Orthostatic tremor: a review of 45 cases.

OBJECTIVE: To evaluate the clinical characteristics, associated features, and treatment response of a large orthostatic tremor series seen over a 26-year period. METHODS: We reviewed the medical records of 45 patients seen between 1987 and 2013 who fulfilled the diagnostic criteria for orthostatic tremor. RESULTS: The mean age at onset was 59.5 years and 23/45 (51%) were men. A family history of any tremor was noted in 23/45 (51%) patients. A family history of orthostatic tremor was reported in 3/45 (7%) patients. 40/45 (89%) had primary orthostatic tremor with (n = 30) or without (n = 10) an associated postural arm tremor. We found that 5/45 (11%) had orthostatic tremor plus additional neurological features. One patient was diagnosed with dementia with Lewy bodies preceded by orthostatic tremor for 20 years. Prospective follow-up data was available for 30/45 patients and averaged 54.4 months. Treatment response to medications was modest and inconsistent. In 11/30 cases, orthostatic tremor worsened over the follow-up period. One patient with primary orthostatic tremor underwent thalamic deep brain stimulation surgery. CONCLUSIONS: In our population of orthostatic tremor patients, mild postural hand tremor was a frequent finding. Over half of our patients had a family history of tremor, but a family history of orthostatic tremor was uncommon. Additional neurological features were seen in the minority of patients and we report possibly the first case of dementia with Lewy bodies associated with orthostatic tremor. Our series is the largest series of orthostatic tremor reported in the literature and contributes to understanding the clinical characteristics of this rare disease.

Amplitude fluctuations in essential tremor.

OBJECTIVE: To assess temporal amplitude variability in patients with essential tremor (ET). METHODS: Patients who satisfied the diagnostic criteria for probable or definite ET were enrolled in the study. Each enrolled patient was first rated using the essential tremor rating assessment scale (TETRAS). Postural and kinetic tremors of the arms were then measured using a quantitative motor assessment system (QMAS) starting at 8:00 AM (T0-baseline) every 2 h for 6 h. Subjects were videotaped performing the tasks. Single subjects consecutively performed each assessment twice during every time-interval. At the end of the study, videos were randomized and blindly rated using TETRAS. RESULTS: Twelve ET subjects were enrolled. QMAS and video scores were directly correlated with high test-retest reliability for each time-interval. Furthermore, the QMAS scores at T0 significantly correlated with in-person rated TETRAS scores as well as with subsequent time-intervals instrumental scores. No significant differences were detected between time-intervals QMAS average measurements using ANOVA. There was a maximal 23% absolute variation in tremor amplitude from baseline as determined by the QMAS. Test for equality of variance showed high measurement variability for subjects with high QMAS scores at T0 and throughout the 6 h of assessment. CONCLUSIONS: Baseline measures are predictive of tremor amplitude at subsequent assessments during the day. High amplitude tremor is associated with high intra-assessment variability.

The many faces of hemifacial spasm: differential diagnosis of unilateral facial spasms.

Hemifacial spasm is defined as unilateral, involuntary, irregular clonic or tonic movement of muscles innervated by the seventh cranial nerve. Most frequently attributed to vascular loop compression at the root exit zone of the facial nerve, there are many other etiologies of unilateral facial movements that must be considered in the differential diagnosis of hemifacial spasm. The primary purpose of this review is to draw attention to the marked heterogeneity of unilateral facial spasms and to focus on clinical characteristics of mimickers of hemifacial spasm and on atypical presentations of nonvascular cases. In addition to a comprehensive review of the literature on hemifacial spasm, medical records and videos of consecutive patients referred to the Movement Disorders Clinic at Baylor College of Medicine for hemifacial spasm between 2000 and 2010 were reviewed, and videos of illustrative cases were edited. Among 215 patients referred for evaluation of hemifacial spasm, 133 (62%) were classified as primary or idiopathic hemifacial spasm (presumably caused by vascular compression of the ipsilateral facial nerve), and 4 (2%) had hereditary hemifacial spasm. Secondary causes were found in 40 patients (19%) and included Bell's palsy (n=23, 11%), facial nerve injury (n=13, 6%), demyelination (n=2), and brain vascular insults (n=2). There were an additional 38 patients (18%) with hemifacial spasm mimickers classified as psychogenic, tics, dystonia, myoclonus, and hemimasticatory spasm. We concluded that although most cases of hemifacial spasm are idiopathic and probably caused by vascular compression of the facial nerve, other etiologies should be considered in the differential diagnosis, particularly if there are atypical features.

