Hyperkinetic Movement Research Articles

The fascinating phenotypic spectrum of SCN1A gain-of-function epilepsies.

The fascinating phenotypic spectrum of SCN1A gain-of-function epilepsies.

Emergencies in movement disorders

Movement disorders can be defined as the abnormality of the speed and form of body movements. Although movement disorders often occur chronically, they can sometimes develop acutely or sub-acutely, and some can be fatal if not diagnosed and treated early. Here, emergencies in movement disorders are discussed under two main headings as emergencies related to hyperkinetic movement disorders and emergencies related to hypokinetic movement disorders. This review draws attention to the importance of that accurate diagnosis and early treatment can be life-saving in emergencies in movement disorders. It also provides recommendations for diagnosis and therapy.

CAMK4-related Case of Hyperkinetic Movement Disorder.

Video 1. Segment 1: This segment shows the patient's hyperkinetic movemets while he is lying on the ground. Segment 2: This segment shows the patient's hyperkinetic movemets and his gait while he is walking with support. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Hyperkinetic movement disorders following SARS-CoV-2 infection and vaccination - an update.

The aim of this review was to summarise current knowledge regarding hyperkinetic movement disorders related to SARS-CoV-2 infection and vaccination in terms of phenomenology, epidemiology, pathogenesis and treatment. After a thorough review of the PubMed and Google Scholar databases (2020-2022), we identified myoclonus and ataxia sometimes accompanied by opsoclonus (AMS) as the two most frequent COVID-19 sequelae, with chorea, tremor and dystonia being very rare. The pathogenesis seems to be variable, but in the majority of AMS cases it was autoimmunological, with good response and recovery after corticosteroids or intravenous immunoglobulins infusions. Vaccination may be complicated by hyperkinetic movement disorders (e.g. tremor, dystonia), but this is very rare. Patients with Deep Brain Simulation depletion should not be postponed due to lockdowns as this may result in fatal outcomes.

Deep Brain Stimulation in the Treatment of Tardive Dyskinesia.

Tardive dyskinesia (TD) is a phenomenon observed following the predominantly long-term use of dopamine receptor blockers (antipsychotics) widely used in psychiatry. TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid, lips, tongue, and cheeks, and less frequently in the limbs, neck, pelvis, and trunk. In some patients, TD takes on an extremely severe form, massively disrupting functioning and, moreover, causing stigmatization and suffering. Deep brain stimulation (DBS), a method used, among others, in Parkinson's disease, is also an effective treatment for TD and often becomes a method of last resort, especially in severe, drug-resistant forms. The group of TD patients who have undergone DBS is still very limited. The procedure is relatively new in TD, so the available reliable clinical studies are few and consist mainly of case reports. Unilateral and bilateral stimulation of two sites has proven efficacy in TD treatment. Most authors describe stimulation of the globus pallidus internus (GPi); less frequent descriptions involve the subthalamic nucleus (STN). In the present paper, we provide up-to-date information on the stimulation of both mentioned brain areas. We also compare the efficacy of the two methods by comparing the two available studies that included the largest groups of patients. Although GPi stimulation is more frequently described in literature, our analysis indicates comparable results (reduction of involuntary movements) with STN DBS.

Oculogyric crisis induced by risperidone in a child withGRIN1variant

The GluN1 subunit of the N-methyl-d-aspartate (NMDA) receptor is encoded by GRIN1 gene. Mutations in this gene can cause neurodevelopmental disorders with or without hyperkinetic movements and seizures. It can be inherited as either autosomal dominant (NDHMSD) or autosomal recessive (NDHMSR). Patients can present with severe psychomotor delay, seizures, behavioral problems, stereotypies, and oculogyric crisis (OGC). There is emerging evidence regarding the molecular interaction between dopamine and NMDA receptors, cross-talk between dopamine and glutamate signaling, and mutations in GRIN1 could affect both glutamatergic and dopaminergic synaptic transmission. Dopamine antagonists, such as risperidone, which is used to treat behavioral problems, can cause extrapyramidal side effects, including OGC. Here, we present a case of an 8-year-old boy with a GRIN1 variant who was treated with risperidone for severe behavioral problems and experienced an OGC for approximately 30 h. The child had no prior history of such event and experienced no re-occurrences after discontinuing risperidone. This case highlights the importance of exercising extra caution while prescribing dopamine antagonists for patients with GRIN1 mutations and reports the efficacy of memantine in treating seizures and behavioral side effects in such patients. In the era of precision medicine, this case represents a good example of how patient's genetic makeup should be considered in prescribing the right medication for the right patient.

