Bickerstaff Brainstem Encephalitis

Bickerstaff brainstem encephalitis is an acute post-infectious autoimmune disorder with ophthalmoplegia, ataxia and altered consciousness or hyperreflexia, mostly associated with anti-GQ1b IgG antibodies. It sits in a spectrum with Miller Fisher syndrome and Guillain-Barre syndrome.

It is rare, with an incidence of about 0.1 in 100,000 each year. It is most common in young to middle aged adults and follows an infection (often respiratory or gastrointestinal, including Campylobacter jejuni and Haemophilus influenzae) in about 70% within 4 weeks.

Pathophysiology. Molecular mimicry between microbial lipo oligosaccharide and GQ1b ganglioside produces antibodies that damage oculomotor nerves and brainstem reticular and cerebellar tracts. GQ1b is rich in oculomotor nerves and muscle spindles.

Presentation is a rapidly progressive course over days to 4 weeks with external ophthalmoplegia, ataxia, drowsiness, stupor or coma, and brisk or absent reflexes with extensor plantar responses. Facial and bulbar weakness, pupil abnormalities, limb weakness and sensory loss may occur. Respiratory failure can develop.

Red flags.

• Falling consciousness or bulbar weakness.
• Forced vital capacity under 20 mL/kg, or rapidly progressive limb weakness.
• Autonomic instability.

Serum anti-GQ1b IgG is positive in about two thirds. CSF shows albuminocytological dissociation in about half (raised protein with few cells). MRI brainstem shows T2 or FLAIR hyperintensity in about 30%, and may be normal. Nerve conduction studies show reduced sensory action potentials. EEG shows slowing. Check glucose, electrolytes, thiamine response, toxicology and infection serology.

Differential diagnosis.

• Wernicke encephalopathy, brainstem stroke and basilar artery occlusion.
• Brainstem demyelination, neuromyelitis optica spectrum disorder and Listeria rhombencephalitis.
• Myasthenia gravis, botulism and Miller Fisher syndrome without encephalopathy.
• Autoimmune encephalitis and Lyme disease.

Give thiamine 500 mg IV three times daily for 3 days when Wernicke encephalopathy is possible, before glucose.

Immunotherapy (start early).

• Intravenous immunoglobulin 0.4 g/kg daily for 5 days. Check renal function, give slowly, and monitor for thrombosis and aseptic meningitis.
• Plasma exchange: 5 exchanges of about 50 mL/kg over 10 to 14 days is an alternative.
• Corticosteroid has no proven benefit. Methylprednisolone 1 g IV daily for 3 days is used in some cases with MRI lesions.

Supportive care. Monitor forced vital capacity and negative inspiratory pressure every 4 to 6 hours, intubate for forced vital capacity under 15 to 20 mL/kg, bulbar failure or falling consciousness, give venous thromboprophylaxis (enoxaparin 40 mg SC daily, 20 mg if creatinine clearance is under 30 mL/min), and manage dysautonomia. Provide eye protection and rehabilitation.

Prognosis. Most recover well within 6 months, but about 10% have residual deficits, and relapses are rare.

Monitoring. Respiratory function, swallowing, neurological state and autonomic parameters.

Referral and escalation. Refer urgently to neurology, with intensive care for reduced consciousness or respiratory compromise.

Special groups. In pregnancy, immunoglobulin is preferred. In children, immunoglobulin is given at the same weight based dose.