Levodopa improves spatial contrast sensitivity in Parkinson's disease.

OBJECTIVE: To study the effect of levodopa on the visual contrast sensitivity of patients with Parkinson's disease. DESIGN: Contrast sensitivity of patients was measured before and after levodopa administration. Patient contrast sensitivity was compared with that of normal controls by repeated-measures analyses of variance. SETTING: Parkinson's disease research center associated with private neurology practice. PATIENTS: Fifteen patients with idiopathic Parkinson's disease (eight men, seven women; mean age, 71.8 years) and 22 normal controls (10 men, 12 women; mean age, 68.0 years) volunteered for the study. INTERVENTION: Levodopa/carbidopa (Sinemet). MAIN OUTCOME MEASURE: Change in contrast sensitivity of parkinsonian patients. RESULTS: Following levodopa treatment, the contrast sensitivity of parkinsonian patients improved significantly at the three lowest spatial frequencies tested (0.4, 1, and 2 cycles per degree). CONCLUSIONS: Levodopa improves low-frequency contrast sensitivity in parkinsonian patients. Initially deficient contrast sensitivity in such patients may be restored to near normal levels by levodopa therapy.

Treatment of chronic Parkinson's disease with controlled-release carbidopa/levodopa.

Controlled-release carbidopa/levodopa 50/200 (SINEMET CR) and standard carbidopa/levodopa (SINEMET 25/100) were compared in a double-blind, six-month, crossover study involving 21 patients with chronic Parkinson's disease and motor response fluctuations. Daily dosage frequency was significantly reduced with SINEMET CR compared with SINEMET 25/100, while the daily amount of levodopa required with SINEMET CR was significantly greater. No significant differences in disability ratings, motor response fluctuations, or safety were detected during double-blind conditions. In the open-label, dose-finding phase of the study, SINEMET CR was superior to standard SINEMET 25/100 in patient ratings of percent "on" time (good motor function), clinical assessments of motor function, and activities of daily living. This finding resulted from a depreciation of the value of the "old drug" rather than an overestimation of the value of the experimental drug. This double-blind study also suggested that elderly male patients with Parkinson's disease derived the greatest benefit from SINEMET CR.

Prolonged serum levodopa levels with controlled-release carbidopa-levodopa in the treatment of Parkinson's disease.

Twenty parkinsonian patients (Hoehn and Yahr scale, I through III) were treated with controlled-release carbidopa-levodopa (CR-2 or CR-3) and standard carbidopa-levodopa (Sinemet, 25 mg/100 mg) in a double-blind, crossover pharmacokinetic and clinical efficacy study. The controlled-release agents had a slower rise to peak plasma values and flatter pharmacokinetic curves than did the standard. The area under the curve for CR-3 was significantly increased by 55.5% as compared with standard agent and by 84.2% as compared with CR-2. No differences in clinical efficacy were found between controlled-release agents and the standard agent for this group of parkinsonian patients with mild to moderate severity. The dissociation between the prolonged serum levodopa levels and unimproved clinical efficacy may have resulted from the absence of patients with prominent motor fluctuations and/or substantial serum levodopa variability that was especially prominent with CR-3.

A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events.

OBJECTIVE: To assess the safety and efficacy of subcutaneous apomorphine hydrochloride administration for off-state (poor motor function) periods in patients with Parkinson disease with motor fluctuations under both inpatient titration and outpatient therapeutic conditions. PATIENTS AND METHODS: Twenty-nine patients had advanced Parkinson disease with 2 hours or more off time despite aggressive oral therapy. Patients randomly received titrated doses of subcutaneous apomorphine hydrochloride (2-10 mg, n = 20) or pH-matched vehicle placebo (n = 9) during an inpatient and 1-month outpatient phase. A change in the United Parkinson Disease Rating Scale motor score 20 minutes after inpatient dosing during a practically defined off-state event and the percentage of injections successfully aborting off-state events were the primary inpatient and outpatient efficacy factors. RESULTS: The average (SEM) levodopa equivalent dose of apomorphine hydrochloride was 5.4 +/- 0.5 mg and the mean placebo dose was 1.0 mL. Mean inpatient United Parkinson Disease Rating Scale motor scores were reduced by 23.9 and 0.1 points (62% and 1%) by apomorphine treatment and placebo, respectively (P<.001). The mean percentage of outpatient injections resulting in successful abortion of off-state events was 95% for apomorphine and 23% for placebo (P<.001). Inpatient response was significantly correlated with and predictive of outpatient efficacy (P<.001). The levodopa dose was not predictive of the apomorphine dose requirement. Frequent adverse events included dyskinesia, yawning, and injection site reactions. CONCLUSION: Apomorphine by intermittent subcutaneous injection is effective and safe for outpatient use to reverse off-state events that occur despite optimized oral therapy.

