Guillain Barre Syndrome – features, diagnosis and treatment

Guillain Barre Syndrome is an immune mediated disorder characterized by acute and severe polyneuropathy. The antigen here is a basic myelin protein P2 and the nerve damage is as a result of T cell mediated injury. Antimyelin antibodies are present in higher titers in early stage of the disease.

A virus illness generally precedes the onset of illness by 1 to 3 weeks. It may be in the form of respiratory or diarrhoeal disease. Various viruses indicted include cytomegalo virus (CMV) HIV and EBV (Epstein-Barr virus) infection. Guillain Barre Syndrome may occur in cases of lymphomas and Lupus erythematosis.

Pathology

There is variable degree of congestion in the meninges and petechial hemorrhages in the substance of the spinal cord. Peripheral nerves show marked degenerative changes in their myelin sheaths with proliferation of the cells and in some cases with swelling and fragmentation of the axis cylinder.

There is presence of inflammatory exudate with round cell infiltration and hemorrhages. Thus there is presence of both inflammatory and degenerative changes in the lower motor neurons.

Clinical features of Guillain Barre Syndrome

There is usually an initial period of febrile illness probably viral infection. There are no neurological features at this stage. This is followed by a period lasting from few days to many weeks and at the end of it, patient complains of headache, vomiting, pain in the back and limbs with stiffness in the neck.

There is parasthesia in the limbs followed by motor weakness of the limbs which spreads upwards. It is usually rapidly progressive. Both the proximal and distal muscles are involved proximal muscles being involved more.

The limbs are paralyzed and flaccid but there is no marked wasting of muscles. Reflexes both superficial and deep are either diminished or absent. Sensory symptoms suggestive of polyneuritis are present and patients complains of tingling and numbness in the limbs.

All forms of sensations may be impaired over the peripheral parts. Autonomic involvement in the form of postural hypotension, bradycardia or tachycardia and fluctuations in blood pressure levels may be seen. Cranial nerve involvement (optic neuritis, Deafness) is rare.

Sphincter involvement is uncommon. Respiratory paralysis may develop due to involvement of intercostal nerves.

Besides features of areflexia, motor weakness and sensory loss, general symptoms of toxemia are present.

Guillain Barre Syndrome

Investigations

Blood count shows polymorph leucocytosis, CSF is yellow and clots spontaneously. Protein content is markedly raised. It shows albumino cytolagic dissociation with a leucocyte count less than 50 cells cmm. (CSF may be normal if examined early. Classical picture of CSF appears if done about a week after the onset of illness).

Diagnosis

Acute infective polyneuritis has got typical features of viral illness preceding the disease and has features of motor weakness, areflexia and sensory loss which is characteristic of the Guillain Barre Syndrome disease.

Diagnostic criteria for Guillain Barre Syndrome

A. Features required for diagnosis

(a) Progressive motor weakness of more than one limb (Can progress to total paralysis of all four extremities)

(b) Areflexia

B. Features strongly supporting the diagnosis

(a) Clinical features: Progression of symptoms and signs over days upto 4 weeks, Relative symmetry of symptoms, Mild sensory symptoms or signs, Cranial nerve involvement especially facial diplegia, Recovery beginning 2-4 weeks after the progression ceases, Autonomic dysfunction, Absence of fever at the onset of illneés.

(b) Cerebrospinal fluid (CSF) picture: Elevated CSF protein after one week of symptoms, Cell counts of   10 mononuclear leucocytes per cmm of CSF, Electerodiagnostic studies, Evidence of nerve conduction slowing or block.

C. Features making diagnosis doubtful: Marked persistent asymmetry or weakness, Marked bladder or bowel dysfunction at the onset or it is persistent there on, Presence of polymorphonuclear leucocytes or >50 mono nuclear leucocytes per cmm of CSF, Sharp sensory level.

Management

Patients of Guillain Barre Syndrome require both supportive as well as definite treatment.

Supportive measures include general nursing care, looking after the skin and prevention of bed sores and contractures. Care of bowel and bladder is important. Nutrition and electrolyte balance be maintained and monitored carefully.

All serious patients of Guillain Barre Syndrome will require treatment in a hospital. Respiratory dysfunction is a serious complication and has to be managed with pressure ventilation and optimal respiratory care in intensive care units (ICU).

