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PubMed1984

Tremor as a feature of chronic relapsing and dysgammaglobulinemic polyneuropathies. Incidence and management.

Seven patients with chronic relapsing polyneuropathy and four patients with dysgammaglobulinemic polyneuropathy had tremor during the course of their illness. The tremor was coarse, irregular, and unrelated to proprioception loss, muscle weakness, or fatigue; it appeared to represent disease activity or an early sign of a new relapse. None of these patients had clinical signs of CNS disease or family history of essential tremor. The tremor in all seven patients with relapsing neuropathy and in one of the three treated patients with dysgammaglobulinemia responded to immunosuppressive drugs that controlled the underlying immune mechanism(s) of the disease. In two patients with dysgammaglobulinemic polyneuropathy, the tremor improved with propranolol hydrochloride.

Adolescent↗
PubMed1998

Diagnostic criteria for essential tremor: a population perspective.

BACKGROUND: Prevalence estimates vary 2750-fold among the 20 studies of essential tremor (ET). It is not clear how the choice of diagnostic criteria affects research results. OBJECTIVE: To determine the impact of alternative sets of diagnostic criteria on the diagnosis of ET. METHODS: As part of the Washington Heights-Inwood Genetic Study of ET (WHIGET), a population-based study of ET, 285 subjects who include 36 case subjects with probable or definite ET, 34 case subjects with possible ET, and 215 normal subjects were interviewed and examined. All diagnoses in WHIGET were assigned by 2 neurologists. Ten of the 20 published prevalence studies of ET provided diagnostic criteria for ET. Criteria differed in terms of requirements for the distribution, duration, and severity of tremor. These 10 sets of criteria were then each separately applied to the subjects in the WHIGET cohort to determine their impact on the diagnosis of ET. RESULTS: Depending on which diagnostic criteria were applied to the WHIGET cohort, the proportion of WHIGET case subjects with definite or probable ET who would have been diagnosed as having ET was as low as 14% and the proportion of WHIGET normal subjects who would have been diagnosed as having ET was as high as 51%. Diagnostic criteria that included a positive family history of ET or a lengthy duration of tremor would have classified many WHIGET case subjects with ET as normal, whereas criteria that did not specify a minimal tremor severity would have classified many WHIGET normal subjects as having ET. CONCLUSIONS: Alternative sets of diagnostic criteria for ET greatly impact on the diagnosis of ET. For population-based studies, information on tremor type and severity rather than family history should be included in diagnostic criteria.

Adolescent↗
PubMed1999

A new twist for stopping the shakes? Revisiting GABAergic therapy for essential tremor.

Aside from physiological tremor, essential tremor (ET) is by far the most common cause of tremor in humans, affecting large numbers of individuals in every human population. The crude prevalence of ET has been conservatively estimated to be between 0.4% and 3.9%, although some estimates of the prevalence of ET among the elderly are higher than 20%. Essential tremor is the most prevalent adult-onset movement disorder, and is also regarded as one of the most common neurological disorders of adults, with a prevalence that is similar to or greater than that of stroke, Alzheimer disease, migraine headache, and lumbosacral pain syndromes. Essential tremor is as much as 20 times more prevalent than Parkinson disease.

Acetates↗
PubMed2002

Body mass index in essential tremor.

BACKGROUND: The pathogenesis of essential tremor (ET) is unknown, but it could be neurodegenerative. Weight loss has been observed in patients with neurodegenerative diseases. OBJECTIVES: To compare body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) in ET cases and controls and to determine whether BMI is correlated with tremor severity and duration. METHODS: Patients with ET were ascertained from the Neurological Institute of New York, New York, NY. Control subjects were recruited from 2 studies at the same institution. Height and weight were measured and BMI was calculated. Dietary data were collected using a Willett Semi-Quantitative Food-Frequency Questionnaire. Tremor severity was assessed using a clinical scale and the Klove Matthews Motor Steadiness Battery. RESULTS: The 78 cases and 242 controls were of similar age. Mean (SD) BMI in cases vs controls was 26.5 (5.0) vs 28.2 (4.8) (P =.008). This difference remained significant in an unconditional linear regression analysis that adjusted for age, sex, ethnicity, and years of education (P =.02). Mean daily caloric intake was similar in cases and controls. In cases, BMI was negatively correlated with both measures of tremor severity (r = -0.22; P =.05 and r = -0.24; P =.03) and with tremor duration (r = -0.22; P =.05). CONCLUSIONS: The BMI was lower in ET cases than in controls, and lower BMI was associated with disease of greater severity and longer duration. Caloric intake did not differ between groups, suggesting that lower BMI is not due to a reduction in calories. Lower BMI may be due to increased energy expenditure in ET.

