Daniel S. Sax

Neurourologic Abnormalities in Multiple Sclerosis

Multiple sclerosis is a demyelinating disease of the central nervous system, often producing abnormalities in sexual function and urinary control. Eighty-six patients with this disorder were referred to our neurourologic facilities for evaluation (45 women and 41 men). Symptomatic voiding dysfunction was present in 84 patients (97 per cent). Sexual dysfunction was present in 29 of the 41 men (71 per cent). Neurourologic evaluation was performed by rapid-fill carbon dioxide cystometry and perineal floor needle electromyography. Several neurourologic patterns were identified in multiple sclerosis patients: the most common cystometry pattern was detrusor hyperreflexia (76 per cent) and the most common electromyography finding was vesico-sphincter dyssynergia (50 per cent). Voiding symptoms alone were not found to correlate with neurourologic findings. The presence of bilateral extensor plantar reflexes was found to indicate the possibility of vesico-sphincter dyssynergia. The addition of sacral-evoked responses to the neurourologic evaluation was useful in the identification and localization of occult sacral cord pathology and was of special significance to men with sexual dysfunction undergoing evaluation for neurogenic impotence. The combination of abnormal perineal electromyography, abnormal sacral latency and detrusor hyperreflexia was suggestive of multilevel spinal cord dysfunction and, possibly, has diagnostic as well as therapeutic significance. Neurourologic patterns were found to change in 4 of 9 patients re-evaluated because of symptom changes or poor treatment responses. Neurourologic testing in multiple sclerosis patients may be used to identify pathologic lesions, characterize sexual and voiding dysfunctions, corroborate neurologic diagnosis in doubtful cases and form a basis for rational treatment planning.

Peripheral neuropathy in arsenic smelter workers.

We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair, and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.

Predictors of nursing home placement in Huntington disease

Objective: To determine whether motor, behavioral, or psychiatric symptoms in Huntington disease (HD) predict skilled nursing facility (SNF) placement. Methods: Subjects were participants in the Huntington Study Group’s Unified Huntington Disease Rating Scale Database (Rochester, NY) between January 1994 and September 1999. Specific motor, psychiatric, and behavioral variables in subjects residing at home and in SNF were analyzed using χ2 and Student’s t-tests. For a subset of subjects for whom longitudinal data existed, a Cox proportional hazards model controlling for age, sex, and disease duration was used. Results: Among 4,809 subjects enrolled, 3,070 had clinically definite HD. Of these, 228 (7.4%) resided in SNF. The SNF residents’ average age was 52 years, average disease duration was 8.6 years, and they were predominantly women (63%). The SNF residents had worse motor function (chorea, bradykinesia, gait abnormality, and imbalance, p < 0.0001); were more likely to have obsessions, compulsions, delusions, and auditory hallucinations; and had more aggressive, disruptive (p < 0.0001), and irritable behaviors (p = 0.0012). For 1,559 subjects, longitudinal data existed (average length of follow-up, 1.9 years), and 87 (5%) moved from home to SNF. In the Cox model, bradykinesia (HR 1.965, 95% CI 1.083 to 3.564), impaired gait (HR 3.004, 95% CI 1.353 to 6.668), and impaired tandem walking (HR 2.546, 95% CI 1.460 to 4.439) were predictive of SNF placement. Conclusions: Institutionalized patients with HD are more motorically, psychiatrically, and behaviorally impaired than their counterparts living at home. However, motor variables alone predicted institutionalization. Treatment strategies that delay the progression of motor dysfunction in HD may postpone the need for institutionalization.

A Case Study of auditory Agnosia: Linguistic and Non-Linguistic Processing

Summary We have evaluated at length an individual who had as a major neurological defect an impaired ability to recognize the nature of heard non-verbal sounds, that is, auditory agnosia. Wood et al.: (1971) have demonstrated that ≪different neural events occur in the left hemisphere during analysis of linguistic vs non-linguistic parameters of the same acoustic signal≫. This case provides additional clinical support for the theoretical position that there may be two central auditory processing mechanisms, one treating linguistic inputs and the other non-linguistic inputs.

