% of patients.
During follow-up, we observed 1 ICH (in the VKAafter
cohort; =1.3%/year) and 6 recurrent events (7.7%/year),
with no significant differences between the NOACafter vs.
VKAafter groups, nor between the early vs. RCT-conform
NOAC-start groups.
Conclusion: In clinical practice, even if NOAC are often
started earlier than in RCTs, the risk of ICH was low. The
rate of recurrent events was six times higher than those of
ICH. These observations may be considered when choosing
the time-point of OAC start after AIS.
Disclosure: This study was supported by a grant from the
Swiss Heart Foundation.
O1207
Endovascular therapy versus medical
care alone for ischemic stroke: a
systematic review and meta-analysis of
10 RCTs
F. Rodrigues1, J.B. Neves2, D. Caldeira1, J.M.M.C. Ferro3,
J. Ferreira1, J. Costa1
1Clinical Pharmacology Unit, Instituto de Medicina
Salute San Raffaele University, Milan, Italy, 3Biostatistics Sofferenza, San Giovanni Rotondo, Italy, 4Department of
Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Neuroscience, University of Turin, Turin, Italy,
5Neuroscienze, Universit di Padova, Padua, Italy,
Giovanni Rotondo, Italy, 4NEuroMuscular Omnicenter,
6Neuroradiology, Universit Vita-Salute San Raffaele, Milan,
Serena Onlus Foundation, Milan, Italy, 5Vita-Salute San
Raffaele University, Milan, Italy, 6Department of Neurology, Italy
San Raffaele Scientific Institute, Vita-Salute San Raffaele Background and aims: Advances in statistical learning
University, Milan, Italy, 7Laboratory of Clinical Molecular theory were applied to assess the diagnostic potential of
Biology and Cytogenetics, San Raffaele Scientific Institute, structural and diffusion tensor (DT) MRI in amyotrophic
Milan, Italy, 8Neuroradiology, Universit Vita-Salute San lateral sclerosis (ALS).
Raffaele, Milan, Italy Methods: 3D T1-weighted and DT MRI were obtained
Background and aims: In order to explore the specific from 113 sporadic (probable, probable-laboratory
C9orf72 MRI signature in amyotrophic lateral sclerosis supported, definite) ALS patients, 22 patients with ALS
(ALS), we investigated structural and functional mimic disorders, and 40 healthy controls. The diagnostic
abnormalities in C9orf72-positive (+) relative to C9orf72- accuracy of precentral cortical thickness measures and DT
negative (-) ALS cases matched for all main clinical MRI metrics of the corticospinal tract and motor callosal
features. fibers were assessed in a testing cohort and externally
Methods: 21 C9orf72(+) ALS patients were compared proved in a validation cohort using a random forest analysis.
with: 22 healthy subjects; 31 C9orf72(-) ALS patients Results: In the testing set (64 randomly selected sporadic
without cognitive impairment [C9orf72(-) motor] matched ALS patients and healthy controls), precentral cortical
for ALSFRS-r score; 26 C9orf72(-) ALS patients matched thickness showed 0.85 accuracy, 0.76 sensitivity, 1.00
for ALSFRS-r score and cognitive deficits [C9orf72(-) specificity in differentiating ALS patients from healthy
plus]; 20 C9orf72(-) ALS patients matched for disease controls, while DT MRI measures distinguished the two
progression rate [C9orf72(-) rate]. All subjects performed groups with 0.77 accuracy, 0.84 sensitivity, 0.65 specificity.
structural, diffusion tensor and resting state functional MRI. In the same group, combination of cortical thickness and
Results: All patients showed cortical thinning of motor and DT MRI metrics improved the classification pattern as
extra-motor brain regions. No cortical areas were more follows: 0.87 accuracy, 0.88 sensitivity, 0.84 specificity. In
affected in C9orf72(+) compared to C9orf72(-) motor and the validation cohort (remaining 49 sporadic ALS vs ALS
plus phenotypes, while occipital thinning was observed in mimic disorders), the diagnostic accuracy was higher for
C9orf72(+) relative to C9orf72(-) rate cases. All patients DT MRI than cortical thickness measures (0.80 vs. 0.65),
showed a damage of the motor callosal fibers and and the combined approach improved the classification
corticospinal tract vs controls. C9orf72(+) patients showed only minimally (accuracy 0.83).
an additional involvement of the right superior longitudinal Conclusion: A multimodal imaging approach that
fasciculus. C9orf72(+) patients exhibited decreased incorporates motor cortical and white matter alterations
functional connectivity of the motor and dorsal attention yields statistically significant improvement in accuracy
networks compared to C9orf72(-) plus patients. In the over using each modality independently in the individual
visual network, C9orf72(+) patients showed increased ALS patient classification. DT MRI technique may be a
functional connectivity relative to controls and all sporadic useful tool in distinguishing ALS from mimic disorders.
phenotypes. Disclosure: Funded by: AriSLA (MacLearnALS Project).
Conclusion: Early occipital structural and functional
alterations appear to be as the C9orf72 specific MRI
signatures in ALS. Functional connectivity patterns relative
to sporadic cases suggest altered connectivity as part of
O1212 O1213
Deconstructing caregiver burden in The CANALS study: a randomized,
amyotrophic lateral sclerosis adding a double-blind, placebo-controlled,
qualitative perspective multicentre study to assess the safety
M. Galvin1, T. Burke2, B. Corr3, C. Madden4, I. Mays5, and efficacy on spasticity symptoms of a
R. McQuillan6, V. Timonen7, A. Staines1, O. Hardiman8 Cannabis Sativa extract in motor neuron
1School of Nursing and Human Sciences, Dublin City
disease patients
University, Dublin, Ireland, 2Psychology, Beaumont
Hospital, Dublin, Ireland, 3Department of Neurology , N. Riva1, G. Mora2, G. Soraru3, C. Lunetta4, M. Clerici5,
National Neuroscience Centre, Beaumont Hospital, Dublin, Y. Falzone6, K. Marinou7, E. Maestri8, R. Fazio6,
Ireland, 4Academic Unit of Neurology, Trinity Biomedical M. Comola2, G. Comi2
Sciences Institute, Trinity College Dublin, Dublin, Ireland,
1San Raffaele Hospital, Milan, Italy, 2Milan, Italy,
5Academic Unit of Neurology, Trinity Biomedical Sciences 3Department of Neurosciences, University of Padova, Padua,
Institute, Trinity College Dublin, Dublin, Ireland, 6Beaumont Italy, 4Centro Clinico NEMO, Milan, Italy, 5Department of
Hospital, and St Francis Hospice, Raheny, Dublin 5, Ireland, Neurology, Division of Neuroscience, Institute of
Dublin, Ireland, 7School of Social Work and Social Policy, Experimental Neurology (INSPE), Milan, Italy, 6Department
Trinity College Dublin, Ireland, Dublin, Ireland, 8Academic of Neurology, San Raffaele Scientific Institute, Vita-Salute
Unit of Neurology, Trinity College Dublin, Dublin, Ireland San Raffaele University, Milan, Italy, 7Salvatore Maugeri
Foundation, IRCSS, Scientific Institute of Milano, Milano
Background and aims: Amyotrophic Lateral Sclerosis
Italy, Milan, Italy, 8NEuroMuscular Omnicentre, Fondazione
(ALS) is a progressive, neurodegenerative disease, affecting Serena Onlus, Milan, Italy
physical, communication and cognitive functioning. A
considerable amount of care for people with ALS is Background and aims: Spasticity is a one of the major
provided in the community by family and friends. Informal determinant of functional loss and decline in quality of life
caregivers face the demands of coping with a rapidly in ALS and other motor neuron disease (MND) patients. In
evolving care situation, physical and cognitive/behavioural recent years, several clinical trials have tested the efficacy
decline of the care-recipient and their own physical, of cannabis on spasticity in multiple sclerosis. The study's
psychological and emotional health needs. primary was to evaluate the safety, tolerability and efficacy
Caregiver burden is a multidimensional construct, a term of a Cannabis Sativa extract medium-term treatment (6
frequently used but rarely deconstructed. A combination of weeks) to improve spasticity in ALS and MND patients.
validated scales and measures with pre-defined variables, Methods: 60 consecutive patients fulfilling specific
and caregivers self-defined difficulties generates a inclusion criteria were randomized and double blinded
comprehensive understanding of burden adding to the allocated to receive a cannabis extract oral spray or placebo.
conceptualization and understanding of the informal Primary end-point was improvement in the modified 5-
caregiver experience. points modified Ashworth Scale (MAS). Secondary End-
Methods: Following population-based recruitment, a semi- points: spasticity, spasm frequency and sleep disruption
structured interview and series of standardised measures (0-10 NRS score); Function: walking ability, functional
were used to assess quality of life, psychological distress scores (ALSFRS-R); pain (0-10 NRS score). The Global
and subjective burden, and in an open-ended question Impression of Change (GIC) for the patient, carer and
informal caregivers (n=81) identified difficult aspects of clinician.
their caregiving experience. Results: The study drug was well tolerated, none of the
Results: Significant associations were found between patients included withdrew from the study. We observed a
caregiver burden, and hours of care provided (p=.012), positive trend for improvement of all outcome measures in
reduced quality of life (p=.014) and increased psychological the active drug arm compared to the placebo group, which
distress (p=.004). The caregiving difficulties were reached statistical significance for the MAS mean score
thematised around managing the practicalities of the ALS (p=0.013) and pain NRS (p=0.013). Patients GIC
condition; the emotional and psychosocial impact; demonstrated a significant subjective improvement in 55%
limitation and restriction, and impact on relationships with of subjects (p=0.001).
self and others. Conclusion: Our pilot study suggests that cannabinoids
Conclusion: Preliminary analysis endorses the value of the may represent a valuable option for spasticity treatment in
deconstruction of burden. Acknowledging objective and MND patients. Moreover, it may have also additional
subjective burden, and difficulties as identified by the beneficial effects such as pain relief. Further studies are
caregivers themselves, can help focus support and needed in order to confirm our results.
interventions for caregivers. Educational and training Disclosure: This study has been funded by Fondazione
programmes for caregivers and health care professionals Italiana di Ricerca per la Sclerosi Laterale Amiotrofica
should recognize the dimensionality of caregiver burden in (AriSLA, CANALS Project).
ALS.
Disclosure: This research was supported by funding from
the Irish Health Research Board Dublin as part of the HRB
Interdisciplinary Capacity Enhancement Awards.
O1214
Neurofilament light chain protein as a
biomarker in ALS differential diagnoses
D. Primdahl1, K. Svenstrup2, K. Winge3, N. Heegaard4,
K. Hansen1
1Neurology, Rigshospitalet, Copenhagen, Denmark,
2Neuromuscular, Rigshospitalet, Copenhagen, Denmark,
3Copenhagen, Denmark, 4Autoimmunology and Biomarkers,
O1217 O1219
Alzheimers disease cerebrospinal-fluid White matter lesion burden and sleep
biomarkers are altered in untreated but disordered breathing in acute stroke
normal in continuous positive airway A. Seiler1, M. Camilo1, S. Ott2, S. Miano3, R. Wiest4,
pressure treated obstructive sleep apnea C. Bassetti1
patients
1Neurology, Bern University Hospital, Berne, Switzerland,
2Pulmonary Medicine, Bern University Hospital, Berne,
C. Liguori, N.B. Mercuri, F. Izzi, G. Sancesario, Switzerland, 3Sleep and Epilepsy Center, Neurocenter of
A. Romigi, A. Cordella, F. Placidi Southern Switzerland, Civic Hospital of Lugano, Lugano,
Department of Systems Medicine, University Hospital of Switzerland, 4Support Center for Advanced Neuroimaging
Rome Tor Vergata, Rome, Italy (SCAN), Institute for Diagnostic and Interventional
Background and aims: Obstructive sleep apnea (OSA) is Neuroradiology, Bern University Hospital, Berne,
a frequent sleep disorder causing sleep fragmentation and Switzerland
intermittent hypoxia. The aim of this study was to evaluate Background and aims: The frequency of sleep-disordered
the effect of OSA on sleep architecture and cerebrospinal- breathing (SDB) is high in acute stroke patients. Few small
fluid (CSF) Alzheimers Disease (AD) biomarkers studies suggested that stroke patients with SDB may present
(-amyloid and tau proteins) in patients affected by an increase in cerebral white matter lesions (WML) of
subjective cognitive impairment (SCI). Moreover, we presumed microvascular origin, which are known to be
investigated CSF AD biomarkers and sleep architecture also associated with a worse outcome.
in SCI patients affected by OSA and well treated by The purpose of this study is to assess prospectively and
continuous positive airway pressure (CPAP) treatment. systematically the relationship between the extent of WML
Methods: We compared CSF AD biomarkers levels and and SDB in patients with acute ischemic stroke or transitory
polysomnographic sleep data in SCI patients, divided in ischemic attack (TIA).
OSA, controls and OSA-CPAP. Moreover, we correlated Methods: All patients with MRI and nocturnal
CSF and polysomnographic data in OSA, controls and polysomnography within 14 days after ischemic stroke or
OSA-CPAP group. TIA were selected from the SAS-CARE cohort (SDB in
Results: OSA patients (n=25) showed the significant TIA/Ischemic Stroke and Continuous Positive Airway
reduction of CSF A42 levels compared to controls (n=15, Pressure Treatment Efficacy; NCT01097967) from two
p<0.001) and OSA-CPAP patients (n=10, p<0.001). centers, Bern and Lugano. SDB was defined as Apnea-
Moreover, two-third of OSA patients, but no control or Hypopnea-Index (AHI) 10. White matter lesions on T2/
OSA-CPAP patient presented pathological CSF A42 FLAIR imaging were graded visually by Fazekas
concentrations (<500 pg/mL). OSA patients also showed classification and also assessed semi-automatically.
reduced sleep quality and continuity compared to controls Results: We included 98 patients, 65 (66%) of whom had
and OSA-CPAP patients. Moreover, correlating SDB. WML were significantly higher in the SDB-group
polysomnographic data with CSF A42 concentrations in (p=.002 for WML volume, p=.001 for periventricular and
the OSA group, we found a significant correlation between deep WML according to Fazekas). WML severity and AHI
lower CSF A42 concentration and lower mean SaO2, and correlated significantly (rs=.321, p=.001 for WML volume;
a significant correlation linking higher CSF tau and rs=.311, p=.002 for periventricular and rs=.290, p=.004 for
phosphorilated tau proteins levels to lower TST and SE and deep WML). Multivariable analysis with adjustment for
higher WASO. age, hypertension, smoking and diabetes showed that
Conclusion: We hypothesize that OSA altering sleep periventricular (p=.023) and deep (p=.035) WML were
homeostasis and producing intermittent hypoxia interferes independently associated with sleep apnea.
with -amyloid metabolism, thus promoting early AD Conclusion: Stroke/TIA patients with SDB have
neuropathological changes. Therefore, OSA represents a significantly more WML than those without SDB.
risk factor for AD pathology; nevertheless, CPAP Moreover, SDB is independently associated with
intervention could restore cerebral -amyloid dynamics. periventricular and deep WML.
Disclosure: Nothing to disclose Disclosure: The Swiss National Science Foundation (SNF
Grant 320030_125069) provided a grant for this study.
O1218
Abstract cancelled
O1220
The comparison of cerebral
hemodynamics between patients with
obstructive sleep apnea syndrome (OSA)
and periodic limb movement disorder
(PLMD) during sleep
Z. Zhang1, M. Schneider2, M. Laures3, M. Qi3,
R. Khatami1
1Barmelweid, Switzerland, 2Center for Sleep Medicine and
Sleep Research, Barmelweid, Switzerland, 3Schlaflabor,
Klinik Barmelweid, Barmelweid, Switzerland
Background and aims: OSA and PLMD are two sleep
disorders characterized by repetitive respiratory or
movement events associated with cortical arousals. They The average graphs of NIRS signals during apnea/hypopnea with
arousal (AHA) events in each patients with OSA. Subfigures show the
are high risk factor of cardiovascular diseases. However, the results per patient. The vertical lines at time 0 second indicate the start
cerebral hemodynamics induced by nocturnal OSA and of apnea/hypopnea (AH). The hemodynamic changes are expressed in
PLM events is still unclear due to technical limitations. arbitrary units (A.U.), as the value at0 second is set at 0.
Methods: We compared the cerebral hemodynamic changes
induced by 432 periodic apneas/hypopneas (AH) with
arousal (AHA) and 459 periodic limb movements with
arousal (PLMA) in eight patients (four patients with PLMD
and OSA, and four patients with OSA) with near-infrared
spectroscopy (NIRS). Heart rate (HR) changes during AHA
and PLMA were also characterized.
Results: We found homogenous periodic fluctuations in
oxygenated (HbO2) and deoxygenated (HHb) haemoglobin
induced by AHA (Fig.1), i.e., HbO2 decreased while HHb
increased during AH with a reversed pattern induced by
consecutive arousal which terminated the respiratory
events. Blood volume (BV) showed the similar patterns as
HHb but with less profound amplitudes. During PLMA
HbO2 and BV first increased and decreased to the baseline Figure.2 The average graphs of NIRS signals during periodic limb
in all the patients (Fig.2), while HHb showed an inconsistent movement with arousal (PLMA) events in each patients with PLMS.
Subfigure (a)-(d) shows the results from each patient, respectively.
pattern even in the same patient. HR started to increase
before the onset of PLMA and returned to baseline after
passing the peak; whereas HR in AHA first decreased
during apnea and increased after arousal onset (Fig.3).
Conclusion: Both AHA and PLMA involve cerebral
hemodynamic changes, but the different hemodynamic
patterns may indicate distinct pathological mechanisms or
autonomic regulation underlying them. The HR changes
may partly account for the cerebral hemodynamic patterns
during PLMA, but not for the ones of AHA.
Figure.3 The average of heart rate (HR) changes during periodic limb
movement with arousal (PLMA) (a) and apnea/hypopnea with arousal
(AHA) (b).
O1221
Does vitamin D play a role in restless legs
syndrome/ Willis Ekbom disease?
A. Stefani, T. Mitterling, G. Weiss, B. Hgl
Medical University of Innsbruck, Innsbruck, Austria
Background and aims: Restless Legs Syndrome (RLS) is
a common sensorimotor disorder characterised by
discomfort during rest and urge to move the limbs,
accompanied by abnormal sensations. Together with genetic
factors, brain iron dysregulation and dopaminergic
dysfunction play an important role in RLS pathogenesis.
Vitamin D affects the nigrostriatal dopaminergic pathway
and has been suggested to be involved in RLS pathogenesis.
We investigated vitamin D levels in RLS and controls.
Methods: This is a preliminary analysis of a larger ongoing
study. 57 RLS patients and 57 age- and sex-matched
controls were included in this analysis. All RLS patients
were clinically evaluated using different scales (incliding
IRLS and RLS-6) and underwent a structured interview. All
participants underwent extended laboratory examination
including 25-OH-VitaminD.
Results: 22.8% of RLS patients had 25-OH-VitaminD
levels<30nmol/l compared to 8% of controls (p=0.022).
After stratification for sex, the difference remained
significant only among women (patients median 48,
interquartile range 29-71 vs. controls median 55,
interquartile range 46-69;p=0.039). A stratification for
early/late onset RLS showed in the subgroup with late onset
RLS (n=14) a strong negative correlation between both
IRLS/RLS-6 and 25-OH-VitaminD levels (r=-0.723,
p=0.003, and r=-0.671, p=0.009, respectively).
