Unified Myoclonus Rating Scale Research Articles

Pallidal deep brain stimulation for patients with myoclonus-dystonia without SGCE mutations.

Pallidal deep brain stimulation (GPi-DBS) is effective for treating myoclonus and dystonia caused by SGCE mutations (DYT-SGCE, DYT11). However, it is unknown whether GPi-DBS is effective for the treatment of myoclonus-dystonia which is not associated with the SGCE gene mutations. In this study, we investigated the efficacy of GPi-DBS in treating myoclonus-dystonia in SGCE mutation-negative cases. Three patients with myoclonus-dystonia without SGCE mutations who underwent GPi-DBS were evaluated preoperatively and 6months postoperatively using the Unified Myoclonus Rating Scale (UMRS) and Fahn-Marsden Dystonia Rating Scale (FMDRS) for myoclonus and dystonia, respectively. In two of the three patients, myoclonus was more evident during action. Myoclonus was predominant at rest in the other patient, and he was unaware of his dystonia symptoms. The results were compared with those of the four DYT-SGCE cases. The mean UMRS score in patients with myoclonus-dystonia without SGCE mutations improved from 61.7 to 33.7 pre- and postoperatively, respectively, and the mean FMDRS score improved from 7.2 to 4.5. However, the degree of improvement in myoclonus-dystonia in patients without SGCE mutations was inferior to that in patients with DYT-SGCE (the UMRS score improved by 45% and 69%, respectively). GPi-DBS is effective for treating myoclonus-dystonia in patients with and without SGCE mutations. GPi-DBS should be considered as a treatment option for myoclonus-dystonia without SGCE mutations.

Detecting negative myoclonus during long-term home measurements using wearables

ObjectiveThe aim of this study was to develop a feasible method for the detection of negative myoclonus (NM) through long-term home measurements in patients with progressive myoclonus epilepsy type 1. MethodsThe number and duration of silent periods (SP) associated with NM were detected during a 48 h home recording using wearable surface electromyography (EMG) sensors. ResultsA newly developed algorithm was able to find short (50–69 ms), intermediate (70–100 ms), and long (101– 500 ms) SPs from EMG data. Negative myoclonus assessed by the algorithm correlated significantly with the video-recorded and physician-evaluated unified myoclonus rating scale (UMRS) scores of NM and action myoclonus. Silent period duration, number, and their combination, correlated strongly and significantly also with the Singer score, which assesses functional status and ambulation. ConclusionsNegative myoclonus can be determined objectively using long-term EMG measurements in home environment. With long-term measurements, we can acquire more reliable quantified information about NM as a symptom, compared to short evaluation at the clinic. SignificanceAs measured using SPs, NM may be a clinically useful measure for monitoring disease progression or assessing antimyoclonic drug effects objectively.

Short- and long-interval intracortical inhibition in EPM1 is related to genotype.

Progressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene, most commonly dodecamer repeat expansions. Although transcranial magnetic stimulation (TMS)-induced long-interval intracortical inhibition (LICI) was previously reported to be normal in EPM1, short-interval intracortical inhibition (SICI) was reduced. We explored the association between these measures and the clinical and genetic features in a separate group of patients with EPM1. TMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter-stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed. The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age- and sex-matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p < .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho=0.872; p < .001) and SICI (rho=0.689; p=.006). Our results strengthen the finding of deranged γ-aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease-modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.

Bilateral Pallidal Stimulation in a Family With Myoclonus Dystonia Syndrome Due to a Mutation in the Sarcoglycan Gene

