Essential tremor.

Essential tremor, including the juvenile and senile variations, may be a result of a disorder of the servomechanism that controls physiologic tremor. Hands and arms are affected most commonly, and the tremor can vary in amplitude as well as frequency. Long-term treatment with propranolol has been helpful for some patients, although older patients are less likely to benefit. Other drugs and behaviour modification therapy have been less successful. Surgical treatment is effective but should probably be reserved for severe cases. An effective instrument for measuring the subjective and objective aspects of the tremor is still needed, as is an effective long-term method of treatment.     

Characteristics of hand tremor time series

Tremor is classified into physiological, essential, and parkinsonian tremor by means of clinical criteria. The aim of our work was to extract quantitative features from the measurements of the acceleration of human postural hand tremor. Different mathematical methods were adopted and modified in order to separate these three types of tremor. Best discrimination between physiological and pathological tremors has been achieved by methods distinguishing nonlinear from linear behavior. On the other hand, methods separating different forms of nonlinear behavior have been found to be superior in discriminating parkinsonian and essential tremor. By these methods physiological and pathological tremors can be separated with an error rate below 20% and essential and parkinsonian tremor with an error rate below 10%. This may help to classify tremor time series by objective mathematical criteria and may increase the understanding of the pathophysiological differences underlying these kinds of tremor.     

帕金森病及运动障碍疾病门诊震颤患者的病因及临床表现分析

目的:总结帕金森病及运动障碍疾病门诊震颤患者的病因及临床表现,以提高门诊震颤患者的诊断率,降低误诊率,为门诊震颤诊断提供临床经验。方法:连续收集西京医院神经内科帕金森病及运动障碍疾病门诊自2015年5月至2016年7月收治的震颤患者进行横断面研究。采用SPSS19.0软件进行统计分析。结果:共纳入400例震颤患者,男性173例(43.3%),女性227例(56.8%),男女之比1:1.3,平均发病年龄54.0岁。40岁以下特发性震颤(ET)最多,41-60岁为帕金森病(PD),60岁以上帕金森病最多。震颤按临床表现形式分为静止性震颤85例(21.3%),动作性震颤137例(34.3%),混合性震颤178例(44.5%)。震颤按病因分类,占比例前三位的分别是:帕金森病(46.3%),特发性震颤(28.5%),心因性震颤(5.8%)。心因性震颤急性起病率及合并焦虑抑郁率最高,而PT画螺旋圈及书写阳性率明显低于其他病因组。结论:门诊震颤患者混合性震颤形式较多见,最常见病因为帕金森病、特发性震颤及心因性震颤;心因性震颤较其他病因所致震颤相比,急性起病率、合并焦虑抑郁率高,而画螺旋圈及书写阳性率低。震颤诊断应先明确震颤的临床特点,然后分析病因以确定诊断及治疗。     

Clinicians’ Tendencies to Under-Rate Parkinsonian Tremors in the Less Affected Hand

The standard assessment method for tremor severity in Parkinson’s disease is visual observation by neurologists using clinical rating scales. This is, therefore, a subjective rating that is dependent on clinical expertise. The objective of this study was to report clinicians’ tendencies to under-rate Parkinsonian tremors in the less affected hand. This was observed through objective tremor measurement with accelerometers. Tremor amplitudes were measured objectively using tri-axis-accelerometers for both hands simultaneously in 53 patients with Parkinson’s disease during resting and postural tremors. The videotaped tremor was rated by neurologists using clinical rating scales. The tremor measured by accelerometer was compared with clinical ratings. Neurologists tended to under-rate the less affected hand in resting tremor when the contralateral hand had severe tremor in Session I. The participating neurologists corrected this tendency in Session II after being informed of it. The under-rating tendency was then repeated by other uninformed neurologists in Session III. Kappa statistics showed high inter-rater agreements and high agreements between estimated scores derived from the accelerometer signals and the mean Clinical Tremor Rating Scale evaluated in every session. Therefore, clinicians need to be aware of this under-rating tendency in visual inspection of the less affected hand in order to make accurate tremor severity assessments.     

Behavioral Relaxation Training for tremor disorders in older adults

Two adult men, aged 86 and 63, with essential tremor and Parkinson's-disease-related tremor, respectively, were provided Behavioral Relaxation Training in reclined and upright seated positions. Multiple measures were recorded, including the Behavioral Relaxation Scale (BRS), clinical and self-rated tremor severity, informant ratings, ratings of disability in activities of daily living (ADL), and forearm EMG. Results showed increased relaxation skills on the BRS, with reductions in EMG, tremor ratings, and some ADL disabilities. Upright BRS scores did not change during reclined training, but improved rapidly during upright training. The second man was found to suffer from dyskinesia when he relaxed during baseline, which declined markedly during training. A two-week follow-up indicated that most improvements were maintained by both men. Statistical analyses of data for each man showed significant changes. These results suggest that relaxation may be useful in the treatment of idiopathic and pathologic tremor disorders in older adults.     

