Calcium channel blockers and beta-blockers in relation to Parkinson's disease. A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. A controlled trial of isoniazid therapy for action tremor in multiple sclerosis. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. Antihypertensive agents and risk of Parkinson's disease, essential tremor and dementia: a population-based prospective study (NEDICES). A Randomized Trial Oral Propranolol versus Metroprolol in Treatment of Neurally Medicated Cyncope. Double-blind comparison of cabergoline and bromocriptine in Parkinson's disease patients with motor fluctuations. Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.
We investigated the risk of Parkinson's disease (PD) associated with calcium channel blockers (CCBs) and beta-blockers in a population-based case-control study of 206 men and women between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 controls without PD or other neurodegenerative disorders who were frequency matched on age, sex, duration of GHC enrollment and clinic. The adjusted odds ratio associated with ever use was 0.85 (95% confidence interval [CI]: 0.43, 1.66) for CCBs, and 1.20 (95% CI: 0.71, 2.03) for beta-blockers. We observed no association with PD risk for either class of medication in terms of duration, dose, number of prescriptions or pattern of use. The weakness of these associations and the absence of additional influence of dose or duration of use argue against any causal interpretation. The aim of this study was to assess the efficacy of lipophilic beta-blockers in preventing recurrent neurocardiogenic syncope and the value of head-up tilt test (HUT) in predicting response to therapy. The efficacy of beta-blockers in recurrent syncope is controversial. The value of HUT in predicting efficacy of therapy has not been investigated. Fifty-six patients (44+/-18 years, 36 women) with recurrent syncope (> 1 event in the last 6 months) of suspected neurocardiogenic origin were included in the study. Independent of the response to HUT, patients were randomized to receive metoprolol or propanolol at the maximal tolerated dose (28 patients, group A, 86+/-23 vs 98+/-29 mg/d) or no pharmacological therapy (28 patients, group B). The primary endpoint was the first recurrence of syncope. During the 1-year of follow-up, 20 patients of group A and 8 of group B had no recurrence. In group A, of 20 patients without recurrences 12 had a positive and 8 a negative HUT result while of 8 patients with recurrences 5 had a positive and 3 a negative response to HUT. In the group B, of 20 patients with recurrences 10 had a positive and 10 a negative HUT result while of 8 patients without recurrences 4 had a positive and 4 a negative response to HUT. In a multivariate Cox-regression analysis, medical therapy was the only independent factor for predicting recurrence of syncope (P = 0.004); HUT had no influence in this regard (P = 0.773). In conclusion, lipophilic beta-blockers appear efficacious in preventing recurrent syncope of suspected neurocardiogenic origin. The efficacy of therapy seems to be not predicted by HUT. Ten patients with clinically definite multiple sclerosis (MS) and action tremor were treated with isoniazid (INH) in a double-blind single crossover trial. The daily dose of INH administered during the 4-week treatment phase of the trial was determined by acetylator phenotype with slow acetylators receiving 12 mg/kg per day and rapid acetylators 20 mg/kg per day. Six of eight patients who completed the trial showed clinical improvement in the postural (alternating) tremor while on INH but the degree was minimal in all cases. Results of tremograms indicated that improvement also occurred in the intentional (synchronous) component of three patients while on INH, but this did not achieve statistical significance. Cerebrospinal fluid (CSF) levels of gamma-aminobutyric acid (GABA) homocarnosine and ornithine were markedly elevated with INH therapy (providing evidence for substantial inhibition of GABA aminotransferase activity and increase in GABA in the CNS), but no correlation was found between the degree of GABA elevation in the CSF and the clinical response. Side effects were minimal and well tolerated. Although INH appears to have a limited therapeutic role, a trial is warranted in MS patients with postural tremor. Deep-brain stimulation through an electrode implanted in the thalamus was developed as an alternative to thalamotomy for the treatment of drug-resistant tremor. Stimulation is thought to be as effective as thalamotomy but to have fewer complications. We examined the effects of these two procedures on the functional abilities of patients with drug-resistant tremor due to Parkinson's disease, essential tremor, or multiple sclerosis.
                Sixty-eight patients (45 with Parkinson's disease, 13 with essential tremor, and 10 with multiple sclerosis) were randomly assigned to undergo thalamotomy or thalamic stimulation. The primary outcome measure was the change in functional abilities six months after surgery, as measured by the Frenchay Activities Index. Scores for this index can range from 0 to 60, with higher scores indicating better function. Secondary outcome measures were the severity of tremor, the number of adverse effects, and patients' assessment of the outcome.