Conclusion: In addition to the known influence of iron
parameters on RLS symptoms, these results corroborate a
possible association between low vitamin D levels and
RLS. Vitamin D levels correlated with RLS symptom
severity in late onset RLS. Vitamin D levels may interact
with RLS symptoms in a subgroup of patients. The potential
role of vitamin D in RLS pathogenesis needs to be further
investigated.
Disclosure: Nothing to disclose
Epilepsy 2
O1222
Efficacy and tolerability of lacosamide
monotherapy in patients with newly
diagnosed epilepsy: A randomized
double-blind trial versus controlled-
release carbamazepine
M. Baulac1, F. Rosenow2, M. Toledo3, K. Terada4, T. Li5,
M. deBacker6, K.J. Werhahn7, M. Brock5
1Hpital de la Piti-Salptrire, Clinique Neurologique,
Paris, France, 2Neurocenter, Goethe University Frankfurt, Table 1: Baseline demographics and epilepsy characteristics
Epilepsy Center Frankfurt Rhine-Main, Frankfurt am Main,
Germany, 3Hospital Vall dHebron, Barcelona, Spain,
4Shizuoka Institute of Epilepsy and Neurological Disorders,
O1224
Verbal learning and memory outcome in
selective amygdalohippocampectomy
versus temporal lobe resection in 108
patients with hippocampal sclerosis
M.T. Foged1, K. Vinter2, L. Kristensen3, M.H. Litman1,
N. Breinegaard4, V. Olesen5, T.W. Kjr6, F.F. Madsen5,
The Danish Epilepsy Surgery Group7, O.B. Paulson1,
L.H. Pinborg1 Table 2, results
1Neurobiology Research Unit and Department of Neurology,
Copenhagen University Hospital, Rigshospitalet, 2Epilepsy
Clinic, Department of Neurology, Copenhagen University
Hospital, Rigshospitalet, 3Danish Epilepsy Centre,
Dianalund, Filadelfia, 4Department of Public Health, Section
of Biostatistics, University of Copenhagen, 5Department of
Neurosurgery, University of Copenhagen, Rigshospitalet,
6Department of Neurophysiology, Copenhagen University
Table 1, methods
O1225 O1226
Exposure-response analysis of adjunctive Sleep-related hypermotor seizures arising
everolimus therapy in patients with outside the frontal lobe: a review of 44
refractory partial-onset seizures surgically treated cases
associated with tuberous sclerosis S. Gibbs, P. Proserpio, A. Losurdo, A. Rubino,
complex (TSC) F. Cardinale, R. Mai, S. Francione, M. Cossu,
J. French1, J. Lawson2, Z. Yapc3, T. Polster4, G. LoRusso, L. Tassi, L. Nobili
Centre for Epilepsy Surgery "C. Munari", Niguarda
R. Nabbout5, P. Curatolo6, P. deVries7, N. Berkowitz8,
Hospital, Milan, Italy
M. Voi8, S. Peyrard9, A. Vaury9, D.N. Franz10
1Epilepsy, NYU Comprehensive Epilepsy Center, New York, Background and aims: Although sleep-related hypermotor
India, 2The Tuberous Sclerosis Multidisciplinary seizures (SHS) usually arise from the frontal lobe, SHS can
Management Clinic, Sydney Childrens Hospital, Randwick, originate from other cerebral regions, especially in patients
Australia, 3Istanbul, Turkey, 4Pediatric Epileptology, Mara with drug-resistant epilepsy. To better characterize this
Hospital, Bielefeld, Germany, 5Paris, France, 66Tor Vergata population, we reviewed the characteristics of patients with
University Hospital, Rome, Italy, 7Division of Child and drug-resistant SHS seen in our centre from October 1997 to
Adolescent Psychiatry, University of Cape Town, Cape Town, September 2015.
South Africa, 8Novartis Pharmaceuticals Corporation, New Methods: Patients with SHS were classified according to
Jersey, USA, 9Novartis Pharmaceuticals S.A.S, Rueil- the location of their seizure onset zone (SOZ): frontal,
Malmaison, France, 10Department of Neurology, Cincinnati temporal, operculo-insular or posterior cortex. Seizure
Childrens Hospital Medical Center, Ohio, USA semiology was categorised according to earliest ictal
Background and aims: To determine response of partial- features using the 4-group classification of Bonini et al. for
onset seizures (POS) in patients with tuberous sclerosis frontal lobe seizure semiology. 1 Patient characteristics,
complex (TSC) to everolimus (EVE) by time-normalized histopathological substrate and the two-year post-operative
EVE Cmin (TNC) values achieved during the core phase Engel outcome were also assessed.
(18 weeks) of a phase 3, placebo-controlled trial. Results: We identified 137 patients with SHS (9.1%). The
Methods: Following an 8-week baseline phase, patients SOZ was located in the frontal lobe in 93 patients and was
(age1-65, stratified for age) with TSC and refractory POS extra-frontal in 44 (32.1%). Table 1 summarises the clinical
on 1-3 antiepileptic drugs were randomized (1:1.09:1) to findings. The most common histopathological substrate was
EVE 3-7 (low trough [LT]) or 9-15 ng/mL (high trough focal cortical dysplasia type II (52%), regardless of the SOZ
[HT]) Cmin target ranges or placebo. Dose adjustments (up location. Analysis of seizure semiology identified an
to 3) were performed during weeks 1-6 and, as needed, epileptic aura in 34 patients (77.3%). Of these, 33 suggested
during the subsequent 12-week maintenance phase to an extra-frontal onset. Figure 1 illustrates how hypermotor
achieve target Cmin. Percentage reduction in POS frequency semiology was expressed.
(RSF) and responder rate (RR) were determined for
different ranges of TNC measured during maintenance
phase.
Results: 366 patients were randomized to EVE LT (n=117),
HT (n=130), or placebo (n=119). Based on intent-to-treat
analysis of the primary endpoints, RSF was significantly
greater with LT (29.3%, P=0.003) and HT (39.6%, P<0.001)
vs. placebo (14.9%), as was the RR with LT (28.2%,
P=0.008) and HT (40%, P<0.001) vs. placebo (15.1%). RR
in patients with TNC <3, 3-7, 7-9, and >9 ng/mL were
14.3% (2/14), 29.9% (44/147), 44.2% (23/52), and 50%
(16/32), respectively. A 2-fold increase in TNC increased
the odds of a response 2.17-fold (95% CI, 1.34-3.52). Safety
profile was similar among patients achieving TNC below Table 1
and above 7 ng/mL.
Conclusion: EVE demonstrated efficacy over placebo and
the response to EVE is related to exposure, with best
responses at higher exposure levels. Safety/tolerability was
acceptable at all concentrations.
Disclosure: The study was sponsored by Novartis
Pharmaceutical Corporation.
O1227
Diagnostic accuracy of Salzburg criteria
for nonconvulsive status epilepticus
M. Leitinger1, E. Trinka1, E. Gardella2, A. Rohracher3,
G. Kalss4, E. Qerama5, J. Hfler1, A.H. Lindberg-Larsen5,
G. Zimmermann3, G. Kuchukhidze4, J. Dobesberger4,
P.B. Langthaler3, S. Beniczky6
1Salzburg, Austria, 2Department of Clinical Neurophysiology,
Danish Epilepsy Center, Dianalund, Denmark, 3Department
Figure 1: Frontal lobe seizure semiology in relation to the extra-frontal of Neurology, Salzburg, Austria, 4Department of Neurology,
seizure onset zone. Paracelsus Medical University Salzburg, Salzburg, Austria,
5Department of Clinical Neurophysiology, Aarhus, Denmark,
Conclusion: In our series, a third of patients with SHS had 6Dianalund, Denmark
an extra-frontal onset. Although clinical findings were
Background and aims: Several EEG-criteria for
similar, semiology (especially auras) as well as EEG and
nonconvulsive status epilepticus (NCSE) have been
MRI results were helpful in identifying an extra-frontal
proposed, but none of them has been clinically validated
onset. Semiology showed more elementary motor features
yet. We assessed diagnostic accuracy of the EEG-criteria
in operculo-insular and posterior regions while temporal
proposed by a panel of experts at the 4th London-Innsbruck-
SOZ tended to have a greater emotional content.
Colloquium on Status Epilepticus in Salzburg, 2013
1Bonini et al. Epilepsia 55(2), 2014
(Salzburg Criteria for NCSE).
Disclosure: Nothing to disclose
Methods: We analyzed data from 220 patients recorded in
three centers. The clinical validation group consisted of 120
consecutive patients with clinical suspicion of NCSE
referred to EEG. Reference standard was the final clinical
diagnosis in the medical reports, based on all clinical and
para-clinical data. We calculated sensitivity, specificity,
positive and negative predictive value, and overall
diagnostic accuracy. We also analyzed a group of 100
consecutive recordings with abnormal EEG-findings, but
without clinical suspicion of NCSE (controls) to further
evaluate the specificity of the criteria.
Results: In the clinical validation group, sensitivity was
97.6% and specificity was 88.6% (overall accuracy: 91.7%).
PPV was 81.6% and NPV was 98.6%. In the control group,
specificity was 97.0%. Therapeutic changes were seen
significantly more often in the group of patients fulfilling
the Salzburg-criteria (83.7%) as compared to patients who
did not (15%) (p< 0.001).
Conclusion: Salzburg Criteria for NCSE have high
diagnostic accuracy, are useful tool in clinical practice, and
can help standardizing further research on NCSE. This is
the first clinical validation study of diagnostic criteria for
NCSE, and it was done in a multicenter approach
Disclosure: Nothing to disclose.
Background and aims: neuromyelitis optica (NMO) is an Houston, USA, 2NeuroRx Research, Montreal, Canada,
3McGill University, Montreal, Canada, 4University Hospital
autoimmune disease mediated by antibodies against the
astrocyte protein aquaporin-4. Interleukin 6 induces AQP4- of Strasbourg, Strasbourg, France, 5Queen Mary University
ab production by plasmablasts and represents a novel of London, London, United Kingdom, 6Technische
therapeutic target. The aim of this study was to evaluate the Universitt Mnchen, Munich, Germany, 7University of
long-term safety and efficacy of tocilizumab, a humanized Miami, Miami, USA, 8F. Hoffmann-La Roche Ltd., Basel,
antibody targeting the interleukin 6 receptor, in NMO and Switzerland, 9Genentech, Inc., South San Francisco, USA,
10Vall d'Hebron University Hospital, Barcelona, Spain
NMO spectrum disorders.
Methods: This is an observational study on six female Background and aims: Ocrelizumab (OCR) is a humanised
patients with a diagnosis of NMO according to the current monoclonal antibody that selectively targets CD20+ B-cells.
diagnostic criteria and on tocilizumab therapy. We evaluated In this analysis, OCR efficacy was evaluated among patients
the safety and efficacy of tocilizumab on relapses, disability with primary progressive MS (PPMS) with and without T1
and MRI activity. gadolinium-enhancing (Gd+) lesions at baseline in a
Results: Patients were followed up for a mean of 13.8 randomised, double-blind, placebo-controlled Phase III
months (SD 6.1) after switching to tocilizumab. All patients study (ORATORIO).
had aquaporin 4-positive NMO (mean duration 13.7 SD 6.1 Methods: A total of 732 patients were randomised (2:1) to
years), and had been treated with different receive OCR 600mg or placebo as two 300mg intravenous
immunosuppressive and immunomodulating agents, infusions 14 days apart every 24 weeks for at least 120
followed by 2 to 7 cycles of rituximab. Despite complete weeks and until a prespecified number of 12-week
CD20-cell depletion during rituximab therapy, they suffered confirmed disability progression (CDP) events occurred.
clinical relapses (mean annualized relapse rate 3.2 SD 2.2) The primary endpoint (time to onset of 12-week CDP) and
and had a mean disability of 7.0 at the EDSS (SD 0.7) secondary endpoints (including time to onset of 24-week
before starting tocilizumab. After switching to tocilizumab CDP and change in total T2 lesion volume from baseline to
no new relapses were observed and the mean EDSS was 120 weeks) were evaluated in the subgroups of patients with
reduced to 6.5 (SD 0.5). At MRI, the volume of T2 lesions and without T1 Gd+ lesions at baseline.
was significantly reduced and no gadolinium enhancement Results: T1 Gd+ lesions were present at baseline in 27.5%
was observed. No adverse reactions have been observed. of OCR-treated patients vs. 24.7% of placebo-treated
Conclusion: Interleukin 6 receptor-blocking therapy can be patients. In patients with and without T1 Gd+ lesions at
effective in therapy-resistant cases of NMO. Larger baseline, respectively, OCR reduced: the risk of 12-week
controlled studies are needed to confirm the efficacy of CDP by 35% (HR, 0.65; p=0.0826) and 16% (HR, 0.84;
tocilizumab. p=0.2441); the risk of 24-week CDP by 33% (HR, 0.67;
Disclosure: Nothing to disclose p=0.1417) and 19% (HR, 0.81; p=0.1783); and total T2
lesion volume by 3.8% vs +12.0% with placebo (p<0.001)
and by 3.1% vs +6.1% with placebo (p<0.001).
Conclusion: In this subgroup analysis of patients with or
without T1 Gd+ lesions at baseline, OCR reduced clinical
and MRI disease activity compared with PBO.
Disclosure: Funded by F. Hoffmann-La Roche Ltd.
O1230 O1231
Myelin lipids attenuate Th17-cell during Anoctamin 2 identified as an autoimmune
autoimmune demyelination target in multiple sclerosis
M. Mycko1, B. Sliwinska1, M. Cichalewska1, B. Ayoglu1, N. Mitsios2, I. Kockum3, T. Olsson3,
H. Cwiklinska1, C.S. Raine2, K.W. Selmaj1 P. Nilsson1
1Department of Neurology, Laboratory of Neuroimmunology, 1SciLifeLab, KTH-Royal Inst of Technology, Stockholm,
Medical University of Lodz, Lodz, Poland, 2Albert Einstein Sweden, 2Neuroscience, Karolinska Institute, Stockholm,
Collge of Medicine, Bronx, USA Sweden, 3Clinical Neuroscience, Karolinska Institute,
Background and aims: Central nervous system (CNS) is Stockholm, Sweden
considered an immune privileged site as its repertoire of Background and aims: Multiple sclerosis (MS) is the most
highly immunogenic molecules remain unseen by the common chronic inflammatory disease of the central
immune system under normal conditions. However, the nervous system and is regarded also as an autoimmune
mechanism underlying this phenomenon, particularly a role condition. The antigenic targets of the autoimmune response
of myelin lipids, has not been fully understood so far. in MS are however not deciphered yet.
Sulfatides constitute a major component of myelin To objective here was to mine the autoantibody repertoire
glycolipids and are known to be capable of raising immune within MS.
response. Methods: We profiled 2,169 plasma samples from MS
Methods: We have performed a set of in vitro and in vivo cases and population-based controls using bead arrays built
experiments, involving cells from C57Bl/6 mice and CD1d with 384 human protein fragments selected from an initial
deficient animal to analyze the an effect of sulfatides on T screening with 11,520 antigens.
helper type 17 (Th17) cell function and differentiation in Results: Our data revealed prominently increased
vitro and in vivo. autoantibody reactivity against the chloride channel protein
Results: We have found that sulfatides stimulation has led anoctamin 2 (ANO2) in MS cases compared to controls.
to suppression of Th17, but not Th1, Th2 or Treg signature This finding was corroborated in independent assays with
of Th-cells upon in vitro stimulation. In vitro differentiation alternative protein constructs, as well as by epitope mapping
of nave Th cells into Th17 was strongly inhibited by the with peptides covering the identified region of ANO2.
sulfatides presence. Sulfatides in vivo administration Additionally, we found a strong interaction between the
resulted in a decrease of a susceptibility to animal model of presence of ANO2 autoantibodies and the HLA complex
multiple sclerosis (MS), experimental autoimmune MS-associated DRB1*15 allele, reinforcing a potential role
encephalomyelitis. Co-incubation with sulfatides led to a for ANO2 auto-reactivity in MS etiopathogenesis. Lastly,
very profound inhibition of T-cell proliferation. The immunofluorescence analysis on human MS brain tissue
suppression of proliferation of T-cells was reversed by revealed ANO2 expression as small cellular aggregates near
inhibition of the galectin-4. and inside MS lesions.
Conclusion: We have identified a new and very potent Conclusion: Taken together, this study describes one of the
mechanism of negative regulation of the Th17 development largest efforts to characterize the autoantibody repertoire
by brain derived sulfatides involving galectin-4. These within MS. The presented findings demonstrate the potential
findings contribute to the understanding of the regulation of for the existence of an ANO2 autoimmune sub-phenotype
T-cell activity by a local CNS tissue milieu that could in MS and lay the ground for further studies focusing on the
provide an insight into immune homeostasis including pathogenic role of ANO2 autoantibodies in MS.
inhibition of autoimmune demyelination. Disclosure: Nothing to disclose
Disclosure: Supported by PSPB-007-2010 grant to MPM,
NCN MAESTRO 2012/04/A/NZ6/004234 grant to KS,
NCN SONATA grant to MC and NCN OPUS grant to HC.
O1232 O1233
Ocrelizumab no evidence of disease Neural correlates of motor fatigue and
activity (NEDA) status at 96 weeks in fatigability in multiple sclerosis: a
relapsing multiple sclerosis patients: functional MRI study
analysis of the OPERA I and OPERA II O. Svolgaard1, K.W. Andersen1, C. Bauer1, K. Madsen1,
studies M. Blinkenberg2, F. Selleberg2, H.R. Siebner1
1Danish Research Centre for Magnetic Resonance, Centre
A. Traboulsee1, D. Arnold2, A. Bar-or3, G. Comi4,
for Functional and Diagnostic Imaging and Research,
H.-P. Hartung5, L. Kappos6, F. Lublin7, K. Selmaj8,
Copenhagen University Hospital Hvidovre, Copenhagen,
G. Klingelschmitt9, D. Masterman10, P. Fontoura9,
Denmark, 2Danish Multiple Sclerosis Center, Copenhagen
P. Chin10, H. Garren9, S. Hauser11 University Hospital Rigshospitalet, Copenhagen, Denmark,
1University of British Columbia, Vancouver, Canada,
Copenhagen, Denmark
2NeuroRx Research, Montreal, Canada, 3McGill University,
Montreal, Canada, 4University Vita-Salute San Raffaele, Background and aims: The neural mechanisms causing
Milan, Italy, 5Heinrich-Heine University Dsseldorf, motor fatigue and fatigability in multiple sclerosis (MS) is
Dsseldorf, Germany, 6University Hospital Basel, Basel, poorly understood and neural correlates of fatigue and
Switzerland, 7Icahn School of Medicine at Mount Sinai, New fatigability in MS is highly needed.
