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Epilepsia Open Apr 2024Myoclonus classically presents as a brief (10-50 ms duration), non-rhythmic jerk movement. The etiology could vary considerably ranging from self-limited to chronic or... (Review)
Review
Myoclonus classically presents as a brief (10-50 ms duration), non-rhythmic jerk movement. The etiology could vary considerably ranging from self-limited to chronic or even progressive disorders, the latter falling into encephalopathic pictures that need a prompt diagnosis. Beyond the etiological classification, others evaluate myoclonus' body distribution (i.e., clinical classification) or the location of the generator (i.e., neurophysiological classification); particularly, knowing the anatomical source of myoclonus gives inputs on the observable clinical patterns, such as EMG bursts duration or EEG correlate, and guides the therapeutic choices. Among all the chronic disorders, myoclonus often presents itself as a manifestation of epilepsy. In this context, myoclonus has many facets. Myoclonus occurs as one, or the only, seizure manifestation while it can also present as a peculiar type of movement disorder; moreover, its electroclinical features within specific genetically determined epileptic syndromes have seldom been investigated. In this review, following a meeting of recognized experts, we provide an up-to-date overview of the neurophysiology and nosology surrounding myoclonus. Through the dedicated exploration of epileptic syndromes, coupled with pragmatic guidance, we aim to furnish clinicians and researchers alike with practical advice for heightened diagnostic management and refined treatment strategies. PLAIN LANGUAGE SUMMARY: In this work, we described myoclonus, a movement characterized by brief, shock-like jerks. Myoclonus could be present in different diseases and its correct diagnosis helps treatment.
Topics: Humans; Myoclonus; Diagnosis, Differential; Movement Disorders; Epilepsy; Epileptic Syndromes
PubMed: 38334331
DOI: 10.1002/epi4.12917 -
Neurobiology of Disease Dec 2019Dystonia and levodopa-induced dyskinesia (LID) are both hyperkinetic movement disorders. Dystonia arises most often spontaneously, although it may be seen after stroke,... (Review)
Review
Dystonia and levodopa-induced dyskinesia (LID) are both hyperkinetic movement disorders. Dystonia arises most often spontaneously, although it may be seen after stroke, injury, or as a result of genetic causes. LID is associated with Parkinson's disease (PD), emerging as a consequence of chronic therapy with levodopa, and may be either dystonic or choreiform. LID and dystonia share important phenomenological properties and mechanisms. Both LID and dystonia are generated by an integrated circuit involving the cortex, basal ganglia, thalamus and cerebellum. They also share dysregulation of striatal cholinergic signaling and abnormalities of striatal synaptic plasticity. The long duration nature of both LID and dystonia suggests that there may be underlying epigenetic dysregulation as a proximate cause. While both may improve after interventions such as deep brain stimulation (DBS), neither currently has a satisfactory medical therapy, and many people are disabled by the symptoms of dystonia and LID. Further study of the fundamental mechanisms connecting these two disorders may lead to novel approaches to treatment or prevention.
Topics: Animals; Antiparkinson Agents; Brain; Dyskinesia, Drug-Induced; Dystonic Disorders; Humans; Levodopa; Parkinson Disease
PubMed: 31445160
DOI: 10.1016/j.nbd.2019.104579 -
Molecular Medicine (Cambridge, Mass.) Mar 2024Loss of dopaminergic neurons underlies the motor symptoms of Parkinson's disease (PD). However stereotypical PD symptoms only manifest after approximately 80% of...
BACKGROUND
Loss of dopaminergic neurons underlies the motor symptoms of Parkinson's disease (PD). However stereotypical PD symptoms only manifest after approximately 80% of dopamine neurons have died making dopamine-related motor phenotypes unreliable markers of the earlier stages of the disease. There are other non-motor symptoms, such as depression, that may present decades before motor symptoms.
