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Tremor and Other Hyperkinetic Movements... Jul 2020Myoclonus-dystonia due to mutations (OMIM: 159900) most commonly presents during childhood with mainly upper body myoclonus, and mild dystonia affecting the neck and...
BACKGROUND
Myoclonus-dystonia due to mutations (OMIM: 159900) most commonly presents during childhood with mainly upper body myoclonus, and mild dystonia affecting the neck and arms.
CASE REPORTS
Herein, we report patients misdiagnosed during childhood with Tourette syndrome and dyskinetic cerebral palsy, and, during adulthood, found to harbor frameshift mutations.
DISCUSSION
Myoclonus-dystonia may be underdiagnosed due to phenotypic misclassification during childhood. mutations should be included in the differential diagnosis of childhood movement disorders that ostensibly manifest with tics, myoclonus, or abnormal posturing secondary to dystonia and/or spasticity.
HIGHLIGHTS
Due to pleiotropy, variable penetrance, broad differential, and hereditary effects of imprinting, the diagnosis of a disorder of childhood onset, myoclonus-dystonia due to mutations, may be delayed until adulthood, often compromising appropriate clinical management and genetic counseling.
Topics: Adult; Cerebral Palsy; Delayed Diagnosis; Dystonic Disorders; Female; Frameshift Mutation; Humans; Male; Middle Aged; Pedigree; Sarcoglycans; Tourette Syndrome
PubMed: 32775037
DOI: 10.5334/tohm.334 -
Clinical Neurophysiology : Official... Dec 2023The 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...
OBJECTIVE
The 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.
METHODS
The number and duration of silent periods (SP) associated with NM were detected during a 48 h home recording using wearable surface electromyography (EMG) sensors.
RESULTS
A 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.
CONCLUSIONS
Negative 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.
SIGNIFICANCE
As measured using SPs, NM may be a clinically useful measure for monitoring disease progression or assessing antimyoclonic drug effects objectively.
Topics: Humans; Myoclonus; Unverricht-Lundborg Syndrome; Electromyography; Wearable Electronic Devices
PubMed: 37952446
DOI: 10.1016/j.clinph.2023.10.005 -
International Journal of Molecular... May 2021Serotonin (5-hydroxytryptamine, 5-HT) plays two important roles in humans-one central and the other peripheral-depending on the location of the 5-HT pools of on either... (Review)
Review
Serotonin (5-hydroxytryptamine, 5-HT) plays two important roles in humans-one central and the other peripheral-depending on the location of the 5-HT pools of on either side of the blood-brain barrier. In the central nervous system it acts as a neurotransmitter, controlling such brain functions as autonomic neural activity, stress response, body temperature, sleep, mood and appetite. This role is very important in intensive care, as in critically ill patients multiple serotoninergic agents like opioids, antiemetics and antidepressants are frequently used. High serotonin levels lead to altered mental status, deliria, rigidity and myoclonus, together recognized as serotonin syndrome. In its role as a peripheral hormone, serotonin is unique in controlling the functions of several organs. In the gastrointestinal tract it is important for regulating motor and secretory functions. Apart from intestinal motility, energy metabolism is regulated by both central and peripheral serotonin signaling. It also has fundamental effects on hemostasis, vascular tone, heart rate, respiratory drive, cell growth and immunity. Serotonin regulates almost all immune cells in response to inflammation, following the activation of platelets.
Topics: Blood-Brain Barrier; Central Nervous System; Critical Illness; Delirium; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Inflammation; Myoclonus; Serotonin; Serotonin Syndrome
PubMed: 34063611
DOI: 10.3390/ijms22094837 -
Brain : a Journal of Neurology Apr 2023Myoclonus dystonia is a childhood-onset hyperkinetic movement disorder with a combined motor and psychiatric phenotype. It represents one of the few autosomal dominant...
Myoclonus dystonia is a childhood-onset hyperkinetic movement disorder with a combined motor and psychiatric phenotype. It represents one of the few autosomal dominant inherited dystonic disorders and is caused by mutations in the ε-sarcoglycan (SGCE) gene. Work to date suggests that dystonia is caused by disruption of neuronal networks, principally basal ganglia-cerebello-thalamo-cortical circuits. Investigation of cortical involvement has primarily focused on disruption to interneuron inhibitory activity, rather than the excitatory activity of cortical pyramidal neurons. Here, we have sought to examine excitatory cortical glutamatergic activity using two approaches: the CRISPR/Cas9 editing of a human embryonic cell line, generating an SGCE compound heterozygous mutation, and three patient-derived induced pluripotent stem cell lines, each gene edited to generate matched wild-type SGCE control lines. Differentiation towards a cortical neuronal phenotype demonstrated no significant differences in either early- (PAX6, FOXG1) or late-stage (CTIP2, TBR1) neurodevelopmental markers. However, functional characterization using Ca2+ imaging and microelectrode array approaches identified an increase in network activity, while single-cell patch clamp studies found a greater propensity towards action potential generation with larger amplitudes and shorter half-widths associated with SGCE mutations. Bulk RNA sequencing analysis identified gene ontological enrichment for 'neuron projection development', 'synaptic signalling' and 'synaptic transmission'. Examination of dendritic morphology found SGCE mutations to be associated with a significantly higher number of branches and longer branch lengths, together with longer ion-channel dense axon initial segments, particularly towards the latter stages of differentiation (Days 80 and 100). Gene expression and protein quantification of key synaptic proteins (synaptophysin, synapsin and PSD95), AMPA and NMDA receptor subunits found no significant differences between the SGCE mutation and matched wild-type lines. By contrast, significant changes to synaptic adhesion molecule expression were identified, namely higher presynaptic neurexin-1 and lower postsynaptic neuroligin-4 levels in the SGCE mutation carrying lines. Our study demonstrates an increased intrinsic excitability of cortical glutamatergic neuronal cells in the context of SGCE mutations, coupled with a more complex neurite morphology and disruption to synaptic adhesion molecules. These changes potentially represent key components to the development of the hyperkinetic clinical phenotype observed in myoclonus dystonia, as well a central feature to the wider spectrum of dystonic disorders, potentially providing targets for future therapeutic development.
