Orthostatic tremor: A review of 45 cases

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

Neuroanatomical correlates of dystonic tremor: A cross-sectional study

PurposeThis study is aimed at investigating the neuroanatomical patterns characterizing dystonic tremor in comparison with essential tremor.MethodsVoxel-based morphometry and cortical thickness data of 12 patients with dystonic tremor, 14 patients with essential tremor and 23 age- and sex-matched healthy control subjects were analyzed.ResultsPatients with dystonic tremor showed a thickening and increased gray matter volume (surviving whole-brain correction for multiple comparisons) of the left sensorimotor cortex when compared to other groups. Otherwise, patients with essential tremor were characterized by a subtle atrophy of the anterior cerebellar cortex.DiscussionOur multimodal structural neuroimaging study demonstrated that patients with dystonic tremor and essential tremor are characterized by different neuroanatomical abnormalities. The involvement of the sensorimotor cortex in patients with dystonic tremor suggests that this disorder may share some pathophysiological mechanisms with focal dystonia.     

Facial tremor in dystonia

BackgroundTremor of the upper/middle part of the face, including the perinasal region and the forehead has been very rarely described in some patients with Parkinson's disease or Essential Tremor. It has not yet been reported in patients with idiopathic dystonia.MethodsWe describe here a series of 8 patients with common forms of idiopathic focal/segmental dystonia with tremor involving the upper/middle part of the face, along with demonstrative videos and electrophysiological recordings.ResultsThe distribution of the tremor was confined to the face in two patients, whereas in six patients tremor was also evident either in the head/lower part of the face or in their upper limbs. Electrophysiological recordings disclosed a slightly irregular tremor with a frequency at about 3–5 Hz.ConclusionsA number of patients with classical forms of dystonia can show a tremor involving the upper/middle part of the face.     

Cerebellar involvement in essential tremor with and without resting tremor: A Diffusion Tensor Imaging study

ObjectiveEssential Tremor with resting tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without resting tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI).MethodsWe studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres.ResultsMD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). Interestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM.ConclusionOur results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology.     

Topography of essential tremor

IntroductionTopography of tremor manifestations is poorly investigated in essential tremor. The present study explores the prevalence and clinical correlates of head and/or voice tremor in essential tremor.MethodsOut of a prospectively designed registry of 972 patients, 884 patients with definite and probable essential tremor had complete information on tremor localization. Demographic and clinical characteristics were compared among four subgroups: group A (without head or voice tremor, n = 619), B (with head but without voice tremor, n = 155), C (with voice but without head tremor, n = 47), and D (with both head and voice tremor, n = 63).ResultsIn our patients, total prevalence of tremor was 24.7% for head, 12.4% for voice and 7.1% for the combination of head and voice. Logistic regression analyses showed that female gender is strongly associated with head tremor, which was confirmed by an additional meta-analysis. Severe hand tremor was the only factor associated with voice tremor. Both female gender and severe hand tremor increase the odds for having the combination of head and voice tremor. For males, hand tremor severity is significantly increased among those with head and voice tremor alone and in combination, but for females only for the combination. Patients with both head and voice tremor have more frequent involvement of legs and other localizations and are less responsive to β-blockers.ConclusionsFemale gender and severe hand tremor may increase the odds of head and/or voice tremor in essential tremor. The association of hand tremor severity with midline tremor is stronger for males than females.     

Dopamine-responsive pattern in tremor patients

BackgroundDiagnosis and treatment of tremor are largely based on clinical assessment. Whereas in some patients tremor may respond to dopaminergic treatment, in general l-Dopa response to tremor varies considerably. The aim of this study was to predict l-Dopa response by accelerometry.MethodsWe included 60 tremor patients and measured harmonic oscillations by accelerometry. In addition to neurological assessment, we performed l-Dopa challenge tests and the individual tremor response was compared to the amount of harmonic oscillations.ResultsWe found a strong correlation between harmonic oscillations and clinical l-Dopa response. Similarly, harmonic oscillations were significantly greater in patients with subjective tremor reduction upon l-Dopa administration.ConclusionsWe conclude that harmonic oscillations are a measure for l-Dopa response to tremor irrespective of the underlying disease. Because of the observational character of the study, any causal relation remains speculative. Nevertheless, we propose a novel, non-invasive approach to predict l-Dopa response in tremor patients.     