Aged↗
PubMed1999

Three-dimensional measurement of essential tremor.

A mechanical linkage device was used to measure the three-dimensional position of the fingertip during a postural task. Thirty patients with essential tremor were tested simultaneously with the device, uniaxial accelerometry, and clinical tremor measures. Eighteen patients were tested again 16+/-4 days later. The device accurately recorded the three-dimensional behavior of essential tremor. Measures from the device included mean three-dimensional velocity, mean three-dimensional dispersion, and power of the three-dimensional acceleration. The logarithms of these measures were strongly correlated (r = .841-.984) with all clinical measures including self-reported tremor disability. The device measures were reliable within and between testing sessions (intraclass correlation coefficients = .971-.977). The performance of the device was superior to uniaxial accelerometry, most likely as a result of the three-dimensional nature of the measurements. We conclude that essential tremor can be validly and reliably quantified during a postural task providing the recording device records movement in three dimensions and the measurements are logarithmically transformed.

Acceleration↗
PubMed2000

Thalamic tremor: correlations with three-dimensional magnetic resonance imaging data and pathophysiological mechanisms.

Tremor associated with a single focal thalamic lesion has rarely been reported. Furthermore, the exact localization of the lesions is difficult to determine because of the imprecision of "conventional" radiology (computed tomography scan and/or "standard" magnetic resonance imaging). The aim of this study was to identify which thalamic structures are involved in tremor associated with a single focal thalamic lesion. We selected two patients who presented with unilateral postural and kinetic tremor of the upper limb related to a localized thalamic infarction. Three-dimensional T1-weighted magnetic resonance imaging sequence (MP-RAGE sequence) was used to determine the precise topography of the lesions by stereotactic analysis using the atlas of Hassler. The lesions were located within the pulvinar, the sensory nuclei, the mediodorsal nucleus, and the ventral lateral posterior nucleus (according to the classification of Hirai and Jones), the latter including the ventral intermediate nucleus (Vim according to the classification of Hassler). However, the Vim was spared. The subthalamic area, which can induce tremor, was not involved. After having compared the topography of the lesions with the clinical findings, we suggest that thalamic tremors may result from the interruption of the cerebellar outflow tract to the Vim within the thalamus.

Adult↗
PubMed2001

Suppression of harmaline-induced tremor in rats by vagus nerve stimulation.

We studied whether vagus nerve stimulation could suppress tremor in the harmaline tremor model in the rat. Animals were chronically implanted with helical leads around the left vagus nerve and a disk-shaped electrode positioned subcutaneously in the dorsal neck. Harmaline-induced tremor was recorded on a physiograph while each animal received a sequence of five 20-minute trials. Each trial consisted of five minutes of pre-stimulation baseline, five minutes of vagus nerve stimulation, and ten minutes of post-stimulation. Vagus nerve stimulation significantly suppressed harmaline-induced tremor. The suppressive effect was present within the first minute of stimulation and was reproducible across the five trials of the study. The results of this study suggest that the central generator or expression of tremor in the harmaline animal model can be suppressed by vagus nerve stimulation.

Animals↗
PubMed2003

Mirtazapine in essential tremor: a double-blind, placebo-controlled pilot study.

