Gordon J. Gilbert

WEIGHT LOSS IN HUNTINGTON DISEASE INCREASES WITH HIGHER CAG REPEAT NUMBER

Objective: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number. Methods: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington’s Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD. Results: In patients with HD, mean body mass index decreased with −0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length. Conclusions: Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics.

Familial Hyperkalemic Paralysis with Myotonia

ALTHOUGH it has long been known that a striking fall in serum potassium level may coincide with the attacks of weakness occurring in familial periodic paralysis, and that the administration of pota...

Neurological Differential Diagnosis, 2nd ed

edited by John Patten, 449 pp., ill., London, Springer-Verlag, 1996 This book has an excellent feature consisting of frequent and clear but simplified explanatory diagrams drawn by the author himself. These effectively demonstrate such features as athetoid and dystonic posturing, blepharospasm, spasmodic torticollis, and the anatomy of the cerebellum. The diagrams should be quite helpful for the medical student, resident, family practitioner, or internist at whom this book appears to be aimed. The anatomic depictions are quite clear, if incomplete. The authors unusual artisitic virtuosity has produced a unique feature rarely found in neurologic texts. His diagramatic display of the evolution of papilledema is beautifully achieved. Special techniques of the neurologic examination, such as visual field confrontation testing, are explicitly illustrated by drawings; figures of radiographs, CT, and …

Familial myoclonus and ataxia. Pathophysiologic implications.

THE NEUROMUSCULAR DISORDER of diffuse myoclonus is regarded as consisting of arrhythmic, asynergic, sudden, brief involuntary contractions involving an integrated response of at least several related motor units. These may be confined to a portion of a muscle, or involve an entire muscle or muscle groups. Myoclonus is “stimulus-sensitive,” being initiated or enhanced by changes in posture, photic or auditory stimulation, drowsiness, or emotional reactions. It may exist as a discrete phenomenon and be distinguished from the entity of “myoclonic or myoclonus epilepsy” which we would like to refer to as the association of generalized myoclonus with grand ma1 convulsions in a setting of progressive cerebral deterioration. In 1921, J. Ramsay Hunt first described the syndrome of “dyssynergia cerebellaris myoclonica.”l He attempted to demonstrate that the association of diffuse myoclonus and signs of cerebellar dysfunction, particularly intention tremor, might signify the presence of a lesion in the dentate nucleus of the cerebellum. His first 4 cases each had epilepsy, myoclonus, and intention tremor. Two additional cases were of twins who, in their third decade, experienced the onset of myoclonus, intention tremor, and a sensory deficit regarded as characteristic of Friedreich‘s ataxia. One of these twins came to autopsy ten years after the onset of his disease, and constituted Hunt’s pathologically verified case. Examination of the nervous system revealed atrophy of the dentate nucleus and rarefaction of the myelin in the superior cerebellar peduncles and, in addition, spinocerebellar tract degeneration. Hunt made it clear that he felt that the association of myoclonus with intention tremor denoted presence of a lesion of the dentate nucleus. He was describing a syndrome and not a disease, as is quite evident from the diversity of his patient material. Epilepsy was not present in two of the original patients included in this syndrome. Yet, “dyssynergia cerebellaris myoclonica” was subsequently interpreted by many authors as a disease combining epilepsy, “myoclonus” and signs of cerebellar dysfunction. In many cases so reported, a distinct myoclonie epilepsy was a feature of a progressive diffuse neuronal degenerative disorder.2-4 “Dyssynergia cerebellaris myoclonica” consequently has come to refer to cases of myoclonic epilepsy in which signs of cerebellar dysfunction are particularly prominent, a usage which is confusing.

FamiIial spasmodic torticolIis

Article abstract Presented are four cases of familial spasmodic torticollis, comprising members of three families. The age of onset tended to be family-specific, and no afflicted family member had evidence of more widespread disease (dystonia musculorum deformans). Familial incidence supports the conclusion that spasmodic torticollis is organic in origin. Familial spasmodic torticollis occurs more often than has been generally recognized.

PERIODIC HYPERSOMNIA AND BULIMIA. THE KLEINE-LEVIN SYNDROME.