ObjectivesThe study aimed to present a family with myoclonus dystonia (M-D) syndrome due to a mutation in the epsilon sarcoglycan gene (SGCE). Three members of the family suffered from treatment-refractory severe myoclonic jerks of the neck, trunk, and upper extremities. The mild dystonic symptoms recognized as cervical dystonia or truncal dystonia affected all individuals. The efficacy of pharmacotherapy, including anticholinergic, dopaminergic, and serotoninergic drugs, has failed. One individual developed an alcohol dependency and suffered from alcoholic epilepsy. Materials and MethodsThe patients were referred for stereotactic surgery. All individuals underwent bilateral implantation of deep brain stimulation (DBS) leads into the posteroventrolateral segment of the globus pallidus internus (GPi). Surgeries were uneventful. The formal preoperative objective assessment included the Unified Myoclonus Rating Scale (UMRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The postoperative UMRS and BFMDRS assessments were done only under continuous stimulation at 3, 6, and 12 months after the surgery and at the last available follow-up ranging from 6 to 15 months (mean, 10 months follow-up). ResultsAt the last follow-up visit, the rest and action parts of UMRS were improved by 93.3% and 88.2%, respectively, when compared to the baseline scores. The motor and disability scales of BFMDRS were improved by 77% and 43% at the last follow-up visit compared to the baseline BFMDRS scores. There were no hardware or stimulation-induced complications over the follow-up period. Positive social adjustment allowed two patients to regain jobs and one patient continued his education and hobbies. ConclusionOur experience gathered in three individuals in the family with a mutation in SGCE indicates that bilateral GPi DBS can be an effective and safe treatment for disabling pharmacological resistant, intractable M-D syndrome.

Is deep brain stimulation useful in Lance–Adams syndrome?

Lance–Adams syndrome (LAS) is a chronic post-hypoxic myoclonus that occurs after successful cardiopulmonary resuscitation. Although many drugs are available to treat this condition, the underlying mechanism of the disease is yet to be understood. Deep brain stimulation (DBS) has been attempted and proven to be partially successful in treating LAS in several cases. Here, we present a 40-year-old woman who developed myoclonus subsequent to cardiopulmonary arrest (CPA) that occurred after her first cesarean delivery at the age of 26 years. The patient underwent implantation of bilateral globus pallidus interna (GPi)-DBS about 14 years after disease onset. Regarding Unified Myoclonus Rating Scale (UMRS), 8% and 20% improvements were observed in action and resting myoclonus, respectively, with high-frequency stimulation as a result of the 3-year follow-up study. In this case, neuromodulation therapy applied 14 years after hypoxia-causing LAS was not sufficiently beneficial.

Wearable monitoring of positive and negative myoclonus in progressive myoclonic epilepsy type 1

ObjectiveTo develop and test wearable monitoring of surface electromyography and motion for detection and quantification of positive and negative myoclonus in patients with progressive myoclonic epilepsy type 1 (EPM1). MethodsSurface electromyography and three-dimensional acceleration were measured from 23 EPM1 patients from the biceps brachii (BB) of the dominant and the extensor digitorum communis (EDC) of the non-dominant arm for 48 hours. The patients self-reported the degree of myoclonus in a diary once an hour. Severity of myoclonus with action was evaluated by using video-recorded Unified Myoclonus Rating Scale (UMRS). Correlations of monitored parameters were quantified with the UMRS scores and the self-reported degrees of myoclonus. ResultsThe monitoring-based myoclonus index correlated significantly (p < 0.001) with the UMRS scores (ρ = 0.883 for BB and ρ = 0.823 for EDC) and with the self-reported myoclonus degrees (ρ = 0.483 for BB and ρ = 0.443 for EDC). Ten patients were assessed as probably having negative myoclonus in UMRS, while our algorithm detected that in twelve patients. ConclusionsWearable monitoring was able to detect both positive and negative myoclonus in EPM1 patients. SignificanceOur method is suitable for quantifying objective, real-life treatment effects at home and progression of myoclonus.