Topics: Humans; Child; Dystonia; Myoclonus; Dystonic Disorders; Mutation; Sarcoglycans
PubMed: 36204995
DOI: 10.1093/brain/awac365 -
Therapeutic Advances in... Dec 2015We describe the case of a young man with treatment-resistant schizophrenia, who developed myoclonus during clozapine titration. This subsequently led to a full... (Review)
Review
We describe the case of a young man with treatment-resistant schizophrenia, who developed myoclonus during clozapine titration. This subsequently led to a full tonic-clonic seizure. Clozapine treatment can result in a range of seizure-like activity, the most well-known being tonic-clonic seizures. This case highlights the importance of recognizing and treating clozapine-induced myoclonus, as it can herald the onset of a full seizure, even at low serum clozapine levels. We highlight the variety of ways myoclonus can present clinically and suggest treatment options.
PubMed: 26834968
DOI: 10.1177/2045125315612015 -
Clinical Case Reports Mar 2020Palatal myoclonus can be primary or secondary. In primary palatal myoclonus, no obvious structural brain lesions can be found within the triangle of Guillain and...
Palatal myoclonus can be primary or secondary. In primary palatal myoclonus, no obvious structural brain lesions can be found within the triangle of Guillain and Mollaret. Common causes of secondary myoclonus include stroke, demyelination, infections, trauma, and neurodegeneration.
PubMed: 32185071
DOI: 10.1002/ccr3.2619 -
Movement Disorders : Official Journal... Sep 2022Prion diseases cause a range of movement disorders involving the cortical, extrapyramidal, and cerebellar systems, and yet there are no large systematic studies of their...
BACKGROUND
Prion diseases cause a range of movement disorders involving the cortical, extrapyramidal, and cerebellar systems, and yet there are no large systematic studies of their prevalence, features, associations, and responses to commonly used treatments.
OBJECTIVES
We sought to describe the natural history and pharmacological management of movement disorders in prion diseases.
METHODS
We studied the serial examination findings, investigation results, and symptomatic treatment recorded for 700 patients with prion diseases and 51 mimics who had been enrolled onto the prospective longitudinal National Prion Monitoring Cohort study between 2008 and 2020. We performed an analysis to identify whether there were patterns of movement disorders associated with disease aetiology, PRNP codon 129 polymorphism, disease severity rating scales, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings.
RESULTS
Gait disturbances, myoclonus, and increased tone are the most frequently observed movement disorders in patients with prion diseases. The typical pattern of early motor dysfunction involves gait disturbance, limb ataxia, impaired smooth pursuit, myoclonus, tremor, and increased limb tone. Disturbances of gait, increased tone, and myoclonus become more prevalent and severe as the disease progresses. Chorea, alien limb phenomenon, and nystagmus were the least frequently observed movement disorders, with these symptoms showing spontaneous resolution in approximately half of symptomatic patients. Disease severity and PRNP codon 129 polymorphism were associated with different movement disorder phenotypes. Antiepileptics and benzodiazepines were found to be effective in treating myoclonus.
CONCLUSIONS
We describe the prevalence, severity, evolution, treatment, and associated features of movement disorders in prion diseases based on a prospective cohort study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Codon; Cohort Studies; Creutzfeldt-Jakob Syndrome; Humans; Longitudinal Studies; Movement Disorders; Myoclonus; Prevalence; Prion Diseases; Prospective Studies
PubMed: 35841311
DOI: 10.1002/mds.29152 -
Journal of Neurology Apr 2024To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future... (Observational Study)
Observational Study
OBJECTIVE
To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future disability.
BACKGROUND
There is a need to better understand the full spectrum of clinical and paraclinical features and long-term impact of SPSD.
