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Neurology India 2023
Topics: Humans; Chorea; Dyskinesias; Hyperglycemic Hyperosmolar Nonketotic Coma
PubMed: 37635540
DOI: 10.4103/0028-3886.383864 -
Indian Journal of Pediatrics Sep 2023
Topics: Humans; Infant; Tremor; Syndrome
PubMed: 37204598
DOI: 10.1007/s12098-023-04641-6 -
Expert Opinion on Drug Safety 2023Levodopa remains the gold standard for treatment of Parkinson's disease (PD). Patients develop complications with disease progression, necessitating adjunctive therapy... (Review)
Review
INTRODUCTION
Levodopa remains the gold standard for treatment of Parkinson's disease (PD). Patients develop complications with disease progression, necessitating adjunctive therapy to control fluctuations in motor and non-motor symptoms and dyskinesia. Knowledge of medication safety and tolerability is critical to ascertain the benefit-risk ratio and select an adjunctive therapy that provides the highest chance for medication adherence. Posing a challenge are the sheer abundance of options, stemming from the development of several new drugs in recent years, as well as differences in commercial drug availability worldwide.
AREAS COVERED
This review evaluates the efficacy, safety, and tolerability of current US FDA-approved pharmacotherapies for levodopa-treated PD patients, including dopamine agonists, monoamine oxidase type-B inhibitors, catechol-O-methyltransferase inhibitors, the N-methyl-D-aspartate receptor antagonist amantadine, and the adenosine receptor antagonist istradefylline. Data were taken from pivotal phase III randomized controlled and post-surveillance studies, when available, that directly led to FDA-approval.
EXPERT OPINION
No strong evidence exists to support use of a specific adjunctive treatment for improving Off time. Only one medication has demonstrated improvement in dyskinesia in levodopa-treated PD patients; however, every patient cannot tolerate it and therefore adjunctive therapy should be tailored to an individual's symptoms and risk for specific adverse effects.
Topics: Humans; Levodopa; Parkinson Disease; Antiparkinson Agents; Catechol O-Methyltransferase; Dyskinesias
PubMed: 37401865
DOI: 10.1080/14740338.2023.2227096 -
Neurology Jan 2024Pediatric movement disorders (PMD) neurologists care for infants, children, and adolescents with conditions that disrupt typical movement; serving as important...
Pediatric movement disorders (PMD) neurologists care for infants, children, and adolescents with conditions that disrupt typical movement; serving as important subspecialist child neurologists in both academic and private practice settings. In contrast to adult movement disorders neurologists whose "bread and butter" is hypokinetic Parkinson disease, PMD subspecialty practice is often dominated by hyperkinetic movement disorders including tics, dystonia, chorea, tremor, and myoclonus. PMD neurology practice intersects with a variety of subspecialties, including neonatology, developmental pediatrics, rehabilitation medicine, epilepsy, child & adolescent psychiatry, psychology, orthopedics, genetics & metabolism, and neurosurgery. Over the past several decades, significant advancements in the PMD field have included operationalizing definitions for distinct movement disorders, recognizing the spectrum of clinical phenotypes, expanding research on genetic and neuroimmunologic causes of movement disorders, and advancing available treatments. Subspecialty training in PMD provides trainees with advanced clinical, diagnostic, procedural, and management skills that reflect the complexities of contemporary practice. The child neurologist who is fascinated by the intricacies of child motor development, appreciates the power of observation skills coupled with a thoughtful physical examination, and is excited by the challenge of the unknown may be well-suited to a career as a PMD specialist.
