American Academy of Neurology 2017 Annual Meeting

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American Academy of Neurology 2017 Annual Meeting
AAN 2017 – American
Academy of Neurology
Annual Meeting
The American Academy of Neurology –
AAN 2017 congress kick starts from
Saturday, April 22 through Friday, April 28 in
Boston, US.
Boston, Massachusetts , Saturday, April 22
2017 : With this year's Annual Meeting of the
American Academy of Neurology (AAN) just begun,
researchers and clinicians from around the world will
come together and share their latest findings with the
global neurology community.
Held in Boston from April 22-28, this year's meeting
will play host to over 10,000 neurology professionals
and over 2700 abstracts covering cutting-edge science,
from preclinical research to extended analyses of
currently available therapeutics.
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Bridging the gap between research and clinical
application is a major theme of the meeting, as evident
in the new “Neuroscience in the Clinic” sessions.
“Until recently, neuroscientists and clinicians moved
for the most part in separate spheres. AAN is making
a concerted effort to invest in connecting basic
science developments to the clinical level, as clinicians
are now more invested in basic science advances as
they affect patient care,” said Albert Favate, MD, co-
director of the Comprehensive Stroke Center at NYU
Langone Medical Center . “These changes may lead
to newer treatment modalities, shorter therapeutic
trials, and hopefully better patient outcomes.”
Further, a clinical discussion session has been added
to the Scientific Platform presentations, “which is
designed to put the cutting-edge scientific data into
the clinical application context and to stimulate
‘bench-to-bedside' conversations, which we hope will
lead to advancing the scientific discoveries into cures
for our neurology patients,” said Natalia Rost, MD,
MPH, FAAN, FAHA, vice chair of the AAN science
committee.
This year's meeting will also offer a more user-friendly
poster session experience thanks to the development
of topic “neighborhoods,” which will make navigating
the thousands of abstracts much easier for attendees.
Dr Rost also pointed out a robust offering of
experiential learning areas, “which provide an
interactive and open-space learning opportunity for
our attendees to engage in.”
The meeting's plenary sessions will feature a star-
studded list of guest lecturers on various topics,
including improving outcomes in epilepsy and early
diagnosis of Alzheimer's. The program also includes
the popular “Controversies in Neurology” plenary
session, in which leaders in the field argue for or
against several topics, including whether focused
ultrasound is better than deep brain stimulation, and
whether disease-modifying drugs should be stopped
in progressive multiple sclerosis.
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American Academy of Neurology 2017 Annual Meeting
Other sessions and topics of interest as indicated by
Dr Favate include forums on management and
education for neurologists-in-training, less exciting
but necessary sessions on ICD 10/CPT coding
updates, since “correct code use is critical to practice
survival,” he said, and practice management updates
for hospitals and accountable care organizations.
Boston, Massachusetts , Saturday, April 22
2017 : Neurologists will finally see the full data from
two phase III trials of the monoclonal antibody
erenumab (formerly AMG 334) for migraine
prevention at the American Academy of Neurology
(AAN) annual meeting in Boston.
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Results from the STRIVE trial will be presented by
Peter Goadsby, MD, PhD, of the University of
California San Francisco, during the clinical trials
plenary on Tuesday morning, while findings from the
ARISE trial will be unveiled by David Dodick, MD,
of the Mayo Clinic in Phoenix, during the emerging
science plenary that evening.
Positive top-line results were announced from both
trials in the fall of 2016 (STRIVE results; ARISE
results), but this will be the first time doctors have a
chance to dig more deeply into the study details.
If the drug is ultimately granted FDA approval,
"physicians will be excited to have another option for
migraine prophylaxis," said Natalia Rost, MD, of
Massachusetts General Hospital in Boston, and chair
of this year's AAN meeting scientific committee.
Experts have long been watching this class of CGRP
inhibitors for migraine, which also includes
galcanezumab, eptinezumab, and fremanezumab.
Neuromuscular Disorders
With the approval of nusinersen for spinal muscular
atrophy (SMA) at the end of 2016, clinicians also will
get details on data that enabled the drug to win an
FDA okay.
During the Tuesday afternoon emerging science
session, Richard Finkel, MD, of Nemours Children's
Hospital in Orlando, will present interim results from
the phase III CHERISH study, which enrolled
children with later-onset (type 2) SMA and was halted
for efficacy. Biogen announced top-line results last
fall.
The phase III ENDEAR study assessed nusinersen in
infantile-onset (type 1) SMA, but the interim results
that were announced in top-line data last August aren't
slated to be presented as emerging science. Patients
from both halted studies were able to enroll in the
SHINE phase III extension study.
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American Academy of Neurology 2017 Annual Meeting

