Postural leg tremor in X-linked spinal and bulbar muscular atrophy

X-linked spinal and bulbar muscular atrophy (SBMA) is an adult-onset neuromuscular disorder caused by a CAG repeat expansion in the androgen receptor gene. Postural hand tremor is well known as a non-motor neuron sign, but to our knowledge postural leg tremor has not been reported. We studied the occurrence and physiological features of postural leg tremor in 12 male patients (38–64 years old) with genetically proven SBMA. Three patients had postural leg tremor with a frequency of 4–7 Hz. In these patients, sensory nerve action potential (SNAP) was not detected in the lower limbs. There were significant differences between the patients with postural leg tremor and those without postural leg tremor in both the SNAP of the sural nerve and the length of the CAG repeat. Phenotypical differences between shorter CAG repeats, which indicate a sensory-dominant phenotype, and longer CAG repeats, which indicate a motor-dominant phenotype, have been previously reported. In the present study, 60% of patients with shorter CAG repeats (<47) showed leg tremor and none of the patients with longer CAG repeats (⩾47) did. Postural leg tremor could be a clinical feature that predicts shorter CAG repeats of the androgen receptor gene.     

Decoding voluntary movements and postural tremor based on thalamic LFPs as a basis for closed-loop stimulation for essential tremor

BackgroundHigh frequency Deep brain stimulation (DBS) targeting motor thalamus is an effective therapy for essential tremor (ET). However, conventional continuous stimulation may deliver unnecessary current to the brain since tremor mainly affects voluntary movements and sustained postures in ET.ObjectiveWe aim to decode both voluntary movements and the presence of postural tremor from the Local field potentials (LFPs) recorded from the electrode implanted in motor thalamus for stimulation, in order to close the loop for DBS so that stimulation could be delivered on demand, without the need for peripheral sensors or additional invasive electrodes.MethodsLFPs from the motor thalamus, surface electromyographic (EMG) signals and/or behavioural measurements were simultaneously recorded in seven ET patients during temporary lead externalisation 3–5 days after the first surgery for DBS when they performed different voluntary upper limb movements. Nine different patients were recorded during the surgery, when they were asked to lift their arms to trigger postural tremor. A machine learning based binary classifier was used to detect voluntary movements and postural tremor based on features extracted from thalamic LFPs.ResultsCross-validation demonstrated that both voluntary movements and postural tremor can be decoded with an average sensitivity of 0.8 and false detection rate of 0.2. Oscillatory activities in the beta frequency bands (13–23 Hz) and the theta frequency bands (4–7 Hz) contributed most to the decoding of movements and postural tremor, respectively, though incorporating features in different frequency bands using a machine learning approach increased the accuracy of decoding.     

Corticomuscular coherence is increased in the small postural tremor of Parkinson's disease.

The mechanisms and electrophysiological characteristics of the postural tremor in Parkinson's disease (PD) have not been defined. We hypothesized that PD subjects with small amplitude postural tremor would show increased corticomuscular coherence at certain frequencies compared to PD subjects without visible tremor. Four groups of participants were studied: (1) Control without postural tremor, (2) Control with small amplitude postural tremor, (3) PD without postural tremor, and (4) PD with small amplitude postural tremor. Accelerometry and electroencephalography-electromyography fast-fourier transform and corticomuscular coherence spectra were generated. Findings showed (1) elevated corticomuscular coherence centered at 12-18 Hz in PD with small amplitude postural tremor; (2) 5-12 Hz accelerometer frequency peaks that did not shift with increasing weight loads in some individuals; and (3) 5-8 Hz accelerometer peaks that shifted frequency with increasing weight loads, consistent with a peripheral-mechanical oscillator in all groups. The small amplitude postural tremor in PD arises from heterogeneous oscillator mechanisms. The discovery of increased corticomuscular coupling shows cortical involvement in the small amplitude postural tremor of PD.     

Imbalance and lower limb tremor in chronic inflammatory demyelinating polyradiculoneuropathy

Background and Aims

Imbalance is a prominent symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although upper limb tremor in CIDP is described, lower limb tremor has not been assessed. The aim of this study was to determine whether lower limb tremor was present in CIDP and assess potential relationships with imbalance.

