Predictive tests in Huntington's disease

Abstract

HD is a dominantly inherited disorder that affects mental and motor systems and includes a rigid form as well as the better known choreic form. Many articles have been devoted to predicting the future onset of the disease in patients who are at risk, but none of the suggested predictors is currently considered completely reliable. Members from individual families do tend to show a similar age of onset, and similar intellectual and motor abnormalities do develop within a single family; but the presence or absence of this dominant gene of high penetrance is not usually certain until the obvious physical signs appear. Predictive tests are of importance not only to decide which person may develop the disorder, but they may also offer a clue to associated or causal features of the disease. This chapter is a review of reported predictive tests in HD, emphasizing the rationale for their use. Psychological testing has often been abnormal early in the course of the disease of some patients, particularly when motor dexterity or apraxia is tested. Family members often insist that various psychological traits enable them to predict which members are affected by the gene. These opinions are summarized. Neurophysiologic tests are briefly reviewed, including new data on increased liklihood of H-reflexes in HD. Electroencephalography was once touted as a possible predictive test but, although there is frequently an association of a low voltage EEG activity with HD, this change is too variable for certainty in prediction. Pneumoencephalography with specific measurements of caudate atrophy is of clinical interest, but a pneumoencephalogram is rarely needed for diagnosis and caudate atrophy may not actually be an early sign. Metabolic changes in HD include the biochemical effects of hypothalamic dysfunction, changes in growth hormone, and reported change in GABA levels in the CSF or brain. Provocative tests have utilized numerous drugs in an attempt to predict the onset of the disease, including particularly physostigmine and L-DOPA. All of the tests elucidate peculiarities of the disease, and all are of ethical as well as neurological interest. Many of the provocative tests utilize quantification of known neurologic features of the disease, such as reduction in saccadic movements of the eye, increased reflexes, or patterns of movement. The ethical problems in predictive tests, especially tests intended to provoke features of the disease, have been a matter of quiet controversy. Should a nontreatable disease be overtly diagnosed? And if so, will it benefit the patient? Can any of the tests tend to accelerate the patient's decline, either by physical or by psychological trauma? This chapter reviews the various predictive tests and their rationale and concludes that none of the tests are totally reliable. Many offer interesting insights into the effects of HD and do broaden the overall significance of this fascinating disorder of basal ganglion function.