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Cureus Mar 2024We report a case involving a 31-year-old male without any known precipitating injuries presenting with involuntary finger movements and rare seizures. There was a noted...
We report a case involving a 31-year-old male without any known precipitating injuries presenting with involuntary finger movements and rare seizures. There was a noted family history of tremulous movements. Yet the characteristics of his finger movements were irregular and not typical of essential tremor (ET). Electrophysiological examinations, including video EEG, showed no epileptic discharges, and brain MRI results were normal. However, somatosensory evoked potentials (SEP) revealed the presence of giant SEP, and a positive cortical (C)-reflex was observed, leading to a clinical diagnosis of benign adult familial myoclonus epilepsy (BAFME). Management with valproic acid and perampanel resulted in a significant reduction of symptoms. This case highlights the necessity of considering BAFME in the differential diagnosis for atypical tremorous finger movements, especially with a relevant family history, and the critical role of electrophysiological findings indicative of cortical hyperexcitability.
PubMed: 38629017
DOI: 10.7759/cureus.56303 -
Cureus Mar 2024Myoclonus-dystonia syndrome (MDS) presents with both rapid myoclonus and dystonia, which is caused by mutations in the sarcoglycan (SGCE) gene. However, its...
Myoclonus-Dystonia Plus Syndrome With Early-Onset Multiple Cerebral Cavernous Malformation Type 1 and Growth Hormone Deficiency Associated With Novel 7q21.13-q21.3 Deletion: A Pediatric Case Report.
Myoclonus-dystonia syndrome (MDS) presents with both rapid myoclonus and dystonia, which is caused by mutations in the sarcoglycan (SGCE) gene. However, its complications and management remain unclear. Here, we report a case involving a girl with MDS due to a 7q21.13-q21.3 microdeletion complicated by early-onset multiple cerebral cavernous malformations (CCMs). The patient presented with myoclonus and dystonia at two and eight years of age, respectively. In addition to MDS, the patient developed growth hormone (GH) deficiency and mild intellectual disability. Magnetic resonance imaging of the brain showed multiple CCMs. Array-based comparative genomic hybridization revealed 7q21.13-21.3 microdeletion. The deletion size was 4.11 Mb, which included SCGE and KRIT1. After the introduction of zonisamide, both myoclonus and dystonia showed improvement, and GH therapy led to an increase in patient height. In cases of MDS, multiple early-onset CCMs and GH deficiency may occur; moreover, careful follow-up management may be necessary.
PubMed: 38628998
DOI: 10.7759/cureus.56294 -
Tremor and Other Hyperkinetic Movements... 2024Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in . A growing, yet still limited number of reports suggested that... (Review)
Review
BACKGROUND
Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in . A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease.
CASE SERIES
We describe two newly identified families harboring the recurrent pathogenic p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on variants linked to hyperkinetic disorders, comparing our cases to described phenotypes.
DISCUSSION
Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes.
Topics: Humans; Dystonia; Myoclonus; Hyperkinesis; Ataxia; Rare Diseases; Syndrome; Membrane Proteins; Spinocerebellar Degenerations; Dystonic Disorders
PubMed: 38617829
DOI: 10.5334/tohm.858 -
Nefrologia 2024We discuss two recent cases from our hospital in which two patients with ESKD receiving periodical hemodialysis (HD) and SarS-Cov-2 infection suffered movement...
We discuss two recent cases from our hospital in which two patients with ESKD receiving periodical hemodialysis (HD) and SarS-Cov-2 infection suffered movement disorders, being the onset related to the HD sessions in both. First case is a 78 year-old woman who is admitted with generalized myoclonic status epilepticus and second case is a 46 year-old male who starts repeatedly suffering myoclonus during his hemodialysis sessions on day +10 after testing positive (asymptomatic infection). There are two main hypotheses when it comes to myoclonus and CNS disorders in COVID19, post-hypoxic origin and inmunomediated postinfectious origin. We wonder if they could both be interacting in patients with kidney disease, and especially in those who receive hemodialysis, maximizing the risk of suffering this type of disorders.
Topics: Aged; Female; Humans; COVID-19; Kidney Failure, Chronic; Myoclonus; Renal Dialysis; SARS-CoV-2
PubMed: 38614889
DOI: 10.1016/j.nefroe.2024.03.015 -
Brain Communications 2024Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in...
Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of (DYT-) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT- and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder.
PubMed: 38601915
DOI: 10.1093/braincomms/fcae105 -
Journal of Movement Disorders Apr 2024Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study...
PURPOSE
Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying NEU1 variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1.
METHODS
First, whole-exome sequencing and detailed clinical examination were performed on the family. Second, structural analysis, including energy, flexibility and polar contacts, was conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed.
