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Neurology(R) Neuroimmunology &... May 2022Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder of the nervous system that classically presents with a combination of characteristic eye movement disorder... (Review)
Review
BACKGROUND AND OBJECTIVES
Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder of the nervous system that classically presents with a combination of characteristic eye movement disorder and myoclonus, in addition to ataxia, irritability, and sleep disturbance. There is good evidence that OMAS is an immune-mediated condition that may be paraneoplastic in the context of neuroblastoma. This syndrome may be associated with long-term cognitive impairment, yet it remains unclear how this is influenced by disease course and treatment. Treatment is largely predicated on immune suppression, but there is limited evidence to indicate an optimal regimen.
METHODS
Following an international multiprofessional workshop in 2004, a body of clinicians and scientists comprising the International OMS Study group continued to meet biennially in a joint professionals and family workshop focusing on pediatric OMAS. Seventeen years after publication of the first report, a writing group was convened to provide a clinical update on the definitions and clinical presentation of OMAS, biomarkers and the role of investigations in a child presenting with OMAS, treatment and management strategies including identification and support of long-term sequelae.
RESULTS
The clinical criteria for diagnosis were reviewed, with a proposed approach to laboratory and radiologic investigation of a child presenting with possible OMAS. The evidence for an upfront vs escalating treatment regimen was reviewed, and a treatment algorithm proposed to recognize both these approaches. Importantly, recommendations on monitoring of immunotherapy response and longer-term follow-up based on an expert consensus are provided.
DISCUSSION
OMAS is a rare neurologic condition that can be associated with poor cognitive outcomes. This report proposes an approach to investigation and treatment of children presenting with OMAS, based on expert international opinion recognizing the limited data available.
Topics: Ataxia; Child; Disease Progression; Humans; Internationality; Neuroblastoma; Ocular Motility Disorders; Opsoclonus-Myoclonus Syndrome
PubMed: 35260471
DOI: 10.1212/NXI.0000000000001153 -
Tremor and Other Hyperkinetic Movements... 2023Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close... (Review)
Review
BACKGROUND
Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.
METHODS
A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 to identify relevant articles for this narrative review.
RESULTS
The spectrum of the phenomenology of PIMD is broad and it encompasses both hyperkinetic and hypokinetic movements. Hemifacial spasm is probably the most common PIMD. Others include dystonia, tremor, parkinsonism, myoclonus, painful leg moving toe syndrome, tics, polyminimyoclonus, and amputation stump dyskinesia. We also highlight conditions such as neuropathic tremor, pseudoathetosis, and -associated myogenic tremor as examples of PIMD.
DISCUSSION
There is considerable heterogeneity among PIMD in terms of severity and nature of injury, natural course, association with pain, and response to treatment. As some patients may have co-existing functional movement disorder, neurologists should be able to differentiate the two disorders. While the exact pathophysiology remains elusive, aberrant central sensitization after peripheral stimuli and maladaptive plasticity in the sensorimotor cortex, on a background of genetic (two-hit hypothesis) or other predisposition, seem to play a role in the pathogenesis of PIMD.
Topics: Humans; Tremor; Movement Disorders; Dystonic Disorders; Tic Disorders; Dyskinesias; Myoclonus
PubMed: 37008994
DOI: 10.5334/tohm.758 -
Brain : a Journal of Neurology Mar 2022Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being...
Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy and movement disorder. We evaluated a large cohort of patients (n = 25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor and ataxia. Later in the disease course, they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibres and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders.
Topics: Alkyl and Aryl Transferases; Child; Dolichols; Humans; Myoclonus; Neurodegenerative Diseases; Retinitis Pigmentosa
PubMed: 34382076
DOI: 10.1093/brain/awab299 -
Annals of Indian Academy of Neurology 2021Myoclonus is a hyperkinetic movement disorder characterized by a sudden, brief, involuntary jerk. Positive myoclonus is caused by abrupt muscle contractions, while... (Review)
Review
Myoclonus is a hyperkinetic movement disorder characterized by a sudden, brief, involuntary jerk. Positive myoclonus is caused by abrupt muscle contractions, while negative myoclonus by sudden cessation of ongoing muscular contractions. Myoclonus can be classified in various ways according to body distribution, relation to activity, neurophysiology, and etiology. The neurophysiological classification of myoclonus by means of electrophysiological tests is helpful in guiding the best therapeutic strategy. Given the diverse etiologies of myoclonus, a thorough history and detailed physical examination are key to the evaluation of myoclonus. These along with basic laboratory testing and neurophysiological studies help in narrowing down the clinical possibilities. Though symptomatic treatment is required in the majority of cases, treatment of the underlying etiology should be the primary aim whenever possible. Symptomatic treatment is often not satisfactory, and a combination of different drugs is often required to control the myoclonus. This review addresses the etiology, classification, clinical approach, and management of myoclonus.
PubMed: 34446993
DOI: 10.4103/aian.AIAN_1180_20 -
Movement Disorders Clinical Practice Jul 2020Many different movement disorders have similar "jerk-like" phenomenology and can be misconstrued as myoclonus. Different types of myoclonus also share similar... (Review)
Review
BACKGROUND
Many different movement disorders have similar "jerk-like" phenomenology and can be misconstrued as myoclonus. Different types of myoclonus also share similar phenomenological characteristics that can be difficult to distinguish solely based on clinical exam. However, they have distinctive physiologic characteristics that can help refine categorization of jerk-like movements.
