The clinical manifestations, mainly attributable to the effects of hypocalcemia, are tetany, paresthesias, muscle cramps, laryngeal spasm, and convulsions. Children with this disease may be irritable and show behavioral changes. In adults with chronic hypocalcemia, calcium deposits occur in the basal ganglia, dentate nuclei, and cerebellar cortex. In such patients we have observed unilateral tremor, a restless choreoathetotic hand, bilateral rigidity, slowness of movement and flexed posture resembling Parkinson disease, and ataxia of the limbs and gait—in various combinations. Interestingly, the multiple skeletal and developmental abnormalities that characterize both pseudohypoparathyroidism (a failure of sensitivity to the hormone) and pseudopseudohypoparathyroidism (short stature, round face, short neck, stocky body build, shortening of metacarpal and metatarsal bones and phalanges from premature epiphyseal closure) are rarely seen in pure hypoparathyroidism.
A similar deposition of iron and calcium in the walls of small blood vessels of the lenticular and dentate nuclei, and to a lesser extent in other parts of the brain, is a common finding in normal older individuals (Fahr disease). It also occurs in animals. Occasionally, it reaches a degree of severity that destroys striatal or dentate neurons. In such cases, CT will reveal the deposits (see Fig. 36-8), but the cause of the deposits is unknown. Apparently some protein in the capillary walls has an avidity for both calcium and iron.
The association of myxedema and cerebellar ataxia has been mentioned sporadically in medical writings since the latter part of the nineteenth century. Jellinek and Kelly described 6 such cases; all showed gait ataxia; in addition, some degree of ataxia of the arms and dysarthria were present in 4, and nystagmus in 2. Cremer and coworkers reported a similar clinical experience based on a study of 24 patients with either primary or secondary hypothyroidism.
There are only a few reports of the pathologic changes. The myxedematous patient described by Price and Netsky had also been an alcoholic, and the clinical signs (ataxia of gait and of the legs) and pathologic changes (loss of Purkinje cells and gliosis of the molecular layer, most pronounced in the vermis) could be distinguished from those caused by alcoholism and malnutrition. Scattered throughout the nervous system of their case were unusual glycogen-containing bodies, similar but not identical to corpora amylacea. These structures, designated myxedema bodies by Price and Netsky, were also observed in the cerebellar white matter of a second case of myxedema; there were no other neuropathologic changes, however, and this patient had shown no ataxia during life. It is difficult to know whether these peculiar bodies have anything to do with myxedema. If they do, it should be possible to demonstrate them in more than 2 cases. Our colleagues did not see them in one carefully studied case of myxedema, nor have they been described by others. Serum creatine kinase (CK) is also slightly elevated in hypothyroidism, presumably because of its slowed metabolism. Thyroid medication corrects the defect in motor coordination and normalizes the CK, raising the possibility that this is the result of a subcellular mechanism.
Table 5-3 summarizes the various causes of cerebellar ataxia, including the metabolic ones. Notable metabolic disorders, some heritable, in which ataxia may be a leading manifestation include GM2 gangliosidosis, possibly sprue (discussed below), and a large number of neonatal and infantile aminoacidopathies.
Effects of Hyperthermia on the Cerebellum