Topics: Adolescent; Adult; Child; Infant; Humans; Neurology; Tremor; Neurologists; Chorea; Parkinson Disease
PubMed: 38165345
DOI: 10.1212/WNL.0000000000208050 -
Epileptic Disorders : International... Oct 2023Progressive Myoclonus Epilepsy (PME) is a rare epilepsy syndrome characterized by the development of progressively worsening myoclonus, ataxia, and seizures. A molecular... (Review)
Review
Progressive Myoclonus Epilepsy (PME) is a rare epilepsy syndrome characterized by the development of progressively worsening myoclonus, ataxia, and seizures. A molecular diagnosis can now be established in approximately 80% of individuals with PME. Almost fifty genetic causes of PME have now been established, although some remain extremely rare. Herein, we provide a review of clinical phenotypes and genotypes of the more commonly encountered PMEs. Using an illustrative case example, we describe appropriate clinical investigation and therapeutic strategies to guide the management of this often relentlessly progressive and devastating epilepsy syndrome. This manuscript in the Genetic Literacy series maps to Learning Objective 1.2 of the ILAE Curriculum for Epileptology (Epileptic Disord. 2019;21:129).
Topics: Humans; Literacy; Myoclonic Epilepsies, Progressive; Unverricht-Lundborg Syndrome; Myoclonus; Ataxia
PubMed: 37616028
DOI: 10.1002/epd2.20152 -
Tropical Doctor Oct 2023Post-hypoxic myoclonus (PHM) is a rare neurological complication having two different variants depending on acute or chronic onset after cardiopulmonary resuscitation... (Review)
Review
Post-hypoxic myoclonus (PHM) is a rare neurological complication having two different variants depending on acute or chronic onset after cardiopulmonary resuscitation following cardiac arrest: myoclonic status epilepticus (MSE) and Lance-Adams syndrome (LAS) respectively. Clinical and simultaneous electro-encephalographic (EEG) and electromyographic (EMG) tracing can distinguish between the two. Anecdotal treatment with benzodiazepines and anaesthetics (in the case of MSE) have been tried. Although limited evidence is available, valproic acid, clonazepam and levetiracetam, either in combination with other drugs or alone, have shown to control epilepsy associated with LAS effectively. Deep brain stimulation is a novel and promising advance in LAS treatment.
Topics: Humans; Myoclonus; Hypoxia; Clonazepam; Cardiopulmonary Resuscitation; Valproic Acid; Syndrome
PubMed: 37287278
DOI: 10.1177/00494755231181153 -
Journal of Neurology Sep 2023We aimed to review our "real-world" experience with the vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine for...
OBJECTIVES
We aimed to review our "real-world" experience with the vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine for treatment of Tourette syndrome, focusing on therapeutic benefits, side effect profile, and accessibility for the off-label use of these drugs.
METHODS
We performed a retrospective chart review, supplemented with a telephone survey, of all our patients treated for their tics with VMAT2 inhibitors over a period of 4 years from January 2017 until January 2021.
RESULTS
We identified 164 patients treated with the various VMAT2 inhibitors (tetrabenazine, n = 135; deutetrabenazine, n = 71; valbenazine, n = 20). Data on the mean treatment duration and daily dosages were collected. The response to VMAT2 inhibitors was assessed by a Likert scale by comparing the symptom severity before initiation and while on treatment. Side effects were mild and mostly consisted of depression as the major side effect but there was no suicidality reported.
CONCLUSION
VMAT2 inhibitors are effective and safe in the treatment of tics associated with Tourette syndrome but are not readily accessible by patients in the United States, partly because of lack of approval by the Food and Drug Administration.
Topics: Humans; United States; Tetrabenazine; Tourette Syndrome; Tics; Tardive Dyskinesia; Retrospective Studies; Vesicular Monoamine Transport Proteins; Drug-Related Side Effects and Adverse Reactions
PubMed: 37301806
DOI: 10.1007/s00415-023-11769-0 -
Journal of Neurochemistry Dec 2023L-Dopa, while treating motor symptoms of Parkinson's disease, can lead to debilitating L-Dopa-induced dyskinesias, limiting its use. To investigate the causative...