OBJECTIVES
In this review, we briefly summarize the clinical, physiologic, and pathophysiologic characteristics of different types of myoclonus. The methodology and technical considerations for the electrophysiologic assessment of jerk-like movements are reviewed. A simplistic pragmatic approach for the classification of myoclonus and other jerk-like movements based on objective electrophysiologic characteristics is proposed.
CONCLUSIONS
Clinical neurophysiology is an underutilized tool in the diagnosis and treatment of movement disorders. Various jerk-like movements have distinguishing physiologic characteristics, differentiated in the milliseconds range, which is beyond human capacity. We argue that the categorization of movement disorders as myoclonus can be refined based on objective physiology that can have important prognostic and therapeutic implications.
PubMed: 32626792
DOI: 10.1002/mdc3.12986 -
Neurotherapeutics : the Journal of the... Oct 2020Myoclonus can cause significant disability for patients. Myoclonus has a strikingly diverse array of underlying etiologies, clinical presentations, and... (Review)
Review
Myoclonus can cause significant disability for patients. Myoclonus has a strikingly diverse array of underlying etiologies, clinical presentations, and pathophysiological mechanisms. Treatment of myoclonus is vital to improving the quality of life of patients with these disorders. The optimal treatment strategy for myoclonus is best determined based upon careful evaluation and consideration of the underlying etiology and neurophysiological classification. Electrophysiological testing including EEG (electroencephalogram) and EMG (electromyogram) data is helpful in determining the neurophysiological classification of myoclonus. The neurophysiological subtypes of myoclonus include cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral. Levetiracetam, valproic acid, and clonazepam are often used to treat cortical myoclonus. In cortical-subcortical myoclonus, treatment of myoclonic seizures is prioritized, valproic acid being the mainstay of therapy. Subcortical-nonsegmental myoclonus may be treated with clonazepam, though numerous agents have been used depending on the etiology. Segmental and peripheral myoclonus are often resistant to treatment, but anticonvulsants and botulinum toxin injections may be of utility depending upon the case. Pharmacological treatments are often hampered by scarce evidence-based knowledge, adverse effects, and variable efficacy of medications.
Topics: Anticonvulsants; Deep Brain Stimulation; Electroencephalography; Electromyography; Electrophysiological Phenomena; Humans; Myoclonus; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 32910414
DOI: 10.1007/s13311-020-00922-6 -
Ugeskrift For Laeger Feb 2023Creutzfeldt-Jakob disease is the most common prion disease in humans. Neuropsychiatric symptoms are common, and objective findings are myoclonus, pyramidal and...
Creutzfeldt-Jakob disease is the most common prion disease in humans. Neuropsychiatric symptoms are common, and objective findings are myoclonus, pyramidal and extrapyramidal including cerebellar dysfunction. This is a case report of a 77-year-old woman with gradual onset of repeated falls due to cerebellar dysfunction. She had severe visuospatial difficulties, and she was unaware of her problems. Her MRI showed increased diffusion restriction in the caudate and lentiform nuclei. Her cerebrospinal fluid real-time quaking-induced conversion test was positive, fulfilling criteria for probable sporadic Creutzfeldt-Jakob disease.
Topics: Humans; Female; Aged; Creutzfeldt-Jakob Syndrome; Accidental Falls; Magnetic Resonance Imaging; Myoclonus
PubMed: 36892320
DOI: No ID Found -
Movement Disorders Clinical Practice Jan 2021A myriad of disorders combine myoclonus and ataxia. Most causes are genetic and an increasing number of genes are being associated with myoclonus-ataxia syndromes (MAS),... (Review)
Review
BACKGROUND
A myriad of disorders combine myoclonus and ataxia. Most causes are genetic and an increasing number of genes are being associated with myoclonus-ataxia syndromes (MAS), due to recent advances in genetic techniques. A proper etiologic diagnosis of MAS is clinically relevant, given the consequences for genetic counseling, treatment, and prognosis.
OBJECTIVES
To review the causes of MAS and to propose a diagnostic algorithm.
METHODS
A comprehensive and structured literature search following PRISMA criteria was conducted to identify those disorders that may combine myoclonus with ataxia.
RESULTS
A total of 135 causes of combined myoclonus and ataxia were identified, of which 30 were charted as the main causes of MAS. These include four acquired entities: opsoclonus-myoclonus-ataxia syndrome, celiac disease, multiple system atrophy, and sporadic prion diseases. The distinction between progressive myoclonus epilepsy and progressive myoclonus ataxia poses one of the main diagnostic dilemmas.
CONCLUSIONS
Diagnostic algorithms for pediatric and adult patients, based on clinical manifestations including epilepsy, are proposed to guide the differential diagnosis and corresponding work-up of the most important and frequent causes of MAS. A list of genes associated with MAS to guide genetic testing strategies is provided. Priority should be given to diagnose or exclude acquired or treatable disorders.
PubMed: 33426154
DOI: 10.1002/mdc3.13106