Atypical Neurological Presentation in a Patient with Uncontrolled Diabetes

Chorea is a disorder characterized by irregular and involuntary hyperkinetic movements associated with malfunctioning the basal ganglia. One of the rarest acquired causes of unilateral or bilateral chorea is hyperglycemia. This is a case of an elderly female diabetic who presented With 3 days history of unilateral involuntary movements of the upper limb and lower limb, irrelevant talk, and altered sensorium. She had a random blood glucose level of 418 mg/dl with hemoglobin A1C (HbA1c) of 15% and normal ketones. Magnetic resonance imaging brain demonstrated T1 hyperintense and T2 flair hypointense right basal ganglia. Diagnosis of nonketotic hyperglycemic chorea was considered. The patient was treated with insulin, antipsychotics, and benzodiazepines and the chorea resolved after proper control of glucose levels. This condition can be reversible with early identification and treatment. This disorder can be prevented with good glycemic control.

Fulminant SSPE Presenting as a Hyperkinetic Movement Disorder.

Fulminant SSPE Presenting as a Hyperkinetic Movement Disorder.

Pediatric-Onset Epilepsy and Developmental Epileptic Encephalopathies Followed by Early-Onset Parkinsonism

Genetic early-onset Parkinsonism is unique due to frequent co-occurrence of hyperkinetic movement disorder(s) (MD), or additional neurological of systemic findings, including epilepsy in up to 10-15% of cases. Based on both the classification of Parkinsonism in children proposed by Leuzzi and coworkers and the 2017 ILAE epilepsies classification, we performed a literature review in PubMed. A few discrete presentations can be identified: Parkinsonism as a late manifestation of complex neurodevelopmental disorders, characterized by developmental and epileptic encephalopathies (DE-EE), with multiple, refractory seizure types and severely abnormal EEG characteristics, with or without preceding hyperkinetic MD; Parkinsonism in the context of syndromic conditions with unspecific reduced seizure threshold in infancy and childhood; neurodegenerative conditions with brain iron accumulation, in which childhood DE-EE is followed by neurodegeneration; and finally, monogenic juvenile Parkinsonism, in which a subset of patients with intellectual disability or developmental delay (ID/DD) develop hypokinetic MD between 10 and 30 years of age, following unspecific, usually well-controlled, childhood epilepsy. This emerging group of genetic conditions leading to epilepsy or DE-EE in childhood followed by juvenile Parkinsonism highlights the need for careful long-term follow-up, especially in the context of ID/DD, in order to readily identify individuals at increased risk of later Parkinsonism.

Hemiballism and chorea with acute/subacute onset: a retrospective series.

Chorea is a hyperkinetic movement disorder with sudden, irregular, random, dance-like involuntary movements, and ballism is usually one-sided, high-amplitude movements at the proximal of the extremities. In the etiology of acute chorea/hemiballismus, it is necessary to distinguish drugs first and then focus on metabolic causes. The most important etiological causes that may provoke acute/subacute onset chorea/hemiballismus are hypo-hyperglycemia and electrolyte disorders. In this study, we aim to present 19 patients who were admitted to our clinic with movement disorder with acute/subacute onset and diagnosed with chorea/hemiballismus. The study was completed with 19 patients. Routine biochemistry, HbA1c level, hemogram, sedimentation, CRP, hepatitis panels, detailed infective parameters, HIV, vitamin B12 level, folate levels, and thyroid function tests were studied. All patients underwent neuro-imaging. 16(84.2%) were female and 3(15.8%) were male. The lowest age of the patients was 48years, the highest age was 89years, and the mean age was 72.21years. Thirteen (68.42%) patients had a diagnosis of diabetes mellitus in their history. The blood glucose levels of these patients at the time of admission: the lowest was 99mg/dl and the highest was 1200mg/dl. HbA1c values of 11(84.61%) of the 13 patients were also found elevated. Thirteen (68.4%) patients had hemiballismus, 4(21.1%) patients had bilateral choreoathetosis in the four extremities, and 2(10.2%) patients had ballism limited to one upper extremity. Chorea/hemiballismus is a movement disorder that is rare and can occur due to a wide range of etiologies. The most common metabolic cause is NKHHS.

