Reliability of a new scale for essential tremor.

BACKGROUND: The objective of this study was to determine the reliability of a new scale for the clinical assessment of essential tremor. The Essential Tremor Rating Assessment Scale contains 9 performance items that rate action tremor in the head, face, voice, limbs, and trunk from 0 to 4 in half-point intervals. Head and limb tremor ratings are defined by specific amplitude ranges in centimeters. METHODS: Videos of 44 patients and 6 controls were rated by 10 specialists on 2 occasions 1-2 months apart. Inter- and intrarater reliability was assessed with a 2-way random-effects intraclass correlation, using an absolute agreement definition. RESULTS: Inter- and intrarater intraclass correlations for head and upper-limb tremor ranged from 0.86 to 0.96, and intraclass correlations for total score were 0.94 and 0.96. The intraclass correlations for voice, face, trunk, and leg were less robust. CONCLUSIONS: This scale is an exceptionally reliable tool for the clinical assessment of essential tremor.

Tremor amplitude is logarithmically related to 4- and 5-point tremor rating scales.

Tremor rating scales (TRSs) are used commonly in the clinical assessment of tremor, but the relationship of a TRS to actual tremor amplitude has never been quantified. Consequently, the resolution of these scales is unknown, and the clinical significance of a 1-point change in TRS is uncertain. We therefore sought to determine the change in tremor amplitude that corresponds to a 1-point change in a typical 5-point TRS. Data from five laboratories were analysed, and 928 patients with various types of hand tremor were studied. Hand tremor was quantified with a graphics tablet in three different labs, an accelerometer in three labs and a mechanical-linkage device in one lab. Tremor in writing, drawing, horizontal posture, rest and finger-nose testing was graded using a variety of TRSs. The relationship between TRS scores and tremor amplitude was computed for each task and laboratory. A logarithmic relationship between a 5-point (0-4) TRS and tremor amplitude (T, measured in centimetres) was found in all five labs, despite widely varying rating scales and transducer methodology. Thus, T2/T1 = 10(alpha(TRS2-TRS1)). The value of alpha ranged from 0.414 to 0.441 for writing, 0.355-0.574 for spiral drawing, 0.441 to 0.488 for rest tremor, 0.266-0.577 for postural tremor and 0.306 for finger-nose testing. For alpha = 0.3, 0.4, 0.5, 0.6 and 0.7, the ratios T2/T1 for a 1-point decrease in TRS are 0.501, 0.398, 0.316, 0.251 and 0.200. Therefore, a 1-point change in TRS represents a substantial change in tremor amplitude. Knowledge of the relationship between TRS and precise measures of tremor is useful in interpreting the clinical significance of changes in TRS produced by disease or therapy.

Striatal deformities of the hand and foot in Parkinson's disease.

Striatal deformities of the hand and foot are abnormal postures that are common in patients with advanced Parkinson's disease (PD); they can present in the early stages of PD and in other parkinsonian disorders. Over a century ago, Charcot and Purves-Stewart recognised these deformities, which cause substantial functional disability and discomfort. The term striatal is used because pathology in the neostriatum (putamen and caudate) has been suggested to cause the deformities, but the pathogenesis is unknown. Misdiagnosis of the deformities is common-particularly when they occur early and in the absence of cardinal parkinsonian signs, such as tremor, bradykinesia, and rigidity-because the hand deformities are similar to those in rheumatoid arthritis, equinovarus foot deformity typically suggests an orthopaedic problem, and toe extension may be thought to be the Babinski sign of upper-motor-neuron syndromes. Here we review the background and clinical features of these deformities to highlight these commonly unrecognised and poorly understood parkinsonian signs.

Pleuropulmonary fibrosis after long-term treatment with the dopamine agonist pergolide for Parkinson Disease.

Dopamine agonists are increasingly used in the treatment of Parkinson disease, but they may cause serious adverse effects. In December 1983, symptoms of Parkinson disease developed in a 55-year-old man with no history of pulmonary disease, smoking, or asbestos exposure. He began treatment with dopamine agonists bromocriptine mesylate (in 1984) and pergolide mesylate (in 1989). In late 2000, pulmonary symptoms developed. Chest radiographs and computed tomographic findings showed a mass in the right upper lobe and effusion. A biopsy specimen showed pleural and parenchymal fibrosis. This syndrome resolved after cessation of pergolide therapy and a switch to pramipexole dihydrochloride. This case draws attention to the association of long-term ergot dopamine agonist therapy with pleuropulmonary fibrosis, which can develop as late as 11 years after the initiation of therapy. We also review evidence that the risk of this complication is substantially lower with the newer nonergot dopamine agonists.