Another treatment for SMA will be highlighted during
the clinical trials plenary session on Tuesday morning
-- Jerry Mendell, MD, of Nationwide Children's
Hospital in Columbus, Ohio, will present early-stage,
phase I results from a trial of AVXS-101, a gene
therapy for SMA.
Mendell will also present results comparing the effects
of eteplirsen on ambulation with historical controls
during that session.
When that drug, an antisense oligonucleotide
compound like nusinersen, was approved to treat
Duchenne muscular dystrophy last September, it
revealed a rift at the FDA: some reviewers agreed with
an advisory committee that did not think there was
enough evidence to support approval, but ultimately
Janet Woodcock, MD, director of the Center for Drug
Evaluation and Research, allowed the drug on the
market.
the FINGER study of preventing cognitive decline in
at-risk elderly patients, and the following abstracts:
Efficacy of Siponimod in Secondary Progressive
Multiple Sclerosis: Results of the Phase 3 Study
(findings from the EXPAND study were reported at
ECTRIMS last October).
Non-invasive Vagus Nerve Stimulation for the Acute
Treatment of Episodic and Chronic Cluster
Headache: Findings from the Randomized, Double-
blind, Sham-controlled ACT2 Study (the device was
approved earlier this week).
Double-blind, Randomized, Placebo-controlled,
Phase III Study (TOLEDO) to Evaluate the Efficacy
of Apomorphine Subcutaneous Infusion in Reducing
OFF Time in Parkinson's Disease Patients with Motor
Fluctuations Not Well Controlled on Optimized
Medical Treatment.

Rost said additional information about how the FDA

arrived at its controversial decision will be provided
during the session.

Cannabidiol and More

All eyes continue to be on cannabidiol, which is
getting yet another showing for its series of epilepsy
trials. During the clinical trials plenary session, Helen
Cross, PhD, of University College London, will
present findings from the GWPCARE1 study in
Dravet syndrome, which was also featured at the
American Epilepsy Society meeting last December.

Clinicians will also get details on a second Lennox-

Gastaut syndrome (LGS) study that hadn't been
presented at that earlier meeting. The AAN offered a
preview of those results from GWPCARE3 this week.

Other late-stage studies from the clinical trials and

emerging science program include an analysis of
antihypertensive treatment of acute cerebral
hemorrhage in the ATACH II trial, more details from Boston, Massachusetts , Saturday, April 22
2017 : Neurological disorders can be difficult to treat,

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American Academy of Neurology 2017 Annual Meeting

and among these epilepsy is one of the most common “Our results suggest that cannabidiol may be effective
worldwide. The World Health Organization (WHO) for those with [LGS] in treating drop seizures,” said
notes that about 50 million people suffer from this study author Anup Patel in an interview for an
chronic disorder around the world. Epileptic patients American Academy of Neurology press release. “This
suffer from recurring seizures and brief moments of is important because this kind of epilepsy is incredibly
involuntary movement. difficult to treat. While there were more side effects
for those taking cannabidiol, they were mostly well-
One type of epilepsy known as the Lennox-Gastaut tolerated. I believe that it may become an important
syndrome (LGS) is particularly difficult to manage. new treatment option for these patients.”
LGS is characterized by multiple types of seizures,
including stiffening and drop seizures. The latter is an
involuntary loss of muscle tone which causes patients
to suddenly go limp and fall down. While that’s
already tough, LGS is also known to affect children.
Plus, intellectual and behavioral problems make
management of this syndrome even more challenging.

While there isn’t any cure yet to LGS or epilepsy in

general, there are available treatments. One particular
form of treatment uses cannabidiol, which is a
molecule from marijuana devoid of properties that
induce a “high.” On Saturday researchers from the
American Academy of Neurology (AAN) released the
results of a clinical study showing how cannabidol
may be effective in reducing seizures in children and
adult patients suffering from LGS.

