Family History Of Tremor Research Articles

Tremor is associated with familial clustering of dystonia

IntroductionDystonia is a movement disorder of variable etiology and clinical presentation and is accompanied by tremor in about 50% of cases. Monogenic causes in dystonia are rare, but also in the group of non-monogenic dystonias 10–30% of patients report a family history of dystonia. This points to a number of patients currently classified as idiopathic that have at least in part an underlying genetic contribution. The present study aims to identify clinical and demographic features associated with heritability of yet idiopathic dystonia. MethodsSeven hundred thirty-three datasets were obtained from the DysTract dystonia registry, patients with acquired dystonia or monogenic causes were excluded. Affected individuals were assigned to a familial and sporadic group, and clinical features were compared across these groups. Additionally, the history of movement disorders was also counted in family members. Results18.2% of patients reported a family history of dystonia. Groups differed in age at onset, disease duration and presence of tremor on a descriptive level. Logistic regression analysis revealed that tremor was the only predictor for a positive family history of dystonia (OR 2.49, CI = 1.54–4.11, p < 0.001). Tremor turned out to be the most common movement disorder in available relatives of patients, and presence of tremor in relatives was associated with tremor in index patients (X2(1) = 16.2, p < 0.001). ConclusionsTremor is associated with an increased risk of familial clustering of dystonia and with a family history of tremor itself. This indicates a hereditable dystonia-tremor syndrome with a clinical spectrum ranging from tremor-predominant diseases to dystonia.

Balance and cognitive impairments are prevalent and correlated with age in presurgical patients with essential tremor

IntroductionEssential tremor (ET) was long considered a monosymptomatic disorder, but this view has given way to a more comprehensive clinical picture that involves consideration of non-tremor symptoms (e.g., balance impairment, cognitive impairment). Recently, the novel designation of “ET-plus” was proposed to reclassify ET patients who demonstrate these non-tremor clinical features, but the prevalence of ET-plus remains poorly defined. The primary aim of our study was to estimate the prevalence of ET-plus among presurgical patients with ET by applying this reclassification scheme. MethodsWe performed a retrospective review of patients with ET being considered for deep brain stimulation or focused ultrasound thalamotomy. Patient demographics and data from their clinical workups were collected. As part of their clinical workup, patients were screened for preexisting balance and cognitive impairment. Patients with ET were designated as ET-plus if they had balance impairment, cognitive impairment, or tremor at rest. We performed a series of Pearson correlations to examine how individual clinical and demographic variables were related. ResultsWe identified 92 patients who met the study criteria. Our results indicate that 87% of the presurgical patients in our cohort met the criteria for reclassification as ET-plus. In addition, we observed robust correlations between patient age and balance impairment, cognitive impairment, history of falls, family history of tremor, and ET-plus reclassification. ConclusionWe propose that balance and gait impairment should be assessed preoperatively alongside neuropsychological evaluation to improve the counseling and treatment of patients with ET-plus.

Clinical Reasoning: A 65-Year-Old Woman With Tremor.

A 65-year-old woman was referred to our hospital for the evaluation of tremor, which had initially appeared in her right upper limb 3 years previously and progressed to her left upper limb and head 2 years previously. The tremor was most prominent during movement, but also occurred during rest. The patient felt unsteady when walking, although she denied falling and slowness of movement and symptoms of dysautonomia (e.g., positional lightheadedness, urinary dysfunction). She reported that her short-term memory had worsened and that the tremor intruded on her activities of daily living. The patient reported no medical history or previous trauma, hypoxic insult, or neurotoxic exposure, and no drug or alcohol use. There was no family history of tremor.

Exploring essential tremor: Results from a large online survey

IntroductionEssential tremor (ET) is one of the most common movement disorders; however, many patients are misdiagnosed and do not receive effective treatment. It is important to better understand the diagnosis, symptoms and treatment patterns to improve care for those with ET. MethodsPersons in the International Essential Tremor Foundation database were invited to complete an online survey, focusing on symptoms, diagnosis, and treatment of ET. ResultsThe survey was emailed to 19,206 persons, with 2864 (14.9%) respondents. Mean age was 65.4 years, median age of tremor onset was 36–40 years, 61% were women, and 64% had a known family history of tremor. Forty-five percent saw multiple physicians before a diagnosis of ET with 65% being diagnosed by a neurologist. Current care is provided by a neurologist in 42%, a family physician in 26% and 28% do not see a physician for ET. Tremor was most commonly reported in the hands/arms (95%). The most commonly affected daily activities included writing, eating, drinking and carrying. Beta-blockers were the most commonly used treatment (42%); however, 33% had no benefit and 35% discontinued due to side effects. Of note, 33% had never received treatment for their tremor. ConclusionThis survey highlights the need for more effective treatments with greater tolerability. Increased awareness among physicians and patients in the diagnosis and treatment of ET is also warranted, with nearly half the respondents seeing multiple physicians before receiving an ET diagnosis and nearly 30% not seeing a physician and/or not receiving treatment for ET.