Though many patients have clinical signs of fatigue of respiratory muscles only 10-30% of patients will require mechanical ventilation. Repeated measurements of vital capacity is predictive parameter for mechanical ventilation. Main indications are:

1. Mechanical ventilatory failure with vital capacity of 12-15 ml/kg. Falling vital capacity over 4-6 hours or clinical signs of fatigue (Brow sweating, Tachycardia, Hyperpnea) may prompt intubation at lSml / kg.

2. P 02 < 70 mm Hg on inspired room air.

3. Severe oropharyngeal paresis with difficulty in clearing secretions or repeated coughing and aspiration after swallowing.

Weaning from ventilator is done when VC exceeds 8-10 ml/kg with adequate oxygenation maintained with 35-40% inspired oxygen. Patients with assisted respiration require tracheostomy.

Extubation is done when there is improvement in bulbar paresis, arterial P02 > 80 mmHg on room air and continuous positive air way pressure of 5-7 cm of water is tolerated without clinical signs of fatigue.

Definitive treatment of Guillain Barre Syndrome

It consists of corticosteroids, plasma pheresis and I.V. Immunoglobulins.

Cortico steroids

Corticosteroids in heavy doses (2mg/kg body weight) have been advocated to prevent extension of the paralysis and hasten recovery. Intravenous steroids (methyl prednisolone (80-120 mg/day) are also employed but results have not been encouraging and use of corticosteroids is now no longer advocated.

Plasma pharesis

Presence of antibodies to nerve antigens or demyelinating serum factors has provided rationale for use of plasmapheresis in Guillain Barre Syndrome. Plasmapheresis removes potentially pathogenic soluble factors (antimyelin antibodies, beat labile proteins or enzymes, cytokines compliment components and inflammatory mediators) from the circulation.

Plasmapheresis favourably modifies poor prognostic factors and maximum benefit is obtained when it is instituted within 1-2 weeks of illness. In the usual regimen a total of 2000m1 of plasma is removed at a time and replaced either with albumin or plasma.

In some centers plasma is replaced by saline. Other options include besides human albumn, fresh frozen plasma and synthetic plasma expanders. Both ultrafillrarion and centrifugation techniques are employed in the process. Usually 4-6 treatments on alternate days are given and completed in 8-14 days.

Indications for starting plamsapharesis in Guillain Barre Syndrome

1. Inability to walk unaided

2. Rapid and significant reduction in serial vital capacity measurements.

3. Onset of bulbar paralysis.

After initial good response some patients may show deterioration necessitating further series of plasma exchange. Such episodes are referred to as “treatment related fluctuations”.

Complications with plasmapheresis include Haemodynamic and cardiovascular disturbances, Hypotension, Acute respiratory distress syndrome, Bleeding, Air embolism, Hepatitis allergic reactions etc.

Intravenous immunoglobulins (IVI 9)

Intravenous immunoglobulins benefit cases of Guillain Barre Syndrome in various ways because of their immune modulatory effect. Various possible mechanisms include interference with T cell activation, inhibition of cytokines, blockage of receptors on macrophages and passive transfer of neutralizing anti-idiotypic antibodies against auto antibodies.

Dose of immunoglobulins recommended is 0.4 gm/kg/day for 5 days. These are as effective as plasmapheresis and have the advantage of ease and safety of their administration. Main drawback is prohibitive cost of this treatment.

Side effects of immunoglobulins therapy include Headache, Precipitation of migraine, Tachycardia, aseptic meningitis, Haemolysis, Paraproteinaemia renal failure. Immune complex arthritis and anaphylaxis. In some cases headache is very severe and treatment might have to be discontinued.

Combination therapy

Intravenous immunoglobulin therapy has been combined with high doses of intravenous methyiprednisoline (500 mg daily for 5 days) and has given good results as compared to single therapy.

Outcome and prognosis

Most patients of Guillain Barre Syndrome recover without any major residual deficit. Speed of recovery varies and may take 6-18 months. Many will fail to reach the early level of activity. No improvement is expected after two years.

Poor prognosis is predicted in patients with severely reduced amplitude of muscle action potential on electromyography, older age, early and prolonged need for ventilatory support and severly progressive disease within 7 days from onset.

Mortality ranges from 2-3% and is usually due to paralysis of respiratory muscles and fulminating infection.

Guidelines for rehabilitation in patients of Guillain Barre Syndrome

Early phase

1. Passive exercises

2. Frequent change of posture (Repositioning)

3. Prevention of bed sores, joint Malalignment

Intermediate phase

Active strengthening of muscles by both passive and active movements.

Late phase

Encouragement to walk Pool exercises

Massage of paralysed limbs Parallel bars use be encouraged.

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