MITIGATING DROP SEIZURES

The clinical study involved 225 people whose average
age was 16 years, with a monthly average of 85 drop Boston, Massachusetts , Saturday, April 22
seizures. They were observed for 14 weeks after being
2017 : Apomorphine, a drug first used to treat
split into three groups: one received a higher daily
advanced Parkinson’s disease in the United States in
dose of cannabidiol (20 mg/kg), another a daily lower
the 1950s, has been confirmed as an effective
dose (10 mg/kg), while a third received a placebo
treatment for the disease.
added to their current medication.
Researchers conducted a prospective, randomised,
The first group showed a 42 percent reduction in drop
double-blind, phase III study, will be presented at the
seizures, while the second showed a 37 percent
American Academy of Neurology’s 69th annual
decrease. Those who took a placebo showed only a 17
meeting in Boston, Massachusetts, on 25 April 2017,
percent reduction. However, mild to moderate side
and found that subcutaneous apomorphine is
effects including decreased appetite and sleepiness
effective in reducing “off” time in Parkinson’s disease
were observed in all three groups.
patients with severe motor fluctuations not controlled
by conventional drug therapy. “Off” time describes
periods of the day when a patient’s medication is not

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American Academy of Neurology 2017 Annual Meeting
working well, causing their Parkinson’s symptoms to
worsen.
The researchers found that those individuals who
were given apomorphine had, on average, 2.5 hours
less “off” time per day compared with those given
placebo, who experienced only a 30 minute per day
reduction in “off” time. This result was observed after
one week of treatment and although the study only
comprised 107 participants, Andrew Lees, co-author
of the study, says the results point to a clear
conclusion. .
“This study has filled a gap in the drugs evidence-
based treatment profile and confirmed the potency of
a drug which is now 150 years old,” says Lees. “The
findings were highly significant so the number of
patients is more than adequate to make definite
conclusions.”
Apomorphine’s use grew in the 1990s when European
doctors began to administer the drug as a
subcutaneous infusion. However, evidence on its
effectiveness and safety has been lacking.
“Although the drug has for many years been licensed
in Europe, Australia and the Far East where it is
recognised as a useful rescue treatment, as well as the
least invasive way of ensuring continuous tonic
stimulation of striatal dopamine receptors, there are
still countries where the pump is not reimbursed. As
a consequence, many patients continue to be denied
what in some situations can be a lifesaving treatment.
“This treatment is much more efficacious than any
treatment available for Alzheimer’s disease or multiple
sclerosis but because it has no patent it remains
underused,” adds Lees.
Janine Barnes, a neurology specialist pharmacist at the
Dudley Group NHS Foundation Trust, describes the
results of the study as “very interesting”.
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“‘Off’ time is a huge problem for Parkinson’s patients
and 2.5 hours less off time is a considerable benefit to
an immobile patient,” says Barnes.
“I often prescribe apomorphine for Parkinson’s
patients when their oral medications are proving less
effective at controlling their motor function. We have
extensive data from open-label studies with
apomorphine that demonstrate its efficacy in reducing
‘off’ time and dyskinesias as well as allowing oral
levodopa dose to be reduced in patients with severe
motor fluctuations that are poorly controlled by
conventional therapy. But evidence from randomised,
blinded studies has been lacking and so this will be a
very useful piece of research.”
Trials are continuing to determine if alternative routes
of administration, such as inhalation, sublingual strips,
oral and patch pumps will be as well tolerated and
efficacious as subcutaneous apomorphine in the long
term.
Boston, Massachusetts, Saturday, April 22
2017 : For people with severe brain injuries,
researchers have found that the rhythm of daily
fluctuations in body temperature is related to their
level of consciousness, according to astudy published
in the the medical journal of the American Academy
of Neurology and will be presented at the AAN 2017
.
"Our study suggests that the closer the body
temperature patterns of a severely brain injured
person are to those of a healthy person's circadian
rhythm, the better they scored on tests of recovery
from coma, especially when looking at arousal, which
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American Academy of Neurology 2017 Annual Meeting
is necessary for consciousness," said study author
Christine Blume, PhD, of the University of Salzburg
in Austria.
Circadian rhythms, which are rhythmic variations in
body functions brought about by the body's internal
clock, are the daily cycles that tell us when to sleep,
wake or eat. This biological clock also regulates many
of the body's other functions including temperature.
It is set by environmental cues, like periods of daylight
and dark.
In healthy people, daily variations in body temperature
closely follow the sleep-wake cycle, the 24-hour daily
sleep pattern controlled by the body's internal clock.
Other studies have found that disruptions to the
sleep-wake cycle may affect various aspects of health
like the immune system and short-term memory.
During a normal sleep-wake cycle, the body's core
temperature fluctuates and can drop one to two
degrees during the early morning hours.
For this study, researchers monitored 18 people with
severe brain injuries, those with unresponsive
wakefulness syndrome and those in a minimally
conscious state. Unresponsive wakefulness syndrome,
also known as a vegetative state, is when someone has
awakened from a coma, is opening his or her eyes and
