Involuntary Movements In Patients Research Articles

Association of early-onset epileptic encephalopathy with involuntary movements – Case series and literature review

Epileptic-dyskinetic encephalopathies are rare epilepsies characterized by early-onset epileptic encephalopathies (EOEEs) with involuntary movement. Herein, we investigated the impact of gene variants in epileptic-dyskinetic encephalopathies. Four independent patients from four families who exhibited involuntary movements were recruited from Tokyo Metropolitan Neurological Hospital. The inclusion criteria were as follows: onset within 1year after birth, frequent seizures, severe developmental delay and accompanying involuntary movements. We detected four genetic mutations, including STXBP1, GNAO1, CYFIP2, and SCN8A variants. The involuntary movements were drug-resistant. However, pallidal electrocoagulation followed by gabapentin were partially effective in treating chorea and ballismus of the extremities in patients with GNAO1 variants, and perampanel partially suppressed seizures and involuntary movements in one patient with a SCN8A variant. Movement disorders are common to many neurodevelopmental disorders, including a variety of EOEEs. Although we could not establish a definitive correlation using genetic variants in patients with EOEE and movement disorders, involuntary movements in patients with EOEEs may be a key diagnostic finding. The usage of genetic variants could prove beneficial in the future as more patients are investigated with epileptic-dyskinetic encephalopathies.

Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia

ABSTRACT Introduction: Tardive dyskinesia (TD) is a hyperkinetic movement disorder that arises as a complication of exposure to dopamine receptor blocking agents. Vesicular monoamine transporter type 2 (VMAT2) inhibitors reduce dyskinesia by decreasing transport of monoamines, including dopamine, into presynaptic vesicles, leaving unpackaged dopamine to be metabolized by monoamine oxidase. Deutetrabenazine was adapted from an earlier VMAT2 inhibitor, tetrabenazine, by substituting three deuterium isotopes in place of three hydrogen isotopes at the site of metabolic degradation to improve upon the pharmacokinetics of the parent compound. Areas covered: The authors reviewed the pivotal trials examining the safety and efficacy of deutetrabenazine, as well as long-term data from an open-label extension. Also reviewed were posters and oral presentations, as well as information from the product label and the United States Food and Drug Administration. Expert opinion: Deutetrabenazine is effective at decreasing dyskinesia in TD, but drug selection and cost-effectiveness between existing VMAT2 inhibitors are evolving areas of study. Other areas of investigation include novel anti-dyskinetic agents and use of deep brain stimulation.

EVALUATE CLINICAL EFFICACY OF BIOCERAMIC TECHNOLOGY ON PSYCHOPATHICALLY RELATED SPASMODIC TORTICOLLIS USING MOTION MEASUREMENTS, COMPUTERIZED ANALYSIS OF FACIAL EMOTIONS AND SPEECH SIGNAL FEATURES

Objective: Spasmodic torticollis is a debilitating neurological movement disorder associated with somatization, obsessive-compulsive, interpersonal sensitivity, depression, and anxiety. Usually, clinician had difficulty to precisely and quantitatively describe clinical outcomes using measurements of patients’ facial and neck movements. Methods: Motion speed changes and direction complexity, computerized facial emotion and assessment, measurement of speech signal features are the quantitative measurements of patients’ head motions, facial expressions, and speech signal features analysis were used to assess clinical effects of bioceramic resonance and photoluminescence of bioceramics (BR&PLB) treatment of psychopathically related spasmodic torticollis. Results: After BR&PLB treatment, there were significant improvements in involuntary movements of patients with spasmodic torticollis measured by motion speed changes and direction complexity (MSCDC). Furthermore, a computerized facial emotion assessment (CFEA) showed that patients expressed greater positive emotions after treatment. Finally, we also performed quantitative assessments on voice analysis of speech signal features (SSF). Conclusions: Our study had achieved three major factors: (i) the clinical efficacy of BR&PLB on psychopathically related spasmodic torticollis; (ii) motion manifestations of spasmodic torticollis in “speed” and “direction” of muscular movements as assessed using “motion measurements” of a computer vision system; and (iii) psychological and emotional factors being directly correlated with the severity of spasmodic torticollis which improved after BR&PLB, and could be qualitatively assessed using FaceReader. This study encourages further investigations of the clinical efficacy of Bioceramic technology on psychopathically related repetitive behavior disorders, and demonstrates effectiveness of MSCDC, CFEA and SSF in providing quantitative assessments of emotion.