DISTURBANCES OF SLEEP PATTERN constitute a fascinating clinical spectrum, bridging the fields of neurology and psychiatry. The insomnia of an anxiety tension state typifies a functional disorder, while frequent bouts of sleep throughout the day and night, when presenting as one aspect of the narcolepsy syndrome, are considered to have an inapparent organic causation. The Kleine-Levin syndrome, of which the twenty-sixth case will be reported below, is characterized by recurrent bouts of hypersomnia and bulimia. A single attack will last for days or weeks, during which the patient will eat ravenously and sleep the rest of the time. In every case reported but one, onset of attacks has been in the second decade. The case reported below is only the third in a female. Furthermore, in contrast to earlier cases, an intensive evaluation has included psychometric and endocrine studies, the results of which are of interest.

Renal effect of subcommissural extract

ONLY IN RECENT YEARS has the profound influence of intracranial regulatory structures upon total body water and electrolyte homeostasis become apparent.l First to be described was the neurohypophysial influence upon the renal excretion of water.2 The protein precursor of the antidiuretic hormone was shown to originate in the supraoptic and paraventricular nuclei of the hypothalamus and to be carried down the axons of these nuclei to the posterior lobe of the pituitary gland for storage before the release of the active octapeptide antidiuretic hormone.3-5 The primary stimulus to this hormonal release was found to be carotid arterial serum hyperosmolarity.1 Recent evidence has implicated the perimammillary posterior and ventral hypothalamus as an integral participant in the regulation of water consumption.6-9 No investigation has clearly indicated that this hypothalamic region includes a receptor site rather than a neural effector circuit for drinking. I t is considered possible that hypothalamobulbar connections currying thirst impulses have been stimulated or destroyed in these investigations.1 Experiments in rats and in sheep have indicated the existence of a specific sodium hunger quantitatively regulating sodium ingestion and altering the taste threshold for sodium in the salt-depleted animal.10-12 By the year 1952, substantial experimental evidence demonstrated that the ingestion of salt and water and the urinary excretion of water are regulated by intracranial receptors and neural effector pathways. In that year, we began investigations into the physiology and anatomy of the subcommissural organ, a small modified ependymal structure in the roof of the cerebral aqueduct just ventral to the posterior commissure.13 Its unique histochemical properties indicated that the subcommissural organ elaborates a secretion and has a very high level of enzymatic activity.14 Gomori’s chromealum hematoxylin phloxine had been developed to stain the insulin-producing beta cells of the pancreas. When Wislockil~ had applied Gomori’s stain to brain tissue, he found that it was taken up selectively by the neurohypophysis, the subcommissural organ secretion, and Reissner’s fiber. This fiber is continuous with and formed by the subcommissural organ and extends downward through the cerebral aqueduct and fourth ventricle to enter and traverse the length of the spinal canal. The similar staining properties of the neurohypophysis and subcommissural organ suggested that the latter might also function in fluid metabolism. Therefore, electrocoagulative ablation of the subcommissural organ was performed in 46 white rats.13 Because of difficulty encountered in the quantitative collection of rat urine, and because the microcoagulation of the subcommissural organ led consistantly to an immediate and severe fall in water consumption, only the relationship of subcommissural organ function to water consumption was investigated at that time. Electrocoagulative ablation of the subcommissural organ markedly depressed water consumption, and dehydration was often so severe that death followed within five days. The intensity of dehydration and the rapidity of death indicated that factors in addition to decreased water consumption were contributing to loss of body fluid. This suggested that urinary loss of sodium and water might be a further consequence of subcommissural organ ablation. Conversely, electrical stimulation of the subcommissural area was found to increase water

Pentoxifylline‐induced musical hallucinations

episodes in 2 years of follow-up, supports this hypothesis. Quinolone antibiotics may lower the seizure threshold through a mechanism involving inhibition of GABA receptor binding. These drugs should be used with caution in patients with preexisting neurologic disease, in particular those with seizure disorders. Further, any patient presenting with an acute confusional state or psychosis in whom a history of quinolone use is obtained should undergo EEG evaluation.

Brueghel syndrome Its distinction from Meige syndrome

A critical historical evaluation of the cranial dystonias supports the separation of the dystonia of the motor trigeminal nerve producing a widely opened mouth (Brueghel syndrome) from the more common facial dystonias with blepharospasm (Meige syndrome).In a patient with Brueghel syndrome, paroxysmal hyperpnea coincided with dystonic gaping; the finding of upbeating nystagmus suggests pontine localization in the pathogenesis of this rare disorder. NEUROLOGY 1996;46: 1767-1769

Spasmodic Torticollis Treated Effectively by Medical Means

SPASMODIC torticollis is an extremely unpleasant and severely disabling organic neurologic disease.1 2 3 4 5 6 The patients head is involuntarily and often painfully rotated and twisted so that he...