The damaging effects of hyperthermia, like those of anoxia, involve the brain diffusely. In the case of hyperthermia, however, the changes are disproportionately severe in the cerebellum. The acute manifestations of profound hyperthermia are coma and convulsions, frequently complicated by shock and renal failure. Patients who survive the initial stage of the illness frequently show signs of widespread cerebral affection, such as confusion and pseudobulbar and spastic paralysis. These abnormalities tend to resolve gradually, leaving the patient with a more or less pure disorder of cerebellar function.
The most extensive account of the effects of hyperthermia is that of Malamud and colleagues. These authors studied 125 fatal cases of heat stroke but their observations are probably applicable to hyperthermia of other types. In patients who survived less than 24 h, the changes consisted mainly of a loss of some of the Purkinje cells and swelling, pyknosis, and disintegration of those that remained. In cases surviving beyond 24 h, there was almost complete degeneration of the Purkinje cells, with gliosis throughout the cerebellar cortex as well as degeneration of the dentate nuclei. The changes in the cerebellar cortex were equally pronounced in the hemispheres and vermis. The unanswered question is whether high temperature alone is an adequate cause or whether it must be combined with hypoxia and ischemia. It is of interest that this syndrome is not seen in patients with infective fevers, malignant hyperthermia, or the malignant neuroleptic syndrome—either the neuropathologic changes or the clinical cerebellar syndrome in survivors.
Cerebellar Syndromes Associated With Celiac Disease (Sprue, Gluten Sensitive Enteropathy)
Most often, the neurologic association with this disease has been a peripheral neuropathy, as described in Chap. 43. In addition, a progressive cerebellar ataxia of gait and limbs, sometimes with polymyoclonus in association with a gluten-sensitive enteropathy, has been the subject of several reports. The underlying cause of the enteropathy is an intestinal allergy to gluten in wheat that produces a villous atrophy of the intestinal mucosa. Between 0.5 and 1 percent of the white population are affected with the intestinal disorder. The classic features are diarrhea and malabsorption but many individuals are asymptomatic (see also Chap. 40).
The neurologic disorder may appear several years after onset of the enteropathy and, in addition to ataxia, usually includes signs of peripheral neuropathy and rarely, myelopathy or encephalopathy (dementia) or psychiatric symptoms (Hallert and Astrom; Hallert and Deerefeldt). A rare spinocerebellar syndrome was described by Cooke and Smith. According to Finelli and colleagues, neurologic abnormalities occur in approximately 10 percent of cases of adult celiac sprue. This subject was reviewed by Bhatia and colleagues and extensively by Hadjivassiliou and colleagues (1998, 2002). The latter authors emphasize the frequent occurrence of ataxia in patients with gluten sensitivity and, more specifically, antibodies to transglutaminase and endomysium, but, curiously, often without overt signs of bowel disease. There is also an association of sprue in more than 90 percent of patients with the HLA DQ2 and DQ8 genotypes. The few cases that have come to autopsy have shown severe cerebellar atrophy, a finding that may also be disclosed by MRI. Hadjivassiliou and colleagues (1998) observed lymphocytic infiltration and perivascular cuffing in the cerebellar cortex and peripheral nerves in 1 autopsied case but not in another, changes that they took to represent immunologic injury to these parts.