Cognitive functioning in progressive myoclonus epilepsy type 1 (Unverricht-Lundborg Disease, EPM1)

ObjectiveThe aim of this neuropsychological study of a large cohort of patients with progressive myoclonus epilepsy type 1 (Unverricht-Lundborg disease, EPM1) was to characterize the cognitive function of EPM1 patients and to explore the association between the disability caused by the disease and cognitive performance. MethodSixty-eight genetically verified EPM1 patients homozygous for the expansion mutation in the CSTB gene (37 males and 31 females aged 35 ± 11) participated in a neuropsychological assessment of intellectual ability, verbal memory, and executive and psychomotor function. The clinical evaluation comprised administering (and video-recording) the unified myoclonus rating scale (UMRS) to assess the severity of each patient’s myoclonus. Forty-six healthy volunteers (19 males and 27 females aged 32 ± 11) served as the control group for the neuropsychological tests. ResultsThe cognitive performance of the EPM1 patient group was impaired. Verbal Intelligence Quotient (VIQ) was below the average range (VIQ < 85) in 49% of the patients; further, Performance Intelligence Quotient (PIQ) was below average in 75% of the patients. The patients performed worse than the controls in both immediate and delayed story recall (p = 0.001); however, in the word list learning task, the patients performed only slightly worse than the controls. The one-hour delayed recall of the learned words was similar in both groups, and the percentage of retained words and story contents did not differ between the patients and controls. The patients were impaired in all of the executive function tests as well as in the psychomotor speed tests (p < 0.001 for all). Also, the patients’ simple psychomotor speed in the tapping task was significantly slowed in comparison to controls (p < 0.001). ConclusionThe patients had impaired performance in the majority of the cognitive measures; they showed the highest level of impairment in all the executive function tests and in the psychomotor speed tests. The measures of these cognitive domains are timed—therefore, it is clear that severe myoclonus limits patients’ performance. In contrast, verbal memory, especially delayed recall, was the least affected cognitive domain.

Delineating the motor phenotype of SGCE-myoclonus dystonia syndrome

ObjectiveTo perform phenotype and genotype characterization in myoclonus-dystonia patients and to validate clinical rating tools. MethodTwo movement disorders experts rated patients with the Burke-Fahn-Marsden and Unified-Myoclonus rating scales using a video-recording protocol. Clinimetric analysis was performed. SGCE mutations were screened by Sanger sequencing and multiplex ligation-dependent probe amplification. Results48 patients were included and 43/48 rated. Mean age at assessment was 12.9±10.5 years (range 3–51) and 88% were ≤18 years of age. Myoclonus was a universal sign with a rostro-caudal severity-gradient. Myoclonus increased in severity and spread to lower limbs during action tests. Stimulus-evoked myoclonus was observed in 86.8% cases. Dystonia was common but mild. It had a focal distribution and was action-induced, causing writer's cramp (69%) and gait dystonia (34%). The severity of both myoclonus and dystonia had a strong impact on hand writing and walking difficulties.The Unified Myoclonus Rating scale showed the best clinimetric properties for the questionnaire, action myoclonus and functional subscales, and exceeded the Burke-Fahn-Marsden scale in its utility in assessing functional impairment in MDS patients.Twenty-one different SGCE mutations were identified in 45/48 patients, eleven being novel (most prevalent p. Val187*, founder mutation in Canary Islands). ConclusionThis study quantifies the severity of the motor phenotype in SGCE-myoclonus dystonia syndrome, with a special focus on children, and identifies disabilities in gross and fine motor tasks that are essential for childhood development. Our results contribute to the knowledge of SGCE-related MDS in the early stage of evolution, where disease-modifying therapies could be initiated in order to prevent long-term social and physical burdens.

A Case Report of Myoclonus-Dystonia with Isolated Myoclonus Phenotype and Novel Mutation Successfully Treated with Deep Brain Stimulation.