York, USA, 8Medical University of Lodz, Lodz, Poland, 9F. Methods: We enrolled 46 right-handed relapsing-remitting
Hoffmann-La Roche Ltd., Basel, Switzerland, 10Genentech, MS patients and 25 age- and sex-matched healthy controls
Inc., South San Francisco, USA, 11University of California, (HC). Fatigue was evaluated with Fatigue Scale for Motor
San Francisco, USA and Cognitive Functions (FSMC), and disability with
Background and aims: MS treatment goals are evolving Expanded Disability Status Scale (EDSS), Nine-Hole Peg
with the emergence of higher-efficacy therapies. No Test and Jebsen Taylor Hand Function Test. Subjects
evidence of disease activity (NEDA) is a composite of underwent whole-brain 3T functional magnetic resonance
clinical and brain MRI findings indicating the absence of imaging while performing a visual guided three-phased
disease activity. This analysis evaluated NEDA in patients precision-grip-task. In the first (pre-fatigue) and final phase
with relapsing MS over 96 weeks in two identical Phase III, (post-fatigue) the subjects altered between resting and
randomised, double-blind, double-dummy trials (OPERA I pressing on a force transducer with right thumb and index
and OPERA II). finger applying 15% of their individual maximal grip-force
Methods: Patients were randomised (1:1) to receive (MGF). In the second phase (fatiguing phase) the subjects
ocrelizumab 600mg every 24 weeks or IFN-1a 44g three- performed a tonic contraction until motor fatigue. Family-
times weekly over 96 weeks. NEDA (defined as no relapses, wise error (FWE) correction was performed at cluster level,
12-week confirmed disability progression [CDP], new/ applying a cluster-forming threshold of Puncorrected<0.001.
enlarging T2 hyperintense lesions or gadolinium-enhancing Significance threshold was set at PFWE<0.05.
T1 lesions) was analysed over 96 weeks. MRI was assessed
at baseline, 24, 48 and 96 weeks.
Results: At 96 weeks, 47.9% and 47.5% of ocrelizumab-
treated patients vs. 29.2% and 25.1% of IFN-1a-treated
patients achieved NEDA in OPERA I (64% increase;
p<0.0001) and OPERA II (89% increase; p<0.0001),
respectively: 80.4%/78.9% of ocrelizumab-treated patients
vs. 66.7%/64.5% of IFN-1a-treated were relapse free;
92.4%/89.4% of ocrelizumab-treated patients vs.
87.8%/84.9% of IFN-1a-treated were without CDP;
91.7%/90.2% of ocrelizumab-treated patients vs.
69.8%/63.9% of IFN-1a-treated were without gadolinium-
enhancing T1 lesions; and 61.7%/60.9% of ocrelizumab-
treated patients vs. 38.7%/38.0% of IFN-1a-treated were
The precision-grip-task
without new/enlarging T2 lesions in OPERA I and OPERA
II, respectively. After week 24, 96.0% of all ocrelizumab-
Results: The MS group had mean EDSS 2.3 (range 0-3.5)
treated patients vs 60.870.9% of IFN-1a-treated patients
and no major functional impairment of the right upper
were without new/enlarging T2 lesions.
extremity. We found a significant group-difference in the
Conclusion: Ocrelizumab consistently resulted in greater
post-pre fatigue contrast in anterior putamen bilaterally. In
NEDA achievement vs. IFN-1a over 96 weeks, with
HC, the activation decreased, whereas MS patients showed
suppression of new/enlarging T2 lesions in nearly all
a relative increase. In addition, in MS the FSMC motor
patients after week 24.
score and the post-pre change in left putamen correlated
Disclosure: Funded by F. Hoffmann-La Roche Ltd.
negatively (r = -0.31, P = 0.04).
Background and aims: Diffuse low-grade gliomas HP, Groupe Hospitalier Piti-Salptrire, Service de
(DLGG) prognosis is variable depending on several factors, Neurologie 2, Paris, 18AP-HP, Groupe Hospitalier Piti
among which the isocitrate deshydrogenase (IDH) mutation Salptrire, Laboratoire de Neuropathologie R Escourolle,
and the 1p19q codeletion. A few studies have suggested Paris, 19GHPS, Paris, 20CHU Poitiers, 21CH Lille, 22CHU
associations between these biological characteristics and Bordeaux, 23GH Pitie-Salptrire Charles Foix, Paris,
the tumour topography. However, correlations between France
tumour biology and other radiological parameters of the Background and aims: BSG in adults are poorly known.
tumour have never been studied. There is no "standard of care" and current data are based on
Methods: The pre-treatment brain MRIs of 198 consecutive retrospective studies showing a great heterogeneity with a
patients with DLGG treated at our neurosurgery department median survival about 6 years. Treatment usually relies on
were included. IDH and 1p19q statuses were collected. radiotherapy. The benefit of chemotherapy is controversial.
MRI were reviewed for determination of lobar topography, Methods: The GLITRAD group was born in 2013 to
tumour volume, and characterisation of the tumour limits coordinate initiatives about this rare tumor in France. It
(bulky or diffuse). We also conducted a voxel-based analysis consists of a multidisciplinary team (30 MD), including
to investigate the relations between the tumour biology and neurooncologists, neuroradiologists, neuropathologists and
its topography at the voxel level. neurosurgerons meeting physically every 6 months and
Results: IDH mutation (p<0.001) and 1p19q (p=0.004) through monthly web conference.
statuses correlated with tumour topography defined by Main objectives
lobar anatomy. Frontal tumours were more frequently IDH- - Creation of a national GLITRAD webmeeting to discuss
mutated (p<0.001) and 1p19q-codeleted (p=0.003) than cases from the whole country
temporo-insular lesions. At the voxel level, however, these - Establishment of a national database on adult BSG
associations were not found. Bulky tumours were more - Establishment of a radiological database including
frequently IDH-mutated (p=0.001) while diffuse tumours diagnostic pitfalls
were more frequently IDH wild-type and 1p19q-conserved - Whenever possible promoting biopsy with molecular
(p=0.001). Larger tumours at diagnosis (possibly linked to profiling
a slower growth rate) were more frequently IDH-mutated - Development of clinical trials to establish a standard
(p<0.001). national strategy
Conclusion: The correlation between the tumour biology Results and achievements: The web meeting (operational
and topography at the lobar but not at the voxel level since September 2013) operates monthly with a requested
suggests an heterogeneity within the tumour regarding IDH quorum in view to collegiality of the decision. After 27
mutation and 1p19q codeletion. IDH wild-type, 1p19q- meetings, 142 cases (corresponding to 102 patients)
conserved, and more rapidly growing temporo-insular originating from 18 French cities, were discussed. In
O1238 O1239
Risk for prescription of psychotropic MEK inhibitor-related rhabdomyolysis
drugs among partners of glioma patients: S. Koeppen1, B. Schilling2, L. Zimmer2, D. Schadendorf2
a nationwide registry study 1Department of Neurology, University of Essen, Essen,
O2104
Neurologic manifestations of congenital
disorders of glycosylation: a clinical
follow-up study of 18 patients
T2-weighted magnetic resonance imaging of the patient's brain before C. Melo1, A. Bandeira2, C. Garrido3, A.M. Fortuna4,
and one month following treatment with thiamine and biotin.
M. Gonalves-Rocha5, S. Figueiroa3, I. Carrilho3,
M. Santos3, D. Quelhas4, E. Martins2
Conclusion: Vitamin-responsive neurological diseases can 1Pediatric Department, Centro Hospitalar do Mdio Ave,
present dramatically and in the absence of risk factors for
Vila Nova de Famalico, Portugal, 2Metabolism Unit,
deficiency. The consideration and timely recognition of Pediatrics Department, Centro Hospitalar do Porto, Porto,
their characteristic phenotypes can facilitate safe and simple Portugal, 3Child Neurology Department, Centro Hospitalar
disease-modifying treatments. do Porto, Porto, Portugal, 4Genetics Department, Centro
Disclosure: Nothing to disclose Hospitalar do Porto, Porto, Portugal, 5Genetics, Hospital of
Braga, Braga, Portugal
O2103 Background and aims: Congenital disorders of
The genetic deficiency of folate cycle, and glycosylation (CDG) are a group of inborn errors of
metabolism in which glycosylation of a variety of proteins
autistic spectrum: the relationship with
and/or lipids is abnormal. They often cause malfunction of
immunodeficiency, demyelination and i/v multiple organ systems, presenting frequently with
immunoglobulin effectiveness neurological manifestations. To describe the neurological
D. Maltsev findings in a cohort of patients with CDG.
Institute of Clinical and Experimental Medicine, National Methods: Review of the medical files and prospective
O'Bogomolets Medical University, Kiev, Ukraine evaluation of a cohort of patients with CDG from a large
Background and aims: The primary folate cycle deficiency Public Hospital Center.
is considered as a genetic predisposition to the development Results: We identified 18 patients with CDG (72% males;
of autistic spectrum disorders in children. There are median age: 15.4 years). Median follow-up time was 11.2
indications of a violation of the immune status and i/v years. Biochemical and molecular studies allowed
immunoglobulin effectiveness in such cases, however, an categorization into 5 subgroups: PMM2 -CDG (n=9),
exhaustive explanation of the associations are not invited. MAN1B1-CDG (n=2), RFT1-CDG (n=1), CDG-Ix (n=4)
Aim: To study the immune status and evaluate the and CDG-IIx (n=2). Intellectual disability was invariably
effectiveness of i/v immunoglobulin in children with present. Movement disorders were identified in 8/18
autistic spectrum disorders who have mutations in the genes patients: stereotypies (5/18), tics (1/18), dystonia (2/18),
of the folate cycle. tremor (3/18) and coreoatethosis (1/18). All the patients
Methods: A prospective controlled study involving 78 with PMM2-CDG and MAN1B1-CDG showed hypotonia
children with autistic spectrum and genetic deficiency of and ataxia. Epilepsy was diagnosed in PMM2-CDG (3/9),
folate cycle, which received i/v immunoglobulin (2 g/kg/ CDG-Ix (3/4) and in 1 patient with CDG-IIx (epileptic
month) for 6-8 months (study group) and 32 similar children encephalopathy). There was no regression or significant
who did not receive immunotherapy (control group).The progression of neurological symptoms. 2 patients died with
data are processed using the method of variation statistics cardiac complications. The most common abnormality on
by Student t-test and Z number of sings for Urbach. cerebral MRI was cerebellar atrophy (9/9 PMM2CDG and
Results: (1) almost all children (92%) showed signs of 2/3 CDG-Ix). PMM2-CDG patients also presented cerebral
primary immunodeficiency with predominant involvement peduncle atrophy (5/9), cortical atrophy (2/9) and corpus
of natural killer cells and natural killer T-cells; (2) callosum hypoplasia (2/9).
abnormally frequent, severe, prolonged episodes of viral Conclusion: In this study of patients with CDG, cerebellar
infections with complications (CMV, EBV, HHV-6, HHV-7, clinical and neuroimaging findings were the most common
measles, rubella, rotavirus, influenza); (3) neuroimaging features. However, intellectual disability, epilepsy and
shown signs of leukoencephalopathy, especially-in the movement disorders were also common in all subgroups.
periventricular zones of parietal lobes; (4) i/v Interestingly, stroke -like episodes and progressive
immunoglobulin contribute to reducing the areas polyneuropathy were not found on this cohort.
leukoencephalopathy and significant improvement in Disclosure: Nothing to disclose
O2105 O2106
Differential contribution of cerebellar Neonatal seizures: a retrospective
resting state functional connectivity analysis (2009-2014)
abnormalities to cognitive impairment in M. Santos1, R. Sousa2, J. Coelho3, F. Duro2,
pediatric and adult patients with multiple R. Machado2, S. Quintas3, T. Moreno3, A. Levy3,
sclerosis T. Santos3
1Neurology, Hospital Prof. Dr. Fernando Fonseca, EPE,
M.A. Rocca1, P. Valsasina1, L. Vacchi1, L. Moiola2, Amadora, Portugal, Amadora/Lisbon, Portugal, 2Department
A. Ghezzi3, P. Veggiotti4, R. Capra5, M.P. Amato6, of Pediatrics, Hospital Santa Maria, Centro Hospitalar de
A. Fiorino7, L. Pippolo8, M.C. Pera4, G. Comi2, Lisboa Norte, Lisbon, Portugal, 3Department of
A. Falini9, M. Filippi1 Neuropediatrics, Hospital Santa Maria, Centro Hospitalar
1Neuroimaging Research Unit, San Raffaele Scientific
de Lisboa Norte, Lisbon, Portugal
Institute, Vita-Salute San Raffaele University, Milan, Italy,
2Department of Neurology, San Raffaele Scientific Institute, Background and aims: Neonatal brain is more prone to
Milan, Italy, 3Multiple Sclerosis Study Center, Hospital of
seizures, being most seizures of this period acute reactive.
Gallarate, Gallarate, Italy, 4Department of Child Neurology We aimed to characterize the neonates hospitalized with
and Psychiatry, C. Mondino National Neurological Institute, seizures.
Pavia, Italy, 5Regional Multiple Sclerosis Center, Presidio di Methods: Retrospective observational study of consecutive
Montichiari, Spedali Civili di Brescia, Brescia, Italy, neonates (28days) with seizures hospitalized in a single
6Department of Neurology, University of Florence, Florence, center (2009-2014). The sample was characterized for
Italy, 7Department of Neurology, San Raffaele Scientific maternal/pregnancy history, seizures features (Volpe
Institute, Vita-Salute San Raffaele University, Milan, Italy, classification), diagnostic workup/etiology, treatment,
8Centro Studi Sclerosi Multipla, Ospedale di Gallarate, follow-up (neurological sequelae/epilepsy). SPSS19 was
Gallarate, Italy, 9Neuroradiology, Universit Vita-Salute San used for statistics.
Raffaele, Milan, Italy Results: 64 neonates (males/female=56.3%/43.8%, mean
Background and aims: We investigated whether resting age=2.77days, SD=4.287) were included. Etiologies were:
state (RS) functional connectivity (FC) abnormalities of hypoxic-ischemic encephalopathy (HIE) (67%), stroke
different functional subregions (right and left CrusI, CrusII (16%), infection (5%), metabolic disease (5%), epileptic
and dentate nucleus) of the cerebellum contribute to syndrome (ES) (1%), other (6%). Patological CTG was
cognitive impairment in pediatric and adult patients with more frequent in HIE (p=0.007). Focal clonic seizures were
multiple sclerosis (MS). the most prevalent (28.1%). Only HIE and stroke had
Methods: RS fMRI scans were acquired from 49 pediatric myoclonic (13%,10%), subtle (12%, 20%) and
MS patients, 40 adult MS patients, 27 pediatric healthy electrographic (10%, 10%) seizures. Onset ranged from 1
controls (HC) and 40 adult HC. Patients with abnormalities day (ES), 1.220.613 (HIE) to 14.676.658 (infection).
in 3 neuropsychological tests were classified as cognitively Conventional EEG was positive in everyone with stroke
impaired (CI). and ES, in 81.4% with HIE and 33.3% with metabolic/
Results: 10 pediatric and 9 adult MS patients were CI. infection disorders. MRI was abnormal in everyone with
Pediatric and adult CI MS patients had a reduced pattern stroke and infection, in 74.4% with HIE. Mortality was
of RS FC between cerebellar subregions and a few frontal 14.1%. HIE, stroke and ES needed more antiepileptics
and temporal areas. For each cerebellar subregion, during hospitalisation (1.60.79, 1.71.06, 7), had at least
compared to pediatric HC, adult HC had a decreased RS FC someone discharged under antiepileptics (11.4%, 20.0%,
in a distributed network of anterior areas. Compared to HC, 100%) and with epilepsy at follow-up (14.3%, 80%, 100%).
MS patients had reduced RS connectivity between the HIE and stroke patients had more motor (31.6%, 66.4%)
cerebellum and the basal ganglia, which was independent and behavior (16.7%, 60.0%) sequelae.
from age and did not contribute to cognitive performance. Conclusion: Almost all seizures were acute reactive and
In pediatric MS patients, decreased RS FC between the HIE was the main cause. Dispite sample size, HIE, stroke
cerebellum and fronto-parietal-temporal regions correlated and ES needed more antiepileptics and had worse
with the presence of cognitive deficits. In adult MS patients, neurological outcome. Subtle and electrographic seizures
a more complex pattern of RS FC abnormalities was prevalence and conventional EEG results emphasize
detected, characterized by the concomitant presence of amplitude-integrated EEG utility.
regions of increased and decreased connectivity, both Disclosure: Nothing to disclose
contributing to cognitive decline.
Conclusion: Different patterns of cerebellar RS FC
abnormalities contribute to cognitive deficits in pediatric
and adult patients with MS, possibly due to the level of
maturation of cerebellar connections.
Disclosure: Partially supported by a grant from Italian
Ministry of Health (GR-2009-1529671).
O2109 O2110
Relevance of functional connectivity The head turning sign in Alzheimer's
abnormalities to cognitive impairment in disease: its relationship with cognitive
neuromyelitis optica spectrum disorder impairment and CSF biomarkers
M.A. Rocca1, P. Valsasina2, F. Savoldi1, G.C. Riccitelli1, M. Tbuas-Pereira1, J. Dures2, R. Arajo1,
M. Radaelli3, P. Preziosa1, G. Comi3, A. Falini4, S. Bernardino3, D. Duro4, B. Santiago2, I. Santana1
M. Filippi1 1Neurology, Centro Hospitalar e Universitrio de Coimbra,
1Neuroimaging Research Unit, Institute of Experimental Coimbra, Portugal, 2Neurology, CHUC, Coimbra, Portugal,
3Psychology Faculty, University of Coimbra, Coimbra,
Neurology, DIvision of Neuroscience, San Raffaele Scientific
Institute, Milan, Italy, 21Neuroimaging Research Unit, San Portugal, 4Coimbra, Portugal
Raffaele Scientific Institute, Vita-Salute San Raffaele Background and aims: The head turning sign (HTS)
University, Milan, Italy, 3Department of Neurology, San consists in a patient's voluntary head movement towards the
Raffaele Scientific Institute, Vita-Salute San Raffaele caregiver, searching for an answer or corroboration, when
University, Milan, Italy, 4Neuroradiology, Universit Vita- directly questioned. Despite being poorly characterized, it
Salute San Raffaele, Milan, Italy appears to be associated with cognitive impairment, namely
Background and aims: Cognitive impairment (CI) is its severity, perception of the disease (insight) and other
frequent in neuromyelitis optica spectrum disorders factors, as depression or anxiety.
(NMOSD). In this study, we explored resting state (RS) Objective: To determine the relationship between HTS and
functional connectivity (FC) abnormalities in the main the severity of cognitive impairment, insight, depression
cognitive networks of NMOSD patients. and CSF biomarkers in Alzheimer's Disease (AD) and
Methods: RS fMRI and neuropsychological evaluation amnestic-Mild Cognitive Impairment (aMCI) patients.
were obtained from 26 NMOSD, 30 multiple sclerosis (MS) Methods: Patients were classified according to: McKhan et
patients and 30 healthy controls (HC). Independent al., 2011 (AD) and Albert et al., 2011 (MCI). HTS presence
component analysis identified the default mode (DMN), and intensity classification was based in a protocol with five
salience (SN), executive control (ECN) and working questions. Insight was measured using Verhey et al., 1993;
memory (WMN) networks. RS FC between-group cognitive impairment by both MMSE and MOCA and
comparisons and correlation with cognitive impairment depression severity by the GDS.
indices (CII) were assessed (SPSS). Results: HTS was present in 30/36 (83.3%) of the AD
Results: 9 NMOSD (35%) and 10 MS patients (33%) were patients and in 12/27(44.4%) of the aMCI. The intensity of
CI. Cognitively preserved (CP) NMOSD and MS patients the sign is higher in AD (p=0.015): median value was 0.0 in
showed higher SN RS FC than HC (p=0.03-0.01). CP MCI and 1.0 in AD. We found a moderate positive
NMOSD had also higher DMN FC than HC (p=0.03). correlation between the intensity of the HTS and the values
Lower DMN, ECN and SN FC was found in CI NMOSD of tau protein (r=0.393, p=0.002), phosphorylated tau
than in CP and HC (p=range 0.0001-0.05). The regional (r=0.300, p=0.002) and MMSE (r=-0.287, p=0.024),
analysis showed decreased cerebellar RS FC in the WMN considering both patients with AD and aMCI.
in CI NMOSD patients (p=range 0.007-0.02). CI MS Conclusion: HTS presence and intensity favour the
experienced decreased parahippocampal and occipital RS diagnostic of AD. Its presence is correlated with cognitive
FC, as well as increased frontal RS FC in the DMN (p=range scores and biomarkers of neurodegeneration, but we did not
0.01-0.03). In NMOSD and MS patients, higher SN RS FC find any association with insight or depression. Further
was correlated with higher global CII. NMOSD patients studies will address the sign's specificity for AD.
showed also significant correlations between higher DMN Disclosure: Nothing to disclose
and ECN RS FC and higher memory and attention CII.