Tardive dyskinesia and other movement disorders secondary to aripiprazole.

The objective of this report is to draw attention to tardive dyskinesia (TD) caused by aripiprazole, a third generation antipsychotic. TD has been traditionally attributed to typical (first-generation) antipsychotics, but other dopamine receptor blocking drugs and atypical (second- and third-generation) neuroleptics are emerging as an important cause of TD. We reviewed the medical records of patients with TD seen at the Baylor College of Medicine Movement Disorders Clinic between 2002 and 2010 to identify patients with TD associated with aripiprazole. Among 236 patients with TD seen over the specified period, 8 (3.4%) were found to have aripiprazole-associated TD. In 5 patients, TD occurred after exclusive exposure to aripiprazole. The mean age at onset was 55.8 ± 14.8 years with a female predominance. The average duration of treatment with aripiprazole was 18.4 ± 26.4 months. Oro-bucco-lingual stereotypy was seen in all patients. In most patients, TD did not spontaneously improve after stopping aripiprazole. Of the 5 patients treated with tetrabenazine, 4 improved during follow-up. Although aripiprazole, a third generation antipsychotic, has been promoted to have a low risk of TD, the drug accounts for about 3.5% of patients with TD evaluated in a movement disorders clinic. This largest reported series draws attention to the growing incidence of TD and other drug-induced movement disorders associated with "atypical antipsychotics."

Thalamic deep brain stimulation for orthostatic tremor.

BACKGROUND: Orthostatic tremor is an uncommon disorder manifest by high frequency, low amplitude leg tremor upon weight bearing. Treatment with oral tremor agents is inconsistent and usually not satisfactory. METHODS: We implanted bilateral ventralis intermedius nuclei deep brain stimulators into an 82-year-old male with refractory orthostatic tremor. RESULTS: The patient had a marked subjective and objective improvement in leg and arm tremor, mainly manifested by an improved ability to stand. DISCUSSION: Bilateral thalamic deep brain stimulation may be considered in refractory cases of orthostatic tremor.

The use of gabapentin enacarbil in the treatment of restless legs syndrome.

Restless legs syndrome (RLS) is a common sleep-related neurological disorder that is characterized by the urge to move, worsening at rest, improvement with activity, and worsening in the evening and night. Dopamine agonists are usually the first-line therapy. Other agents including benzodiazepines, narcotics, and anticonvulsants have been used to treat RLS. Gabapentin has been shown to improve RLS in a small number of clinical studies, but is limited by its short half-life and variable bioavailability. Gabapentin enacarbil is a novel prodrug of gabapentin designed to overcome these pharmacokinetic limitations. In vitro and in vivo studies have demonstrated that gabapentin enacarbil has improved absorption, bioavailability and pharmacokinetics compared with gabapentin. Phase II and III studies have demonstrated that gabapentin enacarbil is generally well tolerated and is useful in the treatment of RLS.

Neuroprotection trials in Parkinson's disease: systematic review.

Treatments to slow the progression are a major unmet need in Parkinson's disease. Detailed assessment of randomized trials testing putative neuroprotective drugs was undertaken to inform the design, reporting, and interpretation of future studies. This study is a systematic review of trials testing neuroprotective drugs. Data were extracted independently by two coauthors. Fifteen completed, published trials involving 4,087 participants tested 13 different drugs in 18 double-blind comparisons with placebo. Seven comparisons involving 2,000 subjects assessed MAO-B inhibitors. The primary outcome was change in the Unified Parkinson's Disease Rating Scale score in eight trials and time to need for dopaminergic therapy in seven. Mean participant age was 62 years, 35% were women, the interval from diagnosis to entry averaged 11 months, and the number of participants averaged 272 (largest = 806). Follow-up averaged <16 months in all but two trials. Detailed randomization methods and success of double-blinding were reported in 20% and 13%, respectively. Based on the investigators' conclusions, six trials were interpreted as consistent with a neuroprotective effect, three as negative, and five as either confounded or not meeting criteria for futility. Neuroprotection trials have involved relatively uniform groups of participants early in the clinical disease course, with outcomes weighted heavily toward motor deterioration. Future trials should include participants with wider ranges of disease stages and assess broader neurological outcomes.