Thyroid Disorders and Movement Disorders-A Systematic Review.

There is overlap between movement disorders and neuroendocrine abnormalities. To provide a systematic review on the association of thyroid dysfunction and movement disorders. Thyroid physiological function and classical thyroid disorders highlighting typical and atypical manifestations including movement disorders, as well as diagnostic procedures, and treatments are discussed. Hypothyroidism may be associated with hypokinetic and hyperkinetic disorders. There is debate whether their concomitance reflects a causal link, is coincidence, or the result of one unmasking the other. Hypothyroidism-associated parkinsonism may resemble idiopathic Parkinson's disease. Hypothyroidism-associated hyperkinetic disorders mainly occur in the context of steroid-responsive encephalopathy with autoimmune thyroiditis, that is, Hashimoto disease, mostly manifesting with tremor, myoclonus, and ataxia present in 28-80%, 42-65% and 33-65% in larger series. Congenital hypothyroidism manifesting with movement disorders, mostly chorea and dystonia, due to Mendelian genetic disease are rare.Hyperthyroidism on the other hand mostly manifests with hyperkinetic movement disorders, typically tremor (present in three quarters of patients). Chorea (present in about 2% of hyperthyroid patients), dystonia, myoclonus, ataxia and paroxysmal movement disorders, as well as parkinsonism have also been reported, with correlation between movement intensity and thyroid hormone levels.On a group level, studies on the role of thyroid dysfunction as a risk factor for the development of PD remain non-conclusive. In view of the treatability of movement disorders associated with thyroid disease, accurate diagnosis is important. The pathophysiology remains poorly understood. More detailed case documentation and systematic studies, along with experimental studies are needed.

BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening.

There are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum. Moreover, this is the first study to present newborn screening findings and mid-term clinical outcome. In this cross-sectional study, patients with a diagnosis of BCKDK deficiency were recruited via investigators' practices through a MetabERN initiative. Clinical, biochemical and genetic data were collected. Dried blood spot (DBS) newborn screening (NBS) amino acid profiles were retrieved from collaborating centres and compared to a healthy newborn reference population. Twenty-one patients with BCKDK mutations were included from 13 families. Patients were diagnosed between 8 months and 16 years (mean: 5.8 years, 43% female). At diagnosis, BCAA levels (leucine, valine and isoleucine) were below reference values in plasma and in CSF. All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18, 16/16 intellectual disability, 17/17 language impairment, 12/17 autism spectrum disorder, 9/21 epilepsy, 12/15 clumsiness, 3/21 had sensorineural hearing loss and 4/20 feeding difficulties. No microcephaly was observed at birth, but 17/20 developed microcephaly during follow-up. Regression was reported in six patients. Movement disorder was observed in 3/21 patients: hyperkinetic movements (1), truncal ataxia (1) and dystonia (2). After treatment with a high-protein diet (≥ 2 g/kg/day) and BCAA supplementation (100-250 mg/kg/day), plasma BCAA increased significantly (P < 0.001), motor functions and head circumference stabilized/improved in 13/13 and in 11/15 patients, respectively. Among cases with follow-up data, none of the three patients starting treatment before 2 years of age developed autism at follow-up. The patient with the earliest age of treatment initiation (8 months) showed normal development at 3 years of age. NBS in DBS identified BCAA levels significantly lower than those of the normal population. This work highlights the potential benefits of dietetic treatment, in particular early introduction of BCAA. Therefore, it is of utmost importance to increase awareness about this treatable disease and consider it as a candidate for early detection by NBS programmes.