Conclusion: Increased RS FC correlated with better
cognitive performance both in NMOSD and MS. In CI
NMOSD reduced RS FC was mainly observed, while CI
MS showed also increased RS FC in some frontal regions,
which might be maladaptive.
Disclosure: Nothing to disclose
O2111 O2112
Predictors and signatures of recovery Functional cognitive control load across
from neglect in acute stroke multiple sclerosis phenotypes: a clinical-
R. Umarova1, C. Kaller2, K. Nitschke1, S. Klppel1, imaging evaluation
L. Beume3, I. Mader1, C. Weiller3 L. Vacchi1, M.A. Rocca1, A. Meani1, M. Rodegher2,
1University Medical Centre , Freiburg, Germany, V. Martinelli2, G. Comi2, A. Falini3, M. Filippi1
2Department of Neurology, University Medical Center, 1Neuroimaging Research Unit, San Raffaele Scientific
Freiburg, Germany, 3University Medical Centre, Freiburg, Institute, Vita-Salute San Raffaele University, Milan, Italy,
Germany 2Department of Neurology, San Raffaele Scientific Institute,
Background and aims: Spatial neglect can either Vita-Salute San Raffaele University, Milan, Italy,
spontaneously resolve or persist after stroke, where the 3Neuroradiology, Universit Vita-Salute San Raffaele, Milan,
Multiple Sclerosis Journal-Experimental, Translational, and pharmaceuticals A. Tourbah has received in the last year,
Clinical. (Genentech, Genzyme, Novartis, Biogen-Idec, consulting and lecturing fees, travel grants and research
Consortium of MS Centers, Department of Defense, support from Medday, Biogen Idec, Sanofi-Genzyme,
National Institutes of Health, National MS Society, Novartis, Merck Serono, Teva Pharma, and Roche
Receptos, Synthon, Teva, Vaccinex). B. Cree (Abbvie,
Biogen-Idec, EMD-Serono, MedImmune, Novartis, O2116
Genzyme/Sanofi Aventis, Teva, Acorda, Hoffman-La
Roche). D. Piani Meier, S. Ritter and D. Tomic (Novartis) Spinal cord volume loss in multiple
sclerosis patients: a 7-year longitudinal
O2115 study
High doses of biotin in progressive C. Tsagkas1, S. Magon1, L. Gaetano1, S. Pezold2,
Y. Naegelin3, M. Amann4, P. Cattin5, J. Wrfel6, O. Bieri7,
multiple sclerosis: extension phase
T. Sprenger8, L. Kappos3, K. Weier1
results of the MS-SPI trial 1Neurology and Medical Image Analysis Center, University
A. Tourbah1, C. Lebrun-Frenay2, G. Edan3, M. Clanet4, Hospital Basel, Basel, Switzerland, 24. Department of
A.-C. Papeix5, S. Vukusic6, J. deSeze7, M. Debouverie8, Biomedical Engineering, University of Basel, Basel,
O. Gout9, P. Clavelou10, G.L. Defer11, D. Laplaud12, Switzerland, 3Neurology, University Hospital Basel, Basel,
T. Moreau13, P. Labauge14, B. Brochet15, F. Sedel5, Switzerland, 4Neurology and Medical Image Analysis Center
J. Pelletier16 and Division of Diagnostic and Interventional
1Rheims, France, 2Nice, France, 3CHU-Hopital Pontchaillou, Neuroradiology, Department of Radiology, University
Rennes, France, 4Toulouse, France, 5Paris, France, 6Lyon Hospital Basel, Basel, Switzerland, 5Department of
Neuroscience Research Centre, Lyons, France, 7Neurology, Biomedical Engineering, University of Basel, Basel,
University Hospital Strasbourg, Strasbourg, France, 8CHU Switzerland, 6Medical Image Analysis Center, Basel,
Nancy, Nancy, France, 9Neurology, Fondation Rothschild, Switzerland, 74Department of Biomedical Engineering and 5.
Paris, France, 10Neurology, CHU de Clermont-Ferrand, Division of Radiological Physics, Department of Radiology,
Clermont-Ferrand, France, 11Neurology, CHU Cte de University Hospital Basel, Basel, Switzerland, 8Neurology,
Nacre, Caen, France, 12Nantes, France, 13CHU, Dijou, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany
France, 14CHU Montpellier, Montpellier, France, 15CHU Introduction: In multiple sclerosis (MS), most previous
Bordeaux, Bordeaux, France, 16Neurology, APHM Timone, studies investigating spinal cord (SC) volume loss were
Marseilles, France performed in cross-sectional settings. We aim at exploring
Background and aims: High dose of Biotin, a co-enzyme the diagnostic and prognostic value of SC volume changes
for acetylCoA carboxylase, a potentially key-enzyme in in MS, as well as potential differences between MS
myelin synthesis was investigated in progressive MS in a subgroups using data of a large MS cohort with 7-year
randomized placebo-controlled trial (MS-SPI). Compared follow-up.
to the placebo, treatment with biotin resulted after 12 Methods: SC volume from 1346 high-resolution
months in the reversion of progression in a significant T1-weighted MPRAGE scans (acquired at a single 1.5T
proportion of patients (p=0.005), improvement of the mean scanner) of 243 MS patients (180 relapsing-remitting
EDSS change (p=0.014) and improvement of the clinical (RRMS), 51 secondary progressive (SPMS), 12 primary
global impression of change (p<0.0001). Here we will progressive (PPMS)) imaged serially over 7 years, were
present the extension phase results after 24 months. segmented using a novel semi-automatic software
Methods: MS-SPI is a randomized, double-blind, placebo- (CORDIAL). SC volume metrics and annualised SC volume
controlled (2:1) trial of oral biotin 300 mg / day in patients loss rate (aSCVLR) were determined per patient. Statistical
with secondary (SPMS) or primary (PPMS) progressive analyses included ANCOVA to investigate between-group
MS. Duration of the placebo-controlled was 48 weeks. The differences and aSCVLR, and Multiple Regression to
blinded phase was followed by a 12 months pre-planned investigate correlations of baseline SC volume with clinical
extension phase where patients under placebo were data.
switched to receive MD1003. Patients and physicians Results: At baseline, RRMS had higher SC volumes over
remained blinded to the treatment administered during the the progressive groups, while in all groups SC volume was
first phase of the study. the strongest explanatory variable for disability (Table 1 &
Results: The last patient completed the study in December 2). The aSCVLR over 7 years was highest for the PPMS
2015. The database will be locked in the end of January group (-2%), while SPMS (-0.64%) and RRMS (-0.45%)
2016. Full statistical analyses will be available by March were not statistically different. Disease duration had no
2016. Results of clinical endpoints will be presented and influence on the aSCVLR in RRMS patients (Table 1).
discussed in the context of other trials in progressive MS.
Conclusion: The 24-month results of the MS-SPI trial will
be discussed in the context of development of high doses of
pharmaceutical grade biotin as a novel treatment for
progressive MS.
Disclosure: The study was sponsored by MedDay
O2117
Human polyomavirus JC and BKV
antibody response in patients with PML
O. Adams1, M. Andre1, H.-P. Hartung2, C. Warnke2
1Virology, Dsseldorf, Dsseldorf, Germany, 2Dsseldorf,
Germany
Background and aims: Progressive multifocal
leukoencephalopathy (PML) is caused by JC polyomavirus
(JCV). Some patients with PML may have a defective
humoral immune response against JCV, which may
contribute to allowing viral mutants to escape the host
immune control (Jelcic et al, Science Translational Medicine
2015). Our objective was to measure and compare JCV and
BKV antibody reactivities in patients with PML and
controls.
Methods: We used a two-step ELISA with VP1 fused to
glutathione S-transferase (GST) as antigen to determine
antibodies quantified in arbitrary units (AU) toward JCV
and BKV. Patients at diagnosis of PML (n=70) and control
patients (n=78) without PML were compared.
Results: JCV positivity and reactivity was higher in PML
patients compared with controls (94.3% versus 73.1%,
p=0.001; mean 459 AU versus 97 AU, p< 0.0001), while
BKV positivity was lower (77.1% versus 93.6, p=0.008).
Conclusion: To our knowledge, this is the first longer-term JCV/BKV-quotients differed between the two groups (3.2
follow-up study of SC volume in MS. The annualised SC versus 0.49, p<0.0001).
volume loss in RRMS was independent of disease duration. Conclusion: As published, patients with PML usually are
SC volume loss was more pronounced in PPMS patients. JCV seropositive and show high antibody reactivities
However, due to the low number of PPMS patients included, against the virus at time of diagnosis. Interestingly, BKV
this finding needs further confirmation. antibody positivity in PML patients is comparably low, and
Disclosure: This project was supported by the Swiss BKV-seropositive PML patients show comparably low
National Science Foundation (SNSF). BKV-antibody levels. Hence, the calculation of the
individual serum JCV/BKV-antibody quotient results in
significant differences between PML- and control patients,
of potential relevance for PML risk stratification. In
summary, low or missing antibody reactivity towards BKV
might be an independent risk factor for developing a PML.
Disclosure: This study is supported by a grant of the Hertie
foundation to Dr. C. Warnke.
O2118
Menarche is not associated with MS
onset or disease activity in a prospective
cohort of CIS women
M.I. Zuluaga1, S. Otero-Romero1, B. Pujal1, I. Galn1,
G. Arrambide1, J. Rio1, M. Comabella1, C. Nos1,
M.J. Arvalo1, A. Vidal-Jordana1, J. Castill1,
B. Rodrguez1, L. Midaglia1, P. Mulero1, R. Mitjana2,
C. Auger2, J. Sastre-Garriga1, A. Rovira2, X. Montalban1,
M. Tintor1
1Centre dEsclerosi Mltiple de Catalunya (Cemcat).
Neurorehabilitation
O2119
Mechanisms of motor plasticity after
stroke
A. Guggisberg, P. Nicolo, A. Schnider
Dept. of Clinical Neurosciences, University Hospital
Geneva, Geneva, Switzerland
Background and aims: Evolution of motor function in the
first months after stroke is stereotypical and consists either
in recovery of about 70% of maximum possible
improvement (proportional recovery, PROP), or in little
to no improvement (poor recovery, POOR). This seems to Figure 2. Change in FA from T0 to T1.
be largely independent of current therapy approaches. Here,
we examined mechanisms of PROP in order to better inform Conclusion: These findings suggest that therapies which
rehabilitation. re-establish CST projections and induce functional
Methods: We performed a longitudinal study including interactions among motor nodes of the affected hemisphere
standardized motor assessments, high-density are needed to boost plasticity, prevent white-matter
electroencephalography (EEG), functional magnetic degradation, and improve motor recovery after stroke.
resonance imaging (fMRI), and diffusion tensor imaging Disclosure: Nothing to disclose
(DTI) on 63 patients with unilateral hemispheric stroke.
Patients were assessed 2-4 weeks (T0) and 3 months (T1)
after stroke onset.
O2120
Results: Patients were clearly segregated into PROP or Risk assessment within 4 days after
POOR groups (Fig. 1A). At T0, PROP patients had greater whiplash injury identifies long-term
integrity of the cortico-spinal tract (CST) (Fig, 1B) and painful and non-painful neurologic
greater EEG and fMRI functional connectivity (FC)
between the affected hemisphere and rest of the brain, in disability: a twelve-year prospective
particular between the ventral premotor area and the study.
primary motor cortex (Fig. 1C). POOR patients suffered M.K. Rasmussen1, T.S. Jensen1, H. Kasch2
from a degradation of fibre tracts in the affected hemisphere 1Neurology, AUH, 1)Danish Pain Research Centre Aarhus
between T0 and T1, which was not observed in PROP University Hospital, Aarhus, Denmark, Aarhus, Denmark,
patients (Fig. 2). Better initial CST integrity correlated with 2Neurology, Research Department, Spinal Cord Injury Centre
greater FC (r>0.30, p<0.03), which was in turn associated of Western Denmark Department of Neurology, Regional
with less white matter degradation between T0 and T1 Hospital of Viborg, Vyborg, Denmark
(r>0.34, p<0.02) Background and aims: The Danish Whiplash Study Group
Risk Assessment Score and stratification based on initial
clinical findings to predict the risk of whiplash-related
disability has previously been presented. We commenced
this study to investigate the burden in the stratified patient
groups now more than a decade post-injury.
Figure 3. Flowchart
O2122 O2123
Transcranial direct current stimulation Effects of action observation therapy on
combined with constraint induced rehabilitation of motor deficits of the
movement therapy facilitates motor dominant right upper limb in patients with
function in chronic stroke patients MS: an exploratory study with functional
K. Figlewski1, J.U. Blicher2, J.F. Nielsen3, K. Severinsen2, MRI
H. Andersen2 S. Fumagalli1, M.A. Rocca1, P. Preziosa1, R. Gatti2,
Institute of clinical medicine, Aarhus University, Aarhus,
1
R. Messina1, F.G. MartinelliBoneschi3, M. Comola3,
Denmark, 2Department of Neurology, Aarhus University G. Comi3, M. Filippi1
Hospital, Aarhus, Denmark, 3Hammel Neurorehabilitation 1Neuroimaging Research Unit, Institute of Experimental
Centre and University Research Clinic, Hammel, Denmark Neurology, Division of Neuroscience, Scientific Institute and
Background and aims: Transcranial Direct Current University Ospedale San Raffaele, Milan, Italy, 2Laboratory
Stimulation (tDCS) may enhance effect of rehabilitation in of Movement Analysis, San Raffaele Scientific Institute, Vita-
chronic stroke patients. Objective of this trial was to Salute San Raffaele University, Milan, Italy, 3Department of
evaluate efficacy of anodal tDCS combined with constraint Neurology, Scientific Institute and University Ospedale San
induced movement therapy (CIMT) of the paretic upper Raffaele, Milan, Italy
limb. Background and aims: Action Observation Therapy
Methods: 44 chronic stroke patients (>3 months since (AOT) facilitates motor system function, possibly through
stroke) participating in a two weeks inpatient CIMT a modulation of mirror neuron system (MNS) recruitment.
treatment were randomly allocated to anodal or sham tDCS Functional MRI (fMRI) was applied to assess whether AOT
for 30 minutes to primary motor cortex. modifies brain activations in healthy controls (HC) and
Primary outcome measure of Wolf Motor Function Test multiple sclerosis (MS) patients with right (R) upper limb
(WMFT) was evaluated at the baseline and post-intervention motor deficits. Correlations between MRI and clinical
by blinded investigators. measures were also explored.
Results: Both groups improved significantly on all WMFT Methods: In this blind, randomized, controlled trial, 71
scores. Between group comparison showed a statistically R-handed subjects (46 HC; 25 MS), were randomized into
significant greater mean change score on the Functional 4 groups: 2 experimental groups (AOT-HC n=23; AOT-MS
Ability Scale of WMFT in the anodal group compared with n=12) and 2 control groups (C-HC n=23; C-MS n=13). The
the sham group (0.56 point vs 0.36; P=0.033). tDCS was training consisted of 10 sessions of 45 minutes in 2 weeks.
well tolerated with no major adverse effects observed. AOT-groups watched 3 videos (5 minutes each) of daily-life
Conclusion: A combination of tDCS with CIMT is more actions alternated by their execution with the R hand;
effective in improving functional ability of the paretic upper C-groups performed the same tasks, but watched landscapes
limb than CIMT alone. videos. At baseline and after 2 weeks (w2), clinical measures
Disclosure: The BEVICA Foundation is acknowledged for and fMRI during object manipulation with the R hand were
financial support. obtained.
Results: At w2, we found an increased activation of MNS
in AOT-HC, the R middle temporal gyrus in C-HC, the R
superior parietal lobule in AOT-MS and the R caudate
nucleus in C-MS. AOT-groups had higher MNS activation
compared to C-groups. At w2, all groups improved in
functional tests, which were correlated with MRI changes.
Conclusion: Motor network and MNS functional changes
occur in HC and MS after AOT, which correlate with motor
improvements. These findings might contribute to develop
new rehabilitative approaches for MS.
Disclosure: Partially supported by grants from FISM
(FISM2012R15) and Italian Ministry of Health (RF-2011-
02350374).
O2124
Whole-hand electrical stimulation in
stroke patients in the subacute stage
K. Schwenker1, M. Christova2, B. Wutzl1, C. Florea1,
H. Bartsch1, A.B. Kunz1, E. Gallasch2, E. Trinka1,
F. Gerstenbrand3, S. Golaszewski1
1Department of Neurology, Paracelsus Medical University
Salzburg, Salzburg, Austria, 2Physiology, Medical University
Graz Austria, Graz, Austria, 3Karl Landsteiner Institute for
Neurorehabilitation and Space Neurology, Vienna, Austria
Background and aims: This study examines the effect of
whole-hand electrical stimulation on motor recovery in
stroke patients at subacute stage. Peripheral electrical
stimulation has been proved to modulate cortical plasticity
in healthy and in patients. Such neuromodulatory effects
have been found after application of electrical hand mesh-
glove stimulation (MGS) in our previous studies on healthy
subjects.
Methods: 20 patients with cortico-subcortical ischemic
stroke and predominantly motor hemiparesis of the upper
extremity were recruited. MGS was applied on the paretic
hand 60 min per day for 3 weeks before standard
rehabilitation training. Hand motor and sensory functions
were evaluated with Wolf Motor Function test, Fugl-Meyer
Assessment score, Nine hole peg test, and Semmes-
Weinstein monofilaments. Single and paired-pulse
transcranial magnetic stimulation (TMS) was applied to
follow corticospinal excitability changes over the treatment
period. Functional magnetic resonance imaging (fMRI) was
conducted to assess the cortical brain reorganization
changes after treatment. Effects of MGS were compared to
control group receiving sham stimulation.
Results: Patients from both groups showed significant
functional improvement as assessed with the motor
functional tests. However the improvement degree for the
MGS group was increased compared to the control group.
These functional effects correlated with neuroplastic
changes within the sensorimotor area as revealed by TMS
and fMRI.
Conclusion: Electrical stimulation applied before
physiotherapeutic training raises motor cortical excitability
in the lesioned cortex so that subsequent training becomes
more effective. The obtained results provide better
understanding of the modulation of central motor controlling
structures by somatosensory stimulation in correlation with
the functional motor recovery.
