Lucien J. Cote

Fibrillary astrocytes proliferate in response to brain injury: A study combining immunoperoxidase technique for glial fibrillary acidic protein and radioautography of tritiated thymidine☆

Abstract To determine whether fibrillary astrocytes proliferate in response to brain injury, cells identified as fibrillary astrocytes using immunoperoxidase technique for glial fibrillary acidic protein (GFAP) were examined for uptake of radiolabeled thymidine by autoradiography. In injured mouse brain, autoradiographic label was present over nuclei of immunoreactive fibrillary astrocytes in the lesion site 1 hr following injection of radiolabeled thymidine. The data suggest that fibrillary astrocytes which are sufficiently differentiated to accumulate GFAP retain the capacity to proliferate in response to injury.

Altered serotonin metabolism in depressed patients with Parkinson's disease

Depression is a common symptom inpatients with Parkinsons disease. It is not related to the severity of the motor symptoms or changes in dopamine metabolism and does not improve on treatment with dopamine agonists. Alterations in serotonin metabolism are found in primary (endogenous) depression. The brain content of serotonin in Parkinsons disease is also reduced, but this has not been related to any manifestation of the disorder. We found that the CSF content of the major metabolite of serotonin, 5-hydroxyindoleacetic acid, was lower in depressed than in nondepressed parkinsonians. The data suggest that the alterations in serotonin metabolism in Parkinsons disease identify a subgroup of patients who are prone to depression.

Analysis of the clinical problems in parkinsonism and the complications of long‐term levodopa therapy

We evaluated the current status of 131 patients with idiopathic parkinsonism who were receiving levodopa therapy. The residual parkinsonian symptoms and signs were tabulated, as were the adverse effects from medication. Response to therapy was correlated with duration of the disease and with duration of treatment. Patients with on-off or wearing-off effects were likely to have been treated for 4 years or longer. Patients treated with levodopa for 4 to 8 years were significantly more impaired with parkinsonism than patients treated for 0 to 3 years, even when patients were matched for total duration of disease. These data suggest that the deterioration of responsiveness after several years of levodopa therapy may be due to the therapy itself. Our findings support the concept that utilization of levodopa therapy should be delayed until a patient becomes significantly impaired in occupational or social situations.

Primary sensory symptoms in parkinsonism

Forty-three of 101 outpatients with parkinsonism reported that they regularly experienced primary sensory symptoms, i.e., spontaneous abnormal sensations not caused by somatic disease. This is in contrast to similar symptoms reported by only 8 percent of a control population. The most striking and severe symptom was burning of the trunk and proximal extremities, occurring in 11 patients. Twenty-nine patients reported spontaneous pain; a variety of other paresthesialike sensations, e.g., tingling, numbness, and formication, occurred in 32 patients. These subjective sensory phenomena were not associated with sensory loss or autonomic or motor signs. In 20 percent of affected individuals (9 percent of the total), sensory symptoms preceded the onset of the movement disorder, causing difficulty in diagnosis. It is concluded that at least some sensory symptoms originate within the nervous system as a manifestation of the disease process and are not secondary effects of the motor disorder.

Risk of Parkinson's disease among first-degree relatives: A community-based study

Objective: To determine the relative risk (RR) and cumulative incidence of idiopathic Parkinsons disease (PD) in first-degree relatives of PD patients compared with relatives of controls from the same geographic region. Design: A family history questionnaire was used to obtain information on all first-degree relatives of cases and controls. A subset of these first-degree relatives was also examined. A Cox proportional hazards model with double-censoring techniques for missing information was used to model the RR for PD, adjusting for gender, ethnicity, and relationship to proband. Results: A total of 1,458 first-degree relatives of 233 PD patients were 2.3 times as likely (95% CI = 1.3 to 4.0) as 7,834 relatives of 1,172 controls to develop PD. The cumulative incidence of PD to age 75 among first-degree relatives of PD patients was 2% compared with 1% among first-degree relatives of controls. The risk in male first-degree relatives was higher than in female relatives (RR = 2.0, 95% CI = 1.1 to 3.4) and the risk in relatives of Caucasians was higher than in African-Americans and Hispanics (RR = 2.4, 95% CI = 1.4 to 4.1). Risk for siblings and parents of probands was similar. Conclusions: Susceptibility to PD is increased in first-degree relatives of both sporadic and familial cases. The pattern of inheritance and the relationship between genetic and environmental risk factors warrant further study. NEUROLOGY 1996;47: 155-160

Memory and executive function impairment predict dementia in Parkinson's disease.

