Paroxysmal Movement Research Articles

Sandifer Syndrome

Sandifer syndrome, named after neurologist Paul Sandifer, was first reported by Marcel Kinsbourne in 1962, who noted an upper gastrointestinal disorder that occurs in children and adolescents with neurological manifestations. Sandifer syndrome is a neurobehavioral disorder that causes a series of paroxysmal dystonic movements in association with gastroesophageal reflux and, in some cases, with hiatal hernia. It is characterized by esophagitis, iron deficiency anemia, and is often mistaken for a seizure of epileptic origin.

Anesthesia Considerations for Cataract Surgery in Patients with Schizophrenia: A Narrative Review.

Schizophrenia is ranked among the top 10 global burdens of disease. About 1% of people meet the diagnostic criteria for this disorder over their lifetime. Schizophrenic patients can develop cataract, particularly related to age and medications, requiring surgery and anesthesia. Many concerning factors, including cognitive function, anxiety, behavioral issues, poor cooperation and paroxysmal movements, may lead to general anesthesia as the default method. Antipsychotic agents should be continued during the perioperative period if possible. Topical/regional anesthesia is suitable in most schizophrenic patients undergoing cataract surgery. It reduces potential drug interactions and many postoperative complications; however, appropriate patient selection is paramount to its success. General anesthesia remains the primary technique for patients who are considered unsuitable for the topical/regional technique. Early involvement of a psychiatrist in the perioperative period, especially for patients requiring general anesthesia, is beneficial but often under-utilized. This narrative review summarizes the anesthetic considerations for cataract surgery in patients with schizophrenia.

Alternating Hemiplegia of Childhood: Genotype-Phenotype Correlations in a Cohort of 39 Italian Patients.

Alternating hemiplegia of childhood is a rare neurological disease characterized by paroxysmal movement disorders and chronic neurological disturbances, with onset before 18 months of age. Mutations in the ATP1A3 gene have been identified in up to 80% of patients. Thirty-nine patients [20 females, 19 males, mean age 25.32 years (7.52–49.34)] have been recruited through the Italian Biobank and Clinical Registry for Alternating Hemiplegia of Childhood. Demographic data, genotype, paroxysmal movement disorders, chronic neurological features, and response to flunarizine have been analyzed. ATP1A3 gene mutations have been detected in 92.3% of patients. Patients have been divided into three groups—p.Asp801Asn mutation patients (26%), p.Glu815Lys cases (23%), and patients with other ATP1A3 mutations—and statistically compared. The Italian cohort has a higher percentage of ATP1A3 gene mutation than reported in literature (92.3%). Our data confirm a more severe phenotype in patients with p.Glu815Lys mutation, with an earlier age of onset of plegic (p = 0.02 in the correlation with other mutations) and tonic attacks. P.Glu815Lys patients most frequently present altered muscle tone, inability to walk (p = 0.01 comparing p.Glu815Lys and p.Asp801Asn mutations), epilepsy, and a more severe grade of dystonia (p < 0.05 comparing p.Glu815Lys and p.Asp801Asn mutations). They have moderate/severe intellectual disability and severe language impairment (p < 0.05). Interestingly, flunarizine seems to be more efficacious in patients with p.Glu815Lys mutation than p.Asp801Asn. In conclusion, our research suggests a genotype–phenotype correlation and provides information on this disorder's features, clinical course, and treatment.

Allelic and phenotypic heterogeneity in Junctophillin-3 related neurodevelopmental and movement disorders

Junctophilin-3 belongs to a triprotein junctional complex implicated in the regulation of neuronal excitability and involved in the formation of junctional membrane structures between voltage-gated ion channels and endoplasmic (ryanodine) reticular receptors. A monoallelic trinucleotide repeat expansion located within the junctophilin-3 gene (JPH3) has been implicated in a rare autosomal dominant (AD) late-onset (and progressive) disorder clinically resembling Huntington disease (HD), and known as HD-like 2 (HDL2; MIM# 606438). Although the exact molecular mechanisms underlying HDL2 has not yet been fully elucidated, toxic gain-of-function of the aberrant transcript (containing the trinucleotide repeat) and loss of expression of (full-length) junctophilin-3 have both been implicated in HDL2 pathophysiology. In this study, we identified by whole exome sequencing (WES) a JPH3 homozygous truncating variant [NM_020655.4: c.17405dup; p.(Val581Argfs*137)]. in a female individual affected with genetically undetermined neurodevelopmental anomalies (including delayed motor milestones, abnormal social communication, language difficulties and borderline cognitive impairment) and paroxysmal attacks of dystonia since her early infancy. Our study expands the JPH3-associated mutational spectrum and clinical phenotypes, implicating the loss of Junctophilin-3 in heterogeneous neurodevelopmental phenotypes and early-onset paroxysmal movement disorders.