Computerized tomography in the diagnosis of central and extrapontine myelinolysis.

In two patients the diagnosis of central pontine myelinolysis (CPM), suspected on clinical grounds, was supported by computerized tomographic (CT) sections made perpendicular to the pons, and confirmed on postmortem examination. Extrapontine myelinolysis was suggested on CT scans in both cases, and confirmed in one. Computerized tomography may prove to be a sensitive and accurate diagnostic test for CPM, and may aid in the detection of associated extrapontine lesions.

Long-acting carbidopa-levodopa in the management of moderate and advanced Parkinson's disease.

Parkinson's disease patients treated chronically with levodopa often develop fluctuations in motor response. Motor fluctuations can be attributed in part to oscillating plasma levodopa concentrations. A controlled-release formulation containing 200 mg of levodopa and 50 mg of carbidopa provides superior plasma levodopa profiles compared with the standard preparation. A multicenter, double-blind trial involving 202 patients with fluctuating motor response found controlled-release carbidopa-levodopa to be safe and tolerable, with improved efficacy compared with the standard formulation. Long-term exposure to the controlled-release formulation, at least for a period of 3 years, does not appear to be associated with any increase in the incidence of adverse side effects.

Eye tracking dysfunction in Alzheimer-type dementia.

Performance on visual tracking tasks was measured in groups of Alzheimer-type dementia, pseudodementia of depression, and elderly normal controls. Smooth pursuit tracking errors were identified by counting the number of catch-up saccades required to compensate for failure of the smooth pursuit system. The group with Alzheimer-type dementia had significantly worse (p less than 0.0001) smooth pursuit tracking than either pseudodementia subjects or elderly normal controls. A strong correlation (r = 0.74, p less than 0.005) was found in Alzheimer patients between severity of visual tracking abnormality and severity of dementia.

Asymmetry of the lateral (sylvian) fissures in man.

We compared the courses of right and left lateral (sylvian) fissures by superimposing left lateral and reversed right lateral photographic slide projections and tracing the sulci and fissures of each hemisphere in different colors. A characteristic pattern of divergence of posterior regions of the lateral fissures was noted in 25 of 36 adult brains. After pursuing similar courses, the right lateral fissure angulates sharply upward into the inferior parietal area while the left one continues posteriorly. As a consequence, on the right, there is a smaller parietal operculum, a shorter planum temporale, a higher sylvian point, and compensatory expansion of the inferior parietal region posterior to the lateral fissure.

Controlled study of the antiparkinsonian activity and tolerability of cabergoline.

Cabergoline, a new ergoline derivative, is a D2-specific dopaminergic agonist that is more potent and longer-acting than other agonist agents. We conducted a randomized, double-blind study of increasing doses of cabergoline taken once a day. Twenty-five patients with Parkinson's disease taking stable doses of levodopa began cabergoline at 0.5 mg. The dose was escalated at weekly intervals to 1.0 mg in 19 patients, 1.5 mg in 14 patients, 2.0 mg in nine patients, and 2.5 mg in four patients. Treatment continued for 8 weeks after titration. Unified Parkinson's Disease Rating Scale scores, Hoehn and Yahr stage of disease, and computerized measures of motor performance improved significantly with cabergoline treatment. Dose-response effects were not significant. No serious adverse experiences occurred during the 13-week trial, and the side-effect profile mirrored other dopaminergic agonists. Cabergoline appears to be a promising agent in the treatment of Parkinson's disease.

