Proximal Tremor Research Articles

A case of treatable encephalopathy, developmental regression, and proximal tremor

Tyrosine hydroxylase (TH) deficiency is an autosomal recessive condition first described as a progressive, early-onset hypokinetic-rigid and dystonic syndrome that was responsive to levodopa. Here we present a child with developmental regression, proximal tremor, and encephalopathy found to have tyrosine hydroxylase deficiency in whom treatment resulted in acquisition of developmental milestones.

Thalamic versus midbrain tremor; two distinct types of Holmes' Tremor: a review of 17 cases.

Holmes Tremor (HT) is a unique and debilitating movement disorder. It usually results from lesions of the midbrain and its connection but can also result from posterior thalamic injury. Clinical examination can help lesion localization between these two areas. We studied the clinical features and their radiological correlations to distinguish midbrain HT (HT-m) from thalamic HT (HT-t). Retrospective review of 17 patients with a HT-type presentation was conducted. Tremor characteristics, associated clinical signs and radiological findings were studied. Eleven patients had a myorythmic rest tremor, large amplitude proximal tremor with goal-directed worsening, with or without mild distal dystonic posturing, representing HT-m. Six patients had slow, large amplitude proximal tremors and distal choreathetoid movements, significant proximal/distal dystonic posturing, associated with proprioceptive sensory loss, representing HT-t. Haemorrhagic lesions were the predominant cause of HT-m; whereas, ischaemia was more commonly associated with HT-t. When assessing patients with HT, attentiveness to the presence of associated signs in the affected limb, such as a proprioceptive sensory deficits and additional movement disorders, can aid lesion localisation, which can have implications for management.

Deep Brain Stimulation and Swimming Performance: A Randomized Within-Person Crossover Study.

To determine whether deep brain stimulation (DBS) causes swimming impairment, we systematically compared swimming ability between DBS on vs off in 18 patients. We conducted a randomized blinded crossover study, comparing swimming ability between DBS on vs off, within participants. Participants swam 3 laps of front crawl and 3 laps of breaststroke. Prespecifed primary outcomes were proportion of lap completed, lap time, and Aquatic Skills Proficiency Assessment (ASPA) score. Prespecified secondary outcomes were a qualitative description of marked changes observed. Eighteen participants with Parkinson disease (n = 13), essential tremor (n = 3), Tourette syndrome (n = 1), or posttraumatic brain injury proximal tremor (n = 1), treated with posterior subthalamic area (n = 15) or globus pallidus interna (n = 3) DBS were assessed. There was no significant effect of DBS on/off status on any outcome measure for front crawl or breaststroke. Three participants showed changes in both qualitative and quantitative assessments. Of these, 1 participant displayed reduction in swimming ability: impairment in all outcomes with DBS on, normalizing with DBS off (the same individual as previously reported). The participant displayed difficulty coordinating limb movement as well as postural control. Two participants showed improvements in lap time and ASPA scores with DBS on. Overall DBS did not impair swimming performance, although 1 patient demonstrated a stimulation-induced drowning hazard. There were no anatomic or clinical features unique to the individual with swimming impairment. Patients should be warned about the possibility of DBS-induced drowning hazard and should swim with capable supervision after DBS. This study provides Class IV evidence that for patients with implanted DBS electrodes, the stimulation on condition, compared with stimulation off, did not significantly impair swimming performance. A formal assessment of unblinding would have been helpful.

Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Refractory Holmes Tremor

Three right-handed patients diagnosed with Holmes tremor (HT), who suffered from pharmacotherapy-refractory tremor, were eligible for unilateral posterior subthalamic area deep brain stimulation (PSA-DBS). All patients were evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Clinical Global Impression scale (CGI) before DBS, 6, and 12 months after the PSA-DBS as well as at the last follow-up. In all patients, we observed a significant improvement of tremor control as demonstrated by changes in the FTMTRS and the CGI scales. Mean improvement of tremor in all patients was 56% for the FTMRTS with a corresponding change in the CGI scale. Our study demonstrates that PSA-DBS is efficacious in the treatment of HT. Indeed, PSA is a promising target for DBS for intractable proximal and distal tremor, even in cases of previous, suboptimal functional neurosurgery. The beneficial effect lasts over a long-term follow-up. PSA-DBS may be considered as an alternative target of DBS in tremor treatment.

Treatment of Hemichoreoathetosis with Arrhythmic Proximal Tremor after Stroke: The Role of Zona Incerta as a Target for Deep Brain Stimulation.