Methods

This was a cross-sectional observational study of prospectively recruited consecutive patients with typical CIDP (N = 25). Clinical phenotyping, lower limb nerve conduction and tremor studies, and posturography analyses were performed. The Berg Balance Scale (BBS) divided CIDP patients into those with “good” and “poor” balance.

Results

Lower limb tremor was evident in 32% of CIDP patients and associated with poor balance (BBS_Tremor 35 [23–46], BBS_{No Tremor} 52 [44–55], p = .035). Tremor frequency was 10.2–12.5 Hz with legs outstretched and on standing, apart from four patients with a lower frequency tremor (3.8–4.6 Hz) while standing. Posturography analysis revealed a high-frequency spectral peak in the vertical axis in 44% of CIDP patients (16.0 ± 0.4 Hz). This was more likely in those with “good” balance (40% vs. 4%, p = .013).

Interpretation

Lower limb tremor is present in one third of CIDP patients and is associated with poor balance. A high-frequency peak on posturography is associated with better balance in CIDP. Lower limb tremor and posturography assessments could serve as important biomarkers of balance in a clinical setting.     

Cerebellar axial postural tremor

Three cases are presented with a predominantly axial postural tremor, without visible palatal tremor. Tremor varied in frequency between 3 and 10 Hz, often jumping from one frequency to another in this band. All three patients had evidence of cerebellar pathology. Cases 1 and 2 developed tremor in the setting of a lateLondon, Englandonset cerebellar degeneration and after excision of a right cerebellar haemangioblastoma, respectively. Etiology was unclear in Case 3. Nevertheless, this patient had a cerebellar dysarthria. The tremor was similar to that sometimes seen in conjunction with palatal tremor, and EMG studies in Case 3 demonstrated a subclinical modulation of palatal muscle activity simultaneous with the truncal tremor. It is suggested that an axial postural tremor may be due to pathology of the cerebellum and its outflow pathways, despite the absence of clinically apparent palatal tremor.     

Effects of thalamic stimulation frequency on intention and postural tremor

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus improves essential tremor. Suppression of the amplitude of the postural tremor component with VIM DBS depends on stimulation frequency. The purpose of this study was to determine the effect of DBS frequency on the intention tremor component, that is, tremor that is enhanced by target-directed movement, and to compare it to the effect of DBS frequency on postural tremor in people with essential tremor. We measured tremor frequency and amplitude during trials of postural holding and voluntary reaching between two targets at 10 different stimulation frequency settings between 0 and 185 Hz. Tremor frequency did not change with changes in stimulation frequency. Amplitude suppression of both intention and postural tremor depended on stimulation frequency. Maximal tremor reduction occurred at approximately 130 Hz for both forms of tremor. However, at optimal frequencies, the percent reduction in tremor amplitude relative to the DBS OFF condition was greater for postural than for intention tremor. These results suggest that VIM DBS stimulation frequencies near 130 Hz may provide maximal control of intention and postural tremor. Identification of optimal stimulation settings should consider assessment of intention tremor, not just postural tremor, as intention tremor may not be as well controlled as postural tremor but may be a better gauge for functional benefit.     

Two cases with postural axial tremor: Consider a genetic origin

We present two cases with postural axial tremor predominantly involving the head, trunk, and shoulders. In the first patient, the postural tremor occurred in multiple attacks a day lasting approximately 10 min. The second patient developed a progressive tremor of his head and arms, worsened during sitting and standing. Electrophysiological supported the postural axial tremor in both patients with a varying 3–10 Hz tremor frequency between different muscles and within the same muscles at different times.Postural axial tremor is a rare and complex movement disorder. The majority of cases are caused by acquired cerebellar pathology. However, isolated cases with underlying genetic disorders are described in literature.Here, we illustrate how to differentiate paroxysmal axial tremor from other axial hyperkinetic movement disorders and extend the genetic heterogeneity of this intriguing movement disorder phenotype.     