We sought to determine whether mirtazapine is safe and well-tolerated as a treatment for essential tremor (ET). We studied mirtazapine in a randomized, double-blind, placebo-controlled, crossover study of 17 ET patients. Patients were started with 15 mg per day of either mirtazapine or placebo for 1 week and the dose was escalated weekly until the targeted dose of 45 mg per day was achieved. This dose was maintained for 2 weeks. Tremor was assessed at baseline and after 14 days of 45 mg of mirtazapine or placebo. There was a minimum washout period of 14 days between the two arms of the study. Tremor assessments included global improvement, Fahn Tolosa Marin Tremor Rating Scale, Beck Depression Inventory and the Parkinson's Disease Questionnaire-39. Patient global improvement ratings indicated that in the placebo condition 12 patients were unchanged and 1 patient was mildly improved. In the mirtazapine condition, 10 patients were unchanged, 2 were moderately improved and 1 was markedly improved. There was no significant improvement with mirtazapine or placebo compared to baseline as measured by the Tremor Rating Scale. Adverse effects were more common in the mirtazapine group and included drowsiness, confusion, dry mouth, weight gain, polyuria, itching, nausea, gait and balance problems, blurred vision, and bad taste. We conclude that the majority of the ET patients do not benefit from mirtazapine. Mirtazapine has significant adverse effects and should be used cautiously in ET patients.

Aged↗
PubMed2001

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor.

Our objective was to investigate the long-term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential tremor. Forty-nine patients were evaluated for DBS between December 1993 and March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and then yearly. Three patients were not implanted, seven were explanted prior to 24 months, 11 were lost to long-term follow-up, and three died from unrelated causes. Twenty-five patients were evaluated with follow-up greater than or equal to 2 years. The last postsurgical follow-up occurred on average 40.2 +/- 14.7 months after surgery. Tremor scores were significantly improved with stimulation on at the long-term follow-up as compared to baseline. There was no change in tremor scores from baseline to long-term follow-up with stimulation off. There was no significant change in any stimulus parameters from 3 months to the long-term follow-up. Three patients had asymptomatic intracerebral hemorrhages and one patient had postoperative seizures. Stimulus-related adverse reactions were mild and easily controlled with changes in stimulus parameters. Device-related complications were common and required repeated surgical procedures. Unilateral DBS of the thalamus has long-term efficacy in some patients for treatment of essential tremor. However, this therapy is compromised by loss of efficacy in some patients and device complications which increase the risk of additional surgical procedures.

Adult↗
PubMed2001

Comparison of clinical vs. electrophysiological methods of diagnosing of essential tremor.

Essential tremor (ET) may be differentiated from normal or enhanced physiological tremor based on a clinical examination or electrophysiological tests such as quantitative computerized tremor analysis. There have been few head to head comparisons of the two methods. Our objective was to estimate diagnostic agreement between these two methods. Cases and controls underwent a clinical evaluation (interview and videotaped examination) and an electrophysiological evaluation (quantitative computerized tremor analysis using accelerometry and electromyography) on the same day, and diagnoses were independently assigned using clinical vs. electrophysiological criteria. Agreement between diagnoses was assessed with a concordance rate and kappa statistic (kappa).Thirty-two (59.3%) of 54 subjects were diagnosed clinically as ET (possible, probable, or definite), compared with 35 (64.8%) of 54 based on tremor analysis. The concordance rate between the two methods of diagnosis was 94.4% (51 of 54). Kappa was 0.88, indicating a level of agreement between diagnoses that was in the "near perfect" range. All of the subjects who received electrophysiological diagnoses of definite ET also received clinical diagnoses of ET. Conversely, all of the subjects who received clinical diagnoses of definite ET also received electrophysiological diagnoses of ET. The agreement between the clinical and electrophysiological diagnosis of ET was substantial, suggesting that study protocols that were to utilize either technique would arrive at similar diagnostic conclusions. In addition, physiological testing can quantify potentially valuable subclinical measurements as well as detect possible additional cases of ET not diagnosed as such during clinical assessments.