Deep brain stimulation (DBS) of the zona incerta has shown promising results in the reduction of medically refractory movement disorders. However, evidence supporting its efficacy in movement disorders secondary to hemorrhagic stroke or hemichoreoathetosis is limited. We describe a 48-year-old man who developed progressive hemichoreoathetosis with an arrhythmic, proximal tremor in his right arm following a thalamic hemorrhagic stroke. Pharmacological treatment was carried out with no change in the Abnormal Involuntary Movement Scale (AIMS) score after 4 weeks (14). After six sessions of botulinum toxin treatment, a subtle improvement in the AIMS score (13) was registered, but no clinical improvement was noted. The arrhythmic proximal movements were significantly improved after DBS of the zona incerta with a major decrease in the patient’s AIMS score (8). The response to DBS occurring after the failure of pharmacological and botulinum toxin treatments suggests that zona incerta DBS may be an alternative for postthalamic hemorrhage movement disorders.

Objective predictors of ‘early tolerance’ to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients

ObjectiveTo identify pre-operative clinical and computerized spiral analysis characteristics that may help ascertain which patients with Essential Tremor (ET) will exhibit ‘early tolerance’ to ventral intermediate nucleus of thalamus (Vim) deep brain stimulation (DBS). MethodsIdentification of comparative characteristics of defined cases of ‘early tolerance’ versus patients with sustained satisfactory response treated with Vim DBS surgery for medically-refractory ET, based on retrospective chart review by a clinician blinded to the findings of computerized spiral analysis. ResultsStatistically significant differences in two spiral analysis indices, SWVI and DoS, were found in the dominant upper limbs of patients who developed ‘early tolerance’, whereas the clinical characteristics were not significantly different. ConclusionObjective measurements of upper limb kinematics using graphonomic tests like spiral analysis should be considered in the pre-operative evaluation for DBS, especially in the setting of moderate-severe predominantly action and proximal postural tremors. SignificanceOurs is the first investigation looking into the pre-operative clinical and objective physiologic characteristics of the patients who develop ‘early tolerance’ to Vim DBS for the treatment of essential tremor. The study has significant implications for pre-operative evaluation and potential surgical target selection for the treatment of tremors.

Postoperative neuroimaging analysis of DRT deep brain stimulation revision surgery for complicated essential tremor

BackgroundWe report a patient who received conventional bilateral deep brain stimulation of the ventral intermediate nucleus of thalamus (Vim) for the treatment of medication refractory essential tremor (ET). After initial beneficial effects, therapeutic efficacy was lost due to a loss of control of his proximal trunkal and extremity tremor. The patient received successful diffusion tensor magnetic resonance imaging fiber tractographic (DTI FT)-assisted DBS revision surgery targeting the dentato-rubro-thalamic tract (DRT) in the subthalamic region (STR).ObjectiveTo report the concept of DTI FT-assisted DRT DBS revision surgery for ET and to show sophisticated postoperative neuroimaging analysis explaining improved symptom control.MethodsAnalysis was based on preoperative DTI sequences and postoperative helical computed tomography (hCT). Leads, stimulation fields, and fibers were reconstructed using commercial software systems (Elements, Brainlab AG, Feldkirchen, Germany; GUIDE XT, Boston Scientific Corp., Boston, MA, USA).ResultsThe patient showed immediate and sustained tremor improvement after DTI FT-assisted revision surgery. Analysis of the two implantations (electrode positions in both instances) revealed a lateral and posterior shift in the pattern of modulation of the cortical fiber pathway projection after revision surgery as compared to initial implantation, explaining a more efficacious stimulation.ConclusionsOur work underpins a possible superiority of direct targeting approaches using advanced neuroimaging technologies to perform personalized DBS surgery. The evaluation of DBS electrode positions with the herein-described neuroimaging simulation technologies will likely improve targeting and revision strategies. Direct targeting with DTI FT-assisted approaches in a variety of indications is the focus of our ongoing research.

Treatment of proximal upper limb tremor with botulinum toxin therapy

Proximal-dominant upper limb tremor is highly disabling, and there is no effective medical therapy. In this study, we evaluated the efficacy of botulinum toxin (BTX) injections for the treatment of proximal tremor. We conducted a retrospective analysis of open-label treatment with BTX in 19 patients with proximal tremor. The response to therapy was graded into four categories according to self-reported improvements in tremor and function. In total, 63% of patients reported moderate or marked benefit, defined as functional improvements sufficient enough to allow feeding or drinking from a cup; whereas 21% of patients reported mild benefit; and 15% of patients reported no benefit. One patient developed severe weakness of shoulder abduction and withdrew from the treatment; otherwise, the therapy was free of side effects. The current findings support the efficacy of BTX therapy in the treatment of proximal upper limb tremor with minimal side effects.

