Diagnosis and treatment of gullian bare syndrome

1. GILLIAN BARE SYNDROME
PROFESSOR MOHAMMED AHMED BAMASHMOS
PROFESSOR OF INTERNAL MEDICINE AND ENDOCRINOLOGY

2. SUMMERY
•Guillain-Barré syndrome is the most common and most severe acute
paralytic neuropathy, with about 100 000 people developing the disorder
every year worldwide. Under the umbrella term of Guillain-Barré syndrome
are several recognisable variants with distinct clinical and pathological
features. The severe, generalised manifestation of Guillain-Barré syndrome
with respiratory failure affects 20–30% of cases.

3. INTRODUCTION
•The clinical journey through Guillain-Barré syndrome follows a typical
pattern that can be readily divided into its constituent phases and
components (figure 1).1
• Demyelinating and axonal forms of the syndrome occur in varying
proportions across different geographical regions, and clinical variants,
such as Miller Fisher syndrome, are readily definable.2
• Within the typical disease course are many less well understood biological
variations, which are considered chronologically in this Seminar.

5. EPDIMIOLOGY
•Most studies that estimate incidence rates of Guillain-Barré syndrome were
done in Europe and North America, and showed a similar range of 0·8–1·9
(median 1·1) cases per 100 000 people per year.15
• The annual incidence rate of Guillain-Barré syndrome increases with age
(0·6 per 100 000 per year in children and 2·7 per 100 000 per year in elderly
people aged 80 years and over) and the disease is slightly more frequent in
males than in females. Seasonal fluctuations, presumably related to
variations in infectious antecedents, have been reported, but these
observations are rarely statistically significant

6. CAUSES
•Guillain-Barré syndrome is a typical post-infectious disorder, as shown by the
rapidly progressive, monophasic disease course (<1 month) shortly after
infection, usually without relapse. Two-thirds of adult patients report preceding
symptoms of a respiratory or gastrointestinal tract infection within 4 weeks of
onset of weakness.22
• Many different preceding infections have been identified in patients with the
disorder, but only for a few microorganisms has an association been shown in
case-control studies. C jejuni is the predominant infection, found in 25–50% of
the adult patients, with a higher frequency in Asian countries.2

7. •Other infections associated with Guillain-Barré syndrome are
cytomegalovirus (CMV), Epstein-Barr virus, influenza A virus, Mycoplasma
pneumoniae, and Haemophilus influenzae.22
•, 25
• An association of Guillain-Barré syndrome with hepatitis E has been
identified in patients from both the Netherlands and Bangladesh.26
•, 27
• An emerging relation between Guillain-Barré syndrome and acute
arbovirus infection including Zika and chikungunya is being closely
monitored and is the subject of major interest as the global epidemic
spreads.

8. •Cases of Guillain-Barré syndrome have also been reported shortly after
vaccination with Semple rabies vaccine and various types of influenza A
virus vaccine. During the 1976 vaccination campaign for H1N1 influenza A
virus, roughly one in 100 000 people who had been vaccinated developed
Guillain-Barré syndrome.31
• Although a similar association was suggested for the H1N1 influenza A
vaccination in 2009, extensive studies showed only 1·6 excess cases of
Guillain-Barré syndrome per 1 000 000 people vaccinated, a frequency
similar to all seasonal flu vaccinations.32

11. PATHOGENESIS

13. •The classic pathological findings in acute inflammatory demyelinating
polyneuropathy are inflammatory infiltrates (consisting mainly of T
cells and macrophages) and areas of segmental demyelination, often
associated with signs of secondary axonal degeneration, which can be
detected in the spinal roots, as well as in the large and small motor
and sensory nerves.27
There is evidence of early complement
activation, which is based on antibody binding to the outer surface of
the Schwann cell and deposition of activated complement
components; such complement activation appears to initiate the
vesiculation of myelin (Figure 2).41
Macrophage invasion is observed
within 1 week after complement-mediated myelin damage occurs.

14. •acute motor axonal neuropathy, IgG and activated complement bind to
the axolemma of motor fibers at the nodes of Ranvier, followed by
formation of the membrane-attack complex.42
The resultant nodal
lengthening is followed by axonal degeneration of motor fibers with
neither lymphocytic inflammation nor demyelination.28,43
There are
autopsy reports indicating that the neurologic signs of the Miller Fisher
syndrome overlap with those of the Guillain–Barré syndrome
(ophthalmoplegia and ataxia in the former and substantial limb
weakness in the latter),44
which suggests that the available
immunohistochemical and electron-microscopical studies do not
accurately differentiate the demyelinating subtype from the axonal
subtype of the Guillain–Barré syndrome.

