Non-motor symptoms are gaining relevance in Parkinson's disease (PD) management but little is known about their progression and contribution to deterioration of quality of life. We followed prospectively 707 PD patients (62 % males) for 2 years. We assessed non-motor symptoms referred to 12 different domains, each including 1-10 specific symptoms, as well as motor state (UPDRS), general cognition, and life quality. Hoehn & Yahr (H&Y) stage was used to categorize patient status (I-II mild; III moderate; IV-V severe). We found that individual non-motor symptoms had variable evolution over the 2-year follow-up with sleep, gastrointestinal, attention/memory and skin disturbances (hyperhidrosis and seborrhea) becoming more prevalent and psychiatric, cardiovascular, and respiratory disorders becoming less prevalent. Development of symptoms in the cardiovascular, apathy, urinary, psychiatric, and fatigue domains was associated with significant life-quality worsening (p < 0.0045, alpha with Bonferroni correction). During the observation period, 123 patients (17 %) worsened clinically while 584 were rated as stable. There was a fivefold greater increase in UPDRS motor score in worse compared with stable patients over 24 months (p < 0.0001 vs. baseline both in stable and worse group). The total number of reported non-motor symptoms increased over 24 months in patients with motor worsening compared to stable ones (p < 0.001). Thirty-nine patients died (3.4 % of patients evaluable at baseline) with mean age at death of 74 years. Deceased patients were older, had significantly higher H&Y stage and motor score, and reported a greater number of non-motor symptoms at baseline. In conclusion, overall non-motor symptom progression does not follow motor deterioration, is symptom-specific, and only development of specific domains negatively impacts quality of life. These results have consequences for drug studies targeting non-motor features.

Both diabetes and admission hyperglycemia in nondiabetic patients are predictors of poor outcome after supratentorial ICH. This may be related to the greater incidence of cerebral and infectious complications in diabetic patients and of cerebral complications in hyperglycemic nondiabetic patients.

Background and Purpose-The purpose of this study was to further analyze the temporal patterns of onset of intracerebral hemorrhage (ICH) and to determine whether or not subgroups with specific clinical characteristics exhibit different patterns of onset. Methods-The daily, weekly, and yearly variations in occurrence of ICH together with the relationship between ICH occurrence and changes in air temperature were evaluated in 1018 patients. Patients were grouped according to the presumed etiology of ICH: hypertensive ICH, secondary ICH, and ICH of undetermined origin. The contribution of demographic and clinical factors to the temporal distributions of ICH was also evaluated. Results-Marked differences in seasonal and diurnal patterns of ICH onset were observed in the different groups. The incidence of hypertensive ICH reflected seasonal and circadian changes in blood pressure, whereas the latter did not seem related to the onset of nonhypertensive ICH. The seasonal pattern was more evident in elderly patients with hypertensive ICH than in younger subjects. No significant weekly variations were observed; however, risk was greater on Monday in the working population. Conclusions-Our results suggest that the higher incidence of ICH in the colder months is due to the effect of low temperatures on blood pressure and that the clustering of ICH events in the morning is due to the increase in sympathetic tone, and consequent increase in blood pressure, on awakening. (Stroke. 2000;31:1538-1544.)

We report biochemical, morphological and neuroradiological findings in a 40-year-old woman affected with type I sialidosis. The clinical symptoms, consisting of a cerebellar syndrome, were first noted at the age of 17 years. The macular cherry-red spot was first observed after 23 years of disease. A CT scan performed at 21 years of age showed enlargement of the fourth ventricle. Nuclear magnetic resonance imaging of the brain performed at the age of 40 showed severe atrophy of the cerebellum and pontine region; atrophy of cerebral hemispheres and of the corpus callosum was also observed. We emphasize the prolonged course of illness in this patient, observed over a long period of time. Of particular interest is the neuroradiological study showing our findings both at the beginning of the disease and after 20 years.

The authors report the sequence of the clinical symptoms in type I sialidosis or cherry-red spot myoclonus syndrome, derived from the cases personally observed and from the literature. They also report neuropathological and neurochemical data. A serial EEG study in a case shows the tendency to a progressive deregulation of cerebral electric activity. Therapeutic attempts to reduce myoclonus, which is one of the more disabling symptoms in this syndrome, are described.

Objectives To explore the impact of sex and age on relationship between prodromal constipation and disease phenotype in Parkinson’s disease at early stages. Methods A total of 385 Parkinson’s disease patients from the PRIAMO study were classified according to the presence of prodromal constipation and followed for 24 months. Multivariable mixed-effect models were applied. All analyses were performed separately for sex (64.1% men) and median age (different by sex: 67 years-old in men and 68 years-old in women). Results As for sex, prodromal constipation was associated with greater odds of attention/memory complaints and apathy symptoms in women only. As for age, prodromal constipation was associated with lower cognitive and higher apathy scores in older patients only. Conclusions Prodromal constipation anticipates lower cognitive performances and more severe apathy since the earliest stages in women and older patients. Sex- and age-related heterogeneity of prodromal markers of Parkinson’s disease may impact disease phenotype.

We report the findings of an electrophysiological study in 9 patients affected by olivopontocerebellar atrophy, 4 with a dominant form and 5 with a sporadic form. Superficial peroneal nerve biopsy was obtained from 2 patients. The electrophysiological alterations were signs of collateral reinnervation and loss of motor units, decrease in sensory potential amplitude and increase in distal motor latency. Only a slight reduction in motor and sensory conduction velocity was observed in some cases. Nerve biopsy showed slight reduction of the number of myelinated fibres. In the first case, fibre diameter distribution was unimodal, due to reduction of myelinated fibres of large diameter, in the second case there was no significant alteration of the fibre distribution. In both cases short internodes were present with no signs of segmental demyelination, remyelination or axonal degeneration. The alterations observed in the peripheral nervous system are probably secondary to a lesion of the posterior root ganglion and the anterior horn cell in the spinal cord.

The distributions of intracerebral hemorrhage (ICH) according to place of onset, degree of physical activity at onset and potential triggering factors were analyzed in 848 patients with ICH. Patients were grouped according to the presumed cause of ICH: hypertensive ICH, secondary ICH and ICH of undetermined origin. The influence of demographic and temporal factors on the relative frequency of events was also assessed. In 30% of the cases, ICH occurred during inactivity or sedentary activity, in 50% during light exertion and in 20% during moderate/vigorous exertion. During inactivity or sedentary activity, hypertensive ICH was significantly less frequent than secondary ICH (OR 0.32; 95% CI 0.21–0.47) and undetermined ICH (OR 0.36; 95% CI 0.23–0.55), whereas during moderate or vigorous exertion hypertensive ICH was more frequent than secondary (OR 1.88; 95% CI 1.16–3.05) and undetermined ICH (OR 2.29; 95% CI 1.31–4.00) Potential triggering factors were observed in 27% of patients and were significantly more frequent in patients with hypertensive ICH than in patients with secondary ICH (OR 2.90; 95% CI 1.85–4.54) or undetermined ICH (OR 2.44; 95% CI 1.54–3.87). Our findings suggest that many potential external triggers that act mainly by raising blood pressure may interact, and their concurrence may favor cerebral hemorrhage, particularly in hypertensive patients. In many cases, these circumstances of increased risk may be mitigated by preventive measures.