P80-F The spectrum of involuntary movements in patients with motor neuron disease – A cross-sectional study

Background We have commonly observed involuntary jerks and tremor in patients with otherwise typical motor neuron disease (MND). We conducted prospective clinical study to explore their prevalence and phenomenology. Materials and methods Seventy-four consecutive patients were clinically examined by movement disorders specialists. Based on regularity and distribution, movements observed at rest were classified as minipolymioclonus (MPMC) or rest thumb tremor (RTT) and movements present during action as action MPMC or action tremor. Results Involuntary movements (IMs) were present in 54 patients (73%). Rest MPMC was present in 26 (35%), RTT in 22 (31%), action MPMC in 22 (30%) and action tremor in 20 patients (27%), with some overlap. Sixteen patients (22%) reported negative impact of IMs on their ability to use hands. Regression model showed that lower distal muscle power and less prominent upper motor neuron (UMN) signs significantly increased the probability of I. Conclusions IMs are common yet largely overlooked feature of MND and may have negative impact on patient’s functional abilities. Lower distal muscle power increased the probability of IMs of fingers and wrist, suggesting that generation of IMs in MND patients is associated with muscle weakness. The presence of UMN signs decreased the probability of IMs, possibly by increasing muscle and joint stiffness. Overall, our findings suggest IMs in MND patients are of peripheral origin. We propose that IMs are caused by activation of enlarged motor units without sufficient previous recruitment of smaller units to smooth their contraction during action and by their spontaneous firing at rest.

The History of Movement Disorder Brain Surgery.

The first surgical procedures for abnormal movement disorders began in the 1930s, when surgeons first proposed ablative techniques of the caudate nucleus or transection of motor (pyramidal) pathways to reduce involuntary movements in patients with Parkinson's related tremor. During the 50-year interval between 1945 and 1995, the development of precise intracranial guiding devices, brain maps, and advanced imaging led to the refinement of appropriate deep brain targets affecting extrapyramidal pathways. Lesional surgery and subsequent neuroaugmentation using deep brain stimulation extended the role of deep brain surgery for a wider group of patients with tremor, rigidity, dyskinesia, and other involuntary movement disorders. Stereotactic radiosurgery has had wide application for tremor. The history of movement disorder surgery reads like a who's who of brilliant and resourceful surgeons who pushed the frontiers of neurosurgery. Even today, practitioners of functional brain surgery are among the most innovative practicing neurosurgeons.

Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial

Tardive dyskinesia results from exposure to dopamine receptor antagonists, such as typical and atypical antipsychotics. If clinically appropriate, clinicians often manage this disorder by lowering the dose of, or discontinuing, the causative drug. There is a significant unmet need for a treatment option that does not disrupt treatment regimens for underlying psychiatric illnesses. We aimed to assess the efficacy, safety, and tolerability of fixed doses of deutetrabenazine-a novel vesicular monoamine transporter-2 inhibitor-in patients with tardive dyskinesia. We did this double-blind, randomised, placebo-controlled, phase 3 trial at 75 centres in the USA and Europe. Patients aged 18-80 years with tardive dyskinesia (≥3 months before screening) were randomly assigned centrally (1:1:1:1), via interactive response technology, to receive one of three fixed doses of deutetrabenazine (12 mg/day, 24 mg/day, or 36 mg/day) or matching placebo. Randomisation was stratified by baseline use of dopamine receptor antagonists. Patients were started on oral deutetrabenazine 12 mg/day, and this dose was increased through week 4 until the randomised dose was achieved, then maintained over 8 weeks. During the treatment period, patients, investigators, their site personnel, and sponsor were masked to group assignment. The primary efficacy endpoint was change in Abnormal Involuntary Movement Scale (AIMS) score from baseline to week 12 in patients with at least one post-baseline rating. The primary efficacy analysis was done in the modified intention-to-treat population (baseline AIMS score ≥6 and at least one post-baseline rating). The safety analysis was done in patients who received any study drug. This trial is registered with ClinicalTrials.gov, number NCT02291861. Between Oct 29, 2014, and Aug 19, 2016, we randomly assigned 298 patients to receive at least one dose of placebo (n=74), deutetrabenazine 12 mg/day (n=75), 24 mg/day (n=74), or 36 mg/day (n=75); 222 patients comprised the modified intention-to-treat population and 293 patients comprised the safety population. From baseline to week 12, the least-squares mean AIMS score improved by -3·3 points (SE 0·42) in the deutetrabenazine 36 mg/day group, -3·2 points (0·45) in the 24 mg/day group, and -2·1 points (0·42) in the 12 mg/day group, with a treatment difference of -1·9 points (SE 0·58, 95% CI -3·09 to -0·79; p=0·001), -1·8 points (0·60, -3·00 to -0·63; p=0·003), and -0·7 points (0·57, -1·84 to 0·42; p=0·217), respectively, versus -1·4 points (0·41) in the placebo group. The rate of adverse events was similar between patients in the deutetrabenazine 36 mg/day group (n=38/74 [51%]), 24 mg/day group (n=32/73 [44%]), and 12 mg/day group (n=36/74 [49%]), and those in the placebo group (n=34/72 [47%]). Serious adverse events were reported in four (5%) patients given deutetrabenazine 36 mg/day, six (8%) patients given 24 mg/day, and two (3%) patients given 12 mg/day, compared with four (6%) patients given placebo. Two (1%) patients in the safety population died, one each in the deutetrabenazine 24 mg/day and 36 mg/day groups; neither death was deemed related to study drug by the investigator or sponsor. Deutetrabenazine 24 mg/day and 36 mg/day provided a significant reduction in tardive dyskinesia, with favourable safety and tolerability. These findings suggest that dosing regimens could be individualised and tailored for patients on the basis of dyskinesia control and tolerability. Teva Pharmaceutical Industries.

Acute Chorea Onset after Hot Food Consumption in a Patient with Moyamoya Disease.

Acute Chorea Onset after Hot Food Consumption in a Patient with Moyamoya Disease.

Topiramate in children and adolescents with Tourette syndrome: A case series

The objective of this study is to evaluate the effect of topiramate on tics in patients with Tourette syndrome (TS). TS is a complex neurobehavioral disorder that emerges in childhood with widely varying patterns of intermittent involuntary/semivoluntary movements expressed as motor and vocal tics. Although neuroleptics are effective anti-tic agents, side effects such as tardive dyskinesia, weight gain, and hepatotoxicity can limit their usefulness. Our use of topiramate followed reports of its effectiveness in reducing involuntary movements in patients with essential tremor. Retrospective patient record was audited using a standardized data collection form in a general child neurology practice. Charts for topiramate-treated patients meeting diagnostic criteria for TS were reviewed. Data for tics, behavior disorders, medication history, and topiramate treatment were extracted. The Shapiro tic severity scale was used to quantify change from baseline. Of 39 children/adolescents with TS treated with topiramate, tic severity was reduced at least 50% in 23 (59%) patients, did not change in five (13%) patients and worsened in two (5%) patients. Topiramate was discontinued and not restarted due to side effects in seven (18%) patients. Topiramate appears to be useful in suppressing tics in patients with TS, but double-blind, randomized controlled studies are needed to document its efficacy.

Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements.

