Bickerstaff's encephalitis and the Miller Fisher syndrome

In 1951 Bickerstaff and Cloake described three cases of ophthalmoplegia under the title of “mesencephalitis and rhomboencephalitis” and suggested that the clinical features were due to a midbrain disturbance.1 In this original report the authors drew attention to the similarities of this condition to Guillain-Barré syndrome, although they concluded that a viral aetiology was more likely. Some 5 years later Miller Fisher published his famous paper on a syndrome of ophthalmoplegia, ataxia, and areflexia2 and suggested that this syndrome was an unusual variant of Guillain-Barré syndrome because of absent reflexes and a raised protein in CSF. He proposed that the high CSF protein and the fact that ophthalmoplegia occurs in more classic Guillain-Barré syndrome suggested that the pathology would prove to be similar. Although the signs were difficult to explain on a purely peripheral basis he “reluctantly” concluded that they should be “interpreted as manifestations of an unusual and unique disturbance of peripheral neurons”. The following year Bickerstaff published “further observations on a grave syndrome with benign prognosis”3 which he continued to regard as a form of encephalitis. In this paper he reviewed his previous cases and described four others. Many of these patients had CSF pleocytosis and marked drowsiness. In one patient postmortem examination disclosed ballooning of myelin sheaths within the brain stem and diffuse loss of Purkinje cells in the cerebellum. Perivascular aggregations of lymphocytes were also seen in the frontal lobes. These changes were thought to suggest that much of the pathophysiology was due to cerebral oedema secondary to either a viral infection or resulting from hypersensitivity to an infection.

A subsequent publication from a group including Bickerstaff came down strongly on the side of an encephalitis in a paper4 that described 18 patients with the syndrome of which many had …