Despite these associations, some authors have been skeptical of a “gluten ataxia” (see the editorial by Cross and Golumbek and the contrary case for a valid connection by Hadjivassiliou et al [2002]). Reports of improvement in the ataxia following the institution of a gluten-free diet are conflicting.
The situation is further complicated by the finding that antigliadin antibodies (which are not autoantibodies but are directed against gluten, the offending agent), while not specific for celiac disease, do correspond to the presence of neurologic manifestations (ataxia and neuropathy); however, the more specific antiendomysium and antitransglutaminase autoantibody markers of sprue have little apparent relation to the presence of neurologic disease. Even more confusing is the claim that half of these patients will have one or another antibody but no clinical enteropathy, making it necessary to perform a small-bowel biopsy to detect villous atrophy.
A gluten-free diet is necessary, not only to reduce the enteropathy, if present, but also to reduce the chances of the later development of a bowel lymphoma. The medical issues relating to celiac disease and the use of antibody tests and bowel biopsy are reviewed by Farrell and Kelly.
We have sought evidence by antibody testing and bowel biopsy of sprue in numerous patients with an ataxia of obscure origin and have only rarely found it. Nevertheless, the evidence presented in the writings of several authors, particularly Hadjivassiliou, suggest that sprue may underlie some cases of subacute ataxia in adults. Paraneoplastic cerebellar degeneration and Creutzfeldt-Jakob disease should always be considered in the differential diagnosis of a case of subacute cerebellar ataxia. Vitamin E deficiency may induce a similar syndrome with features of spinocerebellar dysfunction.
Jejunoileal bypass operations, in addition to causing a chronic arthropathy, neuropathy, and vasculitic skin lesions, may give rise to an episodic confusion and cerebellar ataxia associated with a lactic acidosis and abnormalities of pyruvate metabolism. Overfeeding and fasting are provocative factors (Dahlquist et al).
The point has been made that milder forms of metabolic diseases that cause episodic stupor and coma, if persistent, may have a protracted course and are then difficult to distinguish from the dementias (Chap. 20). Examples are associated with chronic hepatic encephalopathy and the syndromes of episodic hypoglycemia, chronic hypercalcemia (in multiple myeloma, metastatic cancer, and sarcoidosis), hyponatremia, and hypernatremia. Unlike the common types of dementia described in Chap. 20, the acquired metabolic diseases are nearly always accompanied by a degree of drowsiness and inattentiveness—attributes that usually allow an encephalopathic confusional state to be distinguished from a dementia. The presence of asterixis is also an aid. If the onset of the illness is abrupt rather than gradual and of brief duration, and if therapy reverses the condition, restoring full mental clarity, the conclusion is justified that one is dealing with a confusional state, but at any one time in the active phase of the disease, the clinical state may resemble dementia.
In general hospitals, an episodic confusional state lasting days and weeks in the course of a medical illness or following an operation should always raise the suspicion of one of the aforementioned metabolic derangements (or an adverse effect of a drug). Usually, however, if these causes can be excluded, one falls back on a rather unsatisfactory interpretation—that a combination of drugs, fever, toxemia, and unspecifiable metabolic disorders is responsible. The “septic encephalopathy” described earlier in this chapter conforms to this ambiguous notion.