X-linked bulbar and spinal muscular atrophy, or Kennedy disease: clinical, neurophysiological, neuropathological, neuropsychological and molecular study of a large family.

We report the clinical, neurophysiological, neuropsychological, neuropathological and molecular findings in a large family with X-linked bulbar and spinal muscular atrophy (X-BSMA). Molecular study, performed in 28 family members, showed an increase in the number of CAG repeats in 6 affected males (including 2 presymptomatic patients), and in 10 females, of whom 5 were obligate carriers. All symptomatic patients showed, besides the typical manifestation of X-BSMA, neurophysiological signs of sensory nerve involvement, and abnormal findings in neuropsychological tests. Sural nerve biopsy, performed in two patients, was consistent with axonal atrophy and slow-rate degeneration, with secondary demyelination. Neurophysiological alterations were also present in 6 out of 8 carriers, consisting of neurogenic EMG changes in 3 cases and abnormal sensory action potentials (SAP) and reduced conduction velocity of the sural nerve in 3 cases. Abnormalities of at last two neuropsychological tests were found in 6 out of 8 carriers. Alterations of the sensory nerves in X-BSMA patients have been previously reported in some cases; however, we demonstrate for the first time sensory nerve involvement also in carriers. Evidence of central nervous system involvement, with neuropsychological impairment in all symptomatic patients and in some carriers, is another feature of this family, not previously reported in X-BSMA. In spite of the variable phenotypic features, the number of CAG repeats ranged from 40 to 44 in the affected patients, indicating that phenotypic expression was not related to the size of the mutation, but was probably age-related.

Sympathetic skin response in patients with Duchenne muscular dystrophy.

To verify an eventual disfunction of the palmar sympathetic skin activity in Duchenne Muscular Dystrophy, we studied the sympathetic skin response (SSR) with endogenous, Deep Breathing (DB-SSR), exogenous Startle (SE-SSR) and Electric type stimuli (EE-SSR) in a group of patients and a control group. At the same time as the SSR, the heart rate (HR) and the basic R-R interval variation (RRIV) as well as the EMG diaphragmatic activity were checked. In this way, significant differences in the latency (p = 0.02) and amplitude (p = 0.009) values of the EE-SSR and in the amplitude values of the SE-SSR (p = 0.001) and of the DB-SSR (p = 0.02) were noted in the DMD group compared to the control group. In the group of patients the rise in latency of the EE-SSR correlates with the age (p = 0.0001) and with the reduction of its amplitude (p = 0.03). This last parameter correlates with the stage of the illness (p = 0.02). In the control group the mean amplitude of the EE-SSR is approximately 30% greater than that of startle and 50% of deep breathing. Although with amplitudes homogeneously reduced, these ratios are also conserved in the DMD group. Moreover the HR is greater (p = 0.0001) whilst the RRIV is reduced (p = 0.02) in the group of the patients. However these parameters do not correlated either to the cardiac involvement or to the stage of the illness. The presence of the SSR for all the modalities of stimulation indicates the substantial integrity of the afferent and the efferent paths of the ANS. The alterations in latency and amplitude of the SSR in the patients could be the consequence of a lack of dystrophin at the level of the sudoriparous myopithelium in analogy to what has been demonstrated in the mdx mouse.

Incidence of stroke in young adults in the Reggio Emilia area, northern Italy.

A retrospective epidemiological study on the first episode of stroke in young adults aged 15-44 years was carried out in the territory of the Local Health Unit No. 9 in Reggio Emilia (46,491 km2), Italy, from 1987 to 1989. 29 patients were identified: 17 were affected with cerebral infarction and 12 with hemorrhage. All young patients were discharged with diagnostic codes 430-438 according to the International Classification of Disease, i.e. the criteria of the World Health Organisation for stroke definition. All patients had computed tomography or necropsy. The average annual incidence rate per 100,000 population aged 15-44 for all strokes was 13.6 and the 95% confidence interval (CI 95%) was 9.1-19.6. The general population of the same age on January 1, 1987, was 69,845 and 71,920 on December 31, 1989; the incidence rate of stroke was 14.0 for males (CI 95% 7.9-2.3) and 13.2 (CI 95% 7.1-22.2) for females. The average annual incidence rates were 8.0 (CI 95% 4.7-12.2) for cerebral infarction (8.4, CI 95% 3.9-16 for males, 7.6, CI 95% 3.3-14.9 for females), 5.6 (CI 95% 2.9-9.9) for cerebral hemorrhage and 2.8 (CI 95% 1.0-6.1) for both subarachnoid (SAH) and intracerebral hemorrhage (ICH). Based on angiography or necropsy findings, aneurysms or arteriovenous malformations were present in 83% of the patients with SAH and in 66% of the patients with ICH. The 1-month fatality ratio was 0 for cerebral infarction, 50% for SAH and 33% for ICH.(ABSTRACT TRUNCATED AT 250 WORDS)

Kennedy disease in an Italian kindred.

An X-linked adult-onset neurogenic muscular atrophy, chiefly proximal, with late involvement of the distal musculature and medulla oblongata was present in 4 members of a single kindred. Associated in all patients were gynecomastia, impotence and essential tremor. Frederickson type IV hyperlipemia was present in 1 patient. Hormonal stimulation tests in 2 patients elicited a borderline low testicular response in the younger of the 2 and a pathological response in the older patient. On the evidence of these and previously reported cases, Kennedy disease would appear to be characterized by an X-linked proximal neurogenic amyotrophy of adult onset and by a testicular endocrine deficit.

The differential contribution of the verbal code in the course of visual learning: evidence from hemisphere-damaged patients.

Control patients and patients with hemispheric lesion were given a paired-associate memory test made up of meaningful figures and their performance was compared on two measures: number of errors over the first three trials and trials to criterion. Impairment on the former measure was associated with left brain damage and found to be related to the degree of aphasic deficit, suggesting the involvement of the verbal code in the early stages of the learning process. However, analysis of trials to criterion showed that a defective performance was confined to patients of either hemispheric group having posterior lesions and bore non relationship to measures of language impairment. It is inferred that, as the learning process consolidates, the aid provided by verbal mediation to recognizing visual images progressively recedes.