合并静止性震颤的原发性震颤患者临床特点分析

目的了解北京地区社区中老年人原发性震颤(essential tremor,ET)的临床特征及其与预后的关系。方法2000年在北京城区、近郊平原、远郊山区调查了2835名55岁以上中老年人,采用筛查和临床诊断两步法确诊患者。发现ET患者135例,对其中合并静止性震颤的患者进行分析,并于2004年对其进行随访。结果其中合并上肢静止性震颤患者17例,占12.6%,合并静止性震颤组震颤总分、头部震颤的比例、肢体震颤总分均明显高于对照组。两组年龄、性别组成、病史无显著性差异,姿势性震颤和动作性震颤的程度差异不明显。4年后随访到13例(13/17),其中3例死亡,实际调查的10例中有9例仍诊断为ET,另1例诊断为临床很可能ET。结论有相当部分社区ET患者可以合并静止性震颤,合并静止性震颤的患者提示病情较重。     

Directionality of corticomuscular coupling in essential tremor and cortical myoclonic tremor

ObjectiveA role of the motor cortex in tremor generation in essential tremor (ET) is assumed, yet the directionality of corticomuscular coupling is unknown. Our aim is to clarify the role of the motor cortex. To this end we also study ‘familial cortical myoclonic tremor with epilepsy’ (FCMTE) and slow repetitive voluntary movements with a known cortical drive.MethodsDirectionality of corticomuscular coupling (EEG-EMG) was studied with renormalized partial directed coherence (rPDC) during tremor in 25 ET patients, 25 healthy controls (mimicked) and in seven FCMTE patients; and during a self-paced 2 Hz task in eight ET patients and seven healthy controls.ResultsEfferent coupling around tremor frequency was seen in 33% of ET patients, 45.5% of healthy controls, all FCMTE patients, and, around 2 Hz, in all ET patients and all healthy controls. Ascending coupling, seen in the majority of all participants, was weaker in ET than in healthy controls around 5–6 Hz.ConclusionsPossible explanations are that tremor in ET results from faulty subcortical output bypassing the motor cortex; rate-dependent transmission similar to generation of rhythmic movements; and/or faulty feedforward mechanism resulting from decreased afferent (sensory) coupling.SignificanceA linear cortical drive is lacking in the majority of ET patients.     

Computerized tremor analysis of valproate-induced tremor: a comparative study of controlled-release versus conventional valproate

PURPOSE: Valproate (VPA) induces postural tremor in 6-45% of patients. The characteristics of VPA-induced tremor have not yet been quantitatively assessed, and it is not known whether tremor prevalence or severity is affected by VPA formulation (controlled-release CR-VPA vs. conventional VPA). The aim of this study was quantitatively to assess tremor in epilepsy patients receiving VPA and to compare the effects of two VPA formulations (CR-VPA vs. VPA) on tremor severity. METHODS: In a prospective study, 18 consecutive patients with newly diagnosed focal or generalized epilepsy were assigned to receive alternately either VPA (n=10) or CR-VPA (n=8) monotherapy. Computerized tremor analysis was performed at baseline 1 day before initiating VPA treatment and repeated after a seizure-free period of >or=8 weeks, during which VPA doses had remained stable. Rest and postural tremor were recorded by accelerometry, and surface electromyograms (EMGs) were recorded from the wrist flexors and extensors. RESULTS: At baseline, the two groups had similar postural tremor amplitudes. At follow-up, the CR-VPA group had remained at the same level, whereas VPA subjects exhibited a significant increase in tremor amplitudes (p<0.05) despite comparable VPA doses and comparable plasma VPA concentrations at the time of tremor testing. CONCLUSIONS: This is the first study to assess quantitatively VPA-induced tremor by standardized tremor analysis. These results suggest that CR-VPA may cause less tremorigenic activity as compared with standard VPA. The mechanisms underlying this difference are unclear but may include greater peak-trough variation with VPA than with CR-VPA.     

A single oral dose of cannabidiol did not reduce upper limb tremor in patients with essential tremor

