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Estrogen Reduces Motor Disability in Women With Parkinson's Disease

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WESTPORT, Jul 13 (Reuters Health) - Chinese researchers have found that low-dose estrogen therapy is a safe and effective adjunct to existing therapy in postmenopausal patients with Parkinson's disease associated with motor fluctuations. The findings, from a prospective study, are reported in the June 27th issue of Neurology.

Dr. Sing-Kai Lo, from Queen Mary Hospital in Hong Kong, and colleagues explain that although previous studies have suggested that estrogen modulates levels of nigrostriatal dopamine, its effects on Parkinson's disease are unclear.

The investigators carried out a randomized, placebo-controlled trial in order to test the efficacy of low-dose oral conjugated estrogen therapy in 40 postmenopausal women with Parkinson's disease and associated motor fluctuations. Patients were randomized either to 0.625 mg Premarin daily or to placebo over a period of 8 weeks, during which existing antiparkinsonian treatment regimens were left unaltered.

Patients' diaries revealed that low-dose estrogen treatment led to a significant increase in "on" times and a reduction in "off" times, the authors report. These observations were backed up by similar improvements in motor scores, as assessed using subscale III of the Unified Parkinson's Disease Rating Scale.

The research team obtained similar results when they studied a subset of patients with predictable motor fluctuations, although the "improvement in mean subscale III score was marginally not significant." All adverse events were mild and resolved without alterations in treatment.

Dr. Lo's team concludes that "although the improvement observed in motor control did not translate into global improvement...a larger and longer prospective study would be helpful in determining the long-term effects of estrogen in this population."

Neurology 2000;54:2292-2298.

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Remacemide Safe, but Ineffective, as Monotherapy for Parkinson's Disease

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WESTPORT, Apr 25 (Reuters Health) - Remacemide, an investigational therapy for Parkinson's disease, appears to be safe but offers little symptomatic benefit as monotherapy, according to a report in the April 25th issue of Neurology.

Remacemide is a low-affinity NMDA channel blocker that has shown efficacy in combination with low-dose levodopa in animal models of Parkinson's disease, the authors explain. As a glutamate receptor antagonist, it may also have neuroprotective properties.

Dr. Steven R. Schwid, from the University of Rochester in New York, and other members of The Parkinson Study Group compared results from the use of 150-mg, 300-mg or 600-mg daily doses of remacemide with placebo in 200 patients with idiopathic Parkinson's disease who did not require treatment with levodopa or other antiparkinsonian medications.

Patients were able to tolerate up to 600 mg of remacemide daily, the results indicated. That highest dose was more readily tolerated when divided into four 150-mg doses than when given as two 300-mg doses.

The most common side effects associated with remacemide treatment were dizziness, nausea, and vomiting, the investigators report. Remacemide-treated patients also experienced more sleepiness and insomnia than patients in the placebo group did. None of the patients had any serious side effects from any treatment.

There were no differences among treatments in relieving Parkinson's disease symptoms, as measured by the Unified Parkinson's Disease Rating Scale, activities of daily living scales, and patient and clinician Clinical Global Impression scales, the researchers note.

"It is possible that higher dosages or longer treatment periods could produce more benefit," the authors suggest. "Based on its favorable safety profile and several animal studies, further studies of remacemide are warranted as symptomatic therapy in levodopa-treated patients and as a neuroprotective agent," they conclude.

"If ongoing studies confirm that remacemide used in conjunction with dopaminergic therapy improves patients' symptoms, it may be the first of a new class of Parkinson's therapies," Dr. Schwid said in a news release. "If it is also proved to have neuroprotective qualities by preventing the progression of the disease, it could be an even more significant advance in the treatment of Parkinson's disease."

Neurology 2000;54:1583-1588.

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Pallidotomy for Parkinson's Disease Provides Long-Term Benefits

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WESTPORT, Jun 09 (Reuters Health) - Parkinson's disease patients who undergo unilateral pallidotomy realize sustained improvements in some symptoms, according to a report in the June 8th issue of the New England Journal of Medicine.

Several studies report significant improvements during the first year after pallidotomy for intractable Parkinson's disease, but little is known about the long-term outcomes of the procedure, the authors explain.

Dr. Jennifer Fine from the University of Toronto, in Ontario, Canada, and colleagues examined the outcome of unilateral posteroventral medial pallidotomy for medically intractable Parkinson's disease in 20 patients who were followed for 41 to 64 months after surgery.

The mean levodopa-equivalent doses of medications between baseline and the final study visit did not differ, the authors report.

Overall, off-period Unified Parkinson's Disease Rating Scale (UPDRS) scores were 18% better at follow-up than at baseline, the report indicates. However, the researchers detected a trend toward loss of improvement. For example, an improvement of 37.4% over baseline was recorded at 6-month follow-up.

Significant improvements in off-period motor scores, contralateral bradykinesia, tremor, and rigidity were sustained throughout the follow-up, the investigators note, whereas activities of daily living-improvements during the first 6 months were lost in the ensuing months.

On-period contralateral dyskinesia also improved between baseline and the final evaluation, the researchers observe, but there were no long-term benefits in ipsilateral off-period or on-period motor function (including dyskinesia).

Patient age, disease duration, or overall baseline off-period UPDRS score did not correlate with long-term outcomes. "This...is disappointing," Dr. Fine's team comments, "because it provides no insight into the optimal selection of patients for the procedure."

"Our study confirms that the amelioration of contralateral parkinsonian symptoms and medication-related dyskinesia after pallidotomy is sustained for up to 5.5 years," the authors conclude. "Improvements in ipsilateral and axial symptoms are not sustained, and many patients undergo a second, contralateral procedure."

"Pallidotomy is nevertheless a useful treatment in selected patients with medically intractable Parkinson's disease," they add.

N Engl J Med 2000;342:1708-1714.