Isolated Voice Tremor: A Clinical Variant of Essential Tremor or a Distinct Clinical Phenotype?

BackgroundThe consensus statement by the Task Force on Tremor of the International Parkinson and Movement Disorder Society excludes individuals with “isolated voice tremor” as a clinical variant of essential tremor (ET). This clinical viewpoint presents a rationale for reconsideration of “isolated voice tremor” as a clinical variant of ET.MethodsEvidence from the literature was extracted to characterize the clinical phenotype of “isolated voice tremor,” or essential vocal tremor (EVT). Clinical features were extracted from relevant literature available at pubmed.gov using the terms “EVT,” “essential voice tremor,” “primary voice tremor,” and “organic voice tremor.”ResultsThe average age of onset in those with EVT was older than 60 years (range 19–84 years), with 75–93% being female. The typical duration of vocal tremor ranged from 1 to 13 years (average 6 years). The distribution of structures exhibiting tremor included the larynx, soft palate, pharynx, and base of tongue in the majority of patients, with some exhibiting tremor of the head and respiratory musculature. The condition of tremor occurred during speech and quiet respiration in 74% of individuals. Rate of tremor ranged from 4 to 10 Hz. Nearly 70% reported onset of vocal tremor prior to upper limb involvement. Family history of tremor was reported in 38–42% of individuals.DiscussionThose previously classified with EVT demonstrate a similar familial history, rate, tremor classification, and body distribution of ET. EVT is proposed as a clinical variant of ET in the pattern of onset and progression of body distribution from the midline cranial to spinal neural pathways.

Climbing fiber-Purkinje cell synaptic pathology across essential tremor subtypes

BackgroundEssential tremor (ET) is heterogeneous in nature and cases may be subdivided based on clinical features. ET patients may thus be subdivided by age of onset, family history of tremor, and presence of head tremor. We recently described climbing fiber-Purkinje cell (CF-PC) synaptic abnormalities in ET; however, these CF pathological features have not been studied across different ET subtypes. ObjectivesTo explore whether these CF-PC synaptic abnormalities differ across ET subtypes. MethodsWe studied two climbing fiber (CF-PC) synaptic pathologies (CF synaptic density and percentage of CFs in the parallel fiber [PF] territory) in the cerebella of 60 ET cases with a range of clinical presentations and 30 age-matched controls. ResultsCompared to controls, ET cases had lower CF synaptic density and a higher percentage of CFs in the PF territory. ET cases with tremor onset <50 years and tremor onset ≥ 50 years did not differ significantly with respect to CF synaptic density and percentage of CFs in the PF territory. Similar results were found when comparing familial vs. sporadic ET cases, and ET cases with head tremor vs. those without head tremor. Among all ET cases, lower CF synaptic density was associated with lower PC counts and higher torpedo counts. In addition, higher percentage of CFs in the PF territory was associated with lower PC counts and higher torpedo counts. ConclusionsThese findings support the notion that changes in the distribution of CF-PC synapses are broadly part of the neurodegenerative process in the ET cerebellum.

Tremor in a Bassoonist: Tremor in Dystonia or Essential Tremor?