                Functional status improved more in the thalamic-stimulation group than in the thalamotomy group, as indicated by increases in the score for the Frenchay Activities Index (from 31.4 to 36.3 and from 32.0 to 32.5, respectively; difference between groups, 4.4 points; 95 percent confidence interval, 2.0 to 6.9). After adjustment for base-line characteristics, multivariate analysis also showed that the thalamic-stimulation group had greater improvement (difference between groups, 5.1 points; 95 percent confidence interval, 2.3 to 7.9). Tremor was suppressed completely or almost completely in 27 of 34 patients in the thalamotomy group and in 30 of 33 patients in the thalamic-stimulation group. One patient in the thalamic-stimulation group died perioperatively after an intracerebral hemorrhage. With the exception of this incident, thalamic stimulation was associated with significantly fewer adverse effects than thalamotomy. Functional status was reported as improved by 8 patients in the thalamotomy group, as compared with 18 patients in the thalamic-stimulation group (P=0.01).
                Thalamic stimulation and thalamotomy are equally effective for the suppression of drug-resistant tremor, but thalamic stimulation has fewer adverse effects and results in a greater improvement in function. Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson's disease (PD) or dementia. There are no data for essential tremor (ET).
                To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease).
                Prospective population-based study in Spain enrolling 5,278 participants at baseline.
                Use of antihypertensive medications (aside from beta-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not associated with prevalent or incident PD. Calcium channel blocker use was marginally reduced in prevalent dementia cases (OR(adjusted) = 0.63, p = 0.06) but was not associated with reduced risk of incident dementia (RR(adjusted) = 1.02, p = 0.95).
                We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders.
                Copyright 2009 S. Karger AG, Basel. Beta-blockers has been claimed to be useful in chronic prophylaxis of neurally mediated syncope with frequent recurrences. However, efficacy of cardioselective and non-cardioselective beta-blockers has never been compared in a randomized study.
                From October 2003 to December 2004, 62 patients (32 men, mean age 44.8 +/- 19.3 years) who had at least one episode of syncope per month during previous 6-months and had positive tilt test were enrolled in this study. The patients were randomly assigned to receive either propranolol (Group I, n = 31) or metoprolol (Group II, n = 31). After one month, efficacy of treatment was also tested by a repeat head-up tilt test (HUTT).
                There were no statistically significant differences between the two groups with respect to the HUTT pattern (P=0.25) and requirement for sublingual NTG during test (P=0.20). After one month of treatment, oral beta-blockers prevented the occurrence of syncope during second HUTT in 11 patients (35.5%) in the Group I and 9 (29%) patients in the Group II (P=0.58) and delayed the occurrence of symptoms in 9 Group I patients (29%) and 8 Group II patients (16%) (P=0.77). During the 16-months follow-up, 53 patients (85.5%) remained free of syncope. No statistically significant difference was observed between the two groups with respect to recurrence of syncope (P=0.47). In both groups, the patients in whom treatment efficacy was proved by a negative tilt test had similar recurrence of syncope as those patients who had a positive tilt test (Both P>0.05).
                Both cardioselective and noncardioselective oral beta-blockers were similarly effective in preventing recurrence of syncope in patients with neurally-mediated syncope. In both groups, HUTT performed one month after the treatment had no role in prediction of responders. In the present study we compared the efficacy and safety of the new dopamine agonist cabergoline (CBG) with bromocriptine (BCR) in Parkinson's disease (PD). CBG has a very long half-life and can be administered as a single daily dose. Forty-four PD patients with uncontrolled motor fluctuations participated in the study. Patients were randomly and blindly assigned to equivalent doses of either CBG or BCR in addition to preexisting levodopa. Dosage was titrated to optimal, using up to 6 mg of CBG or 40 mg of BCR daily. CBG was given as a single morning dose whereas BCR was administered tid. Sixteen patients were followed for 1 year and 16 additional patients for 6 months. The mean follow-up duration was 9 +/- 5 months. The main effect of both drugs was observed on motor UPDRS scores, rigidity, bradykinesia items, and the percentage of awake hours spent during "on" and "off". In general, the effect of CBG was similar to that of BCR. The percentage of awake hours spent during "on" was higher with CBG as compared with BCR. Adverse events included dyskinesias, orthostatism, confusion, edema, and paresthesias in limbs. These effects were seen at similar frequencies with both drugs. The study shows that CBG given as a single morning dose is at least as efficacious as BCR given tid. CBG is a promising dopamine agonist for the treatment of motor fluctuations in PD. Six patients with severe postural cerebellar tremor were studied in a double-blind, placebo-controlled, crossover trial with isoniazid. Each phase of the study lasted 4 weeks, and in the isoniazid phase patients received an increasing dose up to 1200 mg/d. Patients were studied with self-rating scales, quantitative tremor recording, and blinded ratings of videotapes. All patients improved by at least one method, three improved by all methods, and four improved sufficiently to want to continue with the drug after the trial was finished. There is a definite, but limited, therapeutic role for isoniazid. Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs.
                To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients.
                A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden.
                Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments.
                Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.
In view of this lack of evidence, it is impossible to determine whether beta-blocker therapy is effective and safe for the treatment of tremor in Parkinson's disease. The high frequency of bradycardia in one trial raises some concerns about the prescription of beta-blockers to normotensive elderly patients but the study was too small for the true degree of risk to be calculated.