Essential tremor (ET) is a common clinical syndrome characterized by action tremors affecting both upper limbs that can compromise manual tasks' execution and impair functional and social performance. The primary pharmacological treatment is symptomatic, but effective medicines are somewhat limited. There is a clear need to find new effective therapies for the treatment of ET. Cannabidiol (CBD) is a modulator of CB1 receptor and CB1 agonists can reduce tremors in experimental models. We hypothesized that a single acute CBD intake would reduce tremors in ET patients. We performed a randomized, controlled, double-blind, crossover study on 19 patients with ET. They were 10 males and 9 females, had mean 63 years of age, and mean 23 years of disease duration and had insufficient control of their tremors with the usual pharmacological treatment. They ingested a single oral dose of CBD (300 mg) or placebo in two experimental sessions performed 2-weeks apart. Patients were evaluated immediately before and after oral ingestion (60 min and 210 min), using the Fahn-Tolosa-Marin clinical scale. There was no carryover effect. There were no significant differences in upper limb tremors score, specific motor task tremor scores (writing and drawing/pouring) or clinical impression of change after treatment with placebo or CBD. In conclusion, a single 300 mg oral dose of CBD had no significant effect on the severity of upper limb tremors of ET patients. Our findings did not exclude the possibility that chronic treatment with CBD could have a symptomatic effect.     

特发性震颤的临床特点

目的　探讨特发性震颤 (ET)的临床特点。方法　对 80例 ET患者的临床资料进行分析。结果80例 ET中男 5 0例 ,女 30例 ,发病年龄 3～ 70岁 ,平均 34.6± 16 .3岁 ,病程 6个月～ 6 0年 ,平均 14.2± 9.9年。45例 (5 6 .3% )患者有阳性家族史 ,多呈常染色体显性遗传。临床主要表现为单症状的姿势性震颤 ,累及部位依次为手 (92 .5 % )、咽喉部 (2 1.3% )、头 (2 0 % )、下颏 (17.5 % )等。 17.5 %患者因震颤致日常生活困难。 34例饮酒患者中 ,91.2 %显示对酒精有反应性。 6 .3%患者并发帕金森病 (PD)。 6 1%患者小剂量心得安治疗有效。结论　本组 ET患者男多于女 ,发病年龄轻 ,呈单峰模式 ,临床表现为单症状姿势性震颤 ,部分病例可伴发PD,小剂量心得安治疗大多有效。     

The clinical features and functional impact of valproate-induced tremor

BackgroundTremor is a known side-effect of anticonvulsants, particularly of valproate. However, there is a dearth of information regarding detailed clinical features and functional impact of valproate-induced tremor.MethodsWe studied a cohort of patients treated with anticonvulsants for neurological disorders, through blinded evaluations using the Clinical Rating Scale for Tremor (CRST); we compared the frequency, severity and functional impact of drug-induced tremor between patients treated with valproate and those treated with other anticonvulsants.ResultsFrom a cohort of 218 consecutive patients, 171 were fully evaluated; 118 patients were taking valproate alone or combined with other anticonvulsants and 53 patients were taking other anticonvulsants. Mean age (±SD) at evaluation of the cohort was 32 ± 13 years, females represented 55.6% of cases. Tremor was more frequently observed in patients taking valproate particularly postural upper limb tremor: 49% vs. 15% (right-side) (P < 0.001) and 48.3% vs. 13.2% (left-side), (P < 0.001); had a higher total CRST score: 12.14 vs. 3.06 (P < 0.001), and required more frequently treatment for drug-induced tremor: 23.7% vs. 5.6% (P=0.005) compared with patients taking other anticonvulsants. Among 118 patients taking valproate, women had a higher total CRST score compared with men: 14.54 ± 14.9 vs. 9.56 ± 9.55 (P=0.034). A weak correlation between the total CRST score, dose per Kg of valproate and serum levels of valproate were observed.ConclusionsTremor is frequently observed in patients taking valproate and is severe enough to require treatment in about 24% of cases.     

Structural changes in cerebellar outflow tracts after thalamotomy in essential tremor

BackgroundThis study set out to determine whether structural changes are present outside the thalamus after thalamotomy in patients with essential tremor (ET), specifically in the cerebellorubrothalamic tracts. We hypothesized that diffusion tensor imaging (DTI) would detect these changes.MethodsWe collected DTI scans and analyzed differences in Fractional Anisotropy (FA) and Mean Diffusivity (MD) between the left and right superior and middle cerebellar peduncle in ET patients that have undergone unilateral, left, thalamotomy and ET patients that did not undergo thalamotomy (control group). We used classical ROI-based statistics to determine whether changes are present.ResultsWe found decreased FA and increased MD values in the right superior cerebellar peduncle leading to the left, lesioned thalamus, only in the thalamotomy group.ConclusionsOur study suggests long-term structural changes in the cerebellorubrothalamic tract after thalamotomy. This contributes to further understanding of the biological mechanism following surgical lesions in the basal ganglia.     

Essential tremor: an overdiagnosed condition?