METHODS
Because serotonin is implicated in depression, here we use niche, fast electrochemistry paired with mathematical modelling and machine learning to, for the first time, robustly evaluate serotonin neurochemistry in vivo in real time in a toxicological model of Parkinsonism, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
RESULTS
Mice treated with acute MPTP had lower concentrations of in vivo, evoked and ambient serotonin in the hippocampus, consistent with the clinical comorbidity of depression with PD. These mice did not chemically respond to SSRI, as strongly as control animals did, following the clinical literature showing that antidepressant success during PD is highly variable. Following L-DOPA administration, using a novel machine learning analysis tool, we observed a dynamic shift from evoked serotonin release in the hippocampus to dopamine release. We hypothesize that this finding shows, in real time, that serotonergic neurons uptake L-DOPA and produce dopamine at the expense of serotonin, supporting the significant clinical correlation between L-DOPA and depression. Finally, we found that this post L-DOPA dopamine release was less regulated, staying in the synapse for longer. This finding is perhaps due to lack of autoreceptor control and may provide a ground from which to study L-DOPA induced dyskinesia.
CONCLUSIONS
These results validate key prior hypotheses about the roles of serotonin during PD and open an avenue to study to potentially improve therapeutics for levodopa-induced dyskinesia and depression.
Topics: Mice; Animals; Levodopa; Dopamine; Serotonin; Antiparkinson Agents; Dyskinesia, Drug-Induced; Parkinson Disease; Parkinsonian Disorders; Biomarkers
PubMed: 38429661
DOI: 10.1186/s10020-023-00773-9 -
Journal of Medical Case Reports Jul 2023Dyskinesia is a movement disorder categorized by involuntary movement of muscle. Although dyskinesia can be brought on by taking medications, it can also be a symptom of...
BACKGROUND
Dyskinesia is a movement disorder categorized by involuntary movement of muscle. Although dyskinesia can be brought on by taking medications, it can also be a symptom of a variety of diseases. Antiepileptic drug-induced involuntary movements have been well researched. Rare reports have been made for dyskinesia, a type of dystonia caused by phenytoin. The mechanism of its occurrence must be succinctly studied.
CASE PRESENTATION
A 53-year-old Asian patient taking phenytoin (100 mg twice daily) experienced symptoms of perioral muscle involuntary movement, impaired speech, and generalized tremors and was admitted to the hospital. Brain magnetic resonance imaging showed significant development of encephalomalacia and porencephaly. The serum phenytoin levels were in the toxic range (33 g/ml). These were suggestive of phenytoin-induced dyskinesia. Levetiracetam and clonazepam were initiated, and the patient showed significant improvement in the symptoms.
CONCLUSION
This case presented a substantial reference value for the differential diagnosis and treatment prognosis of phenytoin-induced dyskinesia. The phenytoin-induced dyskinesia in this patient was successfully reversed with prompt identification and treatment. According to the case study's findings, such people may benefit from periodic therapeutic drug monitoring.
Topics: Humans; Middle Aged; Phenytoin; Dyskinesia, Drug-Induced; Anticonvulsants; Levetiracetam; Dystonia
PubMed: 37475012
DOI: 10.1186/s13256-023-04033-6 -
Neurobiology of Disease Oct 2023L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the...
L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the striatonigral direct pathway to LID is widely acknowledged but whether the striatopallidal pathway is involved remains debated. Selective optogenetic stimulation of striatonigral axon terminals induces dyskinesia in mice rendered hemiparkinsonian with the toxin 6-hydroxydopamine (6-OHDA). Here we show that optogenetically-induced dyskinesia is increased by the D2-type dopamine receptor agonist quinpirole. Although the quinpirole effect may be mediated by D2 receptor stimulation in striatopallidal neurons, alternative mechanisms may be responsible as well. To selectively modulate the striatopallidal pathway, we selectively expressed channelrhodopsin-2 (ChR2) in D2 receptor expressing neurons by crossing D2-Cre and ChR2-flox mice. The animals were rendered hemiparkinsonian and implanted with an optic fiber at the ipsilateral external globus pallidus (GPe). Stimulation of ChR2 at striatopallidal axon terminals reduced LID and also general motility during the off L-DOPA state, without modifying the pro-motor effect of low doses of L-DOPA producing mild or no dyskinesia. Overall, the present study shows that D2-type dopamine receptors and the striatopallidal pathway modulate dyskinesia and suggest that targeting striatopallidal axon terminals at the GPe may have therapeutic potential in the management of LID.