Diagnostic Uncertainties: Chorea.

Chorea is a hyperkinetic movement disorder with a multitude of potential etiologies, both acquired and inherited. Although the differential diagnosis for new-onset chorea is extensive, there are often clues in the history, exam, and basic testing that can help to narrow the options. Evaluation for treatable or reversible causes should take priority, as rapid diagnosis can lead to more favorable outcomes. While Huntington's disease is most common genetic cause of chorea, multiple phenocopies also exist and should be considered if Huntington gene testing is negative. The decision of what additional genetic testing to pursue should be based on both clinical and epidemiological factors. The following review provides an overview of the many possible etiologies as well as a practical approach for a patient presenting with new-onset chorea.

Investigation of Phase Shifts Using AUC Diagrams: Application to Differential Diagnosis of Parkinson's Disease and Essential Tremor.

This study was motivated by the well-known problem of the differential diagnosis of Parkinson's disease and essential tremor using the phase shift between the tremor signals in the antagonist muscles of patients. Different phase shifts are typical for different diseases; however, it remains unclear how this parameter can be used for clinical diagnosis. Neurophysiological papers have reported different estimations of the accuracy of this parameter, which varies from insufficient to 100%. To address this issue, we developed special types of area under the ROC curve (AUC) diagrams and used them to analyze the phase shift. Different phase estimations, including the Hilbert instantaneous phase and the cross-wavelet spectrum mean phase, were applied. The results of the investigation of the clinical data revealed several regularities with opposite directions in the phase shift of the electromyographic signals in patients with Parkinson's disease and essential tremor. The detected regularities provide insights into the contradictory results reported in the literature. Moreover, the developed AUC diagrams show the potential for the investigation of neurodegenerative diseases related to the hyperkinetic movements of the extremities and the creation of high-accuracy methods of clinical diagnosis.

Phenotypic Assessment of Pathogenic Variants in GNAO1 and Response to Caffeine in C. elegans Models of the Disease.

De novo mutations affecting the G protein α o subunit (Gαo)-encoding gene (GNAO1) cause childhood-onset developmental delay, hyperkinetic movement disorders, and epilepsy. Recently, we established Caenorhabditis elegans as an informative experimental model for deciphering pathogenic mechanisms associated with GNAO1 defects and identifying new therapies. In this study, we generated two additional gene-edited strains that harbor pathogenic variants which affect residues Glu246 and Arg209-two mutational hotspots in Gαo. In line with previous findings, biallelic changes displayed a variable hypomorphic effect on Gαo-mediated signaling that led to the excessive release of neurotransmitters by different classes of neurons, which, in turn, caused hyperactive egg laying and locomotion. Of note, heterozygous variants showed a cell-specific dominant-negative behavior, which was strictly dependent on the affected residue. As with previously generated mutants (S47G and A221D), caffeine was effective in attenuating the hyperkinetic behavior of R209H and E246K animals, indicating that its efficacy is mutation-independent. Conversely, istradefylline, a selective adenosine A2A receptor antagonist, was effective in R209H animals but not in E246K worms, suggesting that caffeine acts through both adenosine receptor-dependent and receptor-independent mechanisms. Overall, our findings provide new insights into disease mechanisms and further support the potential efficacy of caffeine in controlling dyskinesia associated with pathogenic GNAO1 mutations.