The diagnosis of essential tremor (ET) and its differentiation from other types of tremor is often difficult. In 1994 Bain et al. defined a classical phenotype by studying 20 patients with pure essential tremor and similarly affected family members in at least three generations. We assessed how many of the patients diagnosed by different neurologists at our institution as having ET conformed to this defined phenotype. We randomly selected 50 patients who were diagnosed with ET by any neurologist at the National Hospital for Neurology and Neurosurgery since the publication of the Bain et al. report, and determined the number of patients who had clinical features compatible with the phenotype that it had defined. Only 25 (50%) of these patients had ET so defined. Ten patients clearly had alternative diagnoses: four had clear additional dystonia, two neuropathic tremor, two had unilateral leg tremor, one drud-induced tremor, and one sudden onset after head trauma. The remaining 15 patients also had atypical features including myoclonus (one), onset in a body part other than the arms (six), sudden onset (two), rest tremor (seven), onset after the age of 65 years (four), a family member with an isolated head tremor (one), or reduced armswing (two). The diagnosis of ET is overused even among experienced neurologists, and other types of tremor should be considered in atypical patients before making this diagnosis. Received: 30 November 1999 / Received in revised form: 12 May 2000 / Accepted: 21 June 2000     

The response of the central and peripheral tremor component to octanoic acid in patients with essential tremor

Objective

To investigate the effect of octanoic acid (OA) on the peripheral component of tremor, as well as OA’s differential effects on the central and peripheral tremor component in essential tremor (ET) patients.

Population-based case-control study of essential tremor

Current epidemiologic data on the association between environmental factors and essential tremor (ET) are scanty. In a population-based case-control study we investigated the relationship between some putative risk factors and ET. In the present study, we included all subjects identified during a door-to-door prevalence survey in a Sicilian community, affected by ET, and alive on 1 November 1987 (n=31). Of the 31 prevalent cases of ET, we were able to contact 28 subjects. Twenty-eight controls were randomly selected from the general population and matched to each case for age and sex. Exposure variables were investigated by interviewing the patients and their controls or close relatives, using a structured questionnaire. The odds for habitual alcohol consumption were 0.3, indicating a protective effect. The odds for exposure to agricultural chemicals and domestic animals were 2.5 and 2.7, respectively, suggesting a role as potential risk factors. However, the associations found by us were not statistically significant.

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Sommario Un argomento poco considerato dalle indagini di epidemiologia analitica riguarda la possibile influenza di fattori di rischio ambientali sull'eziologia del tremore essenziale. Scopo del presente lavoro è quello di verificare l'esistenza di un'associazione tra possibile fattori di rischio e il tremore essenziale, attraverso uno studio caso controllo su popolazione. In un precedente studio di prevalenza di tipo porta a porta, abbiamo identificato tutti i pazienti affetti da tremore essenziale residenti net comune di Terrasini net giorno di prevalenza, 1 Novembre 1987 (n=31). A 28 di tale pazienti e a un gruppo di controloi di uguale numerosità, selezionati dalla popolazione generate e appaiati per età e sesso net rapporto di 1:1, è stato possibile somministrare un questionario strutturato, per valutare l'esposizione a diverse variabili ambientali. Il rischio per it consumo abituale di alcool è risultato di 0,3, suggerendo un effetto protettivo per tale assunzione; al contrario l'esposizione ad anticrittogamici e il contatto abituale con animali domestici hanno mostrato rispettivamente un rischio di 2,5 e 2,7, valori questi the candiderebbero tali esposizioni come fattori the aumentano il rischio di sviluppare it tremore essenziale. Nessuna di tale associazioni è comunque risultata statisticamente significativa.

     

特发性震颤的临床特点分析

目的探讨特发性震颤(essential tremor,ET)的临床特点。方法对92例ET患者的临床资料进行回顾性分析。结果92例ET中男58例,女34例,发病年龄12～80岁,平均(50.2±17.3)岁,病程6个月～60年,平均(16.2±8.9)年。49例(53.3%)患者有阳性家族史,多呈常染色体显性遗传,临床主要表现为单症状的姿势性震颤,累及部位依次为手(92.4%)、头(25.0%)、咽喉部(21.7%)、下颏(15.2%)等。16.3%患者因震颤致日常生活困难。42例饮酒患者中,85.7%显示对酒精有反应性。6.5%患者并发帕金森病(Parkinson’s disease,PD)。67.3%患者小剂量普萘洛尔治疗有效。结论本组ET患者男多于女,临床表现为单症状姿势性震颤,部分病例可伴发PD,小剂量普萘洛尔治疗大多有效。