Onset Of Hemiplegia Research Articles

A case of alternating hemiplegia in 2-month-old children with nystagmus as the first symptom: A case report.

This case report delves into the rare neurological condition known as alternating hemiplegia of childhood (AHC), focusing on its clinical manifestations, diagnostic approaches, and treatment options. AHC typically presents in infants under the age of 18 months with intermittent episodes of hemiplegia, often triggered by stressors such as environmental changes, bathing, or emotional stress. Recognizing the clinical features of AHC is crucial for early identification and intervention. The paper presents a case of a 2-month-old child with nystagmus as the initial symptom, followed by limb movement disorder in the left upper limb and weakness in the right limbs. The child's condition did not improve with treatment at an external hospital, highlighting the complexity of the disease and the need for specialized care. After a comprehensive review of the patient's medical history, physical examination, and imaging studies, the child was diagnosed with AHC. The diagnosis was confirmed through video electroencephalogram and whole-exome gene detection, which revealed a de novo mutation in the ATP1A3 gene, identified as pathogenic according to the American College of Medical Genetics and Genomics guidelines. The child was admitted to Peking University First Hospital and treated with levetiracetam and flunarizine oral administration. These medications were chosen for their efficacy in managing the symptoms of AHC, particularly the hemiplegic episodes. Post-treatment, the child experienced a reduction in the frequency and intensity of hemiplegic attacks compared to the initial stage. However, the child still exhibited paroxysmal symptoms and abnormal eye movements, and developmental milestones were delayed, indicating the need for ongoing care and monitoring. This case underscores the importance of early recognition and prompt intervention in managing children with AHC. The varied clinical presentations of AHC necessitate vigilance for early differential diagnosis. Although AHC is currently incurable, appropriate treatment can mitigate the impact of complications and improve the long-term quality of life for affected children, facilitating better societal integration.

Severe Acute Motor Exacerbations (SAME) across Metabolic, Developmental and Genetic Disorders.

Acute presentation of severe motor disorders is a diagnostic and management challenge. We define severe acute motor exacerbations (SAME) as acute/subacute motor symptoms that persist for hours-to-days with a severity that compromise vital signs (temperature, breath, and heart rate) and bulbar function (swallowing/dysphagia). Phenomenology includes dystonia, choreoathetosis, combined movement disorders, weakness, and hemiplegic attacks. SAME can develop in diverse diseases and can be preceded by triggers or catabolic states. Recent descriptions of SAME in complex neurodevelopmental and epileptic encephalopathies have broadened appreciation of this presentation beyond inborn errors of metabolism. A high degree of clinical suspicion is required to identify appropriately targeted investigations and management. We conducted a comprehensive literature analysis of etiologies. Reported triggers are described and classified as per pathophysiological mechanism. A video of six cases displaying multiple SAME with diverse outcomes is provided. We identified 50 different conditions that manifest SAME, some associated with developmental regression. Etiologies include disorders of metabolism: energy substrate, amino acids, complex molecules, vitamins/cofactors, minerals, and neurotransmitters/synaptic vesicle cycling. Non-metabolic neurodegenerative and genetic disorders that present with movement disorders and epilepsy can additionally manifest SAME. A limited number of triggers are grouped here, together with an approach to investigations and general management strategies. Several neurogenetic and neurometabolic disorders manifest SAME. Identifying triggers can help in certain cases narrow the differential diagnosis and guide the expeditious application of targeted therapies to minimize adverse developmental and neurological consequences. This process may inform pathogenesis and eventually improve our understanding of the mechanisms that lead to the development of SAME. © 2024 International Parkinson and Movement Disorder Society.

Navigating the Complexity of Alternating Hemiplegia in Childhood: A Comprehensive Review.