临床不同分期帕金森病患者震颤特点分析

目的研究不同临床分期帕金森病(PD)患者震颤的特点。方法收集2014-11—2015-05首都医科大学附属北京天坛医院神内病房临床确诊或临床诊断PD可能性大的75例患者。患者至少具有一侧上肢静止性或姿势性震颤,按照Hoehn-Yahr分期分为1~1.5期、2~2.5期、3期3组,分别检测各组患者静止、姿势及持物1000g震颤的优势频率、振幅及震颤节律形式。结果 (1)震颤优势频率:静止、姿势状态下为4~7 Hz,1~1.5期与2~2.5期、3期组间比较差异无统计学意义(P0.05)。持物1000g状态下,1~1.5期与2~2.5期、3期组间比较差异有统计学意义(P0.01),1~1.5期患者优势频率除了4~7Hz之外,还有7~10Hz、无规律及无震颤。(2)震颤振幅:随病情进展有下降趋势。(3)震颤节律形式:临床不同分期患者静止、姿势及持物1000g时震颤的节律形式均以交替形式为主,但随着病情进展,非交替节律比例有增加趋势。结论 PD患者震颤属于中枢性震颤,静止、姿势震颤优势频率为4~7Hz,不随病情进展而变化。疾病初期,持物1000g状态震颤优势频率可能受外周调节而表现多样。震颤节律不受病情进展及姿势影响。随病情进展,非交替节律比例有增加趋势,震颤振幅有下降趋势。     

Tremor associated with focal and segmental dystonia

Background and purposeTremor occurs in 10–85% of patients with focal dystonia as so-called dystonic tremor or tremor associated with dystonia. The aim of this study was to assess the incidence and to characterize parameters of tremor accompanying focal and segmental dystonia.Material and methodsOne hundred and twenty-three patients with diagnosis of focal and segmental dystonia together with 51 healthy controls were included in the study. For each participant, clinical examination and objective assessment (accelerometer, electromyography, graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor); with hands extended (postural tremor); during ‘finger-to-nose’ test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, type of tremor was determined as essential tremor type or enhanced physiological type.ResultsThe incidence of tremor was significantly higher in dystonic patients as compared to controls (p = 0.0001). In clinical examination, tremor was found in 50% of dystonic patients, and in instrumental assessment in an additional 10–20%. The most frequent type of tremor was postural and kinetic tremor with 7 Hz frequency and featured essential tremor type. In the control group, tremor was detected in about 10% of subjects as 9-Hz postural tremor of enhanced physiological tremor type. No differences were found between patients with different types of dystonia with respect to the tremor incidence, type and parameters (frequency and severity). No correlations between tremor severity and dystonia severity were found either.     

Tremor induced by thalamic deep brain stimulation in patients with complex regional facial pain.

We report on two patients who developed a new postural and action tremor after chronic stimulation of the contralateral thalamus (VPM nucleus) during treatment of a complex regional facial pain syndrome. The tremor was only present during deep brain stimulation (DBS) and was suppressed with adjustment of the stimulation parameters. Tremor was seen only with low frequency stimulation (50 Hz or lower) and disappeared with higher stimulation frequencies. In addition to being an unusual side effect of thalamic DBS, we believe that this phenomenon affords insight into one possible mechanism underlying essential tremor (ET). A central oscillatory mechanism involving the olivocerebellar complex and the thalamus, which is a part of the cerebro-cerebello-cerebral circuit, is thought to play an important role in the genesis of ET. Induction of a tremor resembling ET in our patients indicates an active role for low frequency stimulation. A plausible explanation for this is that low frequency stimulation in the thalamic area enhances the output of the tremor-producing network. This leads credence to the concept of central oscillations in a "tremor circuit," of which the thalamus is a part, as being important in ET.     

Determinants of physiologic tremor in a large normal population.

OBJECTIVES: It has been well established that peripheral mechanical resonant factors as well as central mechanisms may play a role in the generation of physiological tremor (PT). Furthermore it has been postulated that subject's attributes like age and sex might influence PT. The present study was designed to quantify these influences on PT in a large normal population. METHODS: Physiological hand and finger tremors were measured in a group of 117 normal subjects between 20 and 94 years of age using accelerometry and surface EMG recordings from the forearm flexor and extensor muscles. The hand tremor was measured in a postural position with and without weight, and the finger tremor was recorded with the arm outstretched, forearm supported and hand supported. Hand volume and grip force were measured in each subject. RESULTS: Hand tremor frequency (mean 7.7 Hz) was reduced significantly by added inertia (mean 5.2 Hz) and it was negatively correlated with hand volume while there was no correlation with grip force. Finger tremor showed, subject to the arm position, maximally 3 and at least two distinct frequency bands (1-4, 6-11 and 15-30 Hz) reflecting the resonance frequencies of the whole arm, the hand and the finger, respectively. A significant EMG peak was found in 50-80% of the recordings. This EMG synchronization gave rise to a corresponding accelerometer peak or a significant EMG-EMG coherence in about one-third of the population indicating a central component of PT because its frequency was unaffected by mechanical changes in the periphery. We did not find a significant influence of age on the tremor frequency, while the sex of the subjects slightly but significantly changed the frequency range of hand tremor. Multiple partial correlations revealed, however, that the only direct influence on hand tremor frequency is the hand volume indicating that the influence of sex on hand tremor frequency is an indirect effect produced by the significantly larger hands of male subjects. CONCLUSIONS: In conclusion, the main determinants of PT are the mechanical properties of the oscillating limb. Apart from the dominating peripheral resonance mechanism we found indications of an additional central component of PT in about one-third of the normal population. There was no age dependence of tremor frequency and it was shown that the influence of the subjects' sex on tremor frequency only represents an indirect mechanical effect.     

