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Review
Siva Pesala MD
GBS
History
One of the earliest descriptions of what we know today as Guillain-Barr
syndrome is found in Landry's report on 10 patients with ascending
paralysis in 1859.
GBS is most common and most severe acute paralytic neuropathy ,with about 100
000 people developing the disorder every year worldwide.
Under umbrella term of GBS are several recognisable variants with distinct clinical and
pathological features.
Axonal motor and sensorimotor variants have been described in the last 3 decades
and are mediated by molecular mimicry targeting peripheral nerve motor axons.
Besides the Miller-Fisher syndrome (MFS) and descending weakness, other rare
phenotypic variants have been recently described with pure sensory variant, restricted
autonomic manifestations and the pharyngeal-cervical-brachial pattern.
Epidemiology
Most studies that estimate incidence rates of Guillain-Barr syndrome were done in
Europe and North America, and showed a similar range of 0819 (median 11) cases
per 100000 people per year
The annual incidence rate of Guillain-Barr syndrome increases with age (06 per
100000 per year in children and 27 per 100000 per year in elderly people aged
80 years and over) and the disease is slightly more frequent in males than in females.
Overall, based on the incidence rate and life expectancy, the estimated lifetime risk of
developing Guillain-Barr syndrome for any individual is less than one in 1000.
Epidemiology
The proportions of patients with GBS who have AIDP and AMAN vary greatly
around the world.
These patients generally have a poorer outcome. Whether the preceding infections of
childhood Guillain-Barr syndrome are different has not been established.
Vaccination and GBS
During the 1976 vaccination campaign for H1N1 influenza A virus, roughly 1
in 100000 people who had been vaccinated developed Guillain-Barr
syndrome.
In a survey, none of the 106 patients with Guillain-Barr syndrome who had
been vaccinated against influenza (range of vaccinations per person 137
times, total 775 vaccinations) reported a recurrence of Guillain-Barr
syndrome after the vaccination.
Vaccination and GBS
Generally, no contraindication to the vaccination of patients who previously have had
Guillain-Barr syndrome seems to exist, except for patients
-> Who had vaccination-related Guillain-Barr syndrome, although risk and benefit might be
discussed on a case-by-case basis.
Pathogenesis
The pathology of most European cases of GBS is perivascular multifocal
lymphocytic infiltration with demyelination (Asbury et al. 196), termed acute
inflammatory demyelinating polyradiculoneuropathy (AIDP).
Macrophages penetrate the Schwann cell basal lamina and strip myelin
lamellae.
Consequent activation of
complement leads to disruption of
voltage-gated sodium channel (NaV)
clusters, disruption of the nodal
architecture, and formation of the
membrane attack complex, which
leads to calcium influx.
Van den Berg, B. et al. (2014) GuillainBarr syndrome: pathogenesis, diagnosis, treatment and prognosis
Nat. Rev. Neurol. doi:10.1038/nrneurol.2014.121
Acute inflammatory demyelinating polyradiculoneuropathy-AIDP
Around 5565% of the patients belonged to this category, of whom 76% were
seropositive forCjejuni, compared with 42% in AIDP cases.Among sporadic cases
of Guillain-Barr syndrome, about 1020% are of AMAN type.
Antiganglioside antibodies anti-GM1, GD1a, and GD1b are found in this group.
Electrophysiologically, compound muscle action potential amplitudes are reduced
but motor distal latencies, motor conduction velocities, sensory nerve action
potentials, and F waves are within the normal range.
Acute motor axonal neuropathy
Necropsy studies have shown Wallerian-like degeneration of motor axons.
Most of the patients with MFS present with at least two features and have in
support an elevated CSF protein and characteristic autoantibody(Gq1b).
A less common paraparetic motor variant affects the legs selectively with areflexia
mimicking an acute spinal cord lesion and is associated with back pain.
Clinical features
The most common initial symptom of GBS is acroparesthesia with little objective
sensory loss .
Severe radicular back pain or neuropathic pain affects most cases.
Within a few days, weakness ensues commonly in a symmetric ascending
pattern.
