Guillain Barre Syndrome (gbs) Iman

Guillain-Barre Syndrome (GBS) Iman binti Jeffrey 0611750

Outline Definition Epidemiology Etiology Pathogenesis & Pathology Clinical features Investigations Diagnosis Differential diagnosis Treatment Prognosis

Definition 

Postinfectious polyneuropathy involving mainly motor but sometimes also sensory and autonomic nerves



Affects people of all ages and is not

hereditary 

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Most patients have a demyelinating neuropathy, but primarily axonal degeneration is documented in some cases. also known as: Acute inflammatory demyelinating polyneuropathy (AIDP)

Epidemiology  

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usually in children over 4-9 years overall frequency is 1.9 cases per 100,000 population follows infection or immunization by 10 days follows respiratory tract infection or gastrointestinal infection

Etiology GIT infection Campylobacter jejuni (26-41%) Cytomegalovirus (10-22%) Respiratory tract infection Mycoplasma pneumoniae Ebstein-Barr virus (10%) Vaccines  

Rabies Avian-flu influenza

Pathogenesis Molecular mimicry Cross-reactive immune attack by host Ab & T cell with are directed against the pathogen & nerve components.

Eg: Campylobacter jejuni Immune response directed against capsular LPS producing Ab cross-reacting with myelin to cause demyelination (mimics the gangliosides)

Pathogenesis Presentation of Ag to naïve T cell → activation ↓ Activated T cells attach to venular endothelium of peripheral nerves ↓ Migrate through endothelial lining to perivascular location ↓ Sensitized → contact myelin → segmental demyelination

Pathology Inflammatory lesions scattered throughout the peripheral nervous system Circumscribed areas of myelin loss associated with presence of lymphocytes and macrophages Initial lesion: nodes of Ranvier Myelin damage: penetration of macrophages into basement membrane around nerve fibers & strip myelin away Severe cases: interruption of axon & wallerian degeneration

Clinical Features Weakness o o

o

Onset is gradual and progresses over weeks Lower extremities (unable/refusal to walk)  trunks  upper limbs  bulbar muscles  flaccid tetraplegia = Landry Ascending Paralysis Proximal and distal muscles are involved relatively symmetrically, but asymmetry is found in 9% of patient

Muscle tenderness – At the onset Paraesthesias – in some cases Areflexia (83%)

Clinical Features Bulbar involvement (50%) o o

Dysphagia and facial weakness – signs of impending respiratory failure Interfere with eating. Increase risk of aspiration

Cranial nerve involvement (50%) o o

Facial nerve Oculomotor nerve

Autonomic involvement o o o o o o

Lability of blood pressure Postural hypotension Profound bradycardia Occasional asystole Urinary retention or incontinence (20% of cases, usually transient)

Clinical Features o

o o

o o o

Symptoms of viral meningitis / meningoencephalitis In young children CNS involvement ataxia papilledema Miller-Fisher syndrome External ophtalmoplegia ataxia areflexia

Table 1:Clinical features in 49 children with GBS* Features

Age

Prevalence

7.1years (mean)

Male/female ratio

1.2:1

Weakness

73%

Pain

55%

Ataxia

44%

Paraesthesias

18%

Shortness of breath

4%

* Data from unpublished observation of John Sladky. Two patients had consistent findings of Fisher syndrome

Course Initial phase  Gradually increasing involvement lasts 10-30 days (less than 4 weeks) Plateau phase  Short phase (within 2 weeks)  Long plateau phase → poor prognosis Recovery phase  Within months  Usually complete  Motor sequelae (5-25%)  Relapse & late recurrences (3%)

Investigations Lumbar puncture – cerebrospinal fluid (CSF) o o o o

Elevation of CSF protein (more than twice upper limit of normal) Cell content of CSF is normal (<10 cells/mm³) Glucose level normal Bacterial and viral culture is negative

Electromyography o o

Motor nerve conduction velocities are greatly reduced, and sensory nerve conduction time is often slow evidence of acute denervation of muscle

Serum Creatine Kinase o

Elevated or normal

Muscle biopsy o o

Sural nerve biopsy

 o

o

appear normal in early stages show evidence of denervation atrophy in chronic stages segmental demyelination, focal inflammation, and wallerian degeneration

Serologic testing for Campylobacter infection

This is a high-power image of an nerve stained with the standard H&E. The GBS is fairly acute, and the nerve contains significant inflammation. The majority of the small round nuclei are those of lymphocytes infiltrating the nerve. Some residual myelinated axons can be seen. The denser pink lines (black arrow) are the axons and the bubbly-appearing pink areas surrounding them are myelin sheaths

This is a mid-power image of a nerve which has been stained with a different myelin stain, which stains the myelin blue. There is patchy myelin loss within the nerve. You an also see some small round lymphocyte nuclei.

Subdivision of GBS Subdivision

Clinical manifestation

Sporadic GBS (AIDP)

As mentioned

Acute motor-sensory axonal neuropathy (AMSAN)

Relatively infrequent Severe degeneration of motor and sensory axons Little demyelination Fulminant, extensive and severe weakness with delayed and incomplete recovery

Acute motor-axonal neuropathy (AMAN)

Severe pure motor axonal neuropathy Clinical course and recovery is similar to AIDP

Miller-Fisher syndrome

Triad: ophthalmoplegia, ataxia, & areflexia

Chronic IDP (CIDP)

Neurologic symptoms are slower (>4 weeks)

Diagnosis Required for diagnosis

Progressive motor weakness involving >1 extremities Areflexia or marked hyporeflexia No more than 50 monocytes or 2 granulocytes per µL CSF

Supportive

Initial absence of fever Progression over days to few weeks Onset of recovery 2-4 weeks after cessation of progress Relatively symmetric weakness Mild sensory signs & symptoms Cranial nerve signs Elevation of CSF protein after 1 week of symptom Slowed nerve conduction velocity Autonomic dysfunction

From National Institute of Neurologic and Communicative Disorders and Stroke

Differential Diagnosis      

Spinal cord compression Transverse myelitis Tick paralysis Poliomyelitis Botulism Diphtheria

Treatment Patients with early stages of this acute disease Should be admitted to the hospital for observation because the ascending paralysis may rapidly involve respiratory muscles during the next 24 hour. 

 o o o

Patients with slow progression: may simply be observed for stabilization and spontaneous remission without treatment. Patients with rapidly progressive ascending paralysis: Intravenous immunoglobulin (IVIG), administered for 2, 3, or 5 days Plasmapheresis, steroids, and/or immunosuppressive drugs are alternatives, if IVIG is ineffective Combined administration of immunoglobulin and interferon is effective in some patients.

Supportive care, such as respiratory support, prevention of decubiti in children with flaccid tetraplegia, and treatment of secondary bacterial infections, is important

Prognosis Spontaneous recovery begins within 2–3 weeks. Most regain normal muscular function Tendon reflexes are usually the last function to recover Improvement usually follows a gradient inverse to the direction of involvement. Bulbar and respiratory muscle involvement may lead to death if the syndrome is not recognized and treated 3 clinical features predictive to poor outcome:  Cranial nerve involvement  Intubation  Maximum disability at the time of presentation

References 

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Menkes & Sarnat: Child Neurology, 6th ed. USA, Lippincott Williams & Wilkins, 2000 Aicardi, Jean: Clinics in Developmental Medicine: Diseases of The Nervous System in Childhood, 2nd ed. London, Mac Keith Press, 1998 Behrman, Kliegman, Jenson: Nelson Textbook of Pediatrics, 17th ed. China, Elsevier Saunders, 2004