Disclosure: Nothing to disclose
Figure 1
Conclusion: Diagnosis according to current PPA consensus underlie different profiles of language impairment.
criteria was highly predictive of AD biomarker status. Disclosure: Study Supported by: National Institutes of
Sentence repetition, motor speech, and visual memory were Health (NINDS R01 NS050915, NIA P50 AG03006, NIA
the measures that best differentiated between amyloid P50 AG023501, NIA P01 AG019724); State of California
positive and negative PPA. Positive amyloid neuroimaging (DHS04-35516); Alzheimers Disease Research Center of
in patients with typical nfvPPPA and svPPA does not rule California (03-75271 DHS/ADP/ARCC); Larry L. Hillblom
out the possibility of a primary FTLD pathological diagnosis Foundation; John Douglas French Alzheimers Foundation;
driving the clinical syndrome. Koret Family Foundation; Consortium for Frontotemporal
Disclosure: This work was supported by the National Dementia Research; and McBean Family Foundation.
Institutes of Health, USA; Alzheimers Disease Research
Center of California; John Douglas French Alzheimer's O2204
Foundation; Alfonso Martin Escudero Foundation.
Higher intake of fats and carbohydrates is
O2203 associated with smaller cortical
thickness, whereas higher intake of
In vivo correlates of pathological
vitamins is associated with larger cortical
diagnosis in primary progressive aphasia
thickness
E.G. Spinelli1, M.L. Mandelli2, M. Santos2, G. Vinceti3,
S. Staubo1, J. Aakre2, J. Syrjanen2, M. Mielke2,
C. Watson2, F. Agosta1, B.L. Miller2, W.W. Seeley2,
P. Vemuri2, Y. Geda3, W. Kremers2, M. Machulda2,
M. Filippi1, M.L. Gorno-Tempini2
1Neuroimaging Research Unit, Institute of Experimental D. Knopman2, R. Petersen2, C. Jack2, R. Roberts2
1Charles University, Hradec Krlov, Czech Republic,
Neurology, Division of Neuroscience, San Raffaele Scientific 2Mayo Clinic, Rochester, Minnesota, USA, 3Mayo Clinic,
Institute, Vita-Salute San Raffaele University, Milan, Milan,
Arizona, Scottsdale, Arizona, USA
Italy, 2Memory and Aging Center, University of California
San Francisco, San Francisco, USA, 3Department of Background and aims: High intake of saturated fats,
Neuroscience, University of Modena and Reggio Emilia, transfatty acids, and carbohydrates has been associated with
Modena, Italy increased risk of dementia, and vitamins with a decreased
Background and aims: Large clinicopathological series of risk. Our objective was to study the cross-sectional
prospectively evaluated patients with primary progressive associations of macronutrients and vitamin intake with
aphasia (PPA) are still lacking. The aim of this study was to magnetic resonance imaging (MRI) measures of cortical
investigate the relationship between in vivo clinical and thickness in key regions of interest (ROI) that undergo
neuroimaging features and neuropathologic findings in a atrophy in Alzheimers dementia.
large cohort of PPA patients. Methods: Cognitively normal participants (n=672, mean
Methods: We evaluated clinical, MRI and neuropathologic age=79.8 years, 52.5% men) completed a food frequency
data from 68 patients with sporadic PPA, namely 29 questionnaire and completed MRI to measure cortical
semantic (svPPA), 26 non-fluent (nfvPPA), 9 logopenic thickness. The associations of dietary macronutrients
(lvPPA) and 4 mixed PPA patients. Patterns of grey matter (%calories from proteins, carbohydrates, fats) and vitamins
(GM) and white matter (WM) atrophy at presentation were with cortical thickness measures were examined using
assessed in each clinical and pathologic subgroup. Support generalized linear regression models adjusted for age, sex,
vector machine was used to test GM and WM probability education, vascular disease, and depressive symptoms
maps as predictors of pathologic diagnosis. (significance assessed as p<0.05).
Results: We identified prevalent underlying pathology for Results: Higher %carbohydrate intake was associated with
each PPA variant, as 18/26 (69%) nfvPPA showed 4R-tau a lower entorhinal cortex thickness. Higher %saturated fats,
frontotemporal lobar degeneration (FTLD), 24/29 (83%) %total fat and transfatty acids intake was also associated
svPPA showed FTLD-TDP-C, and all 9 lvPPA had with lower inferior temporal cortex thickness. By contrast,
Alzheimers disease (AD) pathology. Picks disease (PiD) higher intake of vitamins B1, B2, B6 and folate was
was observed in 4 nfvPPA, 2 svPPA and 2 mixed PPA. PiD significantly associated with a larger superior temporal
was associated with severe, early neuropsychiatric cortex thickness. In addition, higher intake of vitamin B2
symptoms and extensive atrophy involving mainly left but and B carotene was significantly associated with a larger
also right frontal and temporal lobes, across all clinical cortical thickness in the temporal pole and dorsolateral
variants. SvPPA-tau had severe medial temporal and prefrontal cortex, respectively.
orbitofrontal GM and WM atrophy and greater executive Conclusion: These results suggest that higher intake of
impairment than svPPA-TDP. NfvPPA-TDP showed saturated, transfats and total fat and carbohydrates (possibly
selective left posterior frontal GM atrophy. WM showed the those with glycemic index) may adversely impact brain
highest accuracy (92.9%) in distinguishing tau and TDP structure, whereas higher intake of dietary vitamins may
pathologies. have beneficial effects. These findings remain to be
Conclusion: Patterns of GM and WM atrophy may suggest validated prospectively, but may have implications for the
pathologic diagnosis within each PPA variant in vivo. PiD role of diet in dementia.
is associated with distinctive behavioral alterations and may Disclosure: Nothing to disclose
O2205 O2206
Skin nerve -synuclein deposits as new Retinal examination in Alzheimer's
biomarkers for dementia with Lewy disease
bodies U.A. Kayabasi1, R.C. Sergott2
V. Donadio1, A. Incensi1, S. Capellari2, G. Rizzo1,
1Istanbul, Turkey, 2Neuro-ophthalmology, Wills Eye Hospital,
R. Pantieri2, M. StanzaniMaserati3, G. Devigili4, Philadelphia, USA
R. Eleopra4, F. Montini3, A. Baruzzi1, R. Liguori1 Background and aims: Optical coherence tomography
1UOC Clinica Neurologica, IRCCS Istituto Scienze (OCT) and fundus autofluorescence (FAF) examinations
Neurologiche Bologna, Bologna, Italy, 2IRCCS Istituto delle provide us with important information about
Scienze Neurologiche, Bologna, Italy, 3IRCCS Istituto delle neurodegenerative diseases. Since the optic nerve and retina
Scienze Neurologiche, UOC Clinica Neurologica, Bologna, share similar structures with the brain, any defect detected
Italy, 4Neurological Unit, Dept of Neuroscience University by OCT and/or FAF may be related to a disease in the
Hospital "Santa Maria della Misericordia" Udine, Udine, nervous system.
Italy Methods: We examined 50 patients with dementia due to
Background and aims: To investigate whether: Alzheimer's disease (AD). The FAF examinations were
1) phosphorylated -synuclein (p-syn) deposits in peripheral performed after which OCT was done through the abnormal
nerves might represent a useful biomarker in dementia (hyperfluorescent or hypofluorescent ) spots or regions. We
Lewy Body (DLB) helping to differentiate DLB from other gave curcumin capsules to all the patients and 20 age-
forms of dementia; matched healthy controls before the tests. OCT and FAF
2) small fiber neuropathy (SFN) may be part of DLB images were examined in a masked fashion by two neuro-
pathological picture contributing to autonomic dysfunctions ophthalmologists.
Methods: 20 well-characterized DLB patients (11 of them Results: In 45 patients with AD, shining dots and spots
complaining autonomic symptoms particularly orthostatic were mostly seen in the outer plexiform, ganglion and nerve
hypotension) were studied together with 23 patients with fiber layers on OCT. Patients who were given curcumin
dementia of different pathogenesis (Dementia without demonstrated patchy hypofluorescent areas with
synuclein- DWS) including 13 patients fulfilling diagnostic hyperfluorescent dot like lesions on FAF and OCT revealed
criteria for Alzheimers disease, 6 with Frontotemporal brighter spots in different retina layers. In the control group,
Dementia and 4 with vascular dementia. 25 age-matched no change was detected after curcumin use
healthy subjects served as controls. Subjects underwent:
nerve conduction velocities from the leg to evaluate large
nerve fibers; skin biopsy from proximal (i.e. cervical) and
distal (i.e. thigh and distal leg) sites to study small nerve
fibers and p-syn deposits, considered the pathological form
of -synuclein.
Results: P-syn was not found in any skin sample in DWS
patients and controls but it was found in all DLB patients
with a proximal-distal gradient with all patients positive in
the cervical site. Patients complaining of autonomic
symptoms showed higher widespread positivity of analyzed
skin samples than patients without autonomic symptoms.
Furthermore DLB patients showed a length-dependent SFN
particularly important in patients complaining autonomic
symptoms. FAF in AD.
Conclusion: 1) p-syn in peripheral nerves is a sensitive
biomarker for DLB diagnosis helping to differentiate DLB Conclusion: We believe that detection of lesions before the
from other forms of dementia; onset of dementia or very early in the course of the disease
2) SFN was part of DLB pathological picture contributing is extremely important. Since curcumin binds to beta-
to induce autonomic symptoms. amyloid, the differences in images before and after
Disclosure: Nothing to disclose curcumin use can be explained by beta-amyloid
accumulation in the retina. OCT and FAF can be trustable
biomarkers in the course of AD.
Disclosure: Nothing to disclose
Headache and pain 1 difference 021 [-020 to 063]), but these differences did
not reach statistical significance.
Conclusion: Our study provided no clear evidence of an
O2207 association between MA and WMH.
Abstract cancelled Disclosure: The study received support from the Lundbeck
Foundation (R93-A8392), Novo Nordisk Foundation &
Fabrikant Vilhelm Pedersen & Hustrus legat, and Fonden til
O2208 Lgevidenskabens Fremme A.P. Mller og Hustru Chastine
Migraine with aura and risk of silent brain Mc-Kinney Mllers Fond til Almene Formaal; Dr. Gaist is
infarcts and white matter hyperintensities funded by Odense University Hospital; Dr. Ashina is funded
by Novo Nordisk Foundation (1014333).
in women: a population-based MRI-study
of Danish twins
D. Gaist1, E. Garde2, M. Blaabjerg1, H. HvilstedNielsen1,
O2209
T. Krigrd1, K. stergaard1, H. SettergrenMller1, Variability of clinical features in attacks of
J. vonBornemannHjelmborg3, C. GbelMadsen4, migraine with aura
P. Iversen2, K. OhmKyvik5, H.R. Siebner2, M. Ashina6 J.M. Hansen1, P.J. Goadsby2, A. Charles3
1Neurology, Odense University Hospital, Odense, Denmark, Copenhagen, Denmark, 2NIHR-Wellcome Trust Kings
1
2Danish Research Centre for Magnetic Resonance, Centre
Clinical Research Facility, Kings College, London, United
for Functional and Diagnostic Imaging and Research, Kingdom, 3Neurology, UCLA, Los Angeles, USA
Copenhagen University Hospital Hvidovre, Copenhagen,
Denmark, 3Epidemiology, Biostatistics and Biodemography, Background and aims: There is significant variability in
Institute of Public Health, University of Southern Denmark, the clinical presentation of migraine, both among patients,
Odense, Denmark, 4Department of Radiology, Centre for and between attacks in an individual patient. We examined
Functional and Diagnostic Imaging and Research, clinical features of migraine with aura in a large group of
Copenhagen University Hospital Hvidovre, Copenhagen, patients enrolled in a clinical trial, and compared
Denmark, 5The Danish Twin Registry, Institute of Public retrospective migraine attack characteristics reported upon
Health, University of Southern Denmark, Odense, Denmark, enrolment in the trial with those recorded prospectively in
6Danish Headache Center and Dept. of Neurology, the trial.
Rigshospitalet Glostrup, Faculty of Medical and Health Methods: Patients with migraine (n=267) with typical
Sciences, University of Copenhagen, Copenhagen, Denmark visual aura in more than 30% of their attacks were enrolled
Background and aims: A small number of population- from 16 centres for a clinical trial. Upon enrolment, patients
based studies reported an association between migraine provided a detailed retrospective description of the clinical
with aura (MA) and risk of silent brain infarcts and white features of their attacks of migraine.
matter hyperintensities (WMH) in women. We investigated Results: Retrospectively reported visual aura symptoms
these relations in a population-based sample of female were variable and often overlapping; most common
twins. symptoms were dots or flashing lights, wavy or jagged
Methods: We contacted female twins, aged 30-60 years lines, blind spots, and tunnel vision. Many patients reported
identified through the population-based Danish Twin more than one visual phenomenon. Approximately half of
Registry. Based on questionnaire responses, twins were the patients reported non-visual aura symptoms, the most
invited to participate in a telephone-based physician- common were numbness and tingling, followed by difficulty
conducted interview. Headache diagnoses were established in recalling or speaking words. There were several
according to the International Headache Society criteria. inconsistencies between the features of prospectively
Cases with MA, their co-twins, and unrelated migraine-free recorded and retrospectively reported attacks. Nausea was
twins (controls) were invited to a brain MRI performed at a prospectively recorded in only 51% of attacks. Phonophobia
single center. Brain scans were assessed for the presence of was not consistently recorded in conjunction with
infarcts, and WMH (visual rating scales and volumetric photophobia.
analyses) blinded to headache diagnoses. Conclusion: These findings are consistent with variable
Results: Comparisons were based on 172 cases, 34 involvement of different brain regions during a migraine
co-twins, and 139 controls. Compared with controls, cases attack. The variable occurrence of nausea, and phonophobia
did not differ with regard to frequency of silent brain in conjunction with photophobia, both defining features of
infarcts (four cases versus 1 control), periventricular WMH migraine, may be an important consideration in designing
scores (adjusted mean difference [95% CI]: -01 [-05 to clinical studies of migraine in which prospectively recorded
02]) or deep WMH scores (adjusted mean difference [95% attacks are diagnosed based on these clinical features.
CI]: 02 [-08 to 11]) assessed by Scheltens scale. Cases Disclosure: This work was supported by the Danish Council
had a slightly higher total WMH volume compared with for Independent Research-Medical Sciences (DFF) (grant/
controls (adjusted mean difference [95% CI]: 017 [-008 to award number 12-127798).
041] cm3) and a similar difference was present in analyses
restricted to twin pairs discordant for MA (adjusted mean
O2210 O2211
Sensory migraine aura is not associated Randomised, double-blind, phase-2 study
with structural grey matter abnormalities and 52-Week interim results of an open-
A. Hougaard1, F.M. Amin1, N.B. Arngrim1, M. Vlachou1, label extension to evaluate AMG334 for
V.A. Larsen2, H. Larsson2, M. Ashina1 the prevention of episodic migraine
1 Danish Headache Center, Copenhagen, Denmark,
H. Sun1, D. Dodick2, P.J. Goadsby3, S. Silberstein4,
2 Rigshospitalet, Copenhagen, Denmark
U. Reuter5, M. Ashina6, J. Saper7, R. Cady8, F. Zhang1,
Background and aims: Migraine with aura (MA) is M.-L. Trotman1, J. Dietrich1, R. Lenz1
characterized by cortical dysfunction. It has been suggested 1Amgen, Thousand Oaks, USA, 2Mayo Clinic, Scottsdale,
that structural grey matter abnormalities predispose MA USA, 3NIHR-Wellcome Trust Kings Clinical Research
patients to experiencing aura attacks. We aimed to Facility, Kings College, London, United Kingdom, 4Jefferson
investigate cortical and subcortical grey matter structure in University, Philadelphia, USA, 5Charit Universittsmedizin
a large group of MA patients with and without sensory aura. Berlin, Berlin, Germany, 6Danish Headache Center and
Methods: We included 60 patients suffering from migraine Dept. of Neurology, Rigshospitalet Glostrup, Faculty of
with typical visual aura and 60 individually age and sex- Medical and Health Sciences, University of Copenhagen,
matched controls. 29 of the patients additionally experienced Copenhagen, Denmark, 7Michigan Head Pain and
sensory aura regularly. We analysed high-resolution Neurological Institute, Ann Arbor, USA, 8Clinvest Research,
structural MR images using two complimentary approaches Banyan Group, Inc., Headache Care Center, Springfield,
and compared patients with and without sensory aura. USA
Patients were also compared to controls. We included age, Background and aims: Calcitonin generelated peptide
gender, attack frequency, and disease duration as covariates (CGRP) plays a role in migraine. We evaluated prevention
in the analyses. of episodic migraine (EM) with AMG334, a human anti-
Results: We found no differences of grey matter density or CGRP receptor monoclonal antibody.
cortical thickness between patients with and without Methods: Adults (N=483) with EM were randomised to
sensory aura. The somatosensory cortex was thinner in monthly subcutaneous AMG334 (7-mg, 21-mg, or 70-mg)
patients (1.92 mm vs. 1.96 mm, P =0.043) and the cingulate or placebo (2:2:2:3). Primary and secondary endpoints were
cortex of patients had a decreased grey matter density (P = assessed at week 12. After completing the double-blind
0.039) compared to controls. These differences were not (DB) phase, patients could continue in an open-label
correlated to the clinical characteristics. extension (OLE) to receive 70-mg AMG334 up to 5 years.
Conclusion: Sensory migraine aura per se is not associated This analysis is based on available efficacy and safety data
with altered grey matter structure. The observed cortical up to week 52 and week 76, respectively.
structural abnormalities have previously been reported in Results: Baseline mean (SD) monthly migraine days was
migraine patients with and without aura. Most likely, these 8.7 (2.7). Week-12 reductions from baseline in monthly
changes are not specifically related to migraine migraine days were significantly greater with 70-mg
pathophysiology. AMG334 than placebo (-3.40 vs. -2.28; p=0.021), but not
Disclosure: Nothing to disclose with lower doses (primary endpoint). Responder rates
(50%) were significantly higher with 70-mg AMG334 than
placebo (47% vs. 30%; p=0.011). Changes in monthly
migraine attacks were not significant from placebo. 383/395
eligible patients entered the OLE. Median exposure was
34.1 weeks. Further reductions from baseline in monthly
migraine days were sustained up to 52 weeks. At Week 52,
62%, 38% and 19% of patients experienced 50%, 75%,
and 100% reduction from baseline in migraine days,
respectively. There were no major safety findings during the
DB phase; tolerability was similar between AMG334 and
placebo. No new safety signals were identified during the
OLE.
Conclusion: AMG334 70-mg demonstrated sustained
efficacy in prevention of EM. The safety/tolerability profile
of AMG334 in this phase 2 study supports continued
development.
Disclosure: This study was supported by Amgen, Inc.
O2212
Cost-effectiveness and feasibility of
telemedicine for primary headaches
K.I. Mueller1, K.B. Alstadhaug2, S.I. Bekkelund1
1Troms, Norway, 2Neurology, Nordland Hospital Trust,
Hospital, Aarhus C, Denmark Conclusion: Diffusion tensor imaging of the sciatic and
Background and aims: To evaluate the use of magnetic tibial nerve showed lower FA values and higher ADC values
resonance (MR) diffusion tensor imaging (DTI) to in diabetic patients with PNP as compared to healthy
demonstrate nerve lesions in patients with type 1 diabetes. controls and non-neuropathic patients. Lower FA values and
Methods: 10 type 1 diabetic patients with polyneuropathy higher ADC may reflect less constriction of flow along the
(+PNP), 10 type 1 diabetic patients without polyneuropathy nerve indicating demyelination and axonal loss PNP.