Dear Editor, Tremor is a common clinical feature in dystonia. It can be seen in both affected and unaffected body parts in patients with dystonia. Clinically, it may not be easily distinguishable from essential tremor, currently defined as a bilateral, largely symmetric postural or kinetic tremor involving the hands and forearms that is visible and persistent, with an associated or isolated head tremor in the absence of abnormal posturing [1]. Efforts to differentiate these types of tremor include using neurophysiological tests such as somatosensory temporal discrimination threshold (TDT) testing, electromyography, accelerometry and reciprocal inhibition [2,3]. In patients with dystonia, TDT values have been found to be prolonged, postulated to reflect abnormalities in the basal ganglia [2,4-6]. On the other hand, investigations on patients diagnosed with essential tremor have revealed TDT values to be normal in those with upper limb tremor [2,7]. To illustrate the use of TDT in tremor diagnosis, we report a case of tremor in a 48-year-old right-handed man. His symptoms began 12 years prior to consult, initially task-specific, beginning in the left hand while playing the bassoon. The tremor progressed to involve both hands, the head, voice and trunk, often simultaneously. Tremor and head pulling to the right would worsen with manual activities and emotional stress. He was seen by several neurologists and was given varying diagnoses of dystonia and essential tremor. Sodium oxybate dampened the tremor, but had to be discontinued due to side effects. Current medications included propranolol extended-release 60 mg daily, topiramate 100 mg twice daily, clonazepam 1 mg twice daily and escitalopram 20 mg daily. The patient’s past medical history was positive for depression, alcoholism (sober for the past eight years) and asthma. There was no family history of tremor, and both parents have a history of strokes. He is a smoker, works as a priest, is separated and lives alone. Exam revealed mildly depressed affect, bradyphrenia and intermittent word-finding difficulty. The Montreal Cognitive Assessment score was 23/30 with errors in the following domains; executive, attention, language, and delayed recall. A high-frequency, asymmetric postural and kinetic tremor was noted in both upper extremities and trunk, as well as a vocal tremor. Right head tilt was present, most prominent on playing the bassoon. There were no sensory tricks. Bilateral arm posturing was noted with walking, greater on the right (Supplementary Video in the Online-only Data Supplement). Magnetic resonance imaging of the brain and a dopamine transporter single photon emission computed tomography scan were performed, which were both unremarkable. He did not undergo DYT gene testing. Somatosensory TDT testing was performed at our institution, with the patient appropriately focusing his attention on the task (reporting one stimulus vs. two). The mean and range (215.83 ± 14.29 ms) of the thresholds for bilateral upper extremities were markedly prolonged, compatible with the results seen in patients with dystonia (110 ± 31.3 ms) [2]. Our case illustrates a tremor in a 48-year-old man that was first noticed to occur in the left hand when playing the bassoon, eventually involving both hands, the head, voice and trunk. Differentiating tremor in dystonia from essential tremor based on clinical criteria alone can be difficult, as both types of tremor are often symmetric, postural and kinetic and the dystonia may not be obvious on initial examination. TDT testing may be a useful tool for this purpose, along with other neurophysiological testing methods [2]. Prolonged thresholds have been found in various dystonia phenotypes, including cervical dystonia, writer’s cramp, blepharospasm, musician’s dystonia and spasmodic dysphonia [2,4]. The dramatically prolonged TDT results, the cervical dystonia noted on examination and the history of nearly simultaneous onset of tremor in the neck and upper extremities suggest that this is likely tremor in dystonia. We are ascribing his cognitive problems to depression, but this aspect will require continued attention. Differentiating tremor in dystonia from essential tremor is important in considering treatment options and further testing, including genetic counseling. Thus, TDT may be another useful neurophysiological tool in making this distinction.

Isolated vocal tremor as a focal phenotype of essential tremor: a retrospective case review.

BackgroundEssential tremor (ET) is a common condition associated with significant physical and psychosocial disability. “Classic” ET is a clinical syndrome of action tremor in the upper limbs and less commonly the head, jaw, voice, trunk, or lower limbs. Current diagnostic criteria for ET exclude isolated vocal tremor (IVT). Failure to recognize IVT as a form of ET may contribute to misdiagnosis and missed opportunities for treatment.MethodsWe conducted a retrospective review of cases referred for voice disturbance. Patients with a primary diagnosis of vocal tremor were included while those with a diagnosis of spasmodic dysphonia where excluded.Results19 cases of vocal tremor were identified, of which 17 patients (89%) were female. The average age of vocal symptom onset was 64 (SD 8.0) and patients had been symptomatic an average of 6 years (SD 4) at their initial visit. 8 patients had IVT while 11 also had evidence of subtle head or limb tremor. 8 patients (42%) had a family history of ET, with vocal tremor specifically identified in 5 of those cases (26%). 11 patients (58%) noted transient tremor improvement after alcohol consumption. Primidone and propranolol were the most common medications prescribed to these patients prior to consultation. 7 patients were given a trial of 1 gm of sodium oxybate in the office as part of a clinical trial, with at least mild improvement in vocal tremor noted by qualitative assessment.ConclusionsET may present as vocal tremor with little or no associated limb tremor. It may be a more common manifestation of ET in women. A family history of tremor and improvement in tremor after consuming alcohol can often be elicited on history. We propose that IVT may be part of the spectrum of ET.Electronic supplementary materialThe online version of this article (doi:10.1186/s40734-015-0016-5) contains supplementary material, which is available to authorized users.