Deep brain stimulation of the globus pallidus internus alleviates involuntary movements in patients with dystonia. However, the mechanism is still not entirely understood. One hypothesis is that deep brain stimulation suppresses abnormally enhanced synchronized oscillatory activity within the motor cortico-basal ganglia network. Here, we explore deep brain stimulation-induced modulation of pathological low frequency (4-12 Hz) pallidal activity that has been described in local field potential recordings in patients with dystonia. Therefore, local field potentials were recorded from 16 hemispheres in 12 patients undergoing deep brain stimulation for severe dystonia using a specially designed amplifier allowing simultaneous high frequency stimulation at therapeutic parameter settings and local field potential recordings. For coherence analysis electroencephalographic activity (EEG) over motor areas and electromyographic activity (EMG) from affected neck muscles were recorded before and immediately after cessation of high frequency stimulation. High frequency stimulation led to a significant reduction of mean power in the 4-12 Hz band by 24.8 ± 7.0% in patients with predominantly phasic dystonia. A significant decrease of coherence between cortical EEG and pallidal local field potential activity in the 4-12 Hz range was revealed for the time period of 30 s after switching off high frequency stimulation. Coherence between EMG activity and pallidal activity was mainly found in patients with phasic dystonic movements where it was suppressed after high frequency stimulation. Our findings suggest that high frequency stimulation may suppress pathologically enhanced low frequency activity in patients with phasic dystonia. These dystonic features are the quickest to respond to high frequency stimulation and may thus directly relate to modulation of pathological basal ganglia activity, whereas improvement in tonic features may depend on long-term plastic changes within the motor network.

Dexmedetomidine suppressed involuntary movement in a patient with cerebral palsy.

Involuntary movements in patients with cerebral palsy can interfere with invasive procedures performed under sedation. We present a case of a 58-year-old man with cerebral palsy, who successfully underwent a cardiac catheterization while sedated with IV dexmedetomidine. The patient's involuntary movements were suppressed, which allowed the cardiologist to perform the procedure on an immobile, cooperative patient, all while maintaining patient comfort, stable hemodynamics, as well as adequate oxygenation and ventilation. This novel use of dexmedetomidine might facilitate monitored anesthesia care in patients otherwise requiring general anesthesia.

Assessment of involuntary choreatic movements in Huntington's disease—Toward objective and quantitative measures

Objective measures of motor impairment may improve the sensitivity and reliability of motor end points in clinical trials. In Huntington's disease, involuntary choreatic movements are one of the hallmarks of motor dysfunction. Chorea is commonly assessed by subitems of the Unified-Huntington's Disease Rating Scale. However, clinical rating scales are limited by inter- and intrarater variability, subjective error, and categorical design. We hypothesized that assessment of position and orientation changes interfering with a static upper extremity holding task may provide objective and quantitative measures of involuntary movements in patients with Huntington's disease. Subjects with symptomatic Huntington's disease (n = 19), premanifest gene carriers (n = 15; Unified-Huntington's Disease Rating Scale total motor score ≤ 3), and matched controls (n = 19) were asked to grasp and lift a device (250 and 500 g) equipped with an electromagnetic sensor. While subjects were instructed to hold the device as stable as possible, changes in position (x, y, z) and orientation (roll, pitch, yaw) were recorded. These were used to calculate a position index and an orientation index, both depicting the amount of choreatic movement interfering with task performance. Both indices were increased in patients with symptomatic Huntington's disease compared with controls and premanifest gene carriers for both weights, whereas only the position index with 500 g was increased in premanifest gene carriers compared with controls. Correlations were observed with the Disease Burden Score based on CAG-repeat length and age and with the Unified-Huntington's Disease Rating Scale. We conclude that quantitative assessment of chorea is feasible in Huntington's disease. The method is safe, noninvasive, and easily applicable and can be used repeatedly in outpatient settings. A use in clinical trials should be further explored in larger cohorts and follow-up studies.

Involuntary movement induced by cerebral ischemia: pathogenesis and surgical outcome.

Involuntary movement is an uncommon manifestation of a transient ischemic attack. It may be induced by cerebral hemodynamic insufficiency, which is associated with several cerebral ischemic diseases. The authors present three cases of limb shaking due to moyamoya disease (MMD) or radiation-induced middle cerebral artery stenosis, and three additional cases of choreic movement due to MMD. Neuroimaging studies and surgical outcomes in these patients were retrospectively analyzed to investigate the pathological mechanism underlying the symptoms and to provide guidance for the management of involuntary movement disorders in cases of ischemic cerebral disease. The patient population included two children and four adults with ages at presentation ranging between 7 and 50 years. The initial presenting symptoms were involuntary movements in all six cases. A magnetic resonance imaging finding common in all cases was a small infarct in the frontal corona radiata, which did not extend to the cortex or basal ganglia. A perfusion defect in the frontoparietal cortical and subcortical regions was demonstrated by single-photon emission computerized tomography in all patients. Improved hemodynamic circulation in the frontoparietal cortical and subcortical regions occurred in parallel with clinical improvement following indirect or direct bypass surgery. Ischemic dysfunction of the frontal cortical and subcortical motor pathways rather than that of the basal ganglia was suspected to be the cause of the observed contralateral involuntary movements. Direct and indirect bypass surgery can be used effectively to treat involuntary movements in patients with cerebral ischemic diseases such as MMD and in those with stenosis of an intracranial major artery.