Abnormal ocular motor function predicts clinical diagnosis of familial ataxia.

Ocular motor performance was significantly impaired in familial ataxia patients as compared with normal controls. Ataxic patients showed prolonged saccadic latencies, longer saccadic refixation times, reduced visual tracking performance, and increased hypermetria. Cutoff values were derived and applied to 15 subjects at risk for developing familial ataxia. Three of 15 showed abnormal values in three or more of four categories of ocular motor performance. Within 3 years, all three subjects were diagnosed on clinical grounds as having familial ataxia. We conclude that ocular motor performance is impaired in familial ataxia and may prove useful for earlier diagnosis.

Immediate-release and controlled-release carbidopa/levodopa in PD: a 5-year randomized multicenter study. Carbidopa/Levodopa Study Group.

OBJECTIVE: To compare effects of immediate-release (IR) and sustained-release (CR) carbidopa/levodopa in levodopa-naive PD patients. BACKGROUND: It was hypothesized that the long-acting preparation would be associated with fewer long-term complications. METHODS: A total of 618 patients were studied in 36 centers worldwide in a blinded, randomized parallel study. Measures of efficacy and adverse reactions were recorded at 3-month intervals for 5 years. Motor fluctuations and dyskinesias were evaluated by a patient diary and a physician-recorded questionnaire. The Nottingham Health Profile (NHP) was used to evaluate quality of life. RESULTS: Approximately 60% of patients completed the trial. After 5 years, the mean dose of IR was 426 mg/day, and the bioavailable dose of CR was 510 mg/day (mean dose, 736 mg/day). After 5 years, 20.6% of the IR group and 21.8% of the CR group had motor fluctuations or dyskinesia. Sixteen percent of both groups had changes in motor response by the questionnaire's definition. There was no significant difference between the two treatment groups. Disability scores and the motor score of the Unified Parkinson Disease Rating Scale (UPDRS) were highest at baseline, improved with therapy, and thereafter worsened over time to reach baseline scoring at the end of 5 years. The CR group was superior to IR for the Activities of Daily Living subsection of the UPDRS for all 5 years and for emotional reactivity and social isolation on the NHP; however, this may have resulted from higher doses of CR that were used. CONCLUSION: Despite the progressive nature of PD, both the immediate-release and sustained-release carbidopa/levodopa formulations maintained a similar level of control in PD after 5 years compared with baseline. Additionally, the low incidence of motor fluctuations or dyskinesia was not significantly different between the treatment groups and may be partly attributed to the relatively low doses of levodopa used throughout the 5-year study.

Head injury as a risk factor for Alzheimer's disease.

A case-control study was performed in which the frequency of prior head injury was assessed in 78 patients with dementia of the Alzheimer type (DAT) and 124 control subjects matched for age, sex, and race. A history of head injury with loss of consciousness was reported in 25.6% of patients and 5.3% and 14.6% of hospital and neighborhood controls, respectively. Matched-pair analysis of patients and hospital controls yielded an odds ratio of 4.50, which was significant (p less than 0.01). The ranges of times of occurrence of head injuries were similar in patients and controls, spanning several decades. The findings suggest a possible etiologic role for head injury in DAT.

Spatial contrast sensitivity is reduced in bilateral Parkinson's disease.

We studied the contrast sensitivity functions of 41 patients with idiopathic Parkinson's disease (PD) with a wide range of parkinsonian symptomatology (Hoehn and Yahr stages 1 to 4) and 22 age-matched control subjects in a parametric design. Results demonstrated reduced contrast sensitivity in PD patients but only in those patients who had progressed beyond Hoehn and Yahr stage 1. Furthermore, there were deficits in contrast sensitivity related to the severity of PD.

Contrast sensitivity dysfunction in Alzheimer's disease.