Topics: Animals; Mice; Levodopa; Quinpirole; Dopamine Agonists; Dyskinesias; Oxidopamine; Receptors, Dopamine D2
PubMed: 37683958
DOI: 10.1016/j.nbd.2023.106278 -
Developmental Medicine and Child... Apr 2020To review orofacial disabilities and their consequences in children with Moebius syndrome (MBS).
AIM
To review orofacial disabilities and their consequences in children with Moebius syndrome (MBS).
METHOD
We retrospectively analysed the records of 32 patients (21 males, 11 females) with non-progressive bilateral facial and abducens palsies who had been examined before 6 months of age.
RESULTS
All facial muscles were severely involved in 17 patients; in the 15 others, partial movements were found in the lower face. Most patients (n=24) were unable to smile. Patients frequently presented with congenital trismus (n=20) and drooling (n=18). Additional palsies involved cranial nerves IX and X (n=18) and XII (n=25). Sucking was absent or weak in 30 patients; swallowing was impaired in 25. During the first month of life, feeding disorders were graded as severe/moderate in 25. Respiratory complications occurred in 17. Severe feeding disorders were associated with congenital trismus (p=0.01) and with cranial nerve IX and X palsy (p=0.01). Growth failure between 1 and 6 months of age, followed by catch-up growth between 6 and 12 months, was observed in 20 patients. Between 2 and 5 years of age, 25 out of 32 patients attained normal oral diet and 28 out of 29 showed normal growth.
INTERPRETATION
Children with MBS frequently require adjusted therapeutic options to prevent failure to thrive. Congenital trismus, cranial nerve IX and X palsy, and laryngeal-tracheal dysfunctions are predictors of severe feeding disorders.
WHAT THIS PAPER ADDS
Moebius syndrome frequently induces reduced oral intake and early failure to thrive. Normal oral diet and growth parameters are attained at 2 to 5 years of age. Congenital trismus, pharyngeal palsy, and laryngeal disorders predict dysphagia.
Topics: Dyskinesias; Facial Muscles; Female; Humans; Infant; Male; Mobius Syndrome; Retrospective Studies
PubMed: 31713842
DOI: 10.1111/dmcn.14379 -
Advanced Science (Weinheim,... Mar 2024Paroxysmal kinesigenic dyskinesia (PKD) is associated with a disturbance of neural circuit and network activities, while its neurophysiological characteristics have not...
Paroxysmal kinesigenic dyskinesia (PKD) is associated with a disturbance of neural circuit and network activities, while its neurophysiological characteristics have not been fully elucidated. This study utilized the high-density electroencephalogram (hd-EEG) signals to detect abnormal brain activity of PKD and provide a neural biomarker for its clinical diagnosis and PKD progression monitoring. The resting hd-EEGs are recorded from two independent datasets and then source-localized for measuring the oscillatory activities and function connectivity (FC) patterns of cortical and subcortical regions. The abnormal elevation of theta oscillation in wildly brain regions represents the most remarkable physiological feature for PKD and these changes returned to healthy control level in remission patients. Another remarkable feature of PKD is the decreased high-gamma FCs in non-remission patients. Subtype analyses report that increased theta oscillations may be related to the emotional factors of PKD, while the decreased high-gamma FCs are related to the motor symptoms. Finally, the authors established connectome-based predictive modelling and successfully identified the remission state in PKD patients in dataset 1 and dataset 2. The findings establish a clinically relevant electroencephalography profile of PKD and indicate that hd-EEG can provide robust neural biomarkers to evaluate the prognosis of PKD.
Topics: Humans; Dystonia; Electroencephalography; Brain
PubMed: 38227367
DOI: 10.1002/advs.202306321 -
Medicina (Kaunas, Lithuania) Feb 2024Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed... (Review)
Review
Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.