15. • ANTIGANGLIOSIDE ANTIBODIES
• Gangliosides, which are composed of a ceramide attached to one or more sugars
(hexoses) and contain sialic acid (N-acetylneuraminic acid) linked to an
oligosaccharide core, are important components of the peripheral nerves. Four
gangliosides — GM1, GD1a, GT1a, and GQ1b — differ with regard to the number
and position of their sialic acids, where M, D, T, and Q represent mono-, di-, tri-,
and quadri-sialosyl groups (Figure 1). IgG autoantibodies to GM1 and GD1a are
associated with acute motor axonal neuropathy and its more extensive and less
extensive subtypes, acute motor–sensory axonal neuropathy and acute
motor-conduction-

16. •IgG autoantibodies to GQ1b, which cross-react with GT1a, are
strongly associated with the Miller Fisher syndrome, its incomplete
forms (acute ophthalmoparesis and acute ataxic neuropathy), and its
central nervous system variant, Bickerstaff's brain-stem encephalitis,
which includes acute ophthalmoplegia, ataxia, and impaired
consciousness after an infectious episode.6,7,46
Patients with
pharyngeal–cervical–brachial weakness are more likely to have IgG
anti-GT1a antibodies, which may cross-react with GQ1b; they are also
less likely to have IgG anti-GD1a antibodies, which suggests a link to
the axonal Guillain–Barré syndrome.37

17. •The localization of these target ganglioside antigens has been
associated with distinct clinical patterns of ophthalmoplegia, ataxia,
and bulbar palsy. GQ1b is strongly expressed in the oculomotor,
trochlear, and abducens nerves, as well as muscle spindles in the
limbs.46,47
The glossopharyngeal and vagus nerves strongly express
GT1a and GQ1b, possibly accounting for dysphagia.

22. •Initial symptoms typically include weakness, numbness, tingling, and pain in
the limbs. The extent, progression, and severity of symptoms vary greatly
among individual patients. The most prominent symptom in patients with
AIDP is bilateral, relatively symmetrical weakness of the limbs that
progresses rapidly. In up to 90 percent of patients with AIDP, symptoms
begin in the legs and advance proximally. The advancing weakness may
compromise respiratory muscles, and about 25 percent of patients who are
hospitalized require mechanical ventilation.4
Respiratory failure is reported
to be more common in patients with rapid progression of symptoms, upper
limb weakness, autonomic dysfunction, or bulbar palsy. The weakness
typically reaches its peak by the second week, followed by a plateau of
variable duration before resolution or stabilization with residual disability.19

23. •Facial, oropharyngeal, and oculomotor muscles may be affected because of
cranial neuropathy, especially in the less common subtypes. Paresthesia in
the feet and hands is common, but sensory symptoms are generally mild,
except for in those patients with the acute motor-sensory axonal neuropathy
subtype. Autonomic symptoms occur in about two-thirds of patients and
include cardiac arrhythmias, orthostasis, blood pressure instability, urinary
retention, and slowing of gastrointestinal motility.20
•Pain, especially with movement, is reported by 50 to 89 percent of patients
with GBS. The pain is described as severe, deep, aching, or cramping
(similar to sciatica) in the affected muscles or back, and is often worse at
night. Because the pain is nociceptive and/or neuropathic, it may be difficult
to control.6
Pain as an initial or prominent early symptom may delay
diagnosis of GBS.

24. DIAGNOSTIC CRITERIA

29. TREATMENT
• Specific treatments to hasten recovery and/or ameliorate symptoms target the aberrant immune
response in GBS. Removing circulating immune complexes via plasma exchange has been shown to
improve the time to recover the ability to walk, the need for artificial ventilation, the duration of
ventilation, and measured muscle strength after one year compared with placebo.30,31
According to
new evidence-based guidelines, plasma exchange is effective and should be used for severe AIDP,
and is probably effective and should be considered for mild AIDP.32
Optimal response is achieved
when plasma exchange is performed within seven days of symptom onset, although there is benefit
up to 30 days after symptom onset.30–33
Some evidence suggests that patients with mild GBS
benefit from two sessions of plasma exchange, whereas patients with moderate to severe disease
appear to require four sessions.33
The role of plasma exchange in children has not been

30. •Intravenous immune globulin therapy has been shown to hasten recovery in
adults and children compared with supportive therapy alone. The typical
dosage is 400 mg per kg per day for five days, although some evidence
suggests that a total of 2 g per kg over two days is equally
effective.34,35
Intravenous immune globulin therapy is easier to manage than
plasma exchange and has significantly fewer complications.31
The initial
response does not necessarily predict the outcome because patients may
stabilize or continue to decline after the therapy. Intravenous immune
globulin therapy should be started within two weeks of symptom onset, and
should be considered for patients who are nonambulatory. The therapy may
have a role two to four weeks after symptom onset as well, but the evidence
of effectiveness is weaker.31

31. •Corticosteroids are not recommended for the treatment of GBS.31,35
A
systematic review of six clinical trials that included 587 patients
treated with different dosages and forms of corticosteroids reported
no difference in mortality or disability outcome between patients
taking corticosteroids and those taking placebo.35
Four additional
studies demonstrated that patients receiving corticosteroids had less
improvement in disability after four weeks of therapy than patients not
treated with corticosteroids, leading to concerns that they may delay
long-term recovery.3
Other therapies have been studied, but the
evidence is limited and of low quality.36,37