IntroductionMyoclonus-dystonia is an inherited disorder characterized by a combination of myoclonic jerks and dystonia. Mutations in the epsilon-sarcoglycan gene (SGCE) represent the main known genetic cause. In the last few years, deep brain stimulation (DBS) has shown significant promise in treating these patients. There is only one report in the literature of a patient with positive SGCE mutation and isolated myoclonus phenotype who has been successfully treated with DBS.Case PresentationWe present a case of a 16-year-old young man with a history of quick jerks since childhood. They progressed gradually over the years involving the entire body and interfering with most of his daily activities. He had no dystonia. Genetic testing identified a single base deletion in exon 3 of the SGCE gene, considered very likely pathogenic. After unsuccessfully trying several oral medications, he underwent DBS of the globus pallidus internus (GPi). His Unified Myoclonus Rating Scale score during rest and with action improved by 92.8% and 82.6%, respectively.DiscussionThe striking effect of DBS on myoclonic jerks confirms the superior benefit of DBS over oral medications. Further study is needed to determine the role of mutation status in predicting DBS response, especially considering that myoclonus-dystonia is genetically heterogeneous.ConclusionOur case confirms the poor response to oral medications and supports the use of GPi DBS for patients with genetically confirmed myoclonus-dystonia and isolated-myoclonus phenotype. In addition, our case represents familial myoclonus-dystonia due to a novel SGCE mutation.Electronic supplementary materialThe online version of this article (10.1007/s40120-020-00186-4) contains supplementary material, which is available to authorized users.

Automatic assessment of the myoclonus severity from videos recorded according to standardized Unified Myoclonus Rating Scale protocol and using human pose and body movement analysis

PurposeMyoclonus in progressive myoclonus epilepsy type 1 (EPM1) patients shows marked variability, which presents a substantial challenge in devising treatment and conducting clinical trials. Consequently, fast and objective myoclonus quantification methods are needed. MethodsTen video-recorded unified myoclonus rating scale (UMRS) myoclonus with action tests were performed on EPM1 patients who were selected for the development and testing of the automatic myoclonus quantification method. Human pose and body movement analyses of the videos were used to identify body keypoints and further analyze movement smoothness and speed. The automatic myoclonus rating scale (ARMS) was developed. It included the jerk count during movement score and the log dimensionless jerk (LDLJ) score to evaluate changes in the smoothness of movement. ResultsThe scores obtained with the automatic analyses showed moderate to strong significant correlation with the UMRS myoclonus with action scores. The jerk count of the primary keypoints and the LDLJ scores were effective in the evaluation of the myoclonic jerks during hand movements. They also correlated moderately to strongly with the total UMRS test panel scores (r2 = 0,77, P = 0,009 for the jerk count score and r2 = 0,88, P = 0,001 for the LDLJ score). The automatic analyses was weaker in quantification of the neck, trunk, and leg myoclonus. ConclusionAutomatic quantification of myoclonic jerks using human pose and body movement analysis of patients’ videos is feasible and was found to be quite consistent with the accepted clinical gold standard quantification method. Based on the results of this study, the automatic analytical method should be further developed and validated to improve myoclonus severity follow-up for EPM1 patients.

Deep brain stimulation for myoclonus dystonia syndrome: a meta-analysis with individual patient data.

Good outcomes have been reported in deep brain stimulation (DBS) for myoclonus-dystonia syndrome (M-D), a heritable disease characterized by childhood-onset myoclonic jerks and dystonia in the upper body. This meta-analysis was to evaluate the clinical outcomes consecutively, compare the stimulation targets, and identify potential prognostic factors. A systematic literature search was performed on PubMed, Web of Science, and Embase. The primary outcome was the percent improvement in Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) scores for dystonia and Unified Myoclonus Rating Scale (UMRS) scores for myoclonus at the last follow-up visit. BFMDRS-disability scores of the patients were also summarized. Pearson correlation analyses were performed to identify the myoclonus and dystonia outcome predictors. Thirty-one studies reporting 71 patients were included. There were significant improvements in BFMDRS-M and BFMDRS-disability scores in each time category and at the last follow-up visit. Mean improvement (%) in UMRS was 79.5 ± 18.2, and 94.1% of the patients showed > 50% improvement in UMRS scores at the last follow-up visit. There was a significant trend toward improved myoclonus outcome with older age at onset and shorter disease duration. Most of the adverse events were mild and transient, and pallidal stimulation seemed to be better with respect to fewer stimulation-induced events. Based on the current data, DBS is effective for even the severe M-D. Surgery at an early stage may predict a better outcome. Although targets do not serve as the outcome predictors, pallidal stimulation may be preferred due to fewer stimulation-induced events.