DESIGN/METHODS
Observational study from 1997 to 2022 at Johns Hopkins. Clinical phenotypes included classic SPS, partial SPS (limb or trunk limited), SPS-plus (classic features plus cerebellar/brainstem involvement), and progressive encephalomyelitis with rigidity and myoclonus (PERM). Outcome measures were modified Rankin scale (mRS) and use of assistive device for ambulation. Multivariate logistic regression was used to assess significant predictors of outcomes.
RESULTS
Cohort included 227 individuals with SPSD with mean follow-up of 10 years; 154 classic, 48 SPS-plus, 16 PERM, and 9 partial. Mean age at symptom onset was 42.9 ± 14.1 years, majority were white (69.2%) and female (75.8%). Median time to diagnosis was 36.2 months (longest for SPS-plus and PERM) and 61.2% were initially misdiagnosed. Most had systemic co-morbidities and required assistive devices for ambulation. Female sex (OR 2.08; CI 1.06-4.11) and initial brainstem/cerebellar involvement (OR 4.41; CI 1.63-14.33) predicted worse outcome by mRS. Older age at symptom onset (OR 1.04; CI 1.01-1.06), female sex (OR 1.99; CI 1.01-4.01), Black race (OR 4.14; CI 1.79-10.63), and initial brainstem/cerebellar involvement (OR 2.44; CI 1.04-7.19) predicted worse outcome by use of assistive device. Early implementation of immunotherapy was associated with better outcomes by either mRS (OR 0.45; CI 0.22-0.92) or use of assistive device (OR 0.79; CI 0.66-0.94).
CONCLUSIONS
We present the expanding phenotypic variability of this rare spectrum of disorders and highlight potential predictors of future disability.
Topics: Humans; Female; Stiff-Person Syndrome; Prognosis; Myoclonus; Comorbidity; Outcome Assessment, Health Care
PubMed: 38078976
DOI: 10.1007/s00415-023-12123-0 -
Neurological Sciences : Official... Mar 2022This study aims to report the clinical heterogeneity of myoclonus in 6 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
OBJECTIVE
This study aims to report the clinical heterogeneity of myoclonus in 6 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS
Patient data were obtained from medical records from the University Hospital Dr. Josep Trueta, Girona, Spain.
RESULTS
Six patients (5 men and 1 woman, aged 60-76 years) presented with different myoclonus phenotypes. All of them had a medical history of hypertension and overweight. The latency of myoclonus appearance ranged from 1 to 129 days. The phenotype most observed was generalized myoclonus. Special phenotypes such as painful legs and moving toes syndrome with jerking feet, Lazarus sign-like, action myoclonus/ataxia syndrome, and segmental myoclonus secondary to myelitis have been described too. Levetiracetam and clonazepam were medications most used successfully. Two patients died for complications not related to myoclonus.
CONCLUSIONS
Our 6 cases highlight the heterogeneity of the clinical spectrum of myoclonus associated to COVID-19 (MYaCO). MYaCO pathogenesis is suspected to be due to an immune-mediated para- or post-infectious phenomenon; nevertheless, further research is needed to elucidate this hypothesis.
Topics: Aged; Ataxia; COVID-19; Cerebellar Ataxia; Female; Humans; Male; Middle Aged; Myoclonus; SARS-CoV-2
PubMed: 34988717
DOI: 10.1007/s10072-021-05802-1 -
European Journal of Neurology Oct 2018Antibodies to glycine receptors (GlyR-Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other... (Review)
Review
BACKGROUND AND PURPOSE
Antibodies to glycine receptors (GlyR-Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other clinical presentations. Our aim was to assess the clinical associations of all patients identified with GlyR-Abs in Queensland, Australia, between April 2014 and May 2017 and to compare these to cases reported in the literature.
METHODS
A literature review identified the clinical features of all published GlyR-Ab-positive cases through online databases. A case series was undertaken via collection of clinical information from all patients diagnosed or known to immunology, pathology or neurological services in Queensland during the study period of 3 years.
RESULTS
In all, 187 GlyR-Ab-positive cases were identified in the literature. The majority (47.6%) had PERM, 22.4% had epilepsy, but the remaining 30% included mixed phenotypes consisting of cerebellar ataxia, movement disorders, demyelination and encephalitis/cognitive dysfunction. By contrast, in our series of 14 cases, eight had clinical presentations consistent with seizures and epilepsy and only three cases had classical features of PERM. There was one case each of global fatiguable weakness with sustained clonus, laryngeal dystonia and movement disorder with hemiballismus and tics. The rate of response to immune therapy was similar in all groups.
CONCLUSION
Antibodies to glycine receptors are linked to a spectrum of neurological disease. The results of the literature review and our case series suggest a greater relationship between GlyR-Abs and epilepsy than previously reported.
Topics: Adolescent; Adult; Aged; Australia; Autoantibodies; Child; Child, Preschool; Encephalitis; Female; Humans; Infant; Male; Middle Aged; Movement Disorders; Muscle Rigidity; Myoclonus; Phenotype; Receptors, Glycine; Young Adult
PubMed: 29904974
DOI: 10.1111/ene.13721