The Successful Use of Regional Anesthesia to Prevent Involuntary Movements in a Patient Undergoing Awake Craniotomy

Implications The authors demonstrate that the combination of single and continuous peripheral nerve blocks allows the control of involuntary movements in patients undergoing awake craniotomy.

Involuntary movements and abnormal spontaneous EMG activity in syringomyelia and syringobulbia.

To describe different types of involuntary movements and abnormal spontaneous electromyographic (EMG) activity in patients with syringomyelia. A comprehensive study on involuntary movements in patients with syringomyelia has not yet been undertaken, to these authors' knowledge. One hundred adult patients with syringomyelia were examined over the last 15 years. Involuntary movements were videotaped and evaluated by two independent observers. Electromyographic recordings were made using bipolar surface electrodes. The H-reflex recovery curve was obtained after stimulation of the median nerve at the elbow and recording from the flexor carpi radialis. Involuntary movements or abnormal postures were observed in 22 patients. Three patients showed segmental spinal myoclonus, nine minipolymyoclonus, and four propriospinal myoclonus. Five patients had unilateral or bilateral hand postural tremor (8-10 Hz). Focal or segmental dystonia was observed in three patients. Electromyography showed spontaneous bursts of grouped action potentials synchronous in muscles innervated by the same spinal segment, synchronous firing of neurogenic motor unit potentials, or continuous motor unit activity. Increased H-reflex responses to conditioning stimuli were found in patients with spinal myoclonus. Long latency responses were obtained during peripheral nerve stimulation in four patients. Four patients had rigidity and abnormal upper limb posture. Respiratory synkinesis was observed in three patients. One patient developed inverse masticatory muscle activity. Patients with syringomyelia showed a wide spectrum of involuntary movements. An increased excitability of spinal motor neurons was probably the basic underlying mechanism.

Late-Onset Schizophrenia: Relationship to Awareness of Abnormal Involuntary Movements and Tobacco Addiction

Although schizophrenia usually emerges at mid to late-adolescence, it has been estimated that almost 20% of schizophrenic patients develop their first symptoms in mid to late life (late-onset schizophrenia). The biological characteristics that distinguish patients with early onset from those with late-onset schizophrenia have not been well delineated. A subgroup of neuroleptic-treated schizophrenic patients develops tardive dyskinesia (TD) and the majority of these patients are unaware of their movements. To investigate whether early and late-onset schizophrenic patients with TD could be differentiated on the basis of awareness of involuntary movements, we compared the prevalence of awareness of these abnormal movements in patients with early (N = 40) and late-onset (N = 15) schizophrenia. We found a significantly higher prevalence of awareness of involuntary movements in patients with late-onset schizophrenia as compared to those with an earlier age of onset (86.6% vs. 25.0%, p < .0001). In a second study, we investigated whether early and late-onset schizophrenia could be differentiated on the basis of dopamine functions in the mesolimbic system. Since tobacco addiction is mediated via limbic dopaminergic functions, we investigated the prevalence of tobacco addiction in patients with early (N = 51) and late-onset (N = 13) schizophrenia. We found a significantly lower prevalence of tobacco addiction in patients with late-onset schizophrenia as compared to those with an earlier age of onset (15.4% vs. 54.9%; X2 = 6.49; p < .01). Our findings support the notion that distinct pathophysiological mechanisms underlie the development of early and late-onset schizophrenia.