We analyzed the association of neuropsychological test impairment at baseline with the development of dementia in idiopathic Parkinsons disease (PD) patients. A cohort of nondemented PD patients from northern Manhattan, NY was followed annually with neurological and neuropsychological evaluations. The neuropsychological battery included tests of verbal and nonverbal memory, orientation, visuospatial ability, language, and abstract reasoning. The association of baseline neuropsychological tests scores with incident dementia was analyzed using Cox proportional hazards models. The analysis controlled for age, gender, education, duration of PD, and the total Unified Parkinsons Disease Rating Scale motor score at baseline. Forty‐five out of 164 patients (27%) became demented during a mean follow‐up of 3.7 ± 2.3 years. Four neuropsychological test scores were significantly associated with incident dementia in the Cox model: total immediate recall (RR: 0.92, 95% CI: 0.87–0.97, P = 0.001) and delayed recall (RR: 0.73, 95% CI: 0.59–0.91, P = 0.005) of the Selective Reminding Test (SRT), letter fluency (RR: 0.87, 95% CI: 0.77–0.99, P = 0.03), and Identities and Oddities of the Mattis Dementia Rating Scale (RR: 0.85, 95% CI: 0.73–0.98, P = 0.03). When the analysis was performed excluding patients with a clinical dementia rating of 0.5 (questionable dementia) at baseline evaluation, total immediate recall and delayed recall were still predictive of dementia in PD. Our results indicate that impairment in verbal memory and executive function are associated with the development of dementia in patients with PD.

Neuropsychological characteristics of preclinical dementia in Parkinson's disease

The goal of this study was to characterize the changes in cognition associated with the earliest, or preclinical, stages of dementia in Parkinsons disease (PD).We administered a comprehensive neuropsychological test battery to a group of initially nondemented PD patients participating in a longitudinal community-based epidemiologic study. We used Cox proportional hazards models to assess the relative risk of incident dementia associated with baseline scores on the neuropsychological tests. Baseline performance on two verbal fluency tasks (letter fluency and category fluency) was significantly and independently associated with incident dementia. Tests of memory, orientation, abstract reasoning, naming, and constructional skill were less sensitive predictors of subsequent dementia. The neuropsychological pattern characterizing the preclinical stages of dementia in PD differed from that described previously in preclinical Alzheimers disease. Results suggest that poor performance on tests of verbal fluency may represent a distinct characteristic of the preclinical phase of dementia in PD. NEUROLOGY 1995;45: 1691-1696

Dyskinesias while awake and periodic movements in sleep in restless legs syndrome Treatment with opioids

In five unrelated patients with the restless legs syndrome, opioid drugs relieved restlessness, dysesthesias, dyskinesias while awake, periodic movements of sleep, and sleep disturbances. When naloxone was given parenterally to two treated patients, the signs and symptoms of the restless legs syndrome reappeared. Naloxone placebo had no effect. Opioid medications may offer a useful therapy for the restless legs syndrome. The endogenous opiate system may be involved in the pathogenesis of the syndrome.

Combined Effect of Age and Severity on the Risk of Dementia in Parkinson's Disease

Age and severity of extrapyramidal signs have been consistently associated with incident dementia in Parkinsons disease. We evaluated the separate and combined effects of age and severity of extrapyramidal signs on the risk of incident dementia in Parkinsons disease in the setting of a population‐based prospective cohort study. Age and the total Unified Parkinsons Disease Rating Scale motor score at baseline evaluation were dichotomized at the median. Four groups of Parkinsons disease patients were defined: younger age/low severity (reference), younger age/high severity, older age/low severity, and older age/high severity. Risk ratios for incident dementia were calculated with Cox proportional hazards models controlling for gender, education, ethnicity, and duration of Parkinsons disease. Of 180 patients, 52 (28.9%) became demented during a mean follow‐up period of 3.6 ± 2.2 years. The median age at baseline of the Parkinsons disease patients was 71.8 years (range, 38.5–95.9 years), and the median total Unified Parkinsons Disease Rating Scale motor score was 24 (range, 2–65). The group with older age/high severity had a significantly increased risk of incident dementia (relative risk, 9.7; 95% confidence interval, 3.9–24.4) compared with the group with younger age/low severity (reference), whereas the groups with older age/low severity (relative risk, 1.6; 95% confidence interval, 0.5–4.8) and younger age/high severity (relative risk, 1.2; 95% confidence interval, 0.5–3.2) did not. These findings suggest that the increased risk of incident dementia in Parkinsons disease associated with age and severity of extrapyramidal signs is related primarily to their combined effect rather than separate effects.

The impact of comorbid disease and injuries on resource use and expenditures in parkinsonism

To the Editor: The article by Pressley et al. provides important information about health care use in Parkinson disease (PD).1 Incidentally, this study shed interesting light on falls and injury mechanisms in PD. Earlier studies noted that arm fractures seemed rare in PD.2 The current survey strongly indicates that injuries in PD affect the upper extremities less often than the lower extremities. In fact, recalculation of the original data shows that in PD, the risk of upper extremity injuries was almost significantly lower compared with controls (table). At first sight, this is unexpected because patients with PD fall predominantly forward (figure 1A)3; such forward falls typically cause wrist fractures because subjects land on the outstretched hand.4 We propose two explanations. One possibility is that patients keep their hands in pockets of their clothes owing to shame of hand tremors. Another explanation is that arm movements are delayed or abnormally directed in PD. We examined protective arm movements in patients with PD placed …