Modeling and Automatic Feedback Control of Tremor: Adaptive Estimation of Deep Brain Stimulation

This paper discusses modeling and automatic feedback control of (postural and rest) tremor for adaptive-control-methodology-based estimation of deep brain stimulation (DBS) parameters. The simplest linear oscillator-based tremor model, between stimulation amplitude and tremor, is investigated by utilizing input-output knowledge. Further, a nonlinear generalization of the oscillator-based tremor model, useful for derivation of a control strategy involving incorporation of parametric-bound knowledge, is provided. Using the Lyapunov method, a robust adaptive output feedback control law, based on measurement of the tremor signal from the fingers of a patient, is formulated to estimate the stimulation amplitude required to control the tremor. By means of the proposed control strategy, an algorithm is developed for estimation of DBS parameters such as amplitude, frequency and pulse width, which provides a framework for development of an automatic clinical device for control of motor symptoms. The DBS parameter estimation results for the proposed control scheme are verified through numerical simulations.     

Biobehavioral Intervention for Older Adults Coping with Essential Tremor

Four questions were addressed: (a) does biobehavioral intervention result in within-session reduction of tremor severity; (b) do relaxation and electromyographic (EMG) biofeedback training produce differential effects; (c) do within-session treatment effects generalize to daily performance; and (d) are reductions in tremor severity maintained at follow-up assessment? Three adults, ages 51, 77, and 83, each with a diagnosis of essential tremor (ET), and a long standing history of tremor of the hands uncontrolled by medication, took part. A repeated pre–post-training single-case experimental design embedded within a sequential A–B–C–D design was used; in addition, 1 participant received a return to the B phase. Outcome measures included within-session clinical and self-ratings of tremor severity, surface electromyography (sEMG) of forearm muscles, and daily self-ratings of tremor at home. Tremor was measured while participants engaged in eating or drinking tasks. The Behavioral Relaxation Scale (BRS) served as a process measure to assess relaxation proficiency. Clinical ratings of tremor and the BRS had high interobserver agreement. Visual inspection and statistical tests of single-case data were used to evaluate outcomes. Each participant showed significant within-session improvements on various measures of tremor and improvement during intervention as compared to baseline phases. There were no clear-cut differences between relaxation and biofeedback phases. Improvements declined somewhat at a 12-week follow-up. Relationships among measures of tremor are discussed. Biobehavioral interventions hold promise for older adults coping with ET. Further research is needed using an array of biobehavioral measures to assess intervention outcome.     

原发性震颤的遗传学进展

就原发性震颤(essential tremor,ET)的遗传学基础作一探讨.ET是最常见的神经疾病之一,其临床表现复杂多样,病因机制尚不清楚.常有家族史,目前已定位3个疾病基因位点,最近发现多巴胺受体D3(the dopamine receptor D3 gene,DRD3)和LINGO1基因变异可能与ET发病相关.     

Alterations of Benzodiazepine Receptor Binding in Tremor Rats with Absence-Like Seizures

Tremor rats begin to exhibit clinical or electrical absence-like seizures after 6 weeks of age, and by 14 weeks of age, all have seizures. Central-type benzodiazepine receptor binding was investigated in tremor rats and control rats, aged 4 weeks and 16 weeks. Significantly lower benzodiazepine receptor density and no differences in affinity were found in the hippocampus of the tremor rats in comparison with that of control rats at both ages. This abnormality is considered to be due to a tremor gene and may be the cause of absence-like seizures in tremor rats. A significantly lower receptor density was found in the cerebellum at 4 weeks of age in the tremor rats than in the control rats. These changes may be related to tremorous movements in the tremor rats. Receptor density was significantly lower in the brainstems of tremor rats and control rats at 16 weeks of age than at 4 weeks of age, and the decrease was more marked in control rats. These facts may reflect a reduced decrease in the response to the dysfunction of gamma-aminobutyric acidergic neurons, or the function of the gamma-aminobutyric acid/benzodiazepine receptor system may be secondarily increased to suppress seizures in 16-week-old tremor rats.     