Paroxysmal Genetic Movement Disorders and Epilepsy.

Paroxysmal movement disorders include paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, paroxysmal exercise-induced dyskinesia, and episodic ataxias. In recent years, there has been renewed interest and recognition of these disorders and their intersection with epilepsy, at the molecular and pathophysiological levels. In this review, we discuss how these distinct phenotypes were constructed from a historical perspective and discuss how they are currently coalescing into established genetic etiologies with extensive pleiotropy, emphasizing clinical phenotyping important for diagnosis and for interpreting results from genetic testing. We discuss insights on the pathophysiology of select disorders and describe shared mechanisms that overlap treatment principles in some of these disorders. In the near future, it is likely that a growing number of genes will be described associating movement disorders and epilepsy, in parallel with improved understanding of disease mechanisms leading to more effective treatments.

From Genotype to Phenotype: Expanding the Clinical Spectrum of CACNA1A Variants in the Era of Next Generation Sequencing.

Ion channel dysfunction is a key pathological substrate of episodic neurological disorders. A classical gene associated to paroxysmal movement disorders is CACNA1A, which codes for the pore-forming subunit of the neuronal calcium channel P/Q. Non-polyglutamine CACNA1A variants underlie familial hemiplegic ataxia type 1 (FHM1) and episodic ataxia type 2 (EA2). Classical paroxysmal manifestations of FHM1 are migraine attacks preceded by motor aura consisting of hemiparesis, aphasia, and disturbances of consciousness until coma. Patients with EA2 suffer of recurrent episodes of vertigo, unbalance, diplopia, and vomiting. Beyond these typical presentations, several reports highlighted manifold clinical features associated with P/Q channelopathies, from chronic progressive cerebellar ataxia to epilepsy and psychiatric disturbances. These manifestations may often outlast the burden of classical episodic symptoms leading to pitfalls in the diagnostic work-up. Lately, the spreading of next generation sequencing techniques linked de novo CACNA1A variants to an even broader phenotypic spectrum including early developmental delay, autism spectrum disorders, epileptic encephalopathy, and early onset paroxysmal dystonia. The age-dependency represents a striking new aspect of these phenotypes und highlights a pivotal role for P/Q channels in the development of the central nervous system in a defined time window. While several reviews addressed the clinical presentation and treatment of FHM1 and EA2, an overview of the newly described age-dependent manifestations is lacking. In this Mini-Review we present a clinical update, delineate genotype-phenotype correlations as well as summarize evidence on the pathophysiological mechanisms underlying the expanded phenotype associated with CACNA1A variants.

Generation of an induced pluripotent stem cell line (ZZUi022-A) from a paroxysmal kinesigenic dyskinesia individual carrying the PRRT2 gene mutation.

Paroxysmal kinesigenic dyskinesia (PKD), the most common type of paroxysmal movement disorders, is caused by mutations in PRRT2 gene. We identified an unreported PRRT2 c. 535 C>T (p. Q 1 7 9 *) pathogenic mutation in a Chinese Han family with PKD and generated an induced pluripotent stem cell (iPSC) line from a patient in the family by reprogramming fibroblasts with sendai virus. The iPSC line was characterized for genetic uniqueness, genomic integrity, pluripotency, and differentiation ability. This iPSC line will be a powerful tool to to study the molecular mechanisms underlying PKD.