Most patients present initially with leg weakness and arm weakness (32%) or
selective proximal and distal leg weakness (56%) often spreading to the arm while
some have onset of weakness in the arms (12%). A descending presentation
mimicking botulism, with onset in the face or arms, is less common.
Clinical features
Fokke et al-Brain -2014-Prospectively collected data from a cohort of 490 patients with GBS, previously involved in
therapeutic or clinical studies, were used to define the demography, clinical presentation, diagnostic investigations, and
clinical course
Clinical features
Besides prominent weakness, patients are hypo- or areflexic within the first few days
but this may be delayed by up to a week.
Hearing loss, papilledema and vocal cord paralysis are less common.
Clinical features
About one-third of patients remain able to walk throughout the course of the
disease, and are often described as mildly affected.
Diagnostic criteria
Ref- Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barr syndrome. Ann
Neurol. 1990;27(Suppl):S21S24
Diagnosis -Features that should raise doubt about the diagnosis of Guillain-Barr syndrome
CSF: increased number of mononuclear cells or polymorphonuclear cells (>50 cells per L).
Severe pulmonary dysfunction with little or no limb weakness at onset.
Severe sensory signs with little or no weakness at onset.
Bladder or bowel dysfunction at onset
Fever at onset.
Sharp spinal cord sensory level.
Marked, persistent asymmetry of weakness.
Persistent bladder or bowel dysfunction.
Slow progression of weakness and without respiratory involvement (consider subacute inflammatory demyelinating
polyneuropathy or acute onset chronic inflammatory demyelinating polyneuropathy).
Mimics of GBS presenting as quadriparesis:*
1.Anterior Horn cell: poliomyelitis or West Nile virus infection (asymmetric weakness)
2.Peripheral Nerve:
1. Critical illness neuropathy
2. Lymphoma / leptomeningeal carcinomatous meningitis
3. Toxic neuropathies: solvent or heavy metals
4. Porphyria
5. Lyme
6. Diphtheria
7. Vasculitic neuropathy
3.Neuromuscular Junction:
1. Myasthenia Gravis
2. Botulism
3. Tick paralysis (children)
4.Muscle:
1. Idiopathic inflammatory myopathies
2. Periodic paralysis
3. Critical illness myopathy
4. Rhabdomyolysis
5. Severe hypokalemia or hypophosphatemia
5.Acute spinal cord lesion
Diagnosis-CSF studies
CSF examination typically shows increased protein with normal CSF white-cell
count(Albumino-cytological dissociation).
CSF protein concentrations in patients with GBS are often normal in the first
week, but increased in more than 90% of the patients at the end of the second
week.
In a large study of patients with the Miller Fisher syndrome (MFS) subtype of GBS,
the proportion of patients with raised CSF total protein increased from 25% in the
1st week to 84% in the 3rd week.
Diagnosis CSF studies
CSF analysis is critically important in all GBS cases and reveals albuminocytologic
dissociation; that is an elevated protein up to 1,800 mg/dl with 10 or less white
cells/in most cases.
Half of GBS cases may have a normal CSF protein in the first week but that
proportion declines to 10% if the test is repeated a week later .
If there are more than 50 cell/per mm3 particularly two weeks of after the
onset of symptoms, one should consider early HIV infection,
leptomeningeal carcinomatosis, CMV polyradiculitis and sarcoidosis.
The differential of pure motor syndrome includes other diseases associated with
quadriparesis/paralysis such as myasthenic crisis, acute presentation of the
idiopathic inflammatory myopathies and the unusual motor neuron disease
patient presenting with acute respiratory failure.
Associated clinical features are often helpful in distinguishing these from GBS.
Fibrillation potentials may occur early on in the course of AMAN and needle electrode
examination is helpful.
In AMSAN the sensory potentials are reduced in amplitude and often absent.
H-reflexes absence may be the only abnormality in 75% of MFS and BBE cases.
NCS
NCS might also have prognostic value because patients with features of
demyelination more often need mechanical ventilation, and low compound
muscle action potentials (CMAPs) are the most consistent findings predictive of
poor outcome.