Orthostatic tremor: a review of 45 cases.

To evaluate the clinical characteristics, associated features, and treatment response of a large orthostatic tremor series seen over a 26-year period. We reviewed the medical records of 45 patients seen between 1987 and 2013 who fulfilled the diagnostic criteria for orthostatic tremor. 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. 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.

A clinical study of non-parkinsonian tremor in Moroccan patients

ObjectiveTo report the characteristics of the most frequent tremors in a population of Moroccan patients. BackgroundTremor is the most common movement disorder. It implies a wide variety of disorders with Parkinson's disease and essential tremor being the most frequent. MethodsA retrospective study of 148 patients with tremor referred to our movement disorders outpatient clinic was performed. Clinical features and treatment regimens were analyzed. Patients with parkinsonian tremor were excluded. ResultsWe included 62 patients with non-parkinsonian tremor. The etiologies were as follows: essential tremor (54.8%), dystonic tremor (19.4%), tremor associated with dystonia (14.5%), enhanced physiological tremor (3.2%), cerebellar tremor (3.2%), psychogenic tremor (3.2%) and Holmes’ tremor (1.6%). The characteristics of essential tremor patients were analyzed. Female patients accounted for 67.6% of patients. Mean age at the onset of tremor was 52.2±16.4 years. Family history of tremor was reported in 17.6% of cases. Tremor affected the arms (94.1%), head (52.9%), voice (35.3%) and legs (8.8%). Tremor was bilateral in 87.5% but was asymmetrical in 50% of patients. Patients had postural tremor (76.5%), kinetic tremor (79.4%) and rest tremor (associated in 11.8%). Treatment relied on propranolol (88.3%), primidone (14.7%), gabapentin (14.7%), clonazepam (14.7%), alprazolam (11.8%), topiramate (5.9%) and, in one patient, radiosurgery. ConclusionsEssential tremor was the predominant diagnosis, confirming its high prevalence. There was a predominance of female patients and a peak of age at onset in the fifth and sixth decades. Asymmetry of the disease was noted in half of patients.

Tremor associated with Klinefelter syndrome —/INS; A case series and review of the literature

Background: Previous case series suggested a link between Klinefelter syndrome (KS) and essential tremor (ET) or an ET-like syndrome. Methods: We investigated three KS-patients with tremor including tremor-analyzes and discuss our data in context to findings from a literature review. The clinical outcome after deep brain stimulation (DBS) is also reviewed. Results: Tremor in KS is predominantly a postural and kinetic tremor that resembles ET. Our patients were further characterized by absent family history for tremor in first degree relatives, lack of subjective alcohol responsiveness inquired by history, and tremor onset in childhood. One of our patients and two cases from literature improved after DBS of the ventral intermediate nucleus (VIM) of the thalamus. Conclusions: Tremor in KS shares several features with ET. If other characteristics such as family history, alcohol responsiveness, and age at tremor onset may serve as discriminating factors from ET, needs to be further investigated. First observations suggest that VIM-DBS may be efficacious.

Prevalence of Essential Tremor on Arosa Island, Spain: a Community-based, Door-to-Door Survey.

The prevalence of essential tremor (ET) is still not well understood and the various studies performed to date have generated highly variable results. Few epidemiologic studies on the prevalence of ET have been reported from Spain. A one-stage door-to-door survey was conducted on Arosa Island, northwestern Spain, to determine the prevalence of ET in the population aged 65 years and older. The diagnostic criteria for ET were the presence of non-dystonic head tremor or moderate- to severe-amplitude tremor on at least four tests of the revised Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) Scale. A total of 65 individuals with ET (28 males, 37 females) were identified, resulting in a crude prevalence of 8.63% (adjusted rate 8.42%). Prevalence increased with advancing age. There were no significant differences in prevalence between sexes in any of the age groups. Among the prevalent cases, 12.3% (n = 8) had been previously diagnosed. Only 29.2% (n = 19) reported functional disability caused by tremor. A family history of tremor was reported in 35.4% (n = 23). The prevalence of ET was higher than that seen in similar populations in Spain and other countries. A high proportion of those with ET were previously undiagnosed. Since Arosa Island has been a relatively isolated area, these results might indicate a predominant role, at least in the elderly, for genetic factors in the development of ET.