Clinical and electromyographic examinations of Parkinsonian tremor

Background: The clinical presentations of postural Parkinsonian tremor are variable and different types of tremors have been described. The aim of this study was to re-evaluate the clinical and electromyographic (EMG) pattern of different tremors in Parkinsonian patients.

Methods: One hundred and ten patients with Parkinsonian tremor were included in the study. Patients were subdivided into four groups according to the presence or absence of postural tremor, in addition to a resting tremor and its EMG pattern. The first group consisted of patients without postural tremor. The second group consisted of patients with fast postural tremor (>7 Hz). The third group consisted of patients with slow postural tremor with alternating EMG activity. Patients with slow postural tremor with synchronous EMG activity were included in the fourth group. In each limb position, the tremor of the most involved body part was graded on the Webster Tremor Scale. Surface EMG recordings of the most involved limb in all positions were performed.

Results: Postural tremor in addition to the rest one was found in 84% of the patients. The postural tremor was with lower amplitude than the rest one. The frequencies and EMG patterns of the postural tremors were different and correlated with some specific clinical symptoms. Patients with alternating postural tremor had a kinetic and intention tremor in addition.

Conclusions: Four different subtypes of Parkinsonian tremor were found according to the presence and type of postural tremor. These subtypes had some differing clinical characteristics and probably different relationships to essential tremor.     

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.     

Sway patterns in orthostatic tremor: impairment of postural control mechanisms.

Sway parameters in orthostatic tremor (OT) patients were compared with age-matched controls. The effects of vision (eyes open or closed), stance width (feet apart or together), and external support (with or without) on sway and 14-18 Hz energy were measured. Sway in OT patients decreased in the presence of each of the stabilizing factors but the extent of benefit obtained by OT patients was significantly less than controls for support for the sagittal plane (22% vs. 42% decrease; P < 0.01) and feet apart in the mediolateral plane (38% vs. 65% decrease; P < 0.01). Three patients with proprioceptive loss also had a reduced response to these factors. Energy in the 14-18 Hz range did not always change in parallel with sway levels. Vision suppresses activity at the OT frequency in patients. Postural control mechanisms in OT remain responsive to postural conditions, but patients differ significantly from normals in the degree of their responsiveness. OT appears to have disruption of the normal generation or processing of proprioceptive signals as one of its important components.     

Myoclonus or tremor in orthostatism: an under-recognized cause of unsteadiness in Parkinson's disease.

Patients with Parkinson's disease (PD) often complain of unsteadiness. This can occur as the result of various neurological dysfunctions, including changes in postural adjustments, loss of postural reflexes, axial akinesia and rigidity, freezing and/or postural hypotension. In some cases these symptoms remain unexplained, and rare cases of unsteadiness have been attributed to tremor on standing. To delineate this condition, we investigated 11 consecutive PD patients with unexplained unsteadiness because of tremor on standing, seen in our department over a 6-year period. All the patients had detailed clinical and electrophysiological investigations based on surface polygraphic electromyographic recordings. Four patients had fast orthostatic tremor (13-18 Hz), one had intermediate orthostatic tremor (8-9 Hz), and three had slow orthostatic tremor (4-6 Hz). The remaining 3 patients had orthostatic myoclonus, a condition that has not previously been reported in PD. Patients with fast tremor improved on clonazepam. Patients with slow tremor and myoclonus improved on levodopa and sometimes benefited further when clonazepam was added. These observations show the usefulness of neurophysiological investigations for diagnosing and treating unexplained unsteadiness in Parkinson's disease.     