Sleep Exacerbations and Facial Twitching: Diagnostic Clues for ADCY5-Related Dyskinesias

Abstract Background Mutations in the adenylate cyclase 5 (ADCY5) gene are associated with childhood-onset paroxysmal dyskinesia. Methods We report a new video-documented case of pediatric ADCY5-related dyskinesia with de novo ADCY5 mutation. Results A boy born to nonconsanguineous parents after an uneventful pregnancy had developmental delay and hypotonia. At the age of 7 months, he presented with paroxysmal jerky–choreic–dystonic involuntary movements in wakefulness involving limbs, trunk, and face, exacerbated by emotional stimuli. These episodes gradually worsened in duration and frequency: at the age of 2.5 years, they occurred up to six times per day, and appeared also during sleep in prolonged bouts; the boy also had basal choreoathetoid–dystonic movements, hyperactivity, paraparetic–ataxic gait, generalized hypotonia with brisk tendon reflexes, drooling, and language delay with intellectual disability. Brain magnetic resonance imaging, electroencephalogram, electromyogram, eye review, metabolic investigations, oligoclonal bands, and autoantibodies were normal. Extensive genetic testing had not let to a diagnosis, until a heterozygous de novo mutation c.1252C &gt; T (p.Arg418Trp) was identified in the ADCY5 gene. Clonazepam had partial effectiveness. The boy walked at the age of 3.5 years. At the age of 5 years, the paroxysmal movement disorder has slightly improved. Conclusion ADCY5 mutations should be considered among the differential diagnoses of early-onset paroxysmal choreic–athetosic–myoclonic–dystonic movement disorder involving limbs, trunk, and face, in patients with global neurological impairment with hypotonia and developmental delay. Facial dyskinesias and exacerbation by drowsiness/sleep and emotional stimuli are important clues that may allow a timely recognition of the disorder and avoidance of unnecessary diagnostic investigations.

Imepitoin for treatment of idiopathic head tremor syndrome in dogs: A randomized, blinded, placebo-controlled study.

BackgroundIdiopathic head tremor syndrome is a paroxysmal movement disorder of unknown etiology. Spontaneous remission may occur, but owners may request treatment in severely affected dogs with continued episodes. Controlled studies of the disease are not available.Hypothesis/ObjectivesA drug with gamma amino butyric acid‐ergic and anxiolytic effects will decrease head tremor episodes.AnimalsTwenty‐four dogs with severe nonremitting head tremor and presumptive clinical diagnosis of idiopathic head tremor syndrome.MethodsProspective, blinded, placebo‐controlled clinical trial to compare imepitoin with placebo in dogs with frequent episodes of idiopathic head tremor. Evaluation of efficacy used the quotient T2/T1 that represented prolongation of the head tremor‐free period compared to a 3‐month baseline. A dog was considered a responder if tremors subsided or if the head tremor‐free period was 3× longer than the longest period during baseline (T2/T1 ≥ 3). Sample size calculations considered a large effect of imepitoin on T2/T1 (Cohen's d = 0.8).ResultsThere were no responders in the placebo group (0/12). In the imepitoin group, the responder rate was 17% (2/12; P = .18) with T2/T1 3.8 and 4.0. Mean T2/T1 was 1.0 ± 1.4 in the imepitoin and 0.4 ± 0.4 in the placebo group (P = .37).Conclusion and Clinical ImportanceImepitoin did not result in a significant overall benefit. Future studies should focus on treatment of subgroups with a common pathophysiology and similar comorbidities.

Re-Establishing Solid Food Consumption in a Person With Traumatic Brain Injury and Extended Food Avoidance/Restriction Using a Multicomponent Behavioral Intervention

We describe and report the results of a multicomponent behavioral intervention for re-establishing solid food consumption in a 26-year-old woman with prolonged food avoidance and restriction which developed following a traumatic brain injury. The intervention was evaluated by direct measurement of daily meal consumption over a period of several months, including an extended follow-up, and resulted in successful resumption of oral feeding. A complicating paroxysmal movement disorder resolved during treatment as well and resolution of the presenting problem led to significant quality of life improvements. We discuss the relationship of the presenting symptoms to avoidant/restrictive food intake disorder and to food rejection behavior seen when substantial damage has occurred to the parietal lobe. The case illustrates the value of assessment-based, individualized intervention design and an integrated neurobehavioral case conceptualization.