Physiological evidence for central modulation of voice tremor

The present report presents an attempt to define the physiological parameter used to describe “voice tremor” in psychological stress evaluating machines, and to find its sources. This parameter was found to be a low frequency (5–20 Hz) random process which frequency modulates the vocal cord waveform and (independently) affects the frequency range of the third speech formant. The frequency variations in unstressed speakers were found to be the result of forced muscular undulations driven by central nervous signals and not of a passive resonant phenomenon. In this paper various physiological and clinical experiments which lead to the above conclusions are discussed. a) It is shown that induced muscular activity in the vocal tract and vocal cord regions can generate tremor in the voice. b) It is shown that relaxed subjects exhibit significant tremor correlation between spontaneously generated speech and EMG, with the EMG leading the speech tremor. c) Tremor in the electrical activity recorded from muscles overlapping vocal tract area was correlated with third formant demodulated signal and vocal cord demodulated pitch tremor was correlated with first formant demodulated tremor. d) Enhanced tremor was found in Parkinson patients and diminished tremor in patients with some traumatic brain injuries.     

A community survey of Parkinson's disease.

In a rural community of 80,000 people 69 patients were identified as having a diagnosis of Parkinson''s disease. After interview and examination we found that 55 met the generally accepted diagnostic criteria for Parkinson''s disease, 4 had possible Parkinson''s disease, 6 had essential tremor, 2 had dementia and 2 had other conditions. The patients with Parkinson''s disease had clinical and epidemiologic characteristics similar to those of patients in previous, mainly hospital-based, studies. These characteristics included mean age at onset (63 years), frequency rate of dementia (20%) and presence of postural tremor (11%). The pattern of treatment varied, some patients receiving more medication than is usual for the severity of their illness, and some patients receiving less than is usual. Parkinson''s disease can be difficult to diagnose and manage because of the clinical variation between patients in presentation and response to treatment.     

Neostriatal muscarinic receptor subtypes involved in the generation of tremulous jaw movements in rodents implications for cholinergic involvement in parkinsonism

Several studies have shown that a number of pharmacological and neurochemical conditions in rats can induce jaw movements that are described as "vacuous" or "tremulous". For several years, there has been some debate about the clinical significance of various drug-induced oral motor syndromes. Nevertheless, considerable evidence now indicates that the non-directed, chewing-like movements induced by cholinomimetics have many of the characteristics of parkinsonian tremor. These movements are characterized largely by vertical deflections of the jaw, which occur in the same 3-7 Hz peak frequency that is typical of parkinsonian tremor. Cholinomimetic-induced tremulous jaw movements are suppressed by a number of different antiparkinsonian drugs, including scopolamine, benztropine, L-DOPA, apomorphine, bromocriptine, ropinirole, pergolide, amantadine, diphenhydramine and clozapine. A combination of anatomical and pharmacological research in rats has implicated M4 receptors in the ventrolateral neostriatum in the generation of tremulous jaw movements. Mice also show cholinomimetic-induced jaw movements, and M4 receptor knockout mice demonstrate subtantially reduced levels of jaw movement activity, as well as increased locomotion. Taken together, these data are consistent with the hypothesis that a centrally-acting M4 antagonist may be useful as a treatment for parkinsonian symptoms, including tremor.     

Significance of the potential role of pharmacological MRI (phMRI) in diagnosis of Parkinson’s disease

The initial diagnosis of Parkinson's disease (PD) is currently based on a clinical assessment.Many patients who receive an initial diagnosis of PD have parkinsonian features related to other diseases s...     

Tremor disorders. Diagnosis and management.

Tremor is commonly encountered in medical practice, but can be difficult to diagnose and manage. It is an involuntary rhythmic oscillation of a body part produced by reciprocally innervated antagonist muscles. Tremors vary in frequency and amplitude and are influenced by physiologic and psychological factors and drugs. Categorization is based on position, posture, and the movement necessary to elicit the tremor. A resting tremor occurs when the body part is in repose. A postural tremor occurs with maintained posture and kinetic tremor with movement. Various pathologic conditions are associated with tremors. Essential tremor, which is the most common, is postural and kinetic, with a frequency between 4 and 8 Hz, and involves mainly the upper extremities and head. Essential tremor responds to treatment with primidone, beta-blockers, and benzodiazepines. Parkinson''s disease causes a 4- to 6-Hz resting tremor in the arms and legs that responds to the use of anticholinergics and a combination of carbidopa and levodopa. Tremor can also be a manifestation of Wilson''s disease, lesions of the cerebellum and midbrain, peripheral neuropathy, trauma, alcohol, and conversion disorders. Treatment should be directed to the underlying condition. Stereotactic thalamotomy of thalamic stimulation is a last resort.     