Family history of idiopathic REM behavior disorder

To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort. A total of 316 patients with polysomnography-confirmed iRBD were recruited from 12 RBD study group centers, along with 316 controls matched on sex and age group. All subjects completed a self-administered questionnaire that collected proxy-reported information on family history of tremor, gait trouble, balance trouble, Parkinson disease, memory loss, and Alzheimer disease. The questionnaire also included a single question that asked about possible symptoms of RBD among first-degree relatives (siblings, parents, and children). A positive family history of dream enactment was reported in 13.8% of iRBD cases compared to 4.8% of controls (odds ratio [OR] = 3.9, 95% confidence interval [CI] 2.0-7.7). ORs were increased for both siblings (OR = 6.1, 95% CI 2.1-18.1) and parents (OR = 3.2, 95% CI 1.4-7.8). We found no significant difference in sex, current age (65.3 ± 10.2 vs 66.9 ± 10.2 years), or age at self-reported RBD onset (55.2 ± 11.7 vs 56.6 ± 15.1 years) in possible familial vs sporadic iRBD. No differences were found in family history of tremor, walking and balance troubles, Parkinson disease, memory loss, or Alzheimer disease. We found increased odds of proxy-reported family history of presumed RBD among individuals with confirmed iRBD. This suggests the possibility of a genetic contribution to RBD.

An unusual presentation of tremor and heart block

An 86-years-old lady presented to hospital with a new onset generalised tremor predominantly involving her upper limbs, the right side more than the left, for about 2 weeks. The tremor was postural – occurred during maintenance of a position against gravity and increased with intention or action i.e. writing, eating etc. She was finding it difficult to hold a tumbler or write a shopping list. Tremor was getting worse to the extent that they adversely affected her day-to-day routine activities. She did not have any associated motor or sensory symptoms. She had no cardiac, respiratory, gastrointestinal or urinary symptoms. There was no history of similar episodes in the past. Her past medical history included ischemic heart disease, hypertension, non insulin dependent diabetes mellitus (NIDDM) and osteoarthritis. She was on aspirin, doxazosin, gliclazide and temazepam. She did not have any known allergies. She had no family history of tremor. She did not smoke and did not consume alcohol. She lived alone in a house and was independently mobile and self-caring. She was in good health and had not seen her GP for sometime.

Early abnormalities in 123I-ioflupane (DaTSCAN) imaging in the fragile X-associated tremor ataxia syndrome (FXTAS): a case report

The fragile X-associated tremor/ataxia (FXTAS) is a late onset neurodegenerative disorder, occurring in male carriers of a premutation expansion (50–200 repeats CGG) in the fragile X mental retardation 1 (FMR1) gene [1], and clinically characterized by phenotypic predominance of either cerebellar ataxia or intention tremor, and variably associated with other features, such as parkinsonism, peripheral neuropathy, autonomic dysfunction and dementia [1]. MRI studies have shown T2-weighted periventricular, subcortical white matter changes, with a specific involvement of middle cerebellar peduncles [1]. The underlying mechanism of FXTAS-associated parkinsonism remains unclear. 123I-ioflupane (DaTSCAN) imaging studies have shown contrasting patterns. In some cases with clear tremor and parkinsonism, DAT scans have been normal [2, 3] although rarely they can be abnormal [4, 5]. In these cases, there has been suggestion of the involvement of the basal ganglia, specifically the dopaminergic system projecting to the putamen. Here, we describe a patient carrying a premutation of FMR1 (82 CGG repeat) and presenting only subtle clinical signs of tremor and typical MRI features and clearly abnormal DaTSCAN examination. A 65-year-old Italian man was admitted to our hospital for the recent appearance of a mild bilateral tremor at upper extremities, which did not impair daily function, and with a genetic confirmation of FMR1 (Xq27.3) premutation (82 CGG repeat expansions). The patient was tested for FMR1 mutations since his daughter was diagnosed with fragile X syndrome with mental retardation at onset. His medical history was not notable for hypertension, hyperlipidemia and thyroid dysfunction. Childhood and adolescent development were normal and his school performance was good. No family history of tremor or movement disorder was reported. General physical examination findings were notable for normal blood pressure without abnormal orthostatic changes. Neurological examination revealed mild action tremor of the upper extremities, with a prevalence of the right arm (7–11 Hz). A moderate rigidity was detected at upper extremities (right [ left). No bradykinesia was detected. Synergy, trajectory, and placement of upperand lower-extremity movements were normal. Cranial nerve findings, deep tendon reflexes, plantar responses, gait and stance were normal. MRI scans showed mild cerebral and cerebellar cortical atrophy. Patchy areas of subependymal and deep white matter of the cerebral hemispheres with increased T2 signal intensity were observed, in the absence of any obvious vascular risk factor. Of note, a slightly increased T2 signal intensity was observed in the middle cerebellar peduncles (Fig. 1). SPECT examination was obtained by injection i.v. with 111 MBq of [123I]FP-CIT for evaluation of striatal dopamine transporter (DAT) density. The uptake of [123I]FP-CIT was significantly reduced in both putamen G. Madeo F. Alemseged A. Pisani (&) Dipartimento di Medicina dei Sistemi, Clinica Neurologica, Universita degli Studi di Roma Tor Vergata, Roma, Italia e-mail: pisani@uniroma2.it