(-PNP) and 10 healthy controls (HC) were included. Disclosure: This work is funded by the UNIK partnership
Diffusion tensor images were acquired to evaluate the foundation, Siemens A/G Copenhagen, the Danish Diabetes
extent of focal lesions in the sciatic and tibial nerve using a Academy supported by the Novo Nordisk Foundation and
3 Tesla scanner. DTI fractional anisotropy (FA) and apparent Aarhus University.
diffusion coefficients (ADC) were calculated. The MR
scans consisted of 16 axial slices of the sciatic nerve and the
tibial nerve. The presence of PNP was determined based on
nerve conduction studies, vibratory perception thresholds
and clinical neurological examination.
O2214 O2215
The role of functional MRI in the Cerebrospinal fluid anti-Caspr2 antibodies
diagnosis and prognosis of patients with determine a subtype of autoimmune
severe chronic disorders of encephalitis with prominent limbic
consciousness symptoms and seizures
B. Wutzl1, C. Florea2, M. Seidl2, A.B. Kunz2, B. Joubert1, M. SaintMartin2, N. Noraz2, G. Picard3,
K. Schwenker2, R. Nardone2, E. Trinka3, V. Rogemond2, F. Ducray4, V. Desestret1, D. Psimaras5,
F. Gerstenbrand4, S. Golaszewski2 J.-Y. Delattre5, J.-C. Antoine6, J. Honnorat1
1Neurology, Paracelsus Medical University Salzburg, 1Lyon Bron, France, 2Neuroscience, INSERM, Lyons,
Salzburg, Austria, 2Salzburg, Austria, 3Department of France, 3Neurology, Hospices Civils de Lyon, Lyons, France,
Neurology, Paracelsus Medical University Salzburg, 4Lyons, France, 5Paris, France, 6CHU Saint-Etienne, Saint-
O2217 O2218
Evaluation by brain MRI of white matter Novel findings in 13 patients with
perivenular lesions in inflammatory micro- autoimmune encephalitis and antibodies
angiopatic ischemia and in demyelinating to the GABAA receptor
multiple sclerosis lesions M. Spatola1, M. Petit-Pedrol1, M. Rosenfeld1, F. Graus2,
L. Massacesi J. Dalmau3
Department of Neurosciences Drugs and Child Health , 1Neuroimmunology, IDIBAPS, Barcelona, Spain, 2Service of
University of Florence, Florence, Italy Neurology, Hospital Clinic, Barcelona, Spain, 3Department
of Neurology, University of Pennsylvania, Philapdelphia,
Background and aims: MRI can detect central veins inside
USA
white matter (WM) lesions, thus discriminating
demyelinating from ischemic lesions due to chronic micro- Background and aims: A novel autoimmune encephalitis
angiopathy or migraine (Mistry et al.; Solomon et al.; 2015). with antibodies to the 13 subunits of the GABAA receptor
However the frequency of this marker in WM lesions due to (GABAAR) was recently reported (Petit-Pedrol et al.,
inflammatory micro-angiopatic ischemia has never been Lancet Neurol, 2014). A recent study suggested that the 2
evaluated. In this study frequency of WM perivenular subunit was also a target, but the syndrome association was
lesions (PVL) was compared between multiple sclerosis unclear (Pettingill et al, Neurology, 2015).
(MS) and systemic autoimmune diseases with WM lesions Methods: We examined for GABAAR antibodies 2754
(SAD). patients referred for antibodies studies (April
Methods: Inclusion criteria: definite MS or SAD. Each 2013-December 2015). Clinical information was obtained
patient received one brain MRI including volumetric T2*- from medical records. Antibodies were determined with live
EPI and FLAIR sequences after gadolinium injection. HEK293 cells expressing the indicated GABAAR subunits.
White matter lesions were considered PV, if intralesional Results: 13 new patients with antibodies to GABAAR and
hypointense signal was completely surrounded by prominent seizures were identified. The median age was
hyperintense signal in at least 2 planes. 47.7 years. Novel findings included cancer in 7 adults
Results: 38 patients (24 MS and 14 SAD) were enrolled. (thymoma, small-cell lung cancer, rectal cancer, or multiple
The SAD group included 5 Behcet syndrome (BS), 4 myeloma), HIV infection in one patient, and a clinical
systemic lupus erythematosus (SLE) and 5 antiphospholipid picture mimicking anti-NMDAR encephalitis in a 10-month
syndrome (APS). Most of the SAD patients (12/14), old child. Treatment was available for 10 patients: 6
fulfilled MS MRI criteria for dissemination in space. The received 1st line immunotherapy (corticosteroids, plasma
median PVL frequency/patient was 89% (range= 68-100%) exchange, IvIg), 3 received 1st and 2nd line therapy
and 15% (range= 0-50%) in the MS and in the SAD group (rituximab, azathioprine, cyclosporine) and 1 was not
respectively (p<0.0001; Mann-Whitney test). In SAD treated. 8 of the 9 treated patients had substantial/complete
patients, BS showed the highest frequency of PVL (median/ recovery, one died from sepsis after neurological
patient: 40%, range= 16-50). PVL frequency/patient >50%, improvement. All patients antibodies recognized the 1
significantly segregated with MS (p<0.001, Fisher test), and/or 3 subunits. The 2 was recognized by antibodies of
resulting in 100% accuracy for this cohort. 6 patients but always in combination with 1 or 3, and
Conclusion: The frequency of PVL is higher in MS than in without any syndrome specificity.
SAD, including those fulfilling MS MRI diagnostic criteria Conclusion: GABAAR antibody-associated encephalitis
for dissemination in space. This MRI marker can improve usually responds to immunotherapy and most patients have
differentiation between the two CNS disorders. partial or complete recovery. The main antibody targets are
Disclosure: Nothing to disclose the 1 and 3 subunits; 2 subunit specificity does not
provide additional diagnostic value.
Disclosure: M. Spatola has received financial support from
Socit Acadmique Vaudoise and Fondation Pierre Mercier
pour la Science. All the other authors report no disclosures
relevant to the manuscript.
O2221 O2222
Status epilepticus in the intensive care Head computed tomographic
unit: incidence and outcome in Australia measurement as an early predictor of
and New Zealand from 2000 to 2013 poor outcome after cardiac arrest
A. Hay1, R. Bellomo1, D. Pilcher2, G. Jackson3, M. MosebyKnappe1, T. Pellis2, I. Dragancea3,
K.-M. Kaukonen4, M. Bailey2 H. Friberg4, J. Horn5, M.A. Kuiper6, N. Nielsen4,
1Intensive Care Unit, Austin Hospital, Melbourne, Australia, A. Roncarati2, T. Cronberg1
2Australia and New Zealand Intensive Care Research Centre, 1Department of Clinical Sciences, Division of Neurology,
Melbourne, Australia, 3Brain Research Institute, Melbourne, Lund University, Lund, Sweden, 2Department of Anesthesia,
Australia, 4Department of Anaesthesiology and Intensive Intensive and Emergency Medical Service AAS 5, Santa
Care, Helsinki University, Helsinki, Finland Maria degli Angeli Hospital, Pordenone, Italy, 3Lund,
Background and aims: Status epilepticus (SE) is a Sweden, 4Department of Clinical Sciences, Division of
neurological emergency and may lead to Intensive Care Anesthesiology and Intensive care, Lund University, Lund,
Unit (ICU) admission. However, little is known about the Sweden, 5Department of Intensive Care, Academic Medical
characteristics and outcome of patients with the ICU Center Amsterdam, Amsterdam, Netherlands, 6Leeuwarden,
admission diagnosis of status epilepticus. Netherlands
Methods: We performed a retrospective study of patients Background and aims: Out-of-hospital cardiac arrest is
admitted to ICU with the primary admission diagnosis of mostly followed by death or disability. Resuscitated patients
SE as recorded in the Australian and New Zealand Intensive usually require intensive care. Head computed tomography
Care Society (ANZICS) Adult Patient Database over more (CT) is easily and rapidly performed to rule out non-cardiac
than a decade. We examined the ICU and population causes of unconsciousness. Its ability to predict poor outcome
incidence, physiological and demographic features of such after cardiac arrest (CA) has not been evaluated in a large
SE patients; compared ventilated and non-ventilated SE clinical trial.
patients and assessed their mortality. Methods: Pre-specified post-hoc analysis of the Target
Results: From 2000-2013, 12,926 patients (1.2% of all ICU Temperature Management (TTM) trial in which 939 patients
admissions) were admitted to ANZ ICUs with SE as the were randomised to treatment at 33C or 36C after return of
main admission diagnosis. Over the study period, the ICU spontaneous circulation. The clinical findings and results from
prevalence, population incidence, ICU length of stay and head CT investigations after CA were protocolised,
the rate of discharge to a rehabilitation facility of SE systematically recorded and correlated with outcome after 6
increased (p<0.0001). In contrast, the use of mechanical months using the Cerebral Performance Category (CPC). Poor
ventilation, hospital length of stay, ICU and hospital neurological outcome was defined as severe cerebral disability,
mortality decreased (p<0.0001). Hospital mortality was 613 vegetative state or death (CPC 3-5).
(4.7%) with 219 (1.7%) patients dying in ICU. Mortality Results: Of 939 patients, 356 patients underwent a head CT
was associated with advancing age, multiple co-morbidities, examination after CA, 3 patients were excluded because of
lower GCS on admission and higher APACHE III scores. errors in data rapport. 314 patients underwent one CT
From 2000 to 2013 ICU mortality decreased from 2.6% to investigation, 39 patients had two CTs reported. CT findings
0.75%. were protocolled in hours after cardiac arrest and were divided
Conclusion: Over a 14-year period in ANZ, there have into 4 subgroups as follows: very early: 24 hours, early: >24
been major changes in the features, treatment and outcome 96 hours, late: 4 days 7days and very late: >7 days. 45% of
of patients admitted to ICU with the primary admission all CTs were done within the first 24 hours. The distributions
diagnosis of SE such that their ICU mortality is now <1%. of findings are shown in Fig. 1. The correlation of CT-findings
Our findings provide a benchmark for future studies of this with patient outcome will be presented.
condition.
Disclosure: Nothing to disclose
O2227 O2228
Structural organisation of the brain Relationship between freezing and
connectome in patients with psychogenic pedunculopontine nucleus' size in
dystonia Parkinson's disease: semi quantitative
S. Basaia1, F. Agosta1, A. Tomic2, E. Sarasso1, M. Svetel2, analysis based on MRI with modified
S. Galantucci1, V.S. Kostic2, M. Filippi1 FGATIR sequence
1Neuroimaging Research Unit, Institute of Experimental
S. Chen1, M. Tir1, P. Monet2, J.-M. Constans2,
Neurology, Division of Neuroscience, San Raffaele Scientific
O. Godefroy1, M. Lefranc3, P. Krystkowiak1
Institute, Vita-Salute San Raffaele University, Milan, Italy,
2Clinic of Neurology, Faculty of Medicine, University of
1Department of Neurology, University Hospital of Amiens,
Amiens, France, 2Department of Radiology, University
Belgrade, Belgrade, Serbia
Hospital of Amiens, Amiens, France, 3Department of
Background and aims: The purpose of this study was to Neurosurgery, University Hospital of Amiens, Amiens,
investigate the structural organization of the brain France
connectome in patients with psychogenic dystonia (pDYT). Background and aims: Gait disorders represent a major
Methods: The study involved 31 pDYT patients and 36 problem in Parkinsons disease (PD). The aim was to
age- and sex-matched healthy controls. All subjects determine the possible relation between pedunculopontine
underwent 3D-T1 weighted and DT MRI. The structural nucleus size (PPN) and occurrence of freezing.
connectome was reconstructed based on brain parcellation Methods: Modified Fast Gray Matter Acquisition T1
and whole brain DT MRI tractography. The affected Inversion Recovery images (FGATIR) was obtained using
structural connections in patients relative to HC were 3 T MRI during pre-surgical procedure for subthalamic
investigated using Network-Based Statistic (p<0.01, 10.000 deep brain stimulation (STN-DBS) for PD. We localized
permutations). PPN and evaluated it semi quantitatively (0 = no atrophy, 1
Results: Compared to controls, pDYT patients showed a = mild atrophy, 2 = moderate atrophy, 3 = severe atrophy).
large brainstem/basal ganglia/frontal network (or principal Results: 30 patients were included: 12 in PD freezer group
connected component) with decreased fractional anisotropy (FOG +), 13 in PD non freezer group (FOG -) and 5 in
(FA) and increased mean diffusivity including the brainstem, control group. The mean stereotactic coordinates for the
left thalamus, putamen, pallidum, pre- and post-central gyri, rostral PPN were 6.58 mm lateral, 2.92 mm posterior to the
right caudate, and anterior cingulate and middle/superior posterior commissure (PC) and 8.87 mm caudal to the
frontal cortex bilaterally. Smaller secondary networks with anterior commissure posterior commissure (AC-PC)
reduced FA were found in the right hemisphere connecting plane, those of the caudal PPN were 7.18 mm lateral, 4.07
the right pre- and post-central gyri to the thalamus and mm posterior to the PC and 13.18 mm caudal to the AC-PC.
middle frontal areas. In pDYT patients, affected connections In FOG+group, there were more PPN measured at 2 or 3
between the right thalamus and putamen and the right compared to FOG group (27% versus 17%). However,
thalamus and precentral gyrus correlated with the total degree of PPN atrophy was not significantly different
phenomenology subscore of the Psychogenic Movement between the three groups.
Disorder (PMD) scale. Conclusion: Our results need to be confirmed by a larger
Conclusion: This study points toward a structural study. Thus, a reduced size of PPN, could have a potential
disconnection of the brainstem/basal ganglia/frontal brain value as predictive factor of occurrence of axial signs in PD
networks in patients with pDYT. Altered structural after STN-DBS. This study highlights the great interest of
connections between basal ganglia and primary modified FGATIR MRI image to evaluate precisely the size
sensorimotor cortex are associated with the severity and of the PPN.
duration of the disease. Future longitudinal studies are Disclosure: Nothing to disclose
warranted to clarify whether these abnormalities reflect a
primary disease process in these networks or are secondary
effects of the disorder.
Disclosure: Nothing to disclose
O2229 O2230
An ongoing phase-2, open-label study of Phosphorilated alpha-synuclein
WTX101 in Wilson disease patients early cutaneous deposits and cardiac
observations autonomic involvement in
A. Czlonkowska1, K.H. Weiss2, A. Ala3, F. Askari4, -Synucleinopathies
D. Nicholl5, M. Schilsky6 M.P. Giannoccaro1, V. Donadio1, A. Incensi2, E. Cason3,
1Warsaw, Poland, 2University Hospital Heidelberg, R. Liguori1
Heidelberg, Germany, 3The Royal Surrey County Hospital 1Bologna, Italy, 2UOC Clinica Neurologica, IRCCS Istituto
NHS Trust, Guildford, United Kingdom, 4University of Scienze Neurologiche Bologna, Bologna, Italy, 3Ospedale
Michigan Hospital, Ann Arbor, USA, 5Sandwell and West Maggiore, Bologna, Italy
Birmingham Hospitals NHS Trust, Birmingham, United
Background and aims: Differential diagnosis among
Kingdom, 6Yale University Medical Centre, New Haven, USA
-Synucleinopathies, including idiopathic Parkinsons
Background and aims: WTX101 (bis-choline disease (iPD), dementia with Lewy bodies (DLB), pure
tetrathiomolybdate) is a de-coppering agent in clinical autonomic failure (PAF) and multiple system atrophy
development for Wilson Disease (WD). The aim of the (MSA), can be challenging in vivo. Cutaneous and cardiac
study is to evaluate the efficacy and safety of WTX101 in autonomic denervation was reported in iPD, DLB and PAF
WD patients. as opposed to MSA and recently the detection of skin nerve
Methods: Patients nave to treatment or treated for 28 phosphorylated--synuclein (p--Syn) deposits provided a
days with chelation or zinc therapy were initiated on 30 or marker for diagnosing and exploring the spreading of the
60 mg WTX101 daily. Dosing was individualized after 6 pathology premortem. We aimed to compare 123I-MIBG
weeks, guided by laboratory and clinical criteria. scintigraphy and skin biopsy findings in -Synucleinopathies
Assessments included safety, hepatic status, copper in order to: 1) verify the relation between myocardial and
parameters and neurological status using the Unified Wilson skin innervations and cutaneous p--Syn deposition; 2)
Disease Rating Scale (UWDRS). identifying patterns of autonomic dysfunction across
Results: The first 6 patients were followed for 8 to 36 multiple sites in vivo.
weeks in the study. Baseline Modified Nazer score ranged Methods: We studied 52 patients (8 DLB, 21 iPD, 13 PAF,
from 1-5 and 5/6 had neurological manifestations. 10 MSA) who underwent 123I-MIBG scintigraphy and skin
Reversible elevated liver function tests after per-protocol biopsies to evaluate skin innervation and p--Syn
dose escalations were observed in the first 2 patents. After deposition.
reducing the initiation dose from 60 mg to 30 mg daily and Results: Skin nerve fiber loss and p--Syn deposits were
dose escalation to a maximum daily dose of 60 mg, documented in all iPD, DLB and PAF patients and were
WTX101 was well tolerated with no SAEs and few AEs. associated with cardiac denervation in 95% of iPD and in
Hepatic status improved or remained stable. Elevated 100% of DLB and PAF cases respectively. Conversely,
baseline free copper on average normalized within 3 normal skin and scintigraphic findings were detected in
months. The UWDRS scores and daily activity improved in MSA. Concordance among MIBG scintigraphy and skin
all neurological patients. biopsy results was observed in 100% of DLB, PAF, and
Conclusion: WTX101 appears safe and well tolerated in MSA and 95% of iPD patients.
WD patients, with improvement in clinical (hepatic and Conclusion: 1) Skin biopsy and 123-MIBG scintigraphy
neurologic) and laboratory assessments. Further clinical can be considered alternative test for the differential
evaluation is warranted. diagnosis of iPD, PAF and DLB versus MSA; 2) although
Disclosure: financial disclosure (honoraria, consultaties), in iPD, PAF and DLB peripheral autonomic involvement is
Wilson therapeutics, WTX101 (Multi-Centre, Open-Label often simultaneously widespread in different autonomic
study) branches.
Disclosure: Nothing to disclose
O3103 O3104
No evidence for increased brain iron The prehospital Aarhus stroke severity
deposition in patients with ischemic white scale for prediction of emergent large
matter disease vessel occlusion: design, validation and
T. Gattringer1, M. Khalil1, C. Langkammer1, M. Jehna2, comparison with other scales
M. Kneihsl1, A. Pichler1, D. Pinter1, K. Petrovic1, S. Hastrup1, D. Damgaard1, S. J. Paaske2, G. Andersen1
S. Ropele1, F. Fazekas1, C. Enzinger1 1 Neurology , Aarhus University Hospital, Aarhus, Denmark,
1Neurology, Medical University of Graz, Graz, Austria, 2 Clinical Epidemiology, Aarhus University, Aarhus, Denmark
2Radiology, Division of Neuroradiology, Medical University
Background and aims: We designed and validated a
of Graz, Graz, Austria
simple prehospital stroke scale to identify emergent large
Background and aims: Increased iron deposition in vessel occlusion (ELVO) in patients with acute ischemic
cerebral deep grey matter (DGM) is a frequent finding in stroke and compared the scale to other published scales.
neurodegenerative disorders, but has also been observed in Methods: A national historical test cohort of 3127 patients
diseases predominantly affecting white matter (WM) like with information on intracranial vessel status (angiography)
multiple sclerosis. The cause for this is unclear. We thus before reperfusion therapy was identified. National
investigated whether WM damage of presumed ischemic Institutes of Health Stroke Scale (NIHSS) items with the
origin is also associated with increased DGM iron. highest predictive value of occlusion of a large intracranial
Methods: We rated WMH severity according to the Fazekas artery were identified and the most optimal combination
scale and measured WMH volume quantitatively using the meeting expert criterion of usability in the prehospital phase
software DISPIMAGE in 61 consecutive patients with was determined. The predictive performance of the
acute transient neurological symptoms (20 males, 41 Prehospital Aarhus Severity Stroke (PASS) scale was
females, mean age: 71.58.3 years) undergoing 3-Tesla- compared with other published scales for ELVO.