Alternating hemiplegia of childhood (AHC) is a complex neurodevelopmental disorder characterized by paroxysmal and transient events of unilateral or bilateral paresis, usually occurring before 18 months of age. Mutations in the ATP1A3 gene, mainly p.Asp801Asn, p.Glu815Lys, and p.Gly947Arg at the protein level, are found in around 80% of the individuals with AHC. Interestingly, these mutations reflect the degree of severity of the neurological symptoms (p.Glu815Lys > p.Asp801Asn > p.Gly947Arg). Some channels involved in this disorder are N-type voltage-gated calcium channels, ATP-sensitive potassium channels, and the sodium/calcium exchanger. In this context, the management of AHC should be divided into the treatment of attacks, prophylactic treatment, and management of comorbidities commonly found in this group of individuals, including epilepsy, attention-deficit/hyperactivity disorder, aggressive behavior, cognitive impairment, movement disorders, and migraine. The importance of an integrated approach with a multidisciplinary team, such as neuropsychologists and dietitians, is worth mentioning, as well as the follow-up with a neurologist. In the present study, we propose new diagnostic criteria for AHC, dividing it into clinical, laboratory, supporting, and atypical features. Also, we review the location of the mutations in the ATP1A3 protein of individuals with AHC, rapid-onset dystonia-parkinsonism (RDP) variants, and early infantile epileptic encephalopathy (variants with hemiplegic attack). We also include a section about the animal models for ATP1A3 disorders.

Ayurvedic Management of Alternate Hemiplegia of Childhood - A Case Report

Alternate hemiplegia of childhood is a rare condition characterized by recurrent temporary episodes of hemiplegic attacks that affect one or the other side of the body. The clinical manifestations may begin at the neonatal period up to the age of 4 years. The reported prevalence is estimated at 1/100000 in children under 16 years old. There are, as of yet, no specific therapies that are uniformly effective in eliminating the episodes associated with AHC. AHC childhood can be correlated with Ayurvedic concept of Skandagraha. Here a case of 8 year old male child had come to our hospital with recurrent hemiplegic attacks having history of involuntary movements. At the end of 10days of IP treatment which included Panchakarma procedures along with internal medication resulted in 5-10% improvement in the overall effect of therapy. Followed by Shamanachikitsa 30-40% improvement was observed. Hence a humble attempt has been made to explore the case.

Frequent Fall: Seizure or Weakness? A Case Report of Alternating Hemiplegia of Childhood

Alternating Hemiplegia of Childhood (AHC) is a complex disease which causes recurrent hemiplegic attacks. Although ATP1A3 gene has been identified as the cause of this neurological entity, many variants are being reported nowadays, adding to the spectrum of ATP1A3 gene-related disorders due to the advancement in genetic testing. Hereby, authors presents a case report of a 3-year-old male child who presented with a complaint of frequent falls while walking with gait abnormality and has been on treatment for seizure disorder since, 5 months of age. On assessing the history and evaluating the child, AHC was suspected and the same was confirmed using genetic tests.

The impact of Transcranial Magnetic Stimulation (TMS) on seizure course in people with and without epilepsy

ObjectiveTo elucidate the effects of single and paired-pulse TMS on seizure activity at electrographic and clinical levels in people with and without epilepsy. MethodsA cohort of 35 people with epilepsy, two people with alternating hemiplegia of childhood (AHC) with no epilepsy, and 16 healthy individuals underwent single or paired-pulse TMS combined with EEG. Clinical records and subject interviews were used to examine seizure frequency four weeks before and after TMS. ResultsThere were no significant differences in seizure frequency in any subject after TMS exposure. There was no occurrence of seizures in healthy individuals, and no worsening of hemiplegic attacks in people with AHC. ConclusionsNo significant changes in seizure activity were found before or after TMS. SignificanceThis study adds evidence on the safety of TMS in people with and without epilepsy with follow-up of four weeks after TMS.

Sudden Onset Hemiplegia and Neglect: A Case Report of Type A Aortic Dissection Presenting as a Code Stroke

Stanford type A acute aortic dissection with ischemic stroke is a rare yet highly morbid presentation of sudden onset neurological symptoms. We present a case of a 57-