An Italian multicentre study of perampanel in progressive myoclonus epilepsies

Perampanel (PER) is a novel anti-seizure medication useful in different types of epilepsy. We intended to assess the effectiveness of PER on cortical myoclonus and seizure frequency in patients with progressive myoclonus epilepsy (PME), using quantitative validated scales.Forty-nine patients aged 36.6 ± 15.6 years with PME of various aetiology (18 EPM1, 12 EPM2, five with sialidosis, one with Kufs disease, one with EPM7, and 12 undetermined) were enrolled between January 2017 and June 2018. PER at the dose of 2–12 mg (5.3 ± 2.5) was added to existing therapy. Myoclonus severity was assessed using a minimal myoclonus scale (MMS) in all the patients before and after 4–6 months of steady PER dose, and by means of the Unified Myoclonus Rating Scale (UMRS) in 20 patients. Logistic regression analysis was used to identify the factors potentially predicting treatment efficacy.Four patients dropped out in the first two months due to psychiatric side effects. In the remaining patients, PER reduced myoclonus severity as assessed using MMS (Wilcoxon test: p < 0.001) and UMRS (p < 0.001), with the ‘Action myoclonus’ section of the UMRS showing the greatest improvement. The patients with EPM1 or EPM1-like phenotype were more likely to improve with PER (p = 0.011). Convulsive seizures which have recurred at least monthly in 17 patients were reduced by >50%. Side effects occurred in 22/49 (44.8%) patients, the most common being irritability followed by drowsiness.PER is effective in treating myoclonus and seizures in PME patients. The frequency of psychiatric side effects suggests the need for careful patient monitoring.

Thalamus Stimulation for Myoclonus Dystonia Syndrome: Five Cases and Long-Term Follow-up

Myoclonic dystonia syndrome (MDS) is a rare inherited movement disorder characterized by the coexistence of myoclonic jerks and dystonia. Deep brain stimulation (DBS) is a promising treatment for patients with MDS that targets the globus pallidus internus or ventral intermediate nucleus (Vim) of the thalamus. However, there are few studies regarding the long-term effects of Vim DBS in patients with MDS and even fewer in those without gene mutations. Two positive and three negative SGCE mutation patients presenting with predominant myoclonus underwent Vim DBS. The Unified Myoclonus Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) were assessed pre- and postoperation. Over an average follow-up period of 50 months, the myoclonus improvement rate was 92.7%. The average improvement in the BFMDRS motor score was 71.4% and the average improvement in the BFMDRS disabling score was 75.8%. This study suggests that Vim DBS can be a safe and effective treatment option for patients with MDS. Vim DBS alone may be preferable for patients with myoclonus-dominated MDS regardless of the identification of an SGCE mutation. Additional globus pallidus internus DBS may be used for progressive dystonia after Vim DBS.

Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances social adjustment.

Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with ε-sarcoglycan (DYT11)-positive myoclonus-dystonia. Consecutive myoclonus-dystonia patients with ε-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.

Alcohol improves cerebellar learning deficit in myoclonus-dystonia: A clinical and electrophysiological investigation.

To characterize neurophysiological subcortical abnormalities in myoclonus-dystonia and their modulation by alcohol administration. Cerebellar associative learning and basal ganglia-brainstem interaction were investigated in 17 myoclonus-dystonia patients with epsilon-sarcoglycan (SGCE) gene mutation and 21 age- and sex-matched healthy controls by means of classical eyeblink conditioning and blink reflex recovery cycle before and after alcohol intake resulting in a breath alcohol concentration of 0.08% (0.8g/l). The alcohol responsiveness of clinical symptoms was evaluated by 3 blinded raters with a standardized video protocol and clinical rating scales including the Unified Myoclonus Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale. Patients showed a significantly reduced number of conditioned eyeblink responses before alcohol administration compared to controls. Whereas the conditioning response rate decreased under alcohol intake in controls, it increased in patients (analysis of variance: alcohol state × group, p = 0.004). Blink reflex recovery cycle before and after alcohol intake did not differ between groups. Myoclonus improved significantly after alcohol intake (p = 0.016). The severity of action myoclonus at baseline correlated negatively with the conditioning response in classical eyeblink conditioning in patients. The combination of findings of reduced baseline acquisition of conditioned eyeblink responses and normal blink reflex recovery cycle in patients who improved significantly with alcohol intake suggests a crucial role of cerebellar networks in the generation of symptoms in these patients. Ann Neurol 2017;82:543-553.