Neurologic Soft Signs in Obsessive-Compulsive Disorder-Reply

<h3>In Reply.—</h3> The study by Bihari and coworkers represents an important replication and extension of our earlier report in theArchives. The authors correctly note that our initial findings are preliminary and require replication and that further comparisons with other psychiatric control groups are needed in particular to establish the specificity of this finding. Bihari et al found significantly more errors and involuntary movements in patients with OCD than in normal controls. While patients with other anxiety and SADS were intermediate on these measures, they scored significantly lower than patients with OCD. Drug-free patients with OCD did not significantly differ from patients with OCD who were treated for at least 8 weeks with serotonin reuptake blocker medication. The authors suggest that while medication may improve OCD symptoms, it does not appear to affect neurologic soft signs. The authors acknowledge that their results must be interpreted with caution in light of the small

Topographic subtypes of tardive dyskinesia in schizophrenic patients aged less than 60 years: relationship to demographic, clinical, treatment, and neuropsychological variables.

There are conflicting reports about factors that may be associated with the development of involuntary movements in patients exposed to long-term neuroleptic treatment. Recent evidence suggests that some of these inconsistencies may relate to the practice of regarding these disorders as a unitary syndrome. There is also evidence that both the topographic distribution of these involuntary movements and the pathophysiological mechanisms underlying them may differ in the young and in the old. In this study, demographic, clinical, treatment and neuropsychological variables were investigated for association with the presence of orofacial and limb-truncal dyskinesias in 57 schizophrenic patients aged less than 60 years. Stepwise multiple logistic regression analysis showed that orofacial dyskinesia, at different degrees of severity, was negatively associated with positive schizophrenic syndrome and with either age at assessment or age at onset of illness. None of the indices of schizophrenic deficit (cognitive impairment, clinical defect state, behavioural deterioration, or neurological dysfunction) was related to orofacial dyskinesia. Limb-truncal involuntary movements were negatively related to current daily dosage of neuroleptics. The findings indicate that these two types of dyskinesia may involve different underlying mechanisms and that, for young schizophrenic patients, current pathophysiological or neurochemical theories of involuntary movement disorders are inadequate in explaining their origins.

Absence of enhanced physiological tremor in patients without muscle or cutaneous afferents.

Patients with proprioceptive loss due to a neuropathy affecting large myelinated sensory nerve fibres were studied to determine the role of somaesthetic sensory inputs in enhanced physiological tremor. Involuntary movements in patients and controls attempting to hold the outstretched arm immobile were recorded during prolonged arm extension. Fatigue led to increased movements in both controls and patients but only the controls developed a rhythmic tremor. These data indicate that enhanced physiological tremor is dependent on somaesthetic afferent input.

Abnormal involuntary movements in patients on long-acting neuroleptics

1. 1. Two hundred and thirty eight patients (144 males, 94 females) on long-acting neuroleptics; mainly fluphenazine decanoate, were surveyed and evaluated for abnormal involuntary movements and associated risk factors. 2. 2. A highly significant correlation was found between the three scales used in the evaluation. 3. 3. The prevalence rate for the transient, acute extrapyramidal syndrome was 37.38%, while that of tardive dyskinesia was 57%. Half of the tardive dyskinesia cases were of minimal severity. Most of these were located in orofacial region. 4. 4. Tardive dyskinesia was more frequent in younger patients but more severe in older age groups. Other associated risk factors were tremors and rigidity, and use of antiparkinsonien drugs. 5. 5. Tardive dyskinesia is a common abnormal involuntary movement in patients on long-acting neuroleptic. Early recognition of TD in this population could help in planning for its prevention by the use of minimum effective dose of medication.

Behandlung extrapyramidaler Bewegungsstörungen mit Tiaprid

In animal experiments Costall and Naylor (1977) showed that Tiaprid, a benzamide derivative of the orthopamids, inhibits dopamine receptors in the caudate nucleus and putamen but not in the mesolimbic system. Involuntary movements in patients with extrapyramidal movement disorders were reduced by 300 mg daily. Good results were obtained in 56% of 93 patients (25 in this study and 68 from the literature). On the whole the efficacy of Tiaprid seems far better than that of neuroleptics, and side effects are definitely fewer.