Adult↗
PubMed2005

Bilateral subthalamic nucleus deep brain stimulation in a patient with cervical dystonia and essential tremor.

The role of subthalamic nucleus (STN) deep brain stimulation (DBS) is well established in Parkinson's disease, but experience with STN DBS in other movement disorders is limited. We report on a patient with medically refractory cervical dystonia and essential tremor resulting in dystonic head tremor and action tremor of the hands who obtained complete tremor suppression and near resolution of her cervical dystonia with bilateral STN stimulation. The results in this case demonstrate that STN DBS can dramatically improve dystonia and tremor in nonparkinsonian movement disorders.

Adult↗
PubMed2005

Clinical and neurophysiologic spectrum of orthostatic tremor: case series of 26 subjects.

Orthostatic tremor (OT) is a condition described as high-frequency tremors predominantly in the legs and trunk, which are present not only in the standing position but also during isometric contraction of the limb muscles. This report is one of the largest OT series describing clinical and neurophysiologic findings in 26 subjects with OT. The main findings included 13.0 to 18.6 Hz leg tremors while standing with varied patterns of phase relationships between the antagonists of the ipsilateral leg and between the homologous muscles of the contralateral leg, short latency tremor onset upon standing with abrupt cessation after sitting, coexistence of tremors in the cranial structures and the arms, and sense of unsteadiness without actual falls. Although the oscillator of OT is most likely located in the brainstem, cerebral cortex, basal ganglia, and cerebellum may also be involved in its pathogenesis.

Aged↗
PubMed2005

John Adams' essential tremor.

John Adams (1735-1826), one of the signers of the Declaration of Independence, was the second President of the United States. Adams had tremor for many years, about which little has been written. We examined John Adams' penmanship over a 62-year period and studied his correspondence and diaries. It is not clear when Adams' tremor began, although in a diary entry dated 6 December 1760, when Adams was 25 years old, there is evidence of low-amplitude kinetic tremor. The tremor continued in his written correspondence, becoming more persistent over time. Later in life, the clarity of his written correspondence diminished, with greater decomposition of characters and a reduction in the size of individual characters. This finding raises some speculation as to whether Adams could have been developing some parkinsonism, although the evidence in favor of this is not compelling. The most likely diagnosis was essential tremor.

Essential Tremor↗
PubMed2006

Effect of amantadine in essential tremor: a randomized, placebo-controlled trial.

There is a need for new medication for essential tremor (ET). Preliminary evidence suggests that amantadine may be effective in the treatment of ET. We studied the effects of amantadine in a double-blind, cross-over, placebo-controlled trial in ET patients. Sixteen patients with ET received amantadine 100 mg b.i.d. and placebo for 15 days, with a 1-week wash-out period between treatments. Major evaluation outcomes consisted of a tremor clinical rating scale, accelerometric recordings, and a self-reported disability scale obtained before drug intake and on study days 1 and 15 of each treatment period. A two-way repeated measures analysis of variance (treatment, time) was applied. Any P value < 0.05 was considered significant. On day 15, amantadine did not demonstrate any significant efficacy in reducing tremor with respect to baseline in any tremor measures. An increase in postural tremor as an adverse effect of amantadine was referred by 37.5% of patients. Results from the present trial indicate amantadine at 100 mg b.i.d. is not effective as a treatment for ET.

Aged↗
PubMed2006

Orthostatic tremor during modification of standing.

Primary orthostatic tremor (OT) occurs only during standing. We studied whether modification of the condition standing influences OT. In seven patients with OT, surface EMG was recorded from both tibialis anterior and gastrocnemius muscles during two maneuvers: relief, whereby the patient was gradually lifted by a crane, and tilting, whereby the patient was tilted by a tilting table to positions of 90 degrees (upright standing), 45 degrees (diagonal position), and 0 degrees (lying position). We determined the parameters tremor frequency, tremor intensity, coherence, and phase shift between the different muscles. Relief did not influence OT. In contrast, tilting modified significantly tremor intensity and phase shifts; tremor frequencies and coherences were not influenced. We chose both these maneuvers because of their different impact on the standing condition: relief modifies the factors afferent input and muscle forcing but not the factor postural set, whereas tilting modifies all three factors. The fact that tilting modifies OT, whereas relief does not, suggests an important role of postural set in OT generation. Afferent input and muscle forcing seem to play less important role.