Post subthalamic area deep brain stimulation for tremors: a mini-review

Deep brain stimulation (DBS) in the thalamic ventrointermediate nucleus (VIM) is the traditional target for the surgical treatment of pharmacologically refractory essential tremor or parkinsonian tremor. Studies in recent years on DBS in posterior subthalamic area (PSA), including the zona incerta and the prelemniscal radiation, have shown promising results in tremor suppression, particularly for those tremors difficult to be well controlled by VIM DBS, such as the proximal postural tremor, distal intention tremor and some cerebellar outflow tremor in various diseases including essential tremor and multiple sclerosis. The adverse effect profile of the PSA DBS is mild and transient, without lasting or striking dysarthria, disequilibrium or tolerance, in contrast to VIM DBS, particularly bilateral DBS. However, the studies on PSA DBS so far are still limited, with a handful of studies on bilateral PSA, and a short follow up duration compared to VIM. More studies are needed for direct comparison of these targets in the future. A review here would help to gain more insight into the benefits and limits of the PSA DBS compared to that in VIM in the clinical management of various tremors, particularly for those difficult to be well controlled by traditional VIM DBS.

ABNORMAL EYE MOVEMENTS IN KENNEDY DISEASE

Kennedy disease, also known as spinal and bulbar muscular atrophy, is a neurodegenerative disease affecting lower motor neurons.1 The underlying genetic abnormality, a triplet (CAG) repeat expansion in the androgen receptor gene on the X chromosome, produces a toxic polyglutamine expansion in the androgen receptor protein.2 The disease is characterized by slowly progressive proximal muscle atrophy, weakness, and fasciculations, with prominent bulbar involvement, tremor, and, reportedly, sparing of eye movements.1,3,4 Stigmata of androgen insufficiency, such as gynecomastia, may be present.3 We report a patient with genetically confirmed Kennedy disease who had abnormal eye movements. ### Case report. A 58-year-old Caucasian man with a history of dyslipidemia and bilateral retinal detachments presented with progressive onset of proximal muscle atrophy, weakness, fasciculations, and tremor over 20 years. He also reported a progressive decline in mobility and fine motor control, as well as dysarthria and dysphagia. He denied sensory symptoms, sphincter disturbance, or visual symptoms, such as diplopia. On examination, there was atrophy of facial, bulbar, and limb muscles. Perioral, tongue, and limb muscle fasciculations were noted. There was moderate weakness of facial, palatal, tongue, and proximal limb muscles, with milder weakness of distal limb muscles. The reflexes were depressed and the plantar responses flexor. There were no cerebellar signs. Mild distal sensory loss was noted in the lower limbs. Visual acuity and color vision were within normal limits. Visual fields were full to confrontation. There was no optic atrophy, and his pupillary responses were normal. Ocular motor examination revealed a small exophoria, no …

Bilateral stimulation of the caudal zona incerta nucleus for tremor control

Introduction:The ventrolateral (VL) nucleus of the thalamus is the commonly chosen target for deep brain stimulation (DBS) to alleviate tremor. However, it has a poor efficacy in alleviating proximal tremor...

Síndrome neurológico de alta presión

Pressure is a thermodynamic variable that, like temperature, affects the states of matter. High pressure is an environmental characteristic of the deep sea. Immersion to depth brings about an increase in pressure of 0.1 MPa (1 atm) for each 10 m of seawater. Humans exposed to high pressure, mostly professional divers, suffer effects that are proportional to their exposure. The nervous system is one of the most sensitive targets of high pressure. The high pressure neurological syndrome (HPNS) begins to show signs at about 1.3 MPa (120 m) and its effects intensify at greater depths. HPNS starts with tremor at the distal extremities, nausea, or moderate psychomotor and cognitive disturbances. More severe consequences are proximal tremor, vomit, hyperreflexia, sleepiness, and psychomotor or cognitive compromise. Fasciculations and myoclonia may occur during severe HPNS. Extreme cases may show psychosis bouts, and focalized or generalized convulsive seizures. Electrophysiological studies during HPNS display an EEG characterized by reduction of high frequency activity (alpha and beta waves) and increased slow activity, modification of evoked potentials of various modalities (auditory, visual, somatosensory), reduced nerve conduction velocity and changes in latency. Studies using experimental animals have shown that these signs and symptoms are progressive and directly dependent on the pressure. HPNS features at neuronal and network levels are depression of synaptic transmission and paradoxical hyperexcitability. HPNS is associated with exposure to high pressure and its related technological means. Experimental findings suggest etiological hypotheses, prevention and therapeutic approaches for this syndrome.