The Inter-rater Variability of Clinical Assessment in Post-anoxic Myoclonus.

BackgroundAcute post-anoxic myoclonus (PAM) can be divided into an unfavorable (generalized/subcortical) and more favorable ((multi)focal/cortical) outcome group that could support prognostication in post-anoxic encephalopathy; however, the inter-rater variability of clinically assessing these PAM subtypes is unknown.MethodsWe prospectively examined PAM patients using a standardized video protocol. Videos were rated by three neurologists who classified PAM phenotype (generalized/(multi)focal), stimulus sensitivity, localization (proximal/distal/both), and severity (Clinical Global Impression-Severity Scale (CGI-S) and Unified Myoclonus Rating Scale (UMRS)).ResultsPoor inter-rater agreement was found for phenotype and stimulus sensitivity (κ=−0.05), moderate agreement for localization (κ=0.46). Substantial agreement was obtained for the CGI-S (intraclass correlation coefficient (ICC)=0.64) and almost perfect agreement for the UMRS (ICC=0.82).DiscussionClinical assessment of PAM is not reproducible between physicians, and should therefore not be used for prognostication. PAM severity measured by the UMRS appears to be reliable; however, the relation between PAM severity and outcome is unknown.

A clinical and neurophysiological motor signature of Unverricht–Lundborg disease

ObjectivesUnverricht–Lundborg disease (ULD) is the most common form of progressive myoclonus epilepsy. Cerebellar dysfunction may appear over time, contributing along with myoclonus to motor disability. The purpose of the present work was to clarify the motor and neurophysiological characteristics of ULD patients. MethodsNine patients with genetically proven ULD were evaluated clinically (medical history collected from patient charts, the Scale for the Assessment and Rating of Ataxia and Unified Myoclonus Rating Scale). Neurophysiological investigations included EEG, surface polymyography, long-loop C-reflexes, somatosensory evoked potentials, EEG jerk-locked back-averaging (JLBA) and oculomotor recordings. All patients underwent brain MRI. Non-parametric Mann-Whitney tests were used to compare ULD patients’ oculomotor parameters with those of a matched group of healthy volunteers (HV). ResultsMyoclonus was activated by action but was virtually absent at rest and poorly induced by stimuli. Positive myoclonus was multifocal, often rhythmic and of brief duration, with top-down pyramidal temporospatial propagation. Cortical neurophysiology revealed a transient wave preceding myoclonus on EEG JLBA (n=8), enlarged somatosensory evoked potentials (n=7) and positive long-loop C-reflexes at rest (n=5). Compared with HV, ULD patients demonstrated decreased saccadic gain, increased gain dispersion and a higher frequency of hypermetric saccades associated with decreased peak velocity. ConclusionA homogeneous motor pattern was delineated that may represent a ULD clinical and neurophysiological signature. Clinical and neurophysiological findings confirmed the pure cortical origin of the permanent myoclonus. Also, oculomotor findings shed new light on ULD pathophysiology by evidencing combined midbrain and cerebellar dysfunction.

Improvement of Post-hypoxic Myoclonus with Bilateral Pallidal Deep Brain Stimulation: A Case Report and Review of the Literature.

BackgroundPost-hypoxic myoclonus (PHM) is a syndrome that occurs when a patient has suffered hypoxic brain injury. The myoclonus is usually multifocal and generalized, often stemming from both cortical and subcortical origins. In severe cases, pharmacological treatments with antiepileptic medications may not satisfactorily control the myoclonus.MethodsWe present a case of a 23-year-old male with chronic medication refractory PHM following a cardiopulmonary arrest related to an asthmatic attack who improved with bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). We review the clinical features of PHM, as well as the preoperative and postoperative Unified Myoclonus Rating Scale scores and DBS programming parameters in this patient and compare them with the three other published PHM-DBS cases in the literature.ResultsThis patient experienced an alleviation of myoclonic jerks at rest and a 39% reduction in action myoclonus with improvement in both positive and negative myoclonus with bilateral GPi-DBS. High frequency stimulation (130 Hz) with amplitudes >2.5 V were needed for the therapeutic response.DiscussionWe demonstrate a robust improvement in a medication refractory PHM patient with bilateral GPi-DBS, and suggest that it is a viable therapeutic option for debilitating post-hypoxic myoclonus.