RESULTS
We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by sialidase activity assay. The cherry-red spot was more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal EEGs and VEPs had a relatively early age of onset, whereas patients with myoclonus had a late onset.
CONCLUSION
Changes in flexibility and local polar contacts may be indicators of the NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.
PubMed: 38600684
DOI: 10.14802/jmd.23145 -
Cureus Mar 2024Clozapine has become a widely popular and effective medication in the treatment of refractory schizophrenia and refractory bipolar disorder. Although the use of...
Clozapine has become a widely popular and effective medication in the treatment of refractory schizophrenia and refractory bipolar disorder. Although the use of clozapine proves to be an effective resort, it has to be closely monitored due to its narrow therapeutic range and multiple dangerous adverse effects. In rare cases, clozapine has been known to cause an antagonistic myoclonic jerk that leads to knee buckling. Here, we present the case of a 29-year-old female who is being treated for schizoaffective disorder, bipolar, manic type, who reported two instances of knee buckling associated with falls while taking clozapine.
PubMed: 38595866
DOI: 10.7759/cureus.55865 -
PloS One 2024Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients.
MATERIAL AND METHODS
The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis.
RESULTS
A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity.
CONCLUSION
In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.
Topics: Adolescent; Humans; Child; Myoclonic Epilepsy, Juvenile; Epilepsy, Absence; Seizures; Drug Resistant Epilepsy; Risk Factors; Electroencephalography; Anticonvulsants
PubMed: 38593118
DOI: 10.1371/journal.pone.0300930 -
The Journal of Biological Chemistry May 2024Lafora disease (LD) is an autosomal recessive myoclonus epilepsy with onset in the teenage years leading to death within a decade of onset. LD is characterized by the...
Lafora disease (LD) is an autosomal recessive myoclonus epilepsy with onset in the teenage years leading to death within a decade of onset. LD is characterized by the overaccumulation of hyperphosphorylated, poorly branched, insoluble, glycogen-like polymers called Lafora bodies. The disease is caused by mutations in either EPM2A, encoding laforin, a dual specificity phosphatase that dephosphorylates glycogen, or EMP2B, encoding malin, an E3-ubiquitin ligase. While glycogen is a widely accepted laforin substrate, substrates for malin have been difficult to identify partly due to the lack of malin antibodies able to detect malin in vivo. Here we describe a mouse model in which the malin gene is modified at the C-terminus to contain the c-myc tag sequence, making an expression of malin-myc readily detectable. Mass spectrometry analyses of immunoprecipitates using c-myc tag antibodies demonstrate that malin interacts with laforin and several glycogen-metabolizing enzymes. To investigate the role of laforin in these interactions we analyzed two additional mouse models: malin-myc/laforin knockout and malin-myc/LaforinCS, where laforin was either absent or the catalytic Cys was genomically mutated to Ser, respectively. The interaction of malin with partner proteins requires laforin but is not dependent on its catalytic activity or the presence of glycogen. Overall, the results demonstrate that laforin and malin form a complex in vivo, which stabilizes malin and enhances interaction with partner proteins to facilitate normal glycogen metabolism. They also provide insights into the development of LD and the rescue of the disease by the catalytically inactive phosphatase.
Topics: Lafora Disease; Animals; Mice; Ubiquitin-Protein Ligases; Protein Tyrosine Phosphatases, Non-Receptor; Humans; Dual-Specificity Phosphatases; Disease Models, Animal; Glycogen
PubMed: 38588813
DOI: 10.1016/j.jbc.2024.107271 -
Cureus Mar 2024Linezolid plays a clinically important role; however, it is responsible for severe pharmacological interactions and side effects, such as myelosuppression, serotonin...
Linezolid plays a clinically important role; however, it is responsible for severe pharmacological interactions and side effects, such as myelosuppression, serotonin syndrome, and lactic acidosis. We report a case of an 80-year-old man treated with venlafaxine for depression. He was admitted with a right femur fracture and submitted to surgical intervention, complicated by local infection. In collected pus was identified multiple microorganisms including resistant to vancomycin. The therapeutic was adjusted to linezolid. On the 36 day of treatment, he developed hypertension, poor peripheral perfusion, and generalized tremor. He was disoriented, with marbled skin, myoclonus, and sinus tachycardia; and apyretic, with no signs of respiratory distress or joint/surgical wound inflammatory signs. Blood tests showed hyperlacticemia and discrete elevation of C-reactive protein but in a decrescent trend, with no other relevant alterations. The diagnosis of lactic acidosis and probable serotonin syndrome secondary to linezolid was made, supported by improvement after the drug suspension.
PubMed: 38586704
DOI: 10.7759/cureus.55672