Dataset Information

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network.

ABSTRACT:

Introduction

Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown.

Methods

Based on the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype.

Results

Ataxia, myoclonus and movement disorders were present in 105/764 adults (13.7%), with the onset coinciding or preceding the diagnosis of the mitochondrial disease in 49/105 (46.7%). Ataxia and parkinsonism were the most represented, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively. Hyperkinetic movement disorders were reported in 15.3% at last follow-up, being the less common reported movement disorders. The pathogenic m.8344A > G and POLG variants were always associated with a movement disorder, while LHON variants and mtDNA single deletions were more commonly found in the subjects who did not present a movement disorder. The most common neuroimaging features were cortical and/or cerebellar atrophy, white matter hyperintensities, basal ganglia abnormalities and nigro-striatal degeneration. Almost 70% of patients with parkinsonism responded to dopaminergic therapy, mainly levodopa, and 50% with myoclonus were successfully treated with levetiracetam.

Conclusion

Movement disorders, mainly ataxia and parkinsonism, are important findings in adult primary mitochondrial diseases. This study underlies the importance of looking for a mitochondrial etiology in the diagnostic flowchart of a movement disorder and may help direct genetic screening in daily practice.

SUBMITTER: Montano V

PROVIDER: S-EPMC8857085 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network.

Montano V V Orsucci D D Carelli V V La Morgia C C Valentino M L ML Lamperti C C Marchet S S Musumeci O O Toscano A A Primiano G G Santorelli F M FM Ticci C C Filosto M M Rubegni A A Mongini T T Tonin P P Servidei S S Ceravolo R R Siciliano G G Mancuso Michelangelo M

Journal of neurology 20210714 3

<h4>Introduction</h4>Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown.<h4>Methods</h4>Based on the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype.<h4>R ...[more]

PMID: 34259909

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Project description:IntroductionMovement disorders are increasingly described in hospitalized and milder cases of SARS-CoV-2 infection, despite a very low prevalence compared to the total patients.MethodsWe reviewed the scientific literature published in English, spanning from the initial descriptions of COVID-19 until January 25, 2021, in the PubMed/MEDLINE database.ResultsWe identified 93 new-onset movement disorders cases (44 articles) from 200 papers screened in the database or reference lists. Myoclonus was present in 63.4% (n = 59), ataxia in 38.7% (n = 36), action/postural tremor in 10.8% (n = 10), rigid-akinetic syndrome in 5.38% (n = 5), oculomotor abnormalities in 20.4% (n = 19), catatonia in 2.1% (n = 2), dystonia in 1.1% (n = 1), chorea in 1.1% (n = 1), functional (psychogenic) movement disorders in 3.2% (n = 3) of the reported COVID-19 cases with any movement disorder. Encephalopathy was a common association (n = 37, 39.78%).DiscussionComprehensive neurophysiological, clinical, and neuroimaging descriptions of movement disorders in the setting of SARS-CoV-2 infection are still lacking, and their pathophysiology may be related to inflammatory, postinfectious, or even indirect mechanisms not specific to SARS-CoV-2, such as ischemic-hypoxic brain insults, drug effects, sepsis, kidney failure. Cortical/subcortical myoclonus, which the cited secondary mechanisms can largely cause, seems to be the most common hyperkinetic abnormal movement, and it might occur in association with encephalopathy and ataxia.ConclusionThis brief review contributes to the clinical description of SARS-CoV-2 potential neurological manifestations, assisting clinical neurologists in identifying features of these uncommon syndromes as a part of COVID-19 symptomatology.Highlights- Movement disorders are probably uncommon neurological manifestations in SARS-CoV-2 infection;- Myoclonus is the most reported movement disorder associated with COVID-19, its clinical complications or pharmacological management;- The pathophysiology is yet not well-understood but can include systemic inflammation, autoimmune mechanisms, or hypoxia.