FC37.1 Differentiating distal and proximal arm tremor by the direction of oscillation in spiral drawings

FC37.1 Differentiating distal and proximal arm tremor by the direction of oscillation in spiral drawings

The direction of oscillation in spiral drawings can be used to differentiate distal and proximal arm tremor

The assessment of the extent of involvement of the distal and proximal joints in a complex arm tremor is important clinically, as tremor generated around the distal and proximal arm joints can be differentially alleviated by surgical intervention to the thalamic and subthalamic targets, respectively. We observed that the tremor present in spiral drawings shows a diagonal directional preference. We hypothesized that the directional preference of tremor within spiral drawings could be related to the involvement of different arm joints. In this study, we tested this hypothesis by: (1) studying simulated tremulous drawings performed by healthy subjects with the joints selectively restrained; (2) recording surface EMGs from the forearm extensor and deltoid muscles during drawing; and (3) mathematical modelling the kinematics of the arm in 2D drawings. Our data showed that a “main diagonal” axis of orientation of the tremor along the orientation of the forearm indicates a predominantly proximal tremor driven by the shoulder, and a “cross diagonal” axis of orientation of tremor (i.e. perpendicular to the forearm) indicates that the tremor is predominantly distal and driven by the elbow or wrist. We conclude that the spiral drawing task can be used as an objective and quantitative method for differentiating the involvement of the proximal and distal arm joints in complex arm tremors.

Mechanical Injury of the Subthalamic Area During Stereotactic Surgery Followed by Improvement of Trunk, Neck, and Face Tremor-Case Report-

A 50-year-old man had undergone right nucleus ventrointermedius (Vim) thalamotomy 1 year previously, resulting in the disappearance of left hand tremor. However, he presented with right distal and proximal tremor including the axial trunk, neck, and head. Deep brain stimulation (DBS) of the left Vim for these symptoms was unsuccessful. Attempts were made to stimulate the left Vim, nucleus ventralis lateralis, and subthalamic nucleus (STN), but no significant improvement was obtained after repeat surgery. However, subsequent improvement of the symptoms including proximal tremor was very marked even without DBS stimulation. Brain magnetic resonance imaging demonstrated lesion and edema in the posteromedial area of the STN. Mechanical injury of the area caused by the surgical procedures may have contributed to the improvement in his persistent symptoms.

Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy: Report of New Cases and Review of the Literature

Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterised by loss of motor function and muscle atrophy due to anterior horn cell degeneration. The most common variant is chromosome 5-linked proximal SMA, ranging in severity from congenital onset and infantile death to onset in adult life. Genetically separate variants with different distribution of weakness and/or additional features such as central nervous system involvement have been described. A rare variant with associated myoclonic epilepsy and lower motor neuron disease had been previously described in three families before the SMN gene, responsible for the common form of SMA, was isolated. We report four patients from two additional families affected by a syndrome characterised by severe and progressive myoclonic epilepsy and proximal weakness, tremor and lower motor neuron disease proven by electrophysiologic and muscle biopsy findings. Extensive metabolic investigations were normal and genetic analysis excluded the SMN gene. This study confirms that the association of myoclonic epilepsy and motor neuron disease represents a separate clinical and genetic entity from chromosome 5-linked SMA, the primary defect of which remains unknown.

Deep brain and motor cortex stimulation for post-stroke movement disorders and post-stroke pain.

Our experience of deep brain stimulation (DBS) and motor cortex stimulation (MCS) in patients with post-stroke movement disorders and post-stroke pain is reviewed. DBS of the thalamic nuclei ventralis oralis posterior et intermedius proved to be useful in more than 70% of patients with post-stroke involuntary movements (hemiballismus, hemichoreo-athetosis, distal resting and/or action tremor, and proximal postural tremor). The effect of DBS of the thalamic nucleus ventralis caudalis or internal capsule on post-stroke pain was usually disappointing. Excellent pain control can be achieved by MCS in approximately 50% of patients with post-stroke pain. In the course of clinical trials on MCS for the control of post-stroke pain, it was found that co-existent post-stroke involuntary movements (hemichoreo-athetosis and resting tremor) could also be controlled by MCS. Post-stroke involuntary movements, especially those in thalamic syndrome, are sometimes associated with post-stroke pain. In such disorders, involuntary movements are attenuated, but the pain in the same patients is often exacerbated by DBS of the thalamic nuclei ventralis oralis posterior et intermedius. MCS could be the therapy of choice under such circumstances. Subjective improvement of voluntary motor performance, which had been impaired in association with mild or moderate hemiparesis, was reported during MCS by approximately 20% of patients with post-stroke pain. Such an effect on voluntary motor performance appears to be caused by an inhibition of their rigidity. The reversibility of DBS and MCS makes them an important option for the control of post-stroke movement disorders and post-stroke pain.

