Bickerstaff brainstem encephalitis in pediatrics - A case report.

Dear Sir,

Bickerstaff's brainstem encephalitis (BBE), together with Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) have been considered to form a continuous clinical spectrum.

In 1951, Bickerstaff and Cloake reported 3 cases of drowsiness, ophthalmoplegia, and ataxia, which they designated ‘mesencephalitis and rhombencephalitis,’ and they proposed that the lesion responsible for these clinical features was in the midbrain. Diagnostic criteria for BBE have been proposed, which are[12]

Progressive, relatively symmetrical external ophthalmoplegia and ataxia by 4 weeks

Disturbance of consciousness or hyperreflexia.

It has been associated with IgM antibodies to GM1b and GalNAc-GD1a after Campylobacter jejuni gastroenteritis.[3]

We report a case of young girl who presented to us with history of fever, acute progressive symmetrical ataxia, and drowsiness. The patient was diagnosed to have BBE. BBE itself being a rare disease, we present this case report from south India.

An 8-year-old girl developed fever followed by headache and vomiting of 2 days duration; along with the headache, patient had dysarthria and drowsiness. The patient had non-projectile vomiting 4 to 5 episodes before getting admitted to the hospital. There was no weakness in the limbs or bulbar weakness or respiratory difficulty nor any sensory complaints. There was no antecedent upper respiratory tract infection or diarrhea. On neurological examination, she was drowsy but was oriented to time, place, and person, was able to comprehend to 3 stage axial commands. On ocular examination, the patient had bilateral gaze-evoked nystagmus; there was mild restriction of the eye movements in all gazes (vertical more than horizontal) and impaired convergence. There was no evidence of ptosis, internal ophthalmoplegia, facial weakness or oropharyngeal weakness, and she had slurred speech. On motor system examination, she had normal power in all 4 limbs; deep tendon reflexes were brisk and had positive babinski. The sensations for pain, temperature, vibration were normal. She had bilaterally symmetrical cerebellar signs. There was impaired finger nose test, dysdiadokinesia and heel to shin test. The patient had wide-based stance and was swaying to either side when attempted to walk. A tentative diagnosis of the brain stem encephalitis was made with this clinical background. The other possible differential diagnosis were pediatric demyelinating diseases (acute demyelinating encephalomyelitis, pediatric multiple sclerosis), mitochondrial disease affecting the brain stem, primary or secondary vasculitis affecting the brain stem was also considered.

Her investigations revealed that the blood-counts and blood-chemistry results were normal. The Antinuclear antibodies were negative; cerebrospinal fluid (CSF) analysis showed albumin cytological dissociation with 5 cells – white blood cells (predominantly lymphocytes) and a protein of 126 mg/dL. CSF lactate and pyruvate were within normal limits. Magnetic resonance imaging (MRI) of brain was normal. EEG revealed moderate diffuse slowing with theta waves in the background indicating the CNS involvement. The nerve conduction studies were normal.

Since the child presented to us with disturbance of consciousness, acute onset of ataxia, symmetrical external ophthalmoplegia, hyperreflexia and positive babinski, which satisfies the clinical criteria and after ruling out the alternate, we came to the diagnosis of Bickerstaff's brainstem encephalitis.

The patient was started on Methyl prednisolone 500 mg/day on day 2 of admission and continued for 3 days and later tapered with oral steroids. The child's symptoms and signs dramatically improved by day 8, first in order of improvement was child's drowsiness on day 3 followed by diplopia, dysarthria, and ataxia which improved over 1 week.

Bickerstaff brainstem encephalitis, Guillain-Barré syndrome (GBS), and Fisher syndrome represent a spectrum of acute post-infectious immune-mediated diseases. It is now recognized that these disorders share many common features, in particular the antecedent infection, the albuminocytological dissociation and also the presence of anti-ganglioside antibodies in certain cases. This suggests that the different syndromes are in fact part of a spectrum of immune-mediated disorder involving the peripheral nerves at one end and the central nervous system at the other.[4]

In a large and extensive study of 62 cases of BBE,[3] it was found that most frequent preceding symptom was upper respiratory infection, and the most frequent initial symptoms were diplopia and gait disturbance; the clinical features of the patients with BBE were characterized as disturbance of consciousness, ophthalmoplegia, hyper-reflexia, and ataxia. Deep sensation was frequently unimpaired despite profound ataxia.[3]

Abnormal lesions (high-intensity areas on T2-weighted images of the brainstem, thalamus, cerebellum, and cerebrum) on MRI findings are present in about one-third of BBE patients; normal MRIs have also been reported for some BBE patients.[56]

From an immunological perspective, anti-GQ1b IgG antibody is frequently detected in sera from patients with BBE.[7]

Effective therapy for BBE has yet to be established. In the study by Odaka et. al., most patients with BBE were given immunotherapy, such as steroids,, plasmapharesis, and IVIg.[3] Fox et al. have suggested that plasmapharesis and IVIg have a beneficial effect in patients with BBE.[8] Randomized controlled trials are needed to establish the value of immunotherapies or other treatments. (Cochrane review) Various treatment modalities have been used for treatment of BBE, including corticosteroids, intravenous immunoglobulin, and plasmapharesis. Our patient was treated with high dose methyl prednisolone for 5 days followed by a taper of oral prednisolone, and she showed dramatic response without residual physical deficits.

BBE has a monophasic remitting course, with 2/3rd of patients becoming symptom-free at 6 months and around 16% patients requiring ventilation. Deaths have been reported in BBE.[9] Thus, patients with BBE need careful observation, and in cases that worsen or have respiratory involvement, immunomodulatory therapy to prevent residual deficit and death needs to be started.