Physostigmine in choreiform movement disorders

Dopaminergic-cholinergic balance is a clinically observable phenomenon in Parkinsons disease and in L-dopa-induced dyskinesia. In a series of 30 patients with a variety of choreiform movement disorders, including Huntingtons disease, L-dopa-induced dyskinesia, and tardive dyskinesia, we have been unable to dernonstrate consistent cholinergic responsiveness. Intravenous physostigmine reduced chorea in Huntingtons disease in only two of 12 patients, whereas choreiform movements were abolished or suppressed in five of seven patients with L-dopa-induced dyskinesias.

Neurologic Evaluation of a Population Exposed to Arsenic in Alaskan Well Water

One hundred forty-seven persons exposed to arsenic from well water were evaluated by neurologic examination and nerve conduction studies. Total arsenic concentrations in well water ranged from 1 to 4781 micrograms/L and from 6 to 4964 micrograms/L in urine; a calculated index of arsenic ingestion ranged from 1 to 4521 micrograms/day. No dose-response relationship existed between arsenic ingestion and symptoms or physical findings compatible with peripheral neuropathy. Five of six persons with symptoms or physical findings suggestive of sensory neuropathy had normal nerve conduction velocities. Thirteen persons with elevated arsenic ingestion but no signs or symptoms of neuropathy had one or more abnormal nerve conduction velocities. No dose-response relationship, however, existed between arsenic ingestion and nerve conduction velocities. The authors concluded that arsenic ingestion from well water at the concentrations found in this Alaskan community did not result in clinical or subclinical neuropathy.

Computed Tomographic, Neurologic, and Neuropsychological Correlates of Huntington'S Disease

Twenty-six patients with Huntingtons disease (HD) and three subjects at risk for HD were evaluated by computed tomographic, neurologic and neuropsychological examinations. These data were used to delineate the sequence of structural changes in early and intermediate HD, and the relationship of these changes to impairment of neurologic and cognitive function. CT scans documented an early neostriatal-frontal focus of atrophy in HD which spreads caudally over the cerebral cortex during the course of the disease. Chorea was positively correlated with caudate atrophy. Functional and cognitive (especially memory and visuospatial) impairments were strongly related to the degree of atrophy. Multiple regression analyses of CT and neuropsychological data further demonstrated that neostriatal changes make a significant contribution to the cognitive as well as to the motor impairments of HD patients.

Interrater agreement in the assessment of motor manifestations of Huntington's disease

With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntingtons disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy‐five clinicians experienced in the evaluation of patients with early HD and six non‐clinicians were shown a videotape compiled from the film archives of the United States–Venezuela Collaborative HD Research Project. Observers were asked to rate a 2–3‐minute segment of the motor examination for each of 17 at‐risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted κ statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted κ = 0.67; standard error (SE) = 0.09). Agreement among the non‐clinicians was only fair (weighted κ = 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients.

A Comparison of the Information Processing Deficits of Patients with Huntington's Chorea and Korsakoff's Syndrome

Patients with Huntingtons Chorea and alcholic Korsakoffs disease were compared on six tests of short-term memory (STM) and of encoding capacity. While the alcoholic Korsakoff patients demonstrated STM disorders related to an increase sensitivity to proactive interference (PI) and to failures in semantic encoding, the Chorea patients had a different pattern of deficits. The Chorea patients, like the Korsakoffs, had STM deficits, but their memory performance did not improve with reductions in PI, and they had different types of encoding deficits than did the Korsakoff patients. These results demonstrate that information processing tasks can be used to empirically differentiate amnesic patients with normal I.Q.s from patients with dementia-related memory impairments.

Motor planning in Parkinson patients

This study was designed to determine if Parkinsonian patients exhibited a deficit in motor planning. Thirty adult males, 15 with Parkinsons disease and 15 normal controls, were given a gestural test which had two components. The first component required the symbolic representation of implement usage on verbal command and on imitation (representational items) and the second component required the imitation of non-symbolic hand positions (non-representational items). The results indicated that Parkinsonian patients performed at a significantly lower gestural level on the representational tasks and made significantly more spatial errors on non-representational tasks than the normal controls.