The relationship between the dopaminergic system and depressive symptoms in cervical dystonia

PurposeCervical dystonia (CD) is associated with tremor/jerks (50%) and psychiatric complaints (17–70%). The dopaminergic system has been implicated in the pathophysiology of CD in animal and imaging studies. Dopamine may be related to the motor as well as non-motor symptoms of CD. CD is associated with reduced striatal dopamine D2/3 (D2/3) receptor and increased dopamine transporter (DAT) binding. There are differences in the dopamine system between CD patients with and without jerks/tremor and psychiatric symptoms.MethodsPatients with CD and healthy controls underwent neurological and psychiatric examinations. Striatal DAT and D2/3 receptor binding were assessed using [123I]FP-CIT and [123I]IBZM SPECT, respectively. The ratio of specific striatal to non-specific binding (binding potential; BPND) was the outcome measure.ResultsTwenty-seven patients with CD and 15 matched controls were included. Nineteen percent of patients fulfilled the criteria for a depression. Striatal DAT BPND was significantly lower in depressed versus non-depressed CD patients. Higher DAT BPND correlated significantly with higher scores on the Unified Myoclonus Rating Scale (UMRS). The striatal D2/3 receptor BPND in CD patients showed a trend towards lower binding compared to controls. The D2/3 BPND was significantly lower in depressed versus non-depressed CD patients. A significant correlation between DAT and D2/3R BPND was found in both in patients and controls.ConclusionsAlterations of striatal DAT and D2/3 receptor binding in CD patients are related mainly to depression. DAT BPND correlates significantly with scores on the UMRS, suggesting a role for dopamine in the pathophysiology of tremor/jerks in CD.

A randomized, controlled, double-blind, crossover trial of zonisamide in myoclonus-dystonia.

To evaluate the efficacy and safety of zonisamide in patients with myoclonus-dystonia. We conducted a randomized, double-blind, placebo-controlled crossover trial of zonisamide (300 mg/d) in 24 patients with myoclonus-dystonia. Each treatment period consisted of a 6-week titration phase followed by a 3-week fixed-dose phase. The periods were separated by a 5-week washout period. The co-primary outcomes were action myoclonus severity (section 4 of the Unified Myoclonus Rating Scale [UMRS 4]) and myoclonus-related functional disability (UMRS 5). Secondary outcomes included dystonia severity, assessed with the movement and disability subscales of the Burke-Fahn-Marsden-Dystonia Rating Scale (BFM), the Clinical Global Impression-Improvement scale (CGI), and safety measures. Wilcoxon signed-rank tests for paired data were used to analyze treatment effects. Twenty-three patients (11 men, 12 women) were analyzed in the intention-to-treat analysis. Zonisamide significantly improved both action myoclonus (median improvement [95% confidence limits] -5 [-9.25 to -1.44], p = 0.003) and myoclonus-related functional disability (median improvement [95% confidence limits] -2 [-2.58 to -2.46], p = 0.007) compared to placebo. Zonisamide also significantly improved dystonia (BFM movement) compared to placebo (median improvement [95% confidence limits] -3 [-8.46 to 0.03], p = 0.009). No difference was found between zonisamide and placebo with respect to the CGI (median improvement [95% confidence limits] -1 [-1.31 to 0.09], p = 0.1). Zonisamide was well-tolerated. Zonisamide is well-tolerated and effective on the motor symptoms of myoclonus-dystonia. This study provides Class I evidence that zonisamide improves myoclonus and related disability in patients with myoclonus-dystonia.