MRI. DGM iron levels of seven predefined structures were Results: PASS scale was composed of 3 combined scores
assed by using R2* sequences. from NIHSS: level of consciousness questions (month/age);
Results: We stratified patients by WMH severity (absent/ gaze palsy/deviation and arm weakness, Figure 1. In
punctate, n=25 versus early confluent/confluent n=36). derivation of PASS 2/3 of the test cohort was used and
Patients with more severe WMH were six years older and showed accuracy (Area Under Curve) of 0.76 for detecting
more often also had old lacunar infarcts. DGM R2* rates large arterial occlusion. Optimal cut-off 2 abnormal scores
did not differ between the two groups, except for the globus showed a sensitivity of 0.66 (95% CI 0.62-0.69); specificity
pallidum with higher R2* rates in patients with no or minor 0.83 (0.81-0.85) and AUC 0.74 (0.72-0.76). Validation on
WMH (34.964.88 versus 32.683.88; p=0.024). The 1/3 of the test cohort showed similar performance, Table 1.
volume of WMH was not correlated with R2* levels in any Patients with a large artery occlusion on angiography with
of the analysed DGM structures. a PASS 2 had a median NIHSS of 17 (IQR =6) as opposed
Conclusion: In patients with WMH of presumed ischemic to PASS<2 with a median NIHSS =6 (IQR =5). The PASS
origin more extensive WM damage was not associated with scale showed equal performance although more simple
higher DGM iron levels despite the fact that they were when compared to other scales predicting ELVO, Table 2.
significantly older. These findings argue against the
assumption that WM damage per se is responsible for
increased iron accumulation observed in multiple sclerosis
and suggest no role of cerebral iron accumulation in
ischemic small vessel disease.
Disclosure: Nothing to disclose
O3106
Gender differences in thrombolysed
stroke patients
M.R. Heldner1, R. Kurmann1, R. Balasubramaniam1,
M.-L. Mono1, F. Pult2, K. Hsieh2, S. Jung3, P. Mordasini2,
J. Gralla2, M. Arnold1, U. Fischer1
1Department of Neurology, Inselspital, University of Bern,
Switzerland, Berne, Switzerland, 2Institute of Diagnostic and
Interventional Neuroradiology, Inselspital, University of
Table 2. Accuracy of the 3ISS, LAMS, RACE and CPSSS in
Bern, Switzerland, Berne, Switzerland, 3Department of
comparison with PASS in prediction of large artery occlusion in the
entire study population. Neurology and Institute of Diagnostic and Interventional
Neuroradiology, Inselspital, University of Bern, Switzerland,
Conclusion: The PASS scale is simple and has promising Berne, Switzerland
accuracy for prediction of ELVO in the field. Background and aims: WISE-group initiative. To assess
Disclosure: Nothing to disclose gender differences in clinical characteristics, treatment and
outcome in thrombolysed stroke patients.
Methods: From January 2010-2015 1211 patients
O3105 (n=524[43.3%] women) were thrombolysed at the Bernese
Vertebrobasilar occlusion stroke: does Stroke Center.
stent retrievers thrombectomy modify the Results: Thrombolysed women were older than men
outcome? (median 77.4 vs. 71 years; p<0.0001), and median NIHSS
score on admission was higher (median 13 vs. 11; p=0.023)
F. Perren1, V. MendesPereira2 as well as premorbid disability (mRS <2: 12.2% vs. 6.7%;
1Geneva, Switzerland, 2Interventional Neuroradiology,
p=0.001). Women had less frequently hypercholesterolemia
University of Toronto University Health Network, Toronto, (54.8% vs. 61.7%; p=0.017) and coronary artery disease
Canada
(14.8% vs. 28.1%; p<0.0001). Stroke etiology was more
Background and aims: Untreated basilar artery occlusions often cardioembolic (49.0% vs. 39.6%; p=0.001) and less
carry a very high morbidity and mortality. Considering the frequently caused by large artery disease (6.7% vs. 13.4%;
unprecedented rates of rapid recanalization shown with p<0.0001) and women had more often atrial fibrillation
stent-based thrombectomy, we looked whether this (47.2% vs. 34.7%; p<0.0001). There was a longer time
therapeutic approach alone or combined to IV thrombolysis delay from admission to imaging in women (median 36 vs.
was superior to IA thrombolysis or bridging therapy. 33 min.;p=0.009) and women had more often an occlusion
Methods: Acute vertebrobasilar occlusions treated either of the main stem of the middle cerebral artery (34.5% vs.
by bridging (IV-IA thrombolysis) therapy or IA-thrombolysis 25.8%; p<0.0001) and less frequently vertebral artery
(group 1) or by stent retrievers thrombectomy alone or occlusions (0.4 vs. 1.6%; p=0.041). Women were less
combined to IV-thrombolysis (group 2) were reviewed. frequently thrombolysed with rtPA alone (29.4% vs. 39.4%;
Efficacy and safety outcomes were compared between the p<0.0001), but were more often treated with mechanical
2 groups. thrombectomy (29% vs. 19.9%; p<0.0001). Women had
Results: 30 consecutive acute vertebrobasilar occlusions: less favorable outcome at 3 months (mRS2: 39.4% vs.
16 patients (10 men, mean age 65 years, admission NIHSS 53.6%; p<0.0001,fatality: 26.5% vs. 21.2%; p=0.042). In
15.5): group 1 and 14 patients (12 men, mean age 62 years, multivariate logistic regression analysis female gender was
admission NIHSS 16.4): group 2, were studied (NIHSS a predictor of unfavorable outcome (mRS3;OR 1.427;
t=0.4053; p>0.05). Both groups improved significantly p=0.045).
after therapy (NIHSS group 1: 10.5; t=3.1782; p<0.01; Conclusion: Clinical characteristics, stroke etiology,
group 2: 5.8; t=5.1436; p<0.0005). However improvement treatment modalities and outcome differ between female
of NIHSS after therapy was significantly better in group 2 and male patients thrombolysed because of an acute
(t=2.2018; p<0.05). Good clinical outcome (mRS<2) was ischemic stroke. Future research should focus on
achieved in only 18.7% of group 1 as compared to 50% of improvement of outcome in female stroke patients.
group 2 (Fischer exact; p>0.05). Complete recanalization Disclosure: Nothing to disclose
(TICI 2b or 3) was obtained in 75% of patients in group 1
and in 92.8% of group 2 (Fishers exact; p>0.05). sICH and
mortality rate were higher in group 1 (31.2%;43.7%) than
in group 2 (7.1%;14.3%) (Fishers exact p>0.05).
Conclusion: Stent-based thrombectomy, combined to IV
thrombolysis or alone, compared with bridging therapy or
IA-thrombolysis alone, improves significantly the early
outcome and results in better (though not significant)
recanalization, late outcome and safety.
Disclosure: Nothing to disclose
Cognitive neurology/
neuropsychology 2
O3108
Influence of lateralised hemispheric
asymmetries upon numerical cognition
and its influence upon pro-social decision
making in Parkinsons disease
Q. Arshad, A. Bonsu, P.A. Malhotra, N. Pavese,
A. Bronstein
Imperial College London, London, United Kingdom Fig 2: Relationship between the mean % UPDRS score and the %
bisection error from the midpoint of the numerical interval A significant
Background and aims: Numerical allocation is closely correlation is observed between mean % UPDRS and numerical
linked with spatial attention mechanisms. That is, numerical magnitude. Pearson correlation (-0.815); P<0.001***
magnitude is superimposed upon a left-right spatially-
orientated representation, termed the mental number line. Conclusion: We provide the first demonstration that
Fronto-parietal lesions that result in a rightward spatial- lateralised numerical biases present in PD, and that
attention bias cause a pathological numerical bias towards functionally these biases influence decision making.
larger magnitudes. Given the demonstration that a rightward Disclosure: Nothing to disclose
visuospatial bias presents in left-sided PD patients during a
line-bisection task, we hypothesized that lateralised
numerical biases may present in PD and functionally these
O3109
biases may impact upon pro-social choices formulated Prevalence of post-stroke cognitive
during a decision making task. disorders: a meta-analysis
Methods: 20 right-handed PD patients participated (10
M. Barbay, O. Godefroy, M. Roussel, M. Diouf,
right-sided, mean age 68.5, 5F; 10 left-sided, mean age
S.G. Grecogvasc
71.7, 3F) and 20 matched controls. All patients, completed
Neurology, University Hospital of Amiens, Amiens, France
the UPDRS rating scale, had a Hoehn and Yahr score of
either 1 or 2, were on dopaminergic medication, non- Background and aims: Post-stroke neurocognitive
demented nor depressed. Subjects performed a mental disorders (PSNCD) have been reported with very variable
number pair bisection task and the dictator game task. prevalence in hospital-based cohorts. The objective of this
Results: We found that left-sided PD patients were study was to assess the prevalence of mild, major and total
significantly biased towards larger numbers (p<0.001), PSNCD by a meta-analysis based on a systematic review of
whilst right-sided PD patients were biased towards smaller hospital-based studies and to determine factors affecting
numbers (p<0.001), compared to age-matched controls. this prevalence.
Further, it was found that numerical bias led to corresponding Methods: Studies were included if they were published in
changes during a pro-social decision making task. That is, English between 1990 and September 2015, based on three
left-sided PD patients who were biased towards larger databases and manual search, about consecutive patients
numbers were found to be more pro-social (i.e. more hospitalized for stroke. Frequency about mild, major and
altruistic) compared to right-sided PD patients who were total PSNCD might be assessed using a neuropsychological
biased towards smaller numbers and correspondingly found battery performed after the acute stage. Heterogeneity of
to be less pro-social. prevalence was analysed using I2 values and Q test.
Prevalence of each study and pooled prevalence were
representing by Forest plot graph. Factors affecting
prevalence were assesing by meta-regression analysis.
Publication bias was evalued by funnel plot and Eggers
method.
Results: Among the 7440 references evaluated, we selected
16 hospital-based studies, involving 3087 patients. The
pooled prevalence of total post-stroke NCD was 53.4%
(IC95%: 46.9-59.8), 16.5% (IC95%: 12.1-20.8) for mild
and 36.4% for major PSNCD (IC95%: 29-43.8).
Heterogeneity analyses were significant (I2>93%). A
Fig 1: mean % bisection error from the midpoint of the numerical publication bias was not excluded for major PSNCD.
interval. Right-
sided PD patients were biased towards smaller
Significant factors affecting total PSNCD were age, post-
numerical magnitudes, whereas the left-sided PD patients were biased
towards larger numerical magnitudes. Data marked *** is significant stroke delay, and threshold scores used to interprete
at p<0.001; Error bars indicate standard error neuropsychological scores ( C7).
Conclusion: More than half of stroke survivors suffers
O3112 O3113
Personality traits could influence Montreal Cognitive Assessment in mild
permeability of transcranial direct current cognitive impairment: correlation with
stimulation in depressed patients cerebral spinal fluid biomarkers and
S.E. Parhizgar1, S.M. Rayegani2, S. Seyedahmadian1, prediction of conversion to dementia
S. Ghafoorfard3 I. Santana1, I. Baldeiras2, D. Duro1, M. Tbuas-Pereira1,
1Tehran University of Medical Sciences, Tehran, 2Physical M.J. Leito3, R. Lemos4, C. Oliveira2, S. Freitas3
medicine and rehabilitation, Shahid Beheshti University of 1Neurology, Centro Hospitalar e Universitrio de Coimbra,
Medical Sciences, Tehran, 3Community Medicine, Tehran Coimbra, Portugal, 2Laboratrio de Neuroqumica, Centro
University of Medical Sciences, Tehran, Iran, Islamic Hospitalar e Universitrio de Coimbra, Coimbra, Portugal,
Republic of 3Center for Neuroscience and Cell Biology, University of
Background and aims: It has been shown in many studies Coimbra, Coimbra, Portugal, 4Faculty of Psychology,
that personality traits have effects on presentation and state University of Coimbra, Coimbra, Portugal
of depressive symptoms. Higher levels of extroversion, Background and aims: Several neuropsychological
criminality, neuroticism, psychoticism, and some other measures as well as CSF biomarkers have been investigated
personality traits have been shown to be accompanied by as predictors of progression from Mild Cognitive
higher incidence rate of depression and anxiety. Transcranial Impairment (MCI) to Alzheimers disease (AD).
direct current stimulation (tDCS) is known as a treatment The aims of the present study were to evaluate the
method in depressive disorders but there are still confusing relationship between the Montreal Cognitive Assessment
reports expressing its distinct therapeutic effects in different (MoCA) and CSF biomarkers and its relevance as a
patient groups. In the present study, we aimed to determine dementia predictor, comparatively to the Mini-Mental State
whether personality traits might condition the impact of Examination (MMSE).
tDCS. Methods: We selected an MCI cohort of 105 patients with
Methods: Patients diagnosed with depressive disorders comprehensive evaluation and longitudinal assessment.
(n=50) referred from psychiatry clinic enrolled in our study. MCI patients were further dichotomized according to CSF-
All patients received active anodal or Sham Transcranial biomarkers profile into two biological subgroups: MCI-AD
Direct Current Stimulation (tDCS) to the left prefrontal (n=53) and MCI-nonAD (n=52).
cortex (2mA, 15 sessions over 3 weeks). Hamilton Rating Results: The MoCA scores were significantly correlated
Scale for Depression (HRSD) and NEO-Five Factor with the levels of CSF t-tau (r=-0.26;p=0.007) and p-tau
Inventory (NEO-FFI) were used to assess subjects' (r=-0.278;p=0.003) while the MMSE scores also correlated
depression scale and personality traits respectively. with CSF Ab42 levels (r=0.326;p=0.001). Statistically
Results: Patients in active tDCS group showed significantly significant differences on MMSE and MoCA scores were
greater improvement in HRSD score in compare with Sham found between the MCI-AD group and the MCI-nonAD
stimulation group (p<0.05). Correlation analyses showed group, with lower scores for MCI-AD patients, on both the
significant direct effect of extroversion score (p= 0.02) and MMSE and the MoCA. The score differences between
reverse effect of neuroticism score (p=0.01) on the amount MCI-AD group and MCI-nonAD group were similar for
of increase in HRSD score after active tDCS. both instruments.
Conclusion: Permeability of tDCS over prefrontal lobe as Considering MCI patients with follow-up 4years (n=79;41
a treatment method for depression is modulated by converted to AD; 38 remained stable), survival analysis
personality traits such as extroversion and neuroticism. showed that MCI patients with MoCA<17 had an increased
Further studies are needed to assess the effect of other risk of converting to AD during follow-up (p=0.015). MCI
personality traits on present treatment modalities in patients with MMSE<23 also showed a slightly increased
depression. risk of conversion to AD (p=0.034). AD (p=0.034).
Disclosure: Nothing to disclose Conclusion: The screening investigated tests both
correlated with CSF biomarkers and showed capacity to
predict conversion to AD without an objective advantage of
the MoCA over the most used MMSE.
Disclosure: Nothing to disclose
O3116 O3117
Self-medication with over-the-counter Overlooked chronic pain in diabetic
analgesics: a survey of patient patients with cognitive impairment
characteristics and attitudes about pain M. Rakusa1, S. Gak2, M. Rakusa3, M. Cokolic3
medication 1Department of Neurology, University Medical Centre
Belgium, 2Neurology, Ghent University Hospital, Ghent, Background and aims: Pain is often under-detected in
Belgium, 3Experimental Clinical and Health Psychology, patients with cognitive impairment. The aim of our study
Ghent University, Ghent, Belgium, 4CIRM, Clinical was to compare prevalence of limb pain in diabetic patients
Pharmacy Unit, University of Lige, Liege, Belgium, with and without cognitive impairment.
5Department of Family Medicine and Primary Health Care, Methods: A 452 random patients from the diabetic
Ghent University, Ghent, Belgium, 6Heymans Institute of outpatient clinic were evaluated for cognitive impairment
Pharmacology, Ghent University, Ghent, Belgium using Clock Drawing Test (CDT) and interviewed about
Background and aims: Pain is a common reason for self- chronic limb pain. Patients were considered cognitively
medication with over-the-counter (OTC) analgesics. impaired if they scored 3 or less out of 4 points on CDT.
However, this self-treating population has remained largely Patients were divided into two groups according to the self-
uncharacterized. reported pain. Differences between groups were evaluated
Methods: Cross-sectional observational community using t-test, Chi-square test. Persons correlation between
pharmacy-based study of individuals self-medicating frequency of chronic pain and cognitive impairment was
regular pain complaints (defined as pain during 1 full day/ evaluated.
month). Participants completed a self-administered Results: In total, there were 199 cognitively impaired
questionnaire assessing (i) pain characteristics, (ii) pain patients (44%) and 56 patients with chronic pain (12.4%).
medication use and (iii) concerns about pain medication The mean age of pain free patients was 6413 years, mean
(using items of the Pain Medication Attitude Questionnaire). duration of diabetes was 12.38.9 years and mean duration
Results: Participants (n=1,889) had a mean age of 52 years of education was 11.52.5 years vs. 659.3 years, 12.78.8
and were predominantly female (74.8%). They reported a years and 112.3 years in patients with pain respectively.
median of 35 pain days and 2 disability days in the past 3 Both groups matched on age, education and diabetes
months. Head (58.6% of the sample), low back (43.6%) and duration.
neck (30.7%) were the most common pain locations. About Chronic pain was more frequent in cognitively normal than
73% had a physician diagnosis (mainly migraine and in impaired patients (39 vs. 17 respectively). Difference
osteoarthritis), and about two-thirds had consulted their between groups was significant and chronic pain negatively
physician for pain in the last 6 months. 38% combined OTC correlated with cognitive impairment (r=-0.11; p=0.28).
analgesics with pain medication on prescription. Conclusion: Our results suggest that chronic pain may be
Paracetamol (used by 68.6% of patients), NSAID (46.8%) overlooked in patients with cognitive impairment and long-
and fixed dose combinations of simple analgesics with term diabetes. It may not be sufficient to rely on patient
coffeine (18.1%) were the most frequently used pain self-report and we need to actively seek for it.
medications. About 40% of our sample showed substantial Disclosure: Nothing to disclose
concern about the perceived need for pain medication and
the perceived potential for harmful effects (side effects,
tolerance and addiction).
Conclusion: This study has shed light on the characteristics
and attitudes of patients with regular pain who self-medicate
with OTC analgesics.
Disclosure: Nothing to disclose
O3118
Tolerability of antiepileptic drugs in
migraine and epilepsy: who is at
increased risk of adverse events?