Nistagmo secundario a albinismo con compromiso ocular en paciente femenina

El nistagmo infantil es infrecuente y representa un desafío diagnóstico para el pediatra. El albinismo es una de sus principales causas, siendo difícil de sospechar en ausencia de compromiso cutáneo evidente, especialmente en pacientes femeninas, debido a que tipo de herencia del albinismo ocular.Objetivo: Describir un caso de nistagmo secundario a albinismo con compromiso ocular aislado en paciente femenina, para discutir el enfoque diagnóstico pediátrico.Caso Clínico: Paciente femenino de 3 semanas de vida, sin antecedentes mórbidos, derivada a neuropediatra y oftalmólogo por movimientos oculares paroxísticos desde las 2 semanas, con estudio con electroencefalograma e imágenes cerebrales normales. A los 3 meses se confirmó translucencia iridiana, nistagmo y astigmatismo hipermetrópico. La valuación dermatológica descartó compromiso cutáneo. Evolucionó con inclinación cefálica hacia abajo y retraso del desarrollo de la coordinación, fue manejada con lentes de corrección y kinesioterapia. A los 3 años, destacaba mejoría de la agudeza visual, disminución del nistagmo y neurodesarrollo normal. La evaluación oftalmológica de ambos padres fue normal y no había antecedentes de nistagmo o albinismo en la familia. Por decisión de los padres no se realizó estudio genético.Conclusión: El diagnóstico de nistagmo secundario a compromiso ocular del albinismo, aún en ausencia de afección cutánea, es clínico; el estudio genético permite confirmar la etiología, sin ser un examen imprescindible, a menos que se considere la planificación familiar. La pesquisa oportuna e intervención multidisciplinaria determinan un mejor pronóstico.

The Genetic Relationship between Paroxysmal Movement Disorders and Epilepsy

The Genetic Relationship between Paroxysmal Movement Disorders and Epilepsy

Continuous video electroencephalogram for herpes simplex encephalitis: a case report and literature review

BackgroundElectroencephalogram (EEG) is an important tool for the diagnosis of herpes simplex virus encephalitis (HSE). However, the diagnosis of non-convulsive status epilepticus (NCSE) in HSE is challenging without the help of continuous video EEG (CVEEG), and whether EEG is a predictor of outcome remains controversial.Case presentationA 63-year-old woman presented with a 5 day history of fever, coma and seizures. Results of EEG, magnetic resonance imaging and polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) were suggestive of herpes simplex encephalitis-1 (HSE-1). Preliminary EEG showed periodic discharges at the prefrontal and temporal lobes, which were particularly synchronized with intermittent lip smacking movements, and the discharges were terminated by diazepam. After 2-week treatment with acyclovir, high-dose hormone pulse therapy and high-dose immunoglobulin therapy, the CSF was improved, but the patient’s consciousness became worsen, consistent with the diffuse slow waves in the delta range and low voltage of EEG activity. In the following 1 month, the patient had non-responsiveness to pain and sound as shown by CVEEG with diffuse slow waves. Sometimes paroxysmal very slow waves (0.5–1 Hz) were synchronized with intermittent paroxysmal eye movements, pupil abnormality, and sweating in the frontal area. After 2 months of treatment, the EEG abnormalities improved to have alpha rhythm.ConclusionThe CVEEG not only helps identify NCSE but can also be used to monitor HSE progression.

Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements. Two main categories of PMDs are recognized based on the phenomenology: Paroxysmal dyskinesias (PxDs) are characterized by transient episodes hyperkinetic movement disorders, while attacks of cerebellar dysfunction are the hallmark of episodic ataxias (EAs). From an etiological point of view, both primary (genetic) and secondary (acquired) causes of PMDs are known. Recognition and diagnosis of PMDs is based on personal and familial medical history, physical examination, detailed reconstruction of ictal phenomenology, neuroimaging, and genetic analysis. Neurophysiological or laboratory tests are reserved for selected cases. Genetic knowledge of PMDs has been largely incremented by the advent of next generation sequencing (NGS) methodologies. The wide number of genes involved in the pathogenesis of PMDs reflects a high complexity of molecular bases of neurotransmission in cerebellar and basal ganglia circuits. In consideration of the broad genetic and phenotypic heterogeneity, a NGS approach by targeted panel for movement disorders, clinical or whole exome sequencing should be preferred, whenever possible, to a single gene approach, in order to increase diagnostic rate. This review is focused on clinical and genetic features of PMDs with the aim to (1) help clinicians to recognize, diagnose and treat patients with PMDs as well as to (2) provide an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders.