Topics: Humans; Myoclonus; Tremor; Dyskinesias; Brain Diseases; Carbamazepine
PubMed: 38541088
DOI: 10.3390/medicina60030362 -
Tremor and Other Hyperkinetic Movements... 2023Functional movement disorders (FMD) are a diagnostic and therapeutic challenge, both to the neurologist and psychiatrists. The phenomenology is varied and can present as... (Review)
Review
BACKGROUND
Functional movement disorders (FMD) are a diagnostic and therapeutic challenge, both to the neurologist and psychiatrists. The phenomenology is varied and can present as tremors, dystonia, jerks/myoclonus, gait disorder, other abnormal movements or a combination. There has been an increase in the use of electrophysiological studies that are an important tool in the evaluation of FMDs.
METHODS
We searched the database platforms of MEDLINE, Google scholar, Web of Sciences, Scopus using the Medical Subject Heading terms (MeSH) for all the articles from 1st January 1970 till November 2022. A total of 658 articles were obtained by the search mechanism. A total of 79 relevant articles were reviewed thoroughly, of which 26 articles that had electrophysiological data were included in the present review.
RESULTS
Variability, distractibility and entertainability can be demonstrated in functional tremors by using multichannel surface electromyography. Voluntary ballistic movements tend to decrease the tremor, while loading the tremulous limb with weight causes the tremor amplitude to increase in functional tremor. Presence of Bereitschaftspotential demonstrates the functional nature of palatal tremor and myoclonus. Co-contraction testing may be helpful in differentiating functional from organic dystonia. The R2 blink reflex recovery cycle has been found to be abnormally enhanced in organic blepharospasm, whereas it is normal in presumed functional blepharospasm. Plasticity is found to be abnormally high in organic dystonia and normal in functional dystonia, in addition to enhanced facilitation in patients with organic dystonia.
CONCLUSIONS
Electrophysiological tests supplement clinical examination and helps in differentiating FMD from organic movement disorders.
Topics: Humans; Tremor; Myoclonus; Dystonia; Blepharospasm; Movement Disorders; Dystonic Disorders; Electrophysiology; Conversion Disorder
PubMed: 38162980
DOI: 10.5334/tohm.793 -
Clinical Autonomic Research : Official... Aug 2021Dyskinesia-hyperpyrexia syndrome (DHS) is a rare but life-threatening disease. The clinical manifestations of this syndrome overlap substantially with Parkinson... (Review)
Review
PURPOSE
Dyskinesia-hyperpyrexia syndrome (DHS) is a rare but life-threatening disease. The clinical manifestations of this syndrome overlap substantially with Parkinson hyperpyrexia syndrome and serotonin syndrome and are often confused by clinicians. The purpose of this review was to enable clinicians to recognize this syndrome and thereby reach a correct diagnosis and provide optimal treatments to improve prognosis in clinical practice.
METHODS
Using the methodology described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a literature search of the PubMed, Embase, and MEDLINE databases using keywords in titles and abstracts of published literature. Quality assessment was performed using the modified Newcastle-Ottawa scale.
RESULTS
A total of 11 patients obtained from nine publications were included in this systematic review. All of the cases occurred in patients with advanced Parkinson's disease (PD) of long disease duration. High ambient temperature was the most common trigger of this syndrome. Hyperpyrexia and dyskinesias were present in all cases. The consciousness disturbances of this syndrome included confusion, hallucination, and lethargy or stupor. Autonomic dysfunction (except for hyperpyrexia) is uncommon in DHS, and only two patients presented with tachycardia. The treatment of this syndrome included supportive interventions (including rehydration, anti-pyretic and anti-infection treatments, and maintaining electrolyte balance), dopaminergic drug reduction and sedation. Two patients died due to DHS.
CONCLUSIONS
We summarized the triggers, clinical features, and treatments of all reported dyskinesia-hyperpyrexia syndrome cases, proposed guiding diagnostic criteria, and established a flow chart to guide diagnoses to quickly identify these three syndromes in clinical practice.
Topics: Dyskinesias; Humans; Parkinson Disease; Syndrome
PubMed: 33826041
DOI: 10.1007/s10286-021-00801-w