Deep brain stimulation for tremor [correction of trauma]: patient selection and evaluation.

The selection of patients with movement disorders for deep brain stimulation is becoming a common neurological and neurosurgical task. Deep brain stimulation is suitable for different forms of tremor, which can often not be treated with medication. This suitability applies for essential tremor, monosymptomatic tremor at rest, cerebellar or multiple sclerosis tremor, Holmes' tremor, primary writing tremor or tremor in neuropathies. The appropriate selection of patients is critical for the outcome of surgical relief of tremors. Considering the risks of any stereotactic intervention, the following must apply: (1) motor symptoms lead to a relevant disability in activities of daily living, despite optimal medical treatment; (2) biological age of the patient; (3) neurosurgical contraindications; (4) the patient is neither demented nor severely depressed. If these conditions are fulfilled, the individual chances of improvement of the target symptoms need to be checked, based on the following guidelines: (1) the kind of tremor, (2) the natural course of the tremor, (3) the chances for medical treatment in a particular patient, (4) the outcome of surgery in a specific condition, (5) the individual risks for a patient to suffer from complications. The outcome of surgery for tremor depends on the clinical type and distribution. Distal limb tremors are easier to treat than proximal limb tremors. Intention tremor is more difficult to treat than rest or postural tremor. The indication for surgical treatment depends on the analysis of the individual risk-benefit ratio, which also has to take into account the patients' social, professional, and familial background. The patient needs to be well informed about his individual risk-benefit ratio and of alternative treatments, before undergoing stereotactic surgery.

Control of post-stroke movement disorders using chronic motor cortex stimulation.

The effects of motor cortex (MC) stimulation on post-stroke movement disorders were analyzed in 50 patients. These individuals either underwent MC stimulation primarily for the purpose of controlling their post-stroke involuntary movements (n = 8) or underwent MC stimulation for the purpose of controlling their post-stroke central pain (n = 42). In the latter patients, the effects of MC stimulation on co-existent involuntary or voluntary movement disorders were analyzed retrospectively. Good control of involuntary movements was observed in 2 of 3 patients with hemichoreo-athetosis, 2 of 2 patients with distal resting or action tremor, and 1 of 3 patients with proximal postural tremor. Subjective improvements in motor performance were reported by 8 patients who had mild motor weakness, and the effects appeared to be attributable to attenuation of rigidity. We consider that these findings justify further clinical studies on MC stimulation for the control of post-stroke movement disorders.

脳卒中後不随意運動の脳内植込み電極と体内埋設刺激ディバイスによる制御

Involuntary movements are not uncommon consequences of stroke, which limit patients' daily activity greatly. Ablative neurosurgical procedures, such as thalamotomy and pallidotomy, for control of involuntary movements always carry a risk associated with creating additional lesions in an already damaged brain, and the results of these procedures are not always satisfactory. Due to the unpredictability of the effects and the irreversibility of the procedures, most physicians have been reluctant to recommend ablative neurosurgical treatments to their patients whose brain is already damaged by stroke. In contrast, there is not such a risk in deep brain stimulation (DBS) therapy. Based on our experience with 25 patients with post-stroke involuntary movements, clinical values of DBS are summarized. A quadripolar DBS electrode is placed in such a way that the most distal contact is located on the ventral part of thalamic VIM nucleus and the most proximal contact in the dorsal part of VOP nucleus. Complete control of involuntary movements has been achieved by DBS in many patients (76%) with hemiballism, hemichoreo-athetosis, jerky dystonic unsteady hand, distal resting and/or action tremor and proximal postural tremor. The effects have continued to be seen for the entire follow-up period ranging 1-9 years in our series. DBS is an ideal therapeutic option to control post-stroke involuntary movements due to the reversibility of the procedure, and alterability of anatomical location and extent of stimulation.