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Bickerstaff's brainstem encephalitis is characterised by acute ophthalmoplegia and ataxia with progressive consciousness disturbance.1 Although Bickerstaff described rigidity in the recovery phase,1 rigidity in the clinical course of Bickerstaff's brainstem encephalitis has rarely been reported.2 We encountered a case in which the initial diagnosis was tetanus, because of the progression of severe rigidity and risus sardonicus, but which turned out to be Bickerstaff's brainstem encephalitis owing to the presence of anti-GQ1b IgG antibody.
A 23 year old man who had had no prior apparent infectious episode began to show dysaesthesia, clumsiness, and slight weakness of all limbs (day 1). Due to rapid exacerbation of these symptoms he was admitted to a hospital the next day. On day 3, he became irritable because of increased anxiety, although he was alert and completely oriented. He was transferred to another hospital for further treatment. There he required assistance in walking because of new severe rigidity in all his limbs. Oral haloperidol (maximum dose 20 mg/day) was given for 10 days to reduce his anxiety, but his symptoms did not lessen. Treatment with intravenous methylprednisolone (1000 mg/day) from day 14 to 16, as well as acyclovir (1500 mg/day) given intravenously, failed to ameliorate his symptoms. On day 17, he was transferred to our hospital for further evaluation and treatment.
Physical examination on day 17 showed a body temperature of 37.0°C, blood pressure 130/80 mm Hg, pulse rate 100 beats/min, respiratory rate 12 /min, and severe hyperhidrosis. Neurological examination showed that he was alert and well oriented. The pupils were isocoric and round but mydriatic. Light reflexes were prompt. Bilateral blephaloptosis was present. Extraocular movement was completely inhibited vertically and horizontally. Restriction of mouth opening and dysarthria similar to risus sardonicus were caused by increased tonus of the masseter muscles. Neither tongue atrophy nor fasciculation was present. Tests for muscle strength and coordination could not be made due to severe rigidity of the neck, trunk, and limbs. Deep tendon reflexes were absent, probably secondary to the rigidity. The Babinski response was negative bilaterally. Voluntary movements were markedly slow, and sitting balance was poor. Opisthotonus was not present. No abnormality was found in the sensory examination. Because of Forley catheter placement due to the patient's severe general condition, we did not evaluate his bladder function.
White blood cell count was 13 320 /mm3 (84% neutrophils), but the erythrocyte sedimentation rate and C reactive protein concentration were normal. Protein in CSF was 144 mg/dl with normal cellularity. No oligoclonal IgG bands were detected in the CSF. Magnetic resonance imaging detected no abnormalities in the brain stem. An EEG was normal. Motor nerve conduction velocities and compound muscle action potentials measured in the right median, ulnar, and posterior tibialis nerves were normal, but no F waves were evoked. Antidromic sensory nerve velocity in the right median nerve was normal, but no sensory activation potentials were evoked in the right ulnar and posterior tibial nerves.
Based on his clinical course and the physical examination, the tentative diagnosis was general tetanus. On day 18, intravenous piperacillin sodium (4000 mg/day) and oral dantrolene sodium (25–50 mg/day) were started. On day 19, 4500 IU human anti-tetanus immunoglobulin (Tetanobulin®, Yoshitomi, Tokyo, Japan) was infused. On day 20, his bilateral blephaloptosis and rigidity of the limbs began to lessen. Subsequently his symptoms and signs improved dramatically. On day 24 he could turn himself over in bed. On day 25 ophthalmoplegia was ameliorated with slight limitation of lateral gaze. On day 26 he could sit independently. On day 32 he could stand without assistance, and on day 37 he could walk independently. During the recovery phase, no ataxia was seen. He has not had a relapse for 2 years and 6 months.
After his recovery, we evaluated the antiganglioside antibodies and antitetanus antibody activity in his serum. An enzyme linked immunosorbent assay3 showed that serum IgG on day 19 had high (4000) anti-GQ1b antibody titre. The IgG antibodies did not react with GM1, GM2, GD1a, GalNAc-GD1a, GD1b, or GT1b. Thin layer chromatography with immunostaining confirmed that the patient's IgG bound strongly to GQ1b, but not to GM1, GD1a, GD1b, or GT1b. No anti-GQ1b IgG antibody was detectable (titre<500) 2 years and 6 months after the onset of neurological symptoms. By contrast, the neutralising antitetanus antibody activity in the serum on day 17 was 0.41–0.75 IU/ml, sufficient for protection against tetanus infection.4
Serum anti-GQ1b IgG antibodies have been found in patients with Miller Fisher syndrome, Guillain-Barré syndrome with ophthalmoparesis, acute ophthalmoparesis, and Bickerstaff's brainstem encephalitis.5 Albumino-cytological dissociation in CSF and poor F wave response of the examined nerve are compatible with Miller Fisher or Guillain-Barré syndrome. The clinical findings, most characteristic of this patient, however, were severe rigidity of the face, neck, trunk, and limbs, which has not been described in Miller Fisher syndrome, Guillain-Barré syndrome, or acute ophthalmoparesis. The extrapyramidal side effect of haloperidol was unlikely because rigidity was present before the drug was administered. Bickerstaff reported the development of parkinsonism, including rigidity, within 2–4 weeks of onset and during the recovery phase in Bickerstaff's brainstem encephalitis, with the exception of a fatal case in which parkinsonism developed before maximal disability.1 Our patient showed rigidity from the beginning. Although an overlap of Guillain-Barré syndrome could not be excluded,2 our diagnosis was Bickerstaff's brainstem encephalitis, because the patient's case was close to the exceptional one reported by Bickerstaff. Antitetanus imunoglobulin is comprised of high dose polyclonal IgGs to tetanus toxin and other types of IgGs and IgMs, and it may have had an effect similar to that of intravenous immunoglobulin in our patient. His dramatic recovery immediately after antitetanus immunoglobulin administration could not be explained as part of a natural course. Although the mechanism for the early appearance of rigidity in our reported case is not clear, Bickerstaff's brainstem encephalitis should be considered the differential diagnosis when rigidity, such as tetanus, is present.
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