having periods of sleep, but remains unresponsive. A
minimally conscious state is when someone shows
signs of awareness.
For one week, researchers continually monitored the
body temperatures of participants with external skin
sensors. With that temperature data, they were able to
determine the length of the circadian rhythm for each
person. Length of temperature cycles of participants
ranged from 23.5 to 26.3 hours.
Researchers also evaluated the level of consciousness
for each person with the Coma Recovery Scale-
Revised, measuring things like response to sound and
ability to open eyes with or without stimulation. They
found that those who scored better on that scale had
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body temperature patterns that more closely aligned
with a healthy 24-hour rhythm.
"This is the first time an association has been found
between circadian variations in body temperature and
arousal in brain-injured patients. Importantly, arousal
is essential for consciousness," said Blume. "Circadian
variations are something doctors should keep in mind
when diagnosing patients. The time of the day when
patients are tested could be crucial. Also, doctors may
want to consider creating environments for patients
that mimic the light patterns of night and day to help
achieve a normal sleep-wake cycle. The hope is that
this may help bring a person with a severe brain injury
closer to consciousness."
The researchers tested bright light stimulation on
eight participants for one week and found positive
effects in two patients. Blume said that larger studies
are needed to test the hypothesis that bright light is
indeed beneficial for patients.
One limitation of the study was that magnetic
resonance imaging (MRI) data was not available to
evaluate the extent of brain damage, especially in the
hypothalamus, the portion of the brain where the
body clock is located.
Blume suggests that future studies look at the
relationship between body temperature rhythms and
other body rhythms like hormone patterns and rest-
activity cycles.
Boston, Massachusetts, Saturday, April 22
2017 : A small, preliminary study may show promise
of a new type of treatment for progressive multiple
sclerosis (MS). Results from the first six people
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American Academy of Neurology 2017 Annual Meeting
enrolled in the phase 1 study, a study designed to
enroll 10 people, are being presented at the American
Academy of Neurology's 69th Annual Meeting in
Boston, April 22 to 28, 2017.
Phase 1 studies are designed to evaluate the safety of
a treatment and identify side effects, using a small
number of participants. While it was not the goal of
this study to measure how effective the treatment was,
symptoms improved for three of the six participants.
"While these results are very preliminary and much
more research is needed, we are excited there were no
serious side effects," said study author Michael
Pender, MD, PhD, of The University of Queensland
in Brisbane, Australia.
The study investigates the relationship between MS
and the Epstein-Barr virus (EBV), a herpes virus that
is extremely common but causes no symptoms in
most people. However, when a person contracts the
virus as a teenager or adult, it often leads to
mononucleosis. Previous research has shown a link
between the virus and MS.
The study involved six people with progressive MS
with moderate to severe disability. People with
progressive MS have a severe condition with slow,
steady worsening of symptoms.
In MS, the body's immune system attacks the nerves
in the central nervous system. As part of the normal
immune response, immune cells called T cells and B
cells work together to protect the body against
infectious agents. In some people with MS, the
immune response may be altered and T cells may be
unable to control EBV-infected B cells, which
accumulate in the brain and produce antibodies that
attack and destroy myelin, the protective layer that
insulates nerves in the brain and spinal cord. This in
turns leads to neurologic dysfunction and symptoms.
Elimination of the EBV-infected B cells may reduce
the destruction of myelin in MS.
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For the study, researchers removed the participants'
own T cells and stimulated them to boost their ability
to recognize and destroy cells infected with Epstein-
Barr virus. They then injected participants with
infusions of escalating doses of T cells every two
weeks for six weeks. They followed the patients
through 26 weeks to look for evidence of side effects
and possible improvement of symptoms.
Three of the participants showed improvement,
starting two to eight weeks after the first infusion.
"One person with secondary progressive MS showed
striking improvement," Pender said. "This participant
had a significant increase in ambulation from 100
yards with a walker at the start of the study, and over
the previous five years, to three quarters of a mile, and
was now also able to walk shorter distances with only
one sided assistance. Lower leg spasms that had
persisted for 20 years resolved."
Pender said another participant with primary
progressive MS showed improved color vision and
visual acuity.
All three responding participants had improvements
in fatigue and ability to perform daily activities.
"The best responses were seen in the two people who
received T cells with the highest amount of reactivity
to the Epstein-Barr virus," Pender said.
None of the six participants had serious side effects.
"Of course, much more research needs to be done
with larger numbers of participants to confirm and
further evaluate these findings," Pender said. "But the
results add to the mounting evidence for a role of the
Epstein-Barr virus infection in MS and set the stage
for further clinical trials."
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American Academy of Neurology 2017 Annual Meeting