M. Romoli1, S. Siliquini1, I. Corbelli1, S. Caproni1,
C. Bedetti1, P. Eusebi2, C. Costa1, P. Sarchielli1,
P. Calabresi1
1Neurology Clinic, University Hospital of Perugia, Perugia,
Italy, 2Department of Public Health, University of Perugia, Fig. 2-Odds ratio of LAEP scores higher than 2 among groups
Perugia, Italy depending on AED treatment. Only significant differences are shown.
Background and aims: Migraine and epilepsy are chronic
disorders, often comorbid, characterised by transient and
recurrent neurological symptoms. Sharing pathophysiologic
and clinical features, both epilepsy and migraine benefit
from antiepileptic drugs (AEDs). In clinical practice,
however, specific differences regarding reported adverse
events (AEs) of AEDs emerge between migraineurs and
epileptic people.
We compared the AEs of valproate (VPA), topiramate
(TPM), and lamotrigine (LTG) among patients suffering
from epilepsy (E), migraine (M), or both (ME).
Methods: We evaluated AEs profile, magnitude and
occurrence rate of 335 patients taking AEDs (figure 1A)
using the Liverpool Adverse Events Profile (LAEP) scale.
Results: AEs were significantly more common with TPM
treatment and among migraineurs, the latter being more
prone to discontinue AEDs (figure 1B). The profile of AEs
with each AEDs varied moving from group to group (figure
2). Moreover, treatment with both TPM and VPA was
Fig. 3-Multivariate logistic regressions of AEs among groups.
associated, in all groups, with worse tolerability profile
compared to LTG. A specific spectrum of AEs was defined
Conclusion: Our data suggest specific drug and disease AE
for each group (figure 3).
profile of AEDs. Specifically, we observed the highest
prevalence of AEs in migraineurs. This finding, given the
average higher dosage of AED used by epileptic patients,
might be considered a clinical implication of central
sensitization mechanisms. Both the profile and tolerability
of AEs, highly influencing quality of life, depended on the
underlying conditions, and deeply impacted on treatment
dropout. What ails patients also ails the AEs they experience:
hence, before starting, switching or stopping AEDs, all
options need to be considered.
Disclosure: Nothing to disclose
O3119
PACAP38 dose-response study in
migraine patients
A.L.H. Vollesen1, S. Guo1, M. Ashina2
1Danish Headache Center, Copenhagen, Denmark, 2Danish
O3122 O3123
Increased serotonin-to-dopamine Unilateral MR-guided high intensity
transporter ratios in Parkinson's disease focused ultrasound ablation of the
dyskinesias: a longitudinal study cerebellothalamic tract in essential tremor
A.-A. Roussakis1, N. Lao-Kaim1, A. MartinBastida1, S. Schreglmann1, S. Haegele-Link2, R. Bauer3,
N. Valle-Guzman2, Z. Kefalopoulou3, G. Paul4, N.A. Wegener4, A. Lebeda2, B. Werner4, E. Martin4,
H. Widner4, M. Politis5, T. Foltynie3, R.A. Barker2, G. Kgi2
P. Piccini1 1Sobell Department of Motor Neuroscience and Movement
1Medicine (Brain Division), Imperial College London, Disorders, University College London (UCL), Institute of
London, United Kingdom, 2Brain Repair Centre, Cambridge Neurology, London, United Kingdom, 2Department of
University, Cambridge, United Kingdom, 3Motor Sobell Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland,
3Department of Neurosurgery, Kantonsspital St.Gallen, St.
Department, University College London, London, United
Kingdom, 4Lund, Sweden, 5Neurosciences, Kings College Gallen, Switzerland, 4Center for Focused Ultrasound,
Hospital, London, United Kingdom University Childern's Hospital, University of Zurich, Zurich,
Background and aims: Serotonergic terminals play an Switzerland
important role in levodopa-induced dyskinesias (LIDs) in Background and aims: We here report results of an
patients with Parkinsons disease (PD). An increased SERT- ongoing trial of unilateral transcranial MR-guided high
over-DAT terminal ratio in the putamen has been proposed intensity focused ultrasound (tcMRgFUS) ablation of the
to be a risk factor for the appearance of LIDs. We cerebellothalamic tract (CTT) in essential tremor (ET).
investigated the temporal relationship between serotonergic tcMRgFUS allows for the selective ablation of deep brain
terminal changes and dopaminergic loss in the putamen and structures under direct MR guidance. As the main cerebellar
the appearance of LIDs. afferent to the thalamic ventral intermedius (VIM) nucleus,
Methods: 12 PD patients underwent PET with 11C-DASB the CTT is part of the ET tremor network.
and 11C-PE2I; which are specific in vivo markers of Methods: Prospective, uncontrolled, open-label, blind-
serotonin (SERT) and dopamine transporters (DAT), assessed, single center interventional study. ET patients
respectively. All patients repeated 11C-DASB and fulfilling criteria for interventional therapy received
11C-PE2I PET after 17 months (11 weeks). ablation of the CTT (ExAblate Neuro tcMRgFUS system).
The simplified reference tissue model was employed using Motor, neuropsychological and manual dexterity
the cerebellum as a reference. 11C-DASB binding potential examinations were assessed pre-, 48h and 1, 3 & 6 months
(BP), 11C-PE2I BP and 11C-DASB-to-11C-PE2I BP ratios post intervention. Standardized video-recordings were rated
were calculated. and tremor sub-scores calculated by a physician not
Results: At baseline, all PD patients were non-dyskinetic. involved in the treatments: overall sum (all items CRST
The mean 11C-DASB BP was 1.28 (0.14), the mean scale), speaking & working (items 15-21). Unilateral hand
11C-PE2I BP was 1.63 (0.41), and the median of the (items 5, 6, 11-14) and drawing & pouring (items 11-14)
SERT-to-DAT ratio was 0.779 (0.19). At follow-up, the sub-scores were calculated per side.
mean 11C-PE2I BP was (1.390.41) reduced by 14.52% Results: 6 patients received tcMRgFUS ablation of the
from baseline (p<0.001); the 11C-DASB BP had only CTT contralateral to the treated hand. Repeated measures
reduced by 4.32% (1.230.19) (p>0.10). Percentage ANOVA determined a statistically significant reduction
changes in 11C-PE2I BP at follow-up were significantly (pre-M6 in %) in the overall sum (p=0.01, 47.8%), speaking
greater than percentage changes in 11C-DASB BP (p<0.05). & working (p=0.016, 84.7%) and unilateral treated hand
The SERT-to-DAT ratios significantly increased by 12.76% (p=0.004, 84.3%) sub-scores, while there was no change in
(p<0.01) over this time. 3 PD patients became dyskinetic; the non-treated hand. 9-HPT, TMT A & B, MMS and MoCA
their SERT-to-DAT ratios were 0.978, 0.878, and 1.282. were unchanged. Transient side effects (n=3) were
Conclusion: The imbalance in the rate of SERT and DAT subjective ipsilateral hand clumsiness and mild gait
decline reflects the increase of the SERTtoDAT ratio over instability (max. 3 months).
time. Our findings suggest that there may be a threshold of Conclusion: Unilateral tcMRgFUS lesioning of the CTT
SERT-over-DAT availability in the putamen, above which was highly efficacious in reducing contralateral hand tremor
PD patients are likely to become dyskinetic. in ET. Adverse effects were mild and transient.
Disclosure: Nothing to disclose Disclosure: Sebastian R. Schreglmann is supported by
research grants by the European Academy of Neurology, the
Swiss Neurological Society and the Swiss National Science
Foundation.
O3126
Peripheral neuropathy in patients with
CPEO associated with single and multiple
mtDNA deletions
D. Lehmann1, M.E. Kornhuber1, C. Clajus1, C.L. Alston2,
A. Wienke3, M. Deschauer1, R.W. Taylor2, S. Zierz1
1Department of Neurology, Martin Luther University Halle-
O3127 O3128
Targeted next generation sequencing to Insulin signalling and cytoskeleton
unravel undiagnosed limb girdle muscular abnormalities contribute to insulin
dystrophies resistance in myotonic dystrophies
E. Mauri1, F. Magri1, M. Savarese2, G. DiFruscio2, G. Meola1, L.V. Renna2, S. Iachettini2, B. Fossati3,
A. Govoni1, M. Moggio1, R. Brusa1, D. Piga1, D. Ronchi1, L. Saraceno1, R. Colombo4, R. Cardani2
R. DelBo1, F. Fortunato3, V. Nigro4, G.P. Comi1 1Department of Biomedical Sciences for Health, University
1IRCCS Foundation Ca' Granda Ospedale Maggiore of Milan, San Donato Mil., Italy, 2Laboratory of Muscle
Policlinico, Dino Ferrari Center, Neuroscience Section, Histopathology and Molecular Biology, IRCCS Policlinico
Department of Pathophysiology and Transplantation, San Donato, San Donato Mil., Italy, 3Department of
University of Milan, Milan, Italy, 2Seconda Universit degli Neurology, IRCCS Policlinico San Donato, San Donato Mil.,
studi di Napoli, Laboratorio di Genetica Medica, Italy, 4Department of Biosciences, University of Milan,
Dipartimento di Biochimica, Biofisica e Patologia generale, Milan, Italy
Naples, Italy, 3University of Milan, Milan, Italy, 4Genetica Background and aims: Myotonic dystrophy type 1 (DM1)
medica, Telethon Institute of Genetics and Medicine, Naples, and type 2 (DM2) are autosomal dominant multisystemic
Italy disorders caused by a nuclear accumulation of toxic RNAs
Background and aims: Limb girdle muscular dystrophies containing CUG/CCUG repeats which lead to aberrant
(LGMD) are heterogeneous neuromuscular disorders alternative splicing of different genes. DM patients are
characterized by limb girdle weakness with infantile, characterized by metabolic dysfunctions such as insulin
childhood or adulthood onset. Clinical, bioptic and imaging resistance, hyperinsulinemia and a fourfold higher risk of
data are fundamental to guide genetic analysis, but 30% of developing diabetes mellitus type 2. The aim of this work is
LGMDs remains without molecular diagnosis. New to investigate the mechanisms that contribute to the
sequencing technologies provide a fast detection of peripheral insulin resistance observed in these patients and
mutations, whose pathogenicity needs to be contextualised. to define if molecular defects in insulin signal are present
Methods: 55 patients with clinical and laboratory data beyond splicing alteration of insulin receptor (IR).
suggestive for LGMD, but no definitive molecular diagnosis Methods: The insulin activation of several proteins
after extensive investigation, underwent NGS screening involved in PI3K or RAS pathway was analysed by western
through Motor HaloPlex Target Enrichment protocol. blot in myotubes derived from 3 DM1, 3 DM2 and 3 healthy
Libraries were run on a HiSeq instrument and analyzed subjects. IR splicing alteration was analysed by RT-PCR.
through a pipeline of bioinformatics analysis (Savarese Since the cytoskeleton is involved in plasma membrane
2014). Variants were confirmed by Sanger sequencing. translocation of the glucose transporter GLUT4, microtubule
Biochemical and protein assays were established to address organizations and GLUT4 translocation have been analyzed
the pathogenetic role. by immunofluorescence.
Results: A definitive molecular diagnosis was achieved in Results: The activation of the insulin pathway appears to be
19 patients (34.5%). In 1 LGMD2B and 1 LGMD2A subject lower in DM than in control myotubes and this alteration
with single heterozygous mutations at Sanger, NGS detected seems to be more evident in DM2 myotubes. Fluorescent
the second mutation. We also identified 2 LGMD2B, 1 analysis of -tubulin shows that DM myotubes exhibit a
LGMD2I, 4 LGMD2D, 2 LGMD2L, 1 LGMD2K, 2 defective microtubule reorganization after insulin
LGMD2A patients. Other disease causing mutations were stimulation associated with a defective GLUT4
identified in DMD, LAMA2, GAA and COL6A1, COL6A2 translocation.
and in COL6A3 genes. In 31 patients the screening Conclusion: These data indicate that post receptor
disclosed several candidate variants with no clear signalling abnormalities and microtubule abnormalities
pathogenetic role, predominantly in TTN, DYSF, LAMA2, might contribute to DM insulin resistance. Further
and NEB genes. 5 patients are still under investigation. investigations will be necessary to identify novel biomarkers
Conclusion: NGS allowed to reach a definitive molecular that could be target for therapeutic intervention to improve
diagnosis in the 34.5% of previously unresolved LGMD the above metabolic dysfunctions of DM patients.
cases. The interpretation of these results is often complex Disclosure: Nothing to disclose
and correlation with the Sanger sequencing, clinical and
bioptic data is essential.
Disclosure: Nothing to disclose
O3129 O3130
Central nervous system abnormalities in A novel clinical tool to classify
late onset Pompe disease (LOPD): facioscapulohumeral muscular dystrophy
evidences from neuropsychological, phenotypes
morphological and functional MRI studies G. Ricci1, L. Ruggiero2, L. Vercelli3, F. Sera4, A. Nikolic1,
O. Musumeci1, S. Marino2, F. Granata3, E. Barca1, F. Mele1, M. Govi1, C. Angelini5, G. Antonini6,
F. Corallo2, S. deSalvo2, L. Bonanno4, R. Morabito3, A. Berardinelli7, E. Bucci6, M. Cao8, G. D'angelo9,
M. Longo3, P. Bramanti2, A. Toscano1 A. DiMuzio10, M. Filosto11, L. Maggi12, M. Moggio13,
1Dpt of Clinical and Experimental Medicine, University of T. Mongini3, E. Pegoraro8, C. Rodolico14, L. Santoro2,
Messina, Messina, Italy, 2IRCCS Centro Neurolesi Bonino G. Siciliano15, G. Tomelleri16, L. Villa13, R. Tupler1
1Department of Life Sciences,, University of Modena and
Pulejo, Messina, Italy, 3Radiological sciences, AOU
Policlinico, Messina, Italy, 4IRCCS Centro Neurolesi Reggio Emilia, Modena, Italy, 2Department of
"Bonino-Pulejo", Messina, Italy Neurosciences, Reproductive Sciences and
Background: Late-onset Pompe disease (LOPD) is a rare, Odontostomatology, University of Naples "Federico II",
3Department of Neuroscience, Center for Neuromuscular
multisystem disorder, affecting limb and respiratory
Diseases, University of Turin, Italy, 4MRC Centre of
muscles, but other organs could be involved. So far, studies
Epidemiology for Child Health, UCL Institute of Child
exploring brain functions in LOPD are lacking.
Health, London, United Kingdom, 5Neurology Unit, San
Aim: To assess morphological and functional brain
Camillo Forlanini Hospital, Lido Venice, 6Department of
alterations in LOPD
Neuroscience, Mental Health and Sensory Organs, S. Andrea
Methods: We studied 16 LOPD patients (7M/9F, Mean age Hospital, University of Rome "Sapienza", Rome, 7C.Mondino
4916). Clinical aspects were pre-symptomatic National Neurological Institute, Pavia, Italy, 8Department of
hyperCKemia (3 patients) and proximal/axial muscle Neurosciences, University of Padua, 9Functional
weakness (13 patients). All patients underwent a Neurorehabilitation Unit for Neuromuscular Disorders,
neuropsychological assessment. We performed 3T MRI IRCCS E.Medea Research Institute, Bosisio Parini, Italy,
obtaining normalized brain volume and resting-state 10Dept di Neuroscience, Imaging and Medical sciences,
functional MRI (Rs-fMRI) for network connectivity. Ospedale Chieti, 11Clinical Neurology, Section for
Patients were divided in two groups: 20-40 (group I) and Neuromuscular Diseases and Neuropathies, University
over 40 years (group II). Morphological and angiographic Hospital "Spedali Civili", Brescia, 12Foundation
evaluation were performed by 3D-FLAIR and 3D-TOF Neurological Institute Carlo Besta, Milan, 13IRCCS Ca
sequences respectively. To quantify the white matter gliotic Granda Ospedale Maggiore Policlinico, University of Milan,
lesions we applied the Fazekas scale whereas Smokers 14Neurosciences, AOU Policlinico, Messina, 15Department of
criteria were applied to detect dolichoectasia in the basilar Clinical and Experimental Medicine, Neurological Clinic,,
artery. University of Pisa, 16Department of Neurological,
Results: 10/16 subjects showed a mild cognitive Neuropsychological, Morphological and Movement Sciences,
impairment. Memory areas were preserved whereas 5/16 University of Verona, Italy
subjects showed abnormal executive functions. At MRI Background and aims: Based on the seven-year experience
data, it was shown a Fazekas score of 1 in 6/16, 2 in 5/16, 3 of the Italian Clinical Network for FSHD (ICNF) we revised
in 1/16, 4 in 3/16 and 5 in 1/16 subjects. the FSHD clinical form to describe in a harmonized manner
According to Smokers criteria, 14/16 patients had the phenotypic spectrum observed in FSHD.
dolichoectasia of vertebrobasilar system. Methods: The new Comprehensive Clinical Evaluation
Rs-fMRI showed significant decreased connectivity in Form (CCEF) defines various clinical categories by the
DMN networks, in both groups, but group II showed a combination of different features. The inter-rater
decreased connectivity in the bilateral frontal gyrus. reproducibility of the CCEF was assessed between two
Significant gray matter atrophy was found in group II. examiners using kappa statistics by evaluating 56 subjects
Conclusion: This study showed frequent morphological carrying the molecular marker used for FSHD diagnosis.
and functional brain alterations. The pathogenesis of these Results: The CCEF classifies: 1) subjects presenting facial
new aspects seems to be related to cerebrovascular and scapular girdle muscle weakness typical of FSHD
abnormalities secondary to the enzyme deficiency (category A, subcategories A1-A3), 2) subjects with muscle
Disclosure: Nothing to disclose weakness limited to scapular girdle or facial muscles
(category B subcategories B1, B2), 3) asymptomatic/
healthy subjects (category C, subcategories C1, C2), 4)
subjects with myopathic phenotype presenting clinical
features not consistent with FSHD canonical phenotype (D,
subcategories D1, D2). The inter-rater reliability study
showed an excellent concordance of the final four CCEF
categories with a kappa equal to 0.90; 95%CI (0.71; 0.97).
Absolute agreement was observed for categories C and D,
an excellent agreement for categories A (Kappa=0.88;
95%CI (0.75; 1.00), and a good agreement for categories B function of the calpain 3 homodimer. Based on findings in
(Kappa=0.79; 95%CI (0.57; 1.00). 10 families, our study indicates that a dominantly inherited
Conclusion: The CCEF supports the harmonized pattern of calpainopathy exists, and should be considered in
phenotypic classification of patients and families. The the diagnostic work-up and genetic counselling of patients
categories outlined by the CCEF may assist diagnosis, with calpainopathy and single-allele aberrations in CAPN3.
genetic counselling and natural history studies. Furthermore Disclosure: Nothing to disclose
the CCEF categories could support selection of patients in
Randomized Clinical Trials. This precise categorization
might also promote the search of genetic factor(s)
contributing to the phenotypic spectrum of disease.
Disclosure: Nothing to disclose
O3131
A heterozygous 21-bp deletion in CAPN3
causes dominantly inherited limb girdle
muscular dystrophy
J. Vissing1, R. Barresi2, N. Witting1, M. vanGhelue3,
L. Gammelgaard4, L. Bindoff5, V. Straub6,
H. Lochmuller6, J. Hudson7, C.M. Wahl8, S. Arnardottir9,
K. Dahlbom10, C. Jonsrud3, M. Dun11
1Department of Neurology, Rigshospitalet, Copenhagen,