Genetics of essential tremor

Essential tremor (ET) is a prevalent condition manifesting with progressive action tremor. Although ET was traditionally viewed as a sporadic disease, a significant proportion of cases report a positive family history of tremor. Autosomal dominant inheritance can be demonstrated in many families. Previously, genome-wide linkage studies in families mapped three loci for ET, hereditary essential tremor-1 (ETM1), ETM2 and ETM3. However, no causal mutation has been replicated in candidate genes within these loci, including dopamine D3 receptor (DRD3) and HS1-binding protein 3 (HS1BP3). Recently, the first genome-wide association study in ET followed by replication studies conducted in diverse populations identified a significant association between the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) SNP rs9652490 and risk for ET Although further novel variants were indentified in LINGO1 and its paralog LINGO2 that may be associated with risk for ET, the pathogenic mechanisms involved remain elusive. Given the possibility that ET as a complex trait may be influenced by the combined effects of rare variants, novel high-throughput technologies sequencing all exons across the genome (exome sequencing) or the whole genome (genome sequencing) may become crucial in understanding/deciphering the genetic background of ET.

Clinical characteristics of essential voice tremor: A study of 34 cases

To describe and characterize essential voice tremor, including signs, symptoms, and severity, and its relation to other manifestations of essential tremor. Description of aspects of treatment is a secondary goal. Descriptive clinical cohort study. Thirty-four patients with essential voice tremor were identified over 40 months. Historical information regarding duration, family history, ethanol effect, arm tremor, and prior diagnosis was collected and examination was performed. Laryngeal and pharyngeal signs were graded using the Vocal Tremor Scoring System (VTSS); arm tremor was scored using the Washington Heights Inwood Genetic Study of Essential Tremor Rating Scale (WHIGET). Patients rated vocal disability using the Voice Handicap Index (VHI). Information regarding treatment was collected both historically and prospectively. Ninety-three percent of patients were female. Voice tremor typically began in the seventh decade (62.9 +/- 15.0 years), and had been present for a mean of 6.7 +/- 13.4 years at the time of presentation. Tremor was present in a first-degree relative in 13 patients (38.2%); nine (26.5%) reported a beneficial effect of ethanol. Only 11 (32.3%) were aware of an arm tremor. Seven patients (20.6%) had been correctly diagnosed prior to evaluation; 16 (47.1%) were undiagnosed, and 10 (29.4%) had been misdiagnosed as spasmodic dysphonia. Clinical features were scored as follows: VTSS = 7.7 +/- 3.3, range 1 to 14; WHIGET = 8.5 +/- 7.5, range 0 to 31; VHI = 71 +/- 28, range 2 to 115. VTSS did not correlate with WHIGET, but did correlate with VHI. Only 56% of treated patients found botulinum toxin helpful. Essential voice tremor appears to affect more women than men. One third to one half of affected individuals have a family history of tremor. About one half of cases occur with upper extremity tremor no more severe than that seen in similarly aged normal individuals, contrary to what has been thought to date. Essential voice tremor is probably more common than is generally suspected, and many cases appear to be undiagnosed many years after onset or are misdiagnosed, most often as spasmodic dysphonia. The key feature is kinetic laryngeal tremor which usually extends beyond the larynx to involve the phonatory apparatus globally. Botulinum toxin may be helpful, but benefit is typically incomplete and not universal. Prolonged postinjection breathiness is the most common barrier to useful treatment.