Palatal myoclonus associated with extremity tremor

Summary Palatal myoclonus associated with extremity movements such as myoclonus or tremor is uncommon and reports are rare. Five patients with palatal myoclonus and a rest tremor are presented. In four patients, a slow rest tremor (3 Hz or less) was present. The tremor persisted on sustained posture and finger-to-nose maneuvers and was usually not synchronous with the palatal movements. It was not associated with clinical manifestations of Parkinson's disease and occurred in conjunction with brain-stem infarction in three patients.     

Amitriptyline enhances the central component of physiological tremor

OBJECTIVES: Postural tremor is a regularly encountered side effect of amitriptyline which can be strong enough to cause discontinuation of therapy. The aim was to characterise amitriptyline induced tremor and to assess if the central or reflex component of physiological tremor was modulated by this drug. METHODS: The postural hand tremor was measured in 15 patients on a clinical rating scale, by power spectral analysis of accelerometer, forearm flexor, and extensor EMG before and after the beginning of amitriptyline treatment for major depression or chronic pain syndrome. A coherence analysis between flexor and extensor muscles on the same side was performed. RESULTS: There was a clinically visible increase in postural tremor in a third of these patients. The tremor amplitude measured by accelerometer total power increased in every patient under amitriptyline. The EMG synchronisation as reflected by significant peaks in the flexor or extensor spectrum generally occurring at higher frequencies (8-18 Hz) than the accelerometric tremor frequencies (6-11 Hz) did not change. The number of patients with a significant flexor-extensor coherence in the 7-15 Hz range increased significantly under amitriptyline, the frequency bands of significant coherence corresponded with the EMG frequencies, and both were independent of changes to the hand's resonant frequency by added inertia. CONCLUSIONS: An enhancement of postural tremor under amitriptyline is a common phenomenon although not always clinically apparent. The increase in EMG-EMG coherence indicates an increased common central drive to the motor units as its frequency is not influenced by peripheral resonance or reflex mechanisms. This is the first account of a drug induced enhancement of the central component of physiological tremor.     

Characterization of subclinical tremor in Parkinson's disease.

The physiological or pathological nature of subclinical tremor amplitude in Parkinson's disease (PD) is not well established. We analyzed characteristics of resting and postural tremors of subclinical amplitude in 17 patients with idiopathic PD without visible resting tremor, having a postural tremor in their least-affected hand rated 0 (12 subjects) or 1 (5 subjects) on Item 21 of the Unified Parkinson's Disease Rating Scale, compared to 17 control subjects matched for age, sex, and handedness. Tremor was recorded at the tip of the index finger using a displacement laser transducer. Overall results show that subclinical resting tremor in PD is significantly different from physiological tremor in terms of amplitude fluctuation, frequency dispersion, harmonic index, and proportional power in 4 to 6 Hz. No significant differences were found for postural tremor. These differences appear to originate mainly from patients with the mixed form of the disease. This study also confirms the preservation of physiological tremor likely originating from a distinct central oscillator in PD. The use of this method in the early and detailed characterization of PD tremors when amplitude is still within normal limits is proposed.     

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.     

Primary orthostatic tremor: further observations in six cases

Summary The clinical and physiological features of six new patients with primary orthostatic tremor are described. We suggest that use of the term primary orthostatic tremor be confined to the clinical syndrome in which unsteadiness when standing is the predominant complaint and accompanied by characteristic electrophysiological findings of a rapid (frequency around 16 Hz), regular leg tremor which is not influenced by peripheral feedback, is synchronous between homologous leg muscles, and in certain postures of the upper limbs, between muscles of the arm and leg. The fast frequency of muscle activity in primary orthostatic tremor of the legs causes unsteadiness when standing (presumably due to partially fused muscle contraction) but only a fine ripple of muscle activity is visible. In contrast, the slower frequency of other leg tremors, for example essential tremor, results in obvious leg movement which is evident in many leg postures, is variable over time and can be reset by a peripheral nerve stimulus. Essential tremor and orthostatic tremor do not respond to the same therapies, suggesting differences in the pharmacological profiles of the two conditions. Accordingly, there are clinical, physiological and pharmacological differences between primary orthostatic and essential tremor. Whether these factors are sufficient to regard these tremors as separate conditions is discussed.