New therapies for the treatment of Parkinson's disease: adenosine A2A receptor antagonists

The development of non-dopaminergic therapies for the treatment of Parkinson's disease (PD) has attracted much interest in recent years. Among new different classes of drugs, adenosine A2A receptor antagonists have emerged as best candidates. The present review will provide an updated summary of the results reported in literature concerning the effects of adenosine A2A antagonists in rodent and primate models of PD. These results show that A2A receptor antagonists improve motor deficits without inducing dyskinesia and counteract parkinsonian tremor. In progress clinical trials have shown that a low dose of L-DOPA plus KW-6002 produced symptomatic relief no different from that produced by an optimal dose of L-DOPA alone, whereas dyskinesias were reduced rendering this class of compounds particularly attractive.     

Selection of the optimal lesion site for the relief of parkinsonian tremor on the basis of spectral analysis of neuronal firing patterns

Techniques for quantitatively describing the firing properties of neurons have been used to identify thalamic cells with a firing pattern which is correlated with EMG activity during tremor. By locating these cells relative to the anterior border of the somatosensory nucleus and the anterior commissure-posterior commissure line, it may be possible to select the optimal lesion site for the relief of parkinsonian tremor on a rational rather than an empirical basis.     

Astrovirus as a possible cause of congenital tremor type AII in piglets?

Background

Congenital tremor is associated with demyelination of the brain and spinal cord and is clinically noted as outbreaks of trembling and shaking in newborn piglets during a limited time-period. Six forms of the disease have been described, where form AII may be caused by an, as yet, unidentified viral infection. This study aimed to investigate the presence of astrovirus and circovirus by sequencing and polymerase chain reaction (PCR) analysis and by relating the findings to the occurrence of disease and lesions in the brain, in 4–6 days-old piglets obtained from a clinical outbreak of congenital tremor.

Results

In piglets with congenital tremor, there were mild to moderate vacuolar changes of the white matter in the cerebrum, brain stem and cerebellum. In healthy piglets, less conspicuous vacuolar changes were detected. One healthy and one diseased piglet were positive for porcine circovirus type 2. The nested pan-PCR showed the presence of astrovirus in at least one brain region in all piglets and by sequencing, two different porcine astrovirus lineages were identified.

Conclusions

The results do not support previous studies identifying porcine circovirus type 2 as the cause of congenital tremor. The demonstration of astrovirus in the brain of piglets suffering from congenital tremor is interesting. However, astrovirus was demonstrated in both healthy and diseased individuals and therefore, further studies are warranted to determine the possible involvement of astrovirus in the pathogenesis of congenital tremor in pigs.

     

Management of Parkinson's Disease: Combined Therapy with Levodopa and Thalamotomy

An increasing number of parkinsonian patients in whom levodopa fails to relieve tremor are being referred for thalamotomy. The literature suggests that in as many as 50 percent of patients treated with levodopa, there is no relief of tremor because of refractoriness to the medication or intractable side effects which limit dosage. Thalamotomy abolishes contralateral tremor in 90 percent of patients, with an associated mortality rate of 1 to 2 percent and morbidity of 6 percent. The relative merits and complications of levodopa and thalamotomy were reviewed and a therapeutic regimen designed in which the two approaches to treatment are combined to most effectively deal with all the symptoms of parkinsonism.     

Is There a Role for Combined EMG-fMRI in Exploring the Pathophysiology of Essential Tremor and Improving Functional Neurosurgery?

Background

Functional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.

Objective

Aim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.

Methods

Simultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.

Results

Analysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.

Conclusion

EMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.     

非典型恶性综合征1 例报告暨文献复习

目的:探讨恶性综合征的病因、发病机制、临床表现及治疗。方法:回顾性分析1例非典型恶性综合征患者1例,结合文献进行分析讨论。结果:患者因高龄、全身状况差、长期并联合应用多种抗精神病药物、合并应用多种其他药物而诱发,表现为肌张力增高,心率增快,血压增高,经过停用抗精神病药,给予甲磺酸溴隐亭片、盐酸金刚烷胺片及对症支持治疗,患者病情好转。结论:恶性综合征是抗精神病药物治疗的严重并发症,其临床表现可无发热等典型表现,且可出现各系统症状,可能首诊于多个科室,各科临床医师均应熟悉该病的临床表现,以便及时作出诊断,及时治疗,改善患者预后。