L-Dopa, while treating motor symptoms of Parkinson's disease, can lead to debilitating L-Dopa-induced dyskinesias, limiting its use. To investigate the causative relationship between neuro-inflammation and dyskinesias, we assessed if striatal M1 and M2 microglia numbers correlated with dyskinesia severity and whether the anti-inflammatories, minocycline and indomethacin, reverse these numbers and mitigate against dyskinesia. In 6-OHDA lesioned mice, we used stereology to assess numbers of striatal M1 and M2 microglia populations in non-lesioned (naïve) and lesioned mice that either received no L-Dopa (PD), remained non-dyskinetic even after L-Dopa (non-LID) or became dyskinetic after L-Dopa treatment (LID). We also assessed the effect of minocycline/indomethacin treatment on striatal M1 and M2 microglia and its anti-dyskinetic potential via AIMs scoring. We report that L-Dopa treatment leading to LIDs exacerbates activated microglia numbers beyond that associated with the PD state; the severity of LIDs is strongly correlated to the ratio of the striatal M1 to M2 microglial numbers; in non-dyskinetic mice, there is no M1/M2 microglia ratio increase above that seen in PD mice; and reducing M1/M2 microglia ratio using anti-inflammatories is anti-dyskinetic. Parkinson's disease is associated with increased inflammation, but this is insufficient to underpin dyskinesia. Given that L-Dopa-treated non-LID mice show the same ratio of M1/M2 microglia as PD mice that received no L-Dopa, and, given minocycline/indomethacin reduces both the ratio of M1/M2 microglia and dyskinesia severity, our data suggest the increased microglial M1/M2 ratio that occurs following L-Dopa treatment is a contributing cause of dyskinesias.
Topics: Rats; Mice; Animals; Levodopa; Parkinson Disease; Microglia; Minocycline; Rats, Sprague-Dawley; Corpus Striatum; Dyskinesias; Oxidopamine; Inflammation; Anti-Inflammatory Agents; Indomethacin; Antiparkinson Agents
PubMed: 37916541
DOI: 10.1111/jnc.15993 -
Current Opinion in Neurology Aug 2023The aim of this review is to showcase the recent developments in the field of diagnosis and treatment of adult-onset focal dystonia. (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to showcase the recent developments in the field of diagnosis and treatment of adult-onset focal dystonia.
RECENT FINDINGS
Accurate phenotyping of focal dystonia is essential in the process of finding an underlying cause, including acquired, genetic, and idiopathic causes. Motor symptoms as well as the associated nonmotor symptoms and their detrimental impact on quality of life have received increased interest over the last years. The diagnostic process is complicated by the steadily increasing numbers of newly discovered genes associated with dystonia. Recent efforts have been aimed at further developing recommendations and algorithms to aid in diagnosis and in navigating the use of diagnostic tools. In terms of treatment, research on DBS is advancing towards a better understanding of the most effective stimulation locations within the globus pallidus. Moreover, with the introduction of the LFP-recording devices, the search continues for an accurate electrophysiological biomarker for dystonia.
SUMMARY
Accurate phenotyping and (sub)classification of patients with dystonia is important for improving diagnosis, subsequent treatment effect and population-based study outcomes in research. Medical practitioners should be attentive to the presence of nonmotor symptoms in dystonia.
Topics: Humans; Adult; Dystonia; Quality of Life; Deep Brain Stimulation; Treatment Outcome; Dystonic Disorders; Globus Pallidus
PubMed: 37381892
DOI: 10.1097/WCO.0000000000001165 -
Current Opinion in Neurobiology Feb 2024L-DOPA-induced dyskinesia (LID) is the most common form of hyperkinetic movement disorder resulting from altered information processing in the cortico-basal ganglia... (Review)
Review
L-DOPA-induced dyskinesia (LID) is the most common form of hyperkinetic movement disorder resulting from altered information processing in the cortico-basal ganglia network. We here review recent advances clarifying the altered interplay between striatal output pathways in this movement disorder. We also review studies revealing structural and synaptic changes to the striatal microcircuitry and altered cortico-striatal activity dynamics in LID. We furthermore highlight the recent progress made in understanding the involvement of cerebellar and brain stem nuclei. These recent developments illustrate that dyskinesia research continues to provide key insights into cellular and circuit-level plasticity within the cortico-basal ganglia network and its interconnected brain regions.
Topics: Humans; Dyskinesia, Drug-Induced; Levodopa; Basal Ganglia; Corpus Striatum; Brain
PubMed: 38184982
DOI: 10.1016/j.conb.2023.102833