Fahr’s disease

A 54 year-old man with a history of bipolar disorder presented to the neurology clinic with a two-year history of tremor affecting both hands that was worse on action. He...

Orthostatic tremor in three brothers

Sirs: Orthostatic tremor (OT) is a rare form of tremor that occurs usually in legs upon standing upright with a typical tremor frequency of 13–18 Hz (for review see references [1, 2]). We report OT in three elderly brothers (patients #1, 2, 3; 69, 68, 63 yrs, respectively) without a family history for OT or essential tremor (ET). They complained of unsteadiness upon standing due to quivering legs since the age of 59, 63 and 50, respectively. They had no leg tremor in positions other than standing, and no arm or head tremor ever occurred. Both patients #1 and #3 suffered from sleep bruxism. Some other family members were reported to also be afflicted by bruxism but not by OT (Fig. 1). There was no jaw tremor in any of the three brothers, confirmed by EMG recording in patient #1. The three brothers have lived in different environments beyond childhood and adolescence and were not exposed to environmental toxins. On examination they showed quivering of the leg muscles during standing that became stronger over time. Arm tremor was not present. No ataxia or gait disturbance was present. EMG recordings showed a 16–17 Hz tremor in the legs during standing and in the upper limbs during isometric contraction in all three patients (Fig. 2). A repetitive nerve stimulation test of the N. accessorius in patient #1 due to ocular and bulbar weakness showed a 19 % decrement at 3 Hz, typical of MG. Testing for antiacetylcholine receptor antibodies was positive while MuSK antibody titers were in the reference range. He had a benign thymoma. Thyroid antibodies were positive, but ANA, ENA and ANCA were negative. Besides tremor patient #2 complained of a hoarse voice for at least 10 years, Dupuytren’s contracture, Peyronie’s disease (induratio penis plastica) and minor lid drop on the right side that was stable for at least 30 years. Further neurological examination was normal for all three patients. Several characteristic features distinguish OT from ET: OT has a uniquely high frequency of 13–18 Hz. Two cases of a 16 and 14 Hz jaw tremor, respectively, without leg tremor are the only reported exceptions [3, 4]. OT is unresponsive to alcohol and β-blocker, only present during standing (or isometric muscle contraction) and usually has no family history of tremor. ET has a frequency of 6–8 Hz, is often familiar and is an action tremor usually of the upper limbs (pure leg tremor without upper limb tremor was observed in only 2.2 % of ET patients [1, 5]. But there is an ongoing debate whether OT might be a variant of ET [6–8]. For example, PET studies revealed hyperactivity of the cerebellum in both OT and ET [9, 10]. To determine whether OT segregated with known loci for ET, a linkage analysis in two identified susceptibility loci for ET on chromosomes 3q13 (ETM1) and 2p24.1 (ETM2) was performed for all three patients and additional family members (IV, 1–4; V, 4; see Fig. 1). DNA was isolated using standard procedures. The STR markers were chosen from GDB (http://www.gdb.org/gdb/) according to their localisation at the two loci ETM1 and ETM2 and typed as described [11]. The constructed haplotypes for both loci in the patients did not co-segregate with OT. There was also no linkage between the identified haplotypes and bruxism. Genetic factors for bruxism have been considered both in children and in adults [12]. But the co-occurrence of OT with bruxism might be incidental. A recent report about OT in monozygotic twins [13] and this report are arguments for a genetic basis of OT. Further genetic analysis has to be performed to clarify the genetic basis of OT and bruxism.

Hereditary chin tremor in Parkinson's disease

Hereditary chin tremor (HCT) is characterized by rhythmical, involuntary movements of the chin muscles usually inherited in an autosomal dominant pattern. We describe a 74-year old man with familial, childhood-onset chin tremor, and a 3-year history of progressive hand tremor, gait difficulty, and other parkinsonian features. Since chin tremor often occurs in Parkinson's disease (PD), a coexistent HCT may not be recognized unless past and family history of tremor is carefully explored.