this rapidly growing demographic. Her studies retired

Boston, Massachusetts, Saturday, April 22
2017 : This year’s Potamkin Prize for Research in
Pick’s, Alzheimer’s, and Related Diseases goes to
Kristine Yaffe of the University of California, San
Francisco, and Claudia Kawas of the University of
California, Irvine. These two pioneers in the
epidemiology of dementia will share the $100,000
prize, which is made possible by the Potamkin Family
Foundation of Miami Lakes, Florida, and rewards
contributions to research in neurodegenerative
disease. Yaffe and Kawas will be honored at the 69th
annual American Academy of Neurology meeting,
held April 22 to 28 in Boston.
the old idea that dementia levels plateau after a certain
age, finding that dementia risk still doubles every five
years even in the oldest old, just as it does starting in
a person’s 60s . While initial findings from 90-plus
pointed to a disconnect between amyloid and tau
pathology at autopsy and dementia, subsequent work
concluded the opposite.
Kawas has also linked decreases in synaptophysin to
dementia in the oldest old, as well as risk factors
including inflammation, visual memory impairment,
and hypertension.

Kristine Yaffe
Boston, Massachusetts, Saturday, April 22
Despite the hundreds of publications Yaffe has
2017 : There's good news for kids with epilepsy.
churned out so far, a central theme emerges from her
While several new drugs have come out in the last
work, and it is that a sizable portion of the dementia
several years for adults with epilepsy, making those
burden in the world is preventable. Yaffe has
drugs available for children and teenagers has been
uncovered myriad modifiable risk factors for
delayed due to the challenges of testing new drugs on
dementia. Findings published throughout the span of
children. But an analysis of all the research published
her career have helped untangle the complex
on adults and children shows that the positive results
relationship between estrogen replacement therapy
seen in adults appear to be similar in children. The
and cognitive decline Her work has exposed cognitive
preliminary meta-analysis will be presented at the
dangers of high cholesterol, cardiovascular and
American Academy of Neurology's 69th Annual
metabolic syndromes such as diabetes and midlife
Meeting in Boston, April 22 to 28, 2017.
obesity, as well as sleep disorders and lack of exercise
. Her studies on thousands of military veterans have
"The results of this analysis may bring new hope for
linked dementia to head trauma or post-traumatic
children and teens with epilepsy and their families,"
stress disorder . Yaffe’s work sends the message that
said Douglas R. Nordli, Jr., MD, of Children's
millions of dementia cases could be prevented
Hospital Los Angeles in Los Angeles, Calif., and a
through behavioral and lifestyle changes .
member of the American Academy of Neurology.

Claudia Kawas The analysis evaluated only studies of people with

As a geriatric neurologist, Kawas has focused on
defining the unique factors that influence dementia in
people over the age of 90. Long before studying the
oldest old became fashionable, Kawas started the 90-
plus study of nonagenarians and centenarians . This
seminal project has yielded dozens of analyses about
primary generalized tonic-clonic seizures. Tonic-
clonic seizures are what people typically think of as a
seizure. They involve loss of consciousness, stiffening
of muscles and jerking movements. Primary
generalized seizures means the whole brain is affected.

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American Academy of Neurology 2017 Annual Meeting

For the analysis, researchers analyzed all randomized,

placebo-controlled trials of drugs for this type of
seizure in adults and children published from 1970 to
2015. The studies were looking at drugs that are taken
in combination with another epilepsy medication.

Seven studies were found that met the criteria, one

study on children, two on both adults and children
and four on adults. The researchers looked at the
average percentage reduction in seizure frequency and
the percentage of people whose seizures were reduced
by 50 percent or more. For the studies in adults, the
results were extrapolated to estimate the effect on
children.

The analysis showed that the effectiveness of the

medicines was similar in adults and children and the
effectiveness of the drugs did not depend on the age
of the patient.

"The results consistently showed that the epilepsy

drug was beneficial compared to the placebo, and the
results were comparable between adult and pediatric
groups," Nordli said. "Since only about 50 percent of
kids become seizure free after trying their first
medication, it's vitally important to have additional
options for kids so they can get back to being kids."

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American Academy of Neurology 2017 Annual Meeting

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