The effects of the acute administration of clozapine on parkinsonian mixed tremor (i.e., resting and postural tremors) were evaluated to establish clozapine's predictive value for long-term response and to determine if there is a difference in the pharmacologic responses of the two tremors. We also investigated the correlation between reduction of tremor and induction of sedation after acute and chronic administration of clozapine. Clozapine (12.5 mg) or placebo were administered po in a double-blind manner to 17 PD patients with mixed L-dopa-resistant tremors. Two patients did not reach 50% improvement and were considered nonresponders. The remaining 15 patients reported moderate to marked reduction of tremor. Responsive patients in the acute test moved on to a long-term, open clozapine add-on study receiving an average daily dose +/- SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A significant reduction of both resting (p < 0.05) and postural (p < 0.05) tremors was observed under clozapine from the first week of treatment through the entire period of the study. There was no statistically significantly difference between the degree of improvement for resting and postural tremors after either single or chronic clozapine administration. Sedation was the only side effect reported after clozapine; however, the time courses of sedation and tremor reduction did not coincide in the acute or in the chronic experimental paradigm, where it decreased considerably in a few weeks in all patients. During long-term clozapine treatment, neither systemic side effects nor worsening of motor disability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with clozapine before defining a case of mixed parkinsonian tremor as resistant tremor and therefore resorting to a neurosurgical approach.
We report a patient with MELAS treated for 24 months with idebenone and riboflavin, during which no stroke-like episodes occurred. Moreover neurological symptoms clearly improved, and a recovery of brain MRI and EEG abnormalities was observed. We conclude that the combined treatment with idebenone and riboflavin may restore the metabolic impairment in MELAS, possibly improving the long-term prognosis in these patients.
Patients with essential tremor (ET) may not respond to commonly used drugs. Clozapine, an atypical neuroleptic drug, has been reported to improve postural Parkinson's disease tremor clinically resembling ET. The effects of a single dose of 12.5 mg clozapine and placebo were evaluated in a randomized, double‐blind, crossover study in 15 drug‐resistant patients with ET. Patient responders with more than 50% improvement after a single dose of clozapine subsequently received the drug (39 ± 9 mg up to 50 mg) unblinded for a period of 15.8 ± 7.7 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients (p <0.01). Sedation was the only side effect reported during the clozapine test; however, the time course of sedation and of the antitremor effect were not coincident. A significant reduction of tremor was reported with chronic clozapine treatment (p <0.01) with no tolerance to drug antitremor effect, whereas sedation markedly decreased after 6–7 weeks of therapy. No clozapine‐induced hematologic side effects were observed in our cohort of patients during long‐term treatment. Our results suggest that in selected drug‐resistant ET cases, clozapine should be considered before resorting to neurosurgical options.
The model can be easily applied when discharging patients who have been hospitalized after an access to the Emergency Department to predict the risk of rehospitalization within 30 days. The prediction can be used to activate focused hospital-primary care transitional interventions. The model has to be validated first in order to be implemented in clinical practice.
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