Neonatal Seizures: Diagnosis, Etiologies, and Management

Neonates are exquisitely susceptible to seizures due to several physiologic factors and combination of risks that are uniquely associated with gestation, delivery, and the immediate postnatal period. Neonatal seizures can be challenging to identify; therefore, it is imperative that clinicians have a high degree of suspicion for seizures based on the clinical history or the presence of encephalopathy with or without paroxysmal abnormal movements. Acute symptomatic neonatal seizures are due to an acute brain injury, whereas neonatal-onset epilepsy may be related to underlying structural, metabolic, or genetic disorders. Though initial, acute treatment is similar, long-term treatment and prognosis varies greatly based on underlying seizure etiology. Early identification and treatment are likely important for long-term outcomes in acute symptomatic seizures, though additional studies are needed to understand optimal seizure control metrics and the ideal duration of treatment. Advances in genetic medicine are increasingly expanding our understanding of neonatal-onset epilepsies and will continue to open doors for personalized medicine to optimize outcomes in this fragile population.

Emerging Subspecialties in Neurology: Sleep medicine fellowship after child neurology residency.

Pediatric sleep medicine is a multidisciplinary field specializing in the diagnosis and treatment of a wide range of sleep disorders in childhood. Child neurology residency training provides highly desired skills keenly applicable for a prospective sleep medicine fellowship applicant. A fundamental neurophysiology background helps foster an advanced proficiency in the scoring and interpretation of overnight polysomnography and multiple sleep latency tests (MSLTs). Attuned skills in differentiating complex paroxysmal movements are key to distinguishing parasomnias from nocturnal seizures. The clinical evaluation for developmental delay is augmented by learning and applying the normative developmental milestones of sleep in evaluating the sleepy, or sleepless, child. Herein the authors provide an overview of pediatric sleep medicine as it relates to the child neurology trainee seeking subspecialty fellowship opportunities.

Nocturnal motor events in epilepsy: Is there a defined physiological network?

ObjectiveParoxysmal nocturnal movements in epilepsy are a recognised phenomenon, however, the mechanisms that produce them and the effect of the underlying epilepsy still remains elusive. In this study, 10 patients were studied to define the cerebral networks corresponding to these movements and explore how epileptiform activity modulated them. MethodsWe compared the change in power of the 25–250 Hz frequency band using event-related synchronization of all stereo-EEG electrodes implanted, during a baseline segment, during nocturnal movements and seizures. ResultsThe underlying network activated during these paroxysmal movements comprised the insula, anterior cingulate, premotor areas and orbitofrontal regions. Three groups emerged, (1) complete overlap, (2) no overlap and (3) partial overlap of ERS changes of the epileptogenic zone within the proposed network and correlation of semiology between nocturnal movements and seizures. ConclusionWe conclude that nocturnal movements are due to a complex interplay within this physiological network of defined anatomical regions. Epileptic activity had significant impact on nocturnal movements but was not required for generation. SignificanceWhere the semiology of the first clinical sign of a seizure consistently matches a patient’s nocturnal movements, we suggest that the underlying epileptogenic zone is potentially located within this defined network.

Paroxysmal Movement Disorders: Recent Advances.

Recent advancements in next-generation sequencing (NGS) have enabled techniques such as whole exome sequencing (WES) and whole genome sequencing (WGS) to be used to study paroxysmal movement disorders (PMDs). This review summarizes how the recent genetic advances have altered our understanding of the pathophysiology and treatment of the PMDs. Recently described disease entities are also discussed. With the recognition of the phenotypic and genotypic heterogeneity that occurs amongst the PMDs, an increasing number of gene mutations are now implicated to cause the disorders. PMDs can also occur as part of a complex phenotype. The increasing complexity of PMDs challenges the way we view and classify them. The identification of new causative genes and their genotype-phenotype correlation will shed more light on the underlying pathophysiology and will facilitate development of genetic testing guidelines and identification of novel drug targets for PMDs.

Paroxysmal movement disorders: Recent advances and proposal of a classification system

The increasing recognition of the phenotypic and genotypic heterogeneity that exists amongst the paroxysmal movement disorders (PMDs) is challenging the way these disorders have been traditionally classified. The present review aims to summarize how recent genetic advances have influenced our understanding of the nosology, pathophysiology and treatment strategies of paroxysmal movement disorders. We propose classifying PMDs using a system that would combine both phenotype and genotype information to allow these disorders to be better categorized and studied. In the era of next generation sequencing, the use of a standardized algorithm and employment of selective genetic screening will lead to greater diagnostic certainty and targeted therapeutics for the patients.

The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics.

This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions. Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection. In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.