MRI of the spine is most useful helps excluding other aetiologies such as transverse
myelitis and compressive causes of polyradiculopathy.
Typical findings in GBS are surface thickening and contarst enhancement on the
conus medullaris and the nerve roots of the cauda equina .The most common site of
enhancement in GuillainBarr syndrome is considered to be anterior nerve roots.
Diagnosis and treatment of GBS
Van den Berg, B. et al. (2014) GuillainBarr syndrome: pathogenesis, diagnosis, treatment and prognosis
Nat. Rev. Neurol. doi:10.1038/nrneurol.2014.121
GBS disability scale
Plasma exchange
In 1978, Brettle et al first drew attention to the improved outcome in a patient with
Guillain-Barr syndrome following plasma exchange.
Plasma exchange beginning within the first two weeks of the illness reduced the
period of hospital stay, the duration of mechanical ventilation.
Plasma exchange
While the PE-treated groups in the North American and French studies did better
than controls, the time to walk and to discharge, and the time spent on a ventilator,
were still fairly long, even in PE-treated patients.
Dramatic improvement within days of beginning treatment is not the rule and if this
occurs, it may have happened regardless of treatment.
Plasma exchange
Limitations include : Invasive, large IV access .
Potential complications :
-Pneumothorax
-Hypotension
-Sepsis
-Pulmonary embolism
-Hemorrhage from vein puncture
-Low platelets ,prolonged clotting parameters, hypocalcemia, citrate toxicity and
anemia.
IVIG
In the final analysis, there was no significant difference in efficacy between plasma
exchange and intravenous immunoglobulin.No significant advantage in combined
treatment was evident.
IVIG-PSGBS RCT trial
Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barr syndrome. Plasma
Exchange/Sandoglobulin Guillain-Barr Syndrome Trial Group.
Lancet. 1997 Jan 25;349(9047):225-30
Corticosteroids
However, many (65%) have minor residual signs or symptoms often making
recovery less than complete .
In a study of 79 cases a year after the onset of GBS, 8% had died (all older than 60),
4% remained bedbound or ventilator dependent, 9% were unable to walk unaided,
17% were unable to run, and 62% had made a complete or almost complete recovery
.
Epidemiological study of Guillain-Barr syndrome in south east England J Rees, R Thompson, N Smeeton, and R Hughes
Outcome and prognosis
Outcome and prognosis
The relapse rate is 5% and it usually occurs within the first eight weeks. The
alternative diagnosis of relapsing-remitting chronic inflammatory demyelinating
polyneuropathy (CIDP) should be considered in relapsing cases.
Outcome and prognosis
Most AMAN patients have more delayed recovery than AIDP while some cases
recover quicker.
Questions???
References
a.Hughes, R. A. & Cornblath, D. R. GuillainBarr syndrome. Lancet 366, 16531666 (2005).
b.van Doorn, P. A., Ruts, L. & Jacobs, B. C. Clinical features, pathogenesis, and treatment of GuillainBarr syndrome. Lancet
Neurol. 7, 939950 (2008).
c.Yuki, N. & Hartung, H. P. GuillainBarr syndrome. N. Engl. J. Med. 366, 22942304 (2012).
d.Asbury, A. K. & Cornblath, D. R. Assessment of current diagnostic criteria for GuillainBarr syndrome. Ann. Neurol. 27 (Suppl.),
S21S24 (1990).
e.Griffin, J. W. et al. GuillainBarr syndrome in northern China. The spectrum of neuropathological changes in clinically defined
cases. Brain 118, 577595 (1995).
f. Hadden, R. D. et al. Electrophysiological classification of GuillainBarr syndrome: clinical associations and outcome. Plasma
Exchange/Sandoglobulin GuillainBarr Syndrome Trial Group. Ann. Neurol. 44, 780788 (1998).
References
g.Kuwabara, S. & Yuki, N. Axonal GuillainBarr syndrome: concepts and controversies. Lancet Neurol. 12, 11801188 (2013).
h.Van der Mech, F. G., Van Doorn, P. A., Meulstee, J., Jennekens, F. G. & GBS-consensus group of the Dutch Neuromuscular
Research Support Centre. Diagnostic and classification criteria for the GuillainBarr syndrome. Eur. Neurol. 45, 133139 (2001).