We compared the spatial contrast sensitivity of six patients with mild to moderate Alzheimer's disease (AD) and six age-matched control subjects in a parametric design. Results demonstrate reduced contrast sensitivity in patients with AD at all but the lowest frequency tested. The results suggest that the effect of AD on spatial contrast sensitivity is stronger at higher frequencies and provide a rationale for complaints of poor vision in AD patients.

Multicenter controlled study of Sinemet CR vs Sinemet (25/100) in advanced Parkinson's disease.

Controlled-release carbidopa/levodopa 50/200 (Sinemet CR) and standard carbidopa/levodopa (Sinemet 25/100) were compared in a multicenter double-blind trial involving 202 patients with advanced Parkinson's disease and motor response fluctuations. Treatment with Sinemet CR significantly reduced daily "off" time. According to both physician and patient global ratings, patients showed significant improvements with Sinemet CR compared to treatment with standard Sinemet. Patients preferred Sinemet CR treatment by a ratio of approximately 2 to 1. Daily dosing frequency was 33% less with Sinemet CR, while daily intake of levodopa required was increased by 25%. The safety profiles of the 2 formulations were similar. We conclude that Sinemet CR is superior to standard Sinemet for many patients with advanced Parkinson's disease, although it does not solve the problem of fluctuating motor performance.

Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.

Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.

Lateral saccadic latencies and handedness.

Lateral saccadic latencies were determined in 18 right-handers and 18 left-handers. Within the right-handed group the mean latency was significantly shorter when looking from the left to the right (242.7 msec) than from right to left (265.0 msec), whereas no significant directional difference was found in the left-handed group. An age effect was also found with longer latencies being associated with increased age. These findings agree with those of Pirozzolo and Rayner (Neuropsychologia 18, 225-229, 1980) and provide further evidence of the pervasiveness of functional asymmetry in the human brain. The present findings suggest that motoric or central integrative mechanisms may contribute more to saccadic directional asymmetries than do perceptual differences.

Families of Alzheimer's victims. Family support to the caregivers.

This study examined the instrumental and social-emotional support provided by families to the primary caregivers of Alzheimer's patients. It was anticipated that the more adequate the support provided by the family, the less sense of burden and the better the coping effectiveness of the caregiver. Ratings of instrumental assistance, social-emotional support, adequacy of support, and coping effectiveness were made by trained raters from transcribed interviews with 23 primary caregivers. Also, a second family member who was usually next closest of kin to the caregiver was interviewed in order to provide another perspective of the support the family provided. While the major caregiving tasks were performed by the primary caregiver, the types of assistance from family that seemed most appreciated were visits and having persons stay with the patient so that the caregiver could take a trip, rest, run errands, or get out of the house for social activities. The majority of caregivers felt a high degree of support from their families and reported low levels of emotional upset resulting from family support efforts. The most common family problems reported were lack of visits, disagreement over level of patient's mental and physical functioning, and disagreement over the type of care required. The data confirmed the hypothesis that family support was positively associated with the caregiver's coping effectiveness. In addition, caregivers who did not receive enough support were most burdened; however, the group receiving the greatest amount of support was the next most burdened, a finding which was unanticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the senile plaque in neuropeptide deficits of Alzheimer's disease.

Senile plaques participate in a cropping of the dendritic tree of enkephalinergic dentate granule cells and hl and subicular pyramidal cells. Somatostatin-containing pyramidal neurons are lost in Alzheimer's disease, whereas nonpyramidal somatostatin neurons are less affected. Fibers containing somatostatin penetrate immature, but not end-stage senile plaques. The senile plaque may precipitate much of the hippocampal denervation seen in Alzheimer's disease.

A novel, adaptable and inexpensive computerized activity meter.

A number of activity meters ranging from fully manual to fully automated have been described. A computerized activity meter, used primarily as a rotational activity chamber, is described. This inexpensive system is built around a Commodore 64 computer interfaced through a circuit board to the meters. Each computer can run four chambers and, as a rotometer, can distinguish quarter and full turns in either direction. The system is easily adapted to record data from various behavioral chambers, including an open field with photocell beams.