Project description:Background and objectiveThe objective of this study was to better delineate the genetic landscape and key clinical characteristics of complex, early-onset, monogenic hyperkinetic movement disorders.MethodsPatients were recruited from 14 international centers. Participating clinicians completed standardized proformas capturing demographic, clinical, and genetic data. Two pediatric movement disorder experts reviewed available video footage, classifying hyperkinetic movements according to published criteria.ResultsOne hundred forty patients with pathogenic variants in 17 different genes (ADCY5, ATP1A3, DDC, DHPR, FOXG1, GCH1, GNAO1, KMT2B, MICU1, NKX2.1, PDE10A, PTPS, SGCE, SLC2A1, SLC6A3, SPR, and TH) were identified. In the majority, hyperkinetic movements were generalized (77%), with most patients (69%) manifesting combined motor semiologies. Parkinsonism-dystonia was characteristic of primary neurotransmitter disorders (DDC, DHPR, PTPS, SLC6A3, SPR, TH); chorea predominated in ADCY5-, ATP1A3-, FOXG1-, NKX2.1-, SLC2A1-, GNAO1-, and PDE10A-related disorders; and stereotypies were a prominent feature in FOXG1- and GNAO1-related disease. Those with generalized hyperkinetic movements had an earlier disease onset than those with focal/segmental distribution (2.5 ± 0.3 vs. 4.7 ± 0.7 years; P = 0.007). Patients with developmental delay also presented with hyperkinetic movements earlier than those with normal neurodevelopment (1.5 ± 2.9 vs. 4.7 ± 3.8 years; P < 0.001). Effective disease-specific therapies included dopaminergic agents for neurotransmitters disorders, ketogenic diet for glucose transporter deficiency, and deep brain stimulation for SGCE-, KMT2B-, and GNAO1-related hyperkinesia.ConclusionsThis study highlights the complex phenotypes observed in children with genetic hyperkinetic movement disorders that can lead to diagnostic difficulty. We provide a comprehensive analysis of motor semiology to guide physicians in the genetic investigation of these patients, to facilitate early diagnosis, precision medicine treatments, and genetic counseling. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Project description:BackgroundFunctional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset.ObjectiveTo assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onset and their relationship with demographical and clinical variables.MethodsWe recruited patients with a "clinically definite" diagnosis of FMD from the Italian Registry of FMD. Patients underwent extensive clinical assessments. For elderly onset, we set a chronological cut-off at 65 years or older according to WHO definition. Multivariate regression models were implemented to estimate adjusted odds ratio of elderly FMD onset related to clinical characteristics.ResultsAmong the 410 patients, 34 (8.2%) experienced elderly-onset FMD, with a mean age at onset of 70.9 years. The most common phenotype was tremor (47.1%), followed by gait disorders, weakness, and dystonia (29.4%, 23.5%, 14.7%, respectively). Eleven elderly patients had a combined phenomenology: 9 exhibited two phenotypes, 2 had three phenotypes. Weakness was isolated in 3/8 patients and combined with another phenotype in 5/8, manifesting as paraplegia (n = 4); upper limb diplegia (n = 2), hemiparesis/hemiplegia (n = 1), and tetraparesis/tetraplegia (n= 1). Non-motor and other functional neurological disorders occurred more frequently in the younger group (89.1%) than the elderly (73.5%). Neurological and non-neurological comorbidities were more prevalent in the elderly group (82.4%) as opposed to the younger (32.7%). In a multivariate regression analysis, elderly-onset FMD was significantly associated with neurological comorbidities, including parkinsonism (OR 6.73) and cerebrovascular diseases (OR 5.48).ConclusionsThese results highlight the importance of achieving an accurate diagnosis of FMD in the elderly, as it is crucial for effectively managing FMD symptoms and addressing neurological comorbidities.

Dataset Information

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network.

Introduction

Methods

Results

Conclusion

Publications

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network.

Similar Datasets

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