Seizure Semiology and Functional Anatomy in the Cerebral Cortex

Understanding the semiology and underlying anatomy of each seizure is essential for epilepsy surgeons. According to the International League Against Epilepsy(ILAE)classification in 2017, seizure types are classified as focal, generalized, or unknown onset, all of which are further classified as motor or non-motor onset. Impairment of awareness is involved in consciousness systems(consisting of subcortical structures such as the thalamus and upper brain stem)and cortical structures(including the frontoparietal association cortices). Seizures with motor features are divided into elementary symptoms for which myoclonic, clonic, and tonic expressions reflect the somatotopy of the primary motor cortex; and integrated or gestural motor expression representing activation of the motor association cortex. A rostrocaudal gradient is demonstrated in hyperkinetic movements in frontal lobe epilepsy. Non-motor epileptic features should be understood together with auras, which correspond to focal aware seizures and hold crucial localizing semiologic values. The correlation between functional anatomy and seizure semiology is justified by invasive recordings such as stereotactic electroencephalography and subdural recordings, and also confirmed by seizure outcomes after resection of supposed epileptogenic zones. In addition to the conventional localization theory, it is necessary to consider the neural network theory for further recognition of the functionally anatomical basis in an incomprehensible demonstration of seizures.

Idiopathic (Oral) and Tardive Dyskinesia: Pathogenesis, Epidemiology, and Treatment

Etymologically, dyskinesia is a combination of the prefix "dys-," which means 'abnormality' and the suffix "-kinesia," which means 'movement.' In a broad sense, dyskinesia indicates hyperkinetic involuntary movements. In a narrow sense, as a general term, dyskinesia refers to combinations of one or more of the following movements: chorea, dystonia, tremor, ballism, athetosis, tics, and myoclonus. In this article, we describe the pathogenesis, epidemiology, and treatment of idiopathic (oral) and tardive dyskinesia.

Audiologic follow up results of child with NGLY1 deficiency

NGLY1 deficiency is a rare in which affected individuals show developmental delay/intellectual disability in the mild to profound range, epilepsy, auditory neuropathy, abnormal liver function, complex hyperkinetic movement disorder and poor growth. Here, we present the follow-up results of hearing status in a patient with NGLY1 deficiency.

Chapter 23 - Tourette syndrome and other tic disorders of childhood

Tics are repetitive, patterned, and nonrhythmic movements or vocalizations/audible sounds that are misplaced in context. Phenomenology and characteristics of tics (e.g., premonitory urge, suppressibility) differentiate them from compulsions, stereotypies, functional tic-like behaviors, and other types of hyperkinetic movement disorders. With a prevalence of approximately 1% in school-aged boys, Tourette syndrome (TS) is considered a common childhood-onset neurodevelopmental disorder, defined by the combination of at least two motor tics and at least one phonic tic lasting more than 1 year. TS is a highly heritable disorder, with a wide spectrum of severity. In some individuals, tics can cause pain, distress, functional impairment, or stigmatization. About 90% of individuals with TS have at least one mental health comorbidity (attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety/depressive disorders). These comorbidities significantly impact patients' quality of life and must therefore be screened and managed accordingly in this population. Treatment of tics is based on behavioral therapies targeting tics (habit reversal training included in the comprehensive behavioral intervention for tics, and exposure and response prevention for tics), in association with medication if needed (e.g., alpha-2-agonists, second-generation antipsychotics). Deep brain stimulation is considered an experimental option in the most severe, treatment-resistant patients. In adulthood, less than 25% of individuals still have moderate or severe tics.

Chapter 21 - Isolated and combined dystonias: Update

Dystonia is a hyperkinetic movement disorder with a unique motor phenomenology that can manifest as an isolated clinical syndrome or combined with other neurological features. This chapter reviews the characteristic features of dystonia phenomenology and the syndromic approach to evaluating the disorders that may allow us to differentiate the isolated and combined syndromes. We also present the most common types of isolated and combined dystonia syndromes. Since accelerated gene discoveries have increased our understanding of the molecular mechanisms of dystonia pathogenesis, we also present isolated and combined dystonia syndromes by shared biological pathways. Examples of these converging mechanisms of the isolated and combined dystonia syndromes include (1) disruption of the integrated response pathway through eukaryotic initiation factor 2 alpha signaling, (2) disease of dopaminergic signaling, (3) alterations in the cerebello-thalamic pathway, and (4) disease of protein mislocalization and stability. The discoveries that isolated and combined dystonia syndromes converge in shared biological pathways will aid in the development of clinical trials and therapeutic strategies targeting these convergent molecular pathways.