Showing papers by "William G. Ondo published in 2002"

A controlled trial of rasagiline in early Parkinson disease: The tempo study

Abstract: CONTEXT Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). OBJECTIVE To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. DESIGN Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. SETTING Academically based movement disorders clinics. PATIENTS Patients with early PD not requiring dopaminergic therapy (n = 404). INTERVENTION Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. MAIN OUTCOME MEASURE The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scal score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. RESULTS Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, -5.66 to -2.73 units; P<.001) and -3.56 units comparing a 2-mg dosage and placebo (95% confidence interval, -5.04 to -2.08 units; P<.001). There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups. CONCLUSIONS Rasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.

Exploring the relationship between Parkinson disease and restless legs syndrome.

Abstract: Background Restless legs syndrome (RLS) and Parkinson disease (PD) are common neurological conditions that respond to dopaminergic therapy. To our knowledge, the relationship between the two has not been thoroughly explored. Methods We consecutively queried 303 patients with PD seen in our clinic for the presence of RLS symptoms, and evaluated their condition with the Epworth Sleepiness Scale and other demographic and sleep measures. We then looked for predictors of RLS in these patients with PD. We also compared a larger group of patients with PD/RLS with a group of patients with RLS alone. Results Of 303 patients with PD, 63 (20.8%) had symptoms of RLS. Neither PD patient demographics nor PD treatments could reliably predict the development of RLS symptoms; however, lower serum ferritin levels were associated with RLS symptoms in our patients with PD (P= .01). In 54 (68%) of the 79 total patients with PD/RLS (including additional patients with PD/RLS seen in the clinic) with reliable age-at-onset data, the PD symptoms preceded the RLS symptoms (χ2test,P Conclusions Symptoms of RLS are common in patients with PD; however, except in patients with a family history of RLS, they seem to reflect a secondary phenomenon, perhaps in relation with lower ferritin levels. There is no evidence that RLS symptoms early in life predispose to the subsequent development of PD.

Olanzapine treatment for dopaminergic-induced hallucinations

Abstract: Atypical antipsychotic medications with lower affinities for D2 receptors are considered useful alternatives to treat drug-induced hallucinations in Parkinson's disease (PD). We conducted a double-blind, placebo-controlled, unforced titration, parallel design study (2:1 drug to placebo randomization ratio) using olanzapine (2.5-10 mg/day to effect) in 30 PD patients with drug-induced hallucinations. We performed an extensive battery of neuropsychological tests, the Unified Parkinson's Disease Rating Scale (UPDRS), assessments of on and off time at baseline and at 9 weeks after starting the medication. Sixteen patients on olanzapine (mean dose, 4.6 mg/night) and 11 on placebo completed the study. Compared with placebo, performance on the UPDRS item 2 (thought disorder), and a structured interview for hallucinations, both tended to improve on drug but neither reached statistical significance. A neuropsychological test battery did not show any significant differences. Total on UPDRS motor scores (P < 0.05) and timed tapping (P < 0.01) worsened while on drug compared to placebo. Bradykinesia (P < 0.01) and gait (P < 0.001) items on the UPDRS largely accounted for this deterioration. After completion of the study, 8 of 16 patients randomly assigned to drug continued olanzapine at a mean dose of 2.4 mg/day. However, at the last recorded visit only 5 of 24 (20.8%) of all patients exposed to drug (including those originally randomly assigned to placebo) remained on olanzapine. In patients with PD, low-dose olanzapine did not significantly improve hallucinations but did worsen motor function.

Tetrabenazine treatment for Huntington's disease-associated chorea

Abstract: Tetrabenazine (TBZ), a monoamine depleter and dopamine receptor blocker, is used to treat a variety of hyperkinetic movement disorders. The objective was to study the efficacy and tolerability of TBZ for chorea associated with Huntington's disease (HD). Nineteen patients (12 female), mean age 56.3 +/- 12.4 years (range 37-76 years) diagnosed with HD were prospectively evaluated at initial and follow-up visits using a modified Abnormal Involuntary Movement Scale (AIMS). Patients were videotaped, and the randomized videotapes were rated with the motor subset of the AIMS by two investigators who were blinded to treatment assignment. Eighteen patients completed and were rated after 5.9 +/- 3.3 months (range 2-11) at a final mean TBZ dose of 62.5 +/- 37.4 mg/day (range 25-150). The blinded videotaped motor scores showed that 15 were better on TBZ, 2 were better before TBZ, and 1 was unchanged (p < 0.001, Wilcoxon signed rank test). The mean score improved from 16.2 +/- 4.8 to 12.8 +/- 4.4. Adverse events included akathisia, insomnia, constipation, depression, drooling, and subjective weakness. All 18 of these patients have continued to take TBZ since completion of the study. TBZ was well tolerated and resulted in a significant improvement in modified AIMS scores in HD patients. These results support the use of TBZ for chorea in patients with HD.

Vascular parkinsonism: clinical correlates predicting motor improvement after lumbar puncture.

Abstract: Vascular parkinsonism (VP) is a poorly defined entity which has clinical, and perhaps pathological, overlap with other diagnoses. Although classical VP involves lesions of the basal ganglia, the majority of cases actually show diffuse subcortical white matter changes (SCWMC) on imaging. The exact pathologies of these white matter changes are debated and likely heterogeneous, but are generally thought to represent areas of chronic or recurrent partial ischemia. Cerebrospinal fluid (CSF) drainage is the treatment for NPH and has been reported to improve symptoms in some patients with idiopathic NPH and associated SCWMC. To determine whether historical, clinical, or radiographic factors predict improvement in VP patients after CSF drainage, we removed 35-40 ml of CSF via lumbar punctures (LP) from 40 patients and compared responders with nonresponders for a variety of demographics, clinical features, and blindly interpreted magnetic resonance images (MRI). Fifteen patients (37.5%) reported "significant and irrefutable" gait improvement after LP. Twelve (30.0%) reported no effect and 13 (32.5%) reported mild or very transient improvement. Timed gait in a subset of patients improved (P < 0.05) immediately after LP. Clinically, improvement after CSF removal was predicted by any positive response to levodopa (P < 0.001), the lack of vertical gaze palsies (P < 0.05), the lack of a pure freezing gait (P < 0.05), and the lack of hypotensive episodes (P < 0.05). Blinded MRI interpretation did not find features which clearly predicted response. Some patients diagnosed with VP improved after LP. Clinically, these patients tended to resemble idiopathic PD, whereas nonresponders more closely resembled progressive supranuclear palsy (PSP). These results warrant further investigation and also raise the possibility of testing CSF drainage in patients with idiopathic PD complicated by SCWMC.

Physiological assessment of paroxysmal dystonia secondary to subacute sclerosing panencephalitis.

Abstract: We report on a 26-year-old woman with subacute sclerosing panencephalitis (SSPE) who presented with frequent paroxysmal dystonic posturing. Electroencephalogram demonstrated generalized 5 to 10-second episodes of high-amplitude (150-300 microV) delta activity alternating with 10 to 20-second periods of theta activity (40-50 microV). The patient experienced episodes of dystonic posturing coinciding with the periods of delta activity. Ictal Tc-99m Ceretec SPECT demonstrated marked increased activity in the bilateral caudate (R>L). The frequency and amplitude of the episodes initially markedly improved after the addition of carbamazepine. We suggest that the movements seen in this case of SSPE may represent basal ganglia ictal activity.