Afferent Pathways↗
PubMed2006

HS1-BP3 gene variant is common in familial essential tremor.

Essential tremor (ET) is a movement disorder characterized by a postural or kinetic tremor of the hands, head, or voice. It is typically a familial condition and affects 1% to 4% of the general population. The trait is genetically linked to chromosome 2p in some families. A variant (828C-->G) in exon 7 of the hematopoietic-specific protein 1 binding protein 3 gene (HS1-BP3) on chromosome 2p recently has been found to segregate with ET in 2 families. To determine the frequency of this variant in a larger series, we studied patients with ET, Parkinson disease (PD), and controls without tremor. Affected singletons representing 73 families from the United States with dominantly inherited ET, 35 individuals with PD, and 304 healthy controls older than age 60 were tested for the 828C-->G variant in exon 7 of the HS1-BP3 gene by a BseYI restriction enzyme digest of the polymerase chain reaction product. Heterozygous carriers of the mutant allele were identified in 12 individuals with ET (16.4%) and in 1 individual with PD and postural tremor (3%). All of the healthy controls (608 chromosomes) were homozygous for the wild-type allele. The 828C-->G genetic variant in the HS1-BP3 gene occurs relatively frequently in subjects with ET. The variant may also be found in some individuals with PD and postural tremor. The HS1-BP3 gene plays a putative role in regulating catecholamine and serotonin metabolism, but the functional consequences of the amino acid substitution (A265G) caused by this genetic variant is unknown.

Aged↗
PubMed2006

Blinded placebo crossover study of gabapentin in primary orthostatic tremor.

Primary orthostatic tremor (OT) is a rare but disabling condition characterized by leg tremor and feelings of instability during stance. Previous studies have reported a reduction in OT symptoms with gabapentin treatment. In this study, we report on the benefits of gabapentin treatment in a double-blind placebo-controlled crossover study of 6 OT patients. First, the maximally effective gabapentin dosage (600-2,700 mg/day) for each patient was determined during an initial dose-titration phase. Patients were then studied 7 days after drug withdrawal and again after two 2-week periods of treatment with either gabapentin or placebo, using force platform posturography to quantify postural sway and tremor. Other medications for OT were continued unchanged. Symptomatic response was assessed by a patient-rated severity scale and quality of life (QOL) questionnaire. All patients reported an increase in symptoms during the washout phase and symptom reduction (50%-75%) during gabapentin treatment. Tremor amplitude was reduced to 79% +/- 11% and sway area to 71% +/- 11% of the placebo state. QOL improved in all patients, no adverse drug effects were noted, and symptomatic benefit was maintained at follow-up (mean = 19 months). The findings confirm that gabapentin is an effective treatment for OT, reducing both tremor and postural instability and improving quality of life, and support its use as add-on or first-line therapy for OT.

Aged↗
PubMed2006

Neurosurgical treatment of tremor in mitochondrial encephalopathy.

A 53-year-old woman underwent several ischemic stroke-like episodes and later developed incomplete, bilateral ophthalmoplegia, left vision deterioration, and bilateral tremor. The clinical course, laboratory data, and muscle histology led to a diagnosis of mitochondrial encephalomyopathy. No other etiology could be identified in the background of her disabling bilateral postural-kinetic tremor. As this tremor did not respond to pharmacological therapy, left thalamotomy and subsequently right thalamic deep brain stimulator (DBS) implantation were performed, which resulted in an excellent clinical outcome. The Fahn-Tolosa-Marin Tremor Rating Scale improved from 110 to 11 points. This case suggests that the rare tremor caused by mitochondrial encephalopathy may be treated long-term with either thalamotomy or thalamic DBS implantation.

Electric Stimulation Therapy↗