Dopamine agonists in Parkinson's disease.

Levodopa (LD), the immediate precursor of dopamine, is the most effective agent in the treatment of Parkinson's disease (PD). While quite successful in treating the primary motor deficits of PD, most patients eventually develop LD-related motor fluctuation, dyskinesias and other adverse effects associated with chronic LD therapy. There is also concern that LD is neurotoxic, although this has not been demonstrated in any in vivo studies. Dopamine agonists (DAs) have been shown to be about as effective as LD in symptomatic treatment of mild-to-moderate PD. In addition, there is a lower tendency to develop motor fluctuations and dyskinesias with DA treatment than after initiation of therapy with LD. Furthermore, there is preclinical and clinical data to suggest a slowing of neurodegeneration with DAs. The adverse effects of DAs are similar to those experienced with LD, except that the ergot agents are associated with a small risk of tissue fibrosis not noted with the non-ergot DAs.

Benefits and risks of pharmacological treatments for essential tremor.

Essential tremor can cause significant functional disability in some patients. The arms are the most common body part affected and cause the most functional disability. The treatment of essential tremor includes medications, surgical options and other forms of therapy. Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor. Treatment for essential tremor is recommended if the tremor causes functional disability. If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability. The currently available medications can improve tremor in approximately 50% of the patients. If the tremor is disabling, treatment should be initiated with either primidone or propranolol. If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination. If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used. If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit. Other medications that may be helpful include gabapentin or topiramate. If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor. Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used. There are other medications that have been tried in essential tremor and have questionable efficacy. These drugs include carbonic anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine. If the patient still has disabling tremor after medication trials, surgical options are usually considered. Surgical options include thalamotomy and deep brain stimulation of the thalamus. These surgical options provide adequate tremor control in approximately 90% of the patients. Surgical morbidity and mortality for these procedures is low. Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation. In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures. The use of medication and/or surgery can provide adequate tremor control in the majority of the patients.

Tetrabenazine treatment for Huntington's disease-associated chorea.

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.

Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease.

We completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg/day) and 12 weeks (200 mg/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies.

Treatment options for Parkinson's disease.

PURPOSE OF REVIEW: Parkinson's disease is a common neurodegenerative disorder. Clinical trials designed to assess the safety and efficacy of novel neuroprotective as well as symptomatic medical and surgical strategies are being performed to increase and enhance treatment options. The purpose of this review is to summarize these therapeutic options, emphasizing reports published in the last year. RECENT FINDINGS: Experimental therapeutics in Parkinson's disease has focused on prevention of levodopa complications, treatment of dyskinesias associated with levodopa therapy, surgical intervention and neuroprotection. SUMMARY: There are at least four important implications of the recent therapeutic trials: (1) the incidence of levodopa-related dyskinesias decreases as a result of initial use of dopamine agonists; (2) surgery, primarily in the form of the bilateral, high-frequency stimulation of the subthalamic nucleus, is highly effective in patients who are responsive to levodopa but experience marked motor fluctuation or other complications; (3) while neuroprotection has not yet been demonstrated with any currently used therapeutic agent, improved understanding of mechanisms of cell death will undoubtedly result in the discovery of new drugs with potential disease-modifying effects; and (4) implantation of fetal mesencephalon tissue and other grafts may be effective in younger patients with Parkinson's disease, but is associated with significant complications and remains experimental.

Intrafamilial phenotypic variability of the DYT1 dystonia: from asymptomatic TOR1A gene carrier status to dystonic storm.

When primary torsion dystonia is caused by a GAG deletion in the TOR1A gene (DYT1 dystonia), it typically presents with an early-onset dystonia involving distal limbs, subsequently spreading to a generalized dystonia. We describe a large family with an unusually broad variability in the clinical features of their dystonia both with regard to severity and age of onset. The proband of this family succumbed in his second decade to malignant generalized dystonia, whereas other family members carrying the same mutation are either asymptomatic or display dystonia that may be focal, segmental, multifocal, or generalized in distribution. One family member had onset of her dystonia at age 64 years, probably the oldest reported in genetically confirmed DYT1 dystonia. We conclude that marked phenotypic heterogeneity characterizes some families with DYT1 dystonia, suggesting a role for genetic, environmental, or other modifiers. These findings have implications for genetic testing and counseling.