References
1.Sejvar, JJ, Baughman, AL, Wise, M, and Morgan, OW. Population incidence of Guillain-Barr syndrome: a systematic review
and meta-analysis. Neuroepidemiology. 2011; 36: 123133
2. Webb, AJ, Brain, SA, Wood, R, Rinaldi, S, and Turner, MR. Seasonal variation in Guillain-Barr syndrome: a systematic
review, meta-analysis and Oxfordshire cohort study. J Neurol Neurosurg Psychiatry. 2015; 86: 11961201
3.Huang, WC, Lu, CL, and Chen, SC. A 15-year nationwide epidemiological analysis of Guillain-Barr syndrome in Taiwan.
Neuroepidemiology. 2015; 44: 249254
4.Jackson, BR, Zegarra, JA, Lpez-Gatell, H..., and for the GBS Outbreak Investigation Team.Binational outbreak of Guillain-
Barr syndrome associated with Campylobacter jejuni infection, Mexico and USA, 2011. Epidemiol Infect. 2014; 142: 10891099
5.Jacobs, BC, Rothbarth, PH, van der Mech, FG et al. The spectrum of antecedent infections in Guillain-Barr syndrome: a
case-control study. Neurology. 1998; 51: 11101115
References
6.Islam, Z, Jacobs, BC, van Belkum, A et al. Axonal variant of Guillain-Barre syndrome associated with Campylobacter infection
in Bangladesh. Neurology. 2010; 74: 581587
7.Rees, JH, Soudain, SE, Gregson, NA, and Hughes, RA. Campylobacter jejuni infection and Guillain-Barr syndrome. N Engl J
Med. 1995; 333: 13741379
8.Mori, M, Kuwabara, S, Miyake, M et al. Haemophilus influenzae infection and Guillain-Barr syndrome. Brain. 2000; 123:
21712178
9. Geurtsvankessel, CH, Islam, Z, Mohammad, QD, Jacobs, BC, Endtz, HP, and Osterhaus, AD.Hepatitis E and Guillain-Barre
syndrome. Clin Infect Dis. 2013; 57: 13691370
10.van den Berg, B, van der Eijk, AA, Pas, SD et al. Guillain-Barr syndrome associated with preceding hepatitis E virus
infection. Neurology. 2014; 82: 491497
11.Musso, D, Cao-Lormeau, VM, and Gubler, DJ. Zika virus: following the path of dengue and chikungunya?. Lancet. 2015; 386:
243244
References
12.Ho, TW, Willison, HJ, Nachamkin, I et al. Anti-GD1a antibody is associated with axonal but not demyelinating forms of
Guillain-Barr syndrome. Ann Neurol. 1999; 45: 168173
13. Jacobs, BC, van Doorn, PA, Schmitz, PI et al. Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barr
syndrome. Ann Neurol. 1996; 40: 181187
14 .Schonberger, LB, Bregman, DJ, Sullivan-Bolyai, JZ et al. Guillain-Barre syndrome following vaccination in the National
Influenza Immunization Program, United States, 19761977. Am J Epidemiol. 1979; 110: 105123
15. Lehmann, HC, Hartung, HP, Kieseier, BC, and Hughes, RA. Guillain-Barr syndrome after exposure to influenza virus.
Lancet Infect Dis. 2010; 10: 643651
16. Salmon, DA, Proschan, M, Forshee, R..., and for the H1N1 GBS Meta-Analysis Working Group.Association between Guillain-
Barr syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis. Lancet. 2013; 381:
14611468
References
17. Guillain-Barr syndrome common concerns. ((accessed Feb 1, 2016).)
http://www.cdc.gov/vaccinesafety/Concerns/gbs.html
18. Kuitwaard, K, Bos-Eyssen, ME, Blomkwist-Markens, PH, and van Doorn, PA. Recurrences, vaccinations and long-term
symptoms in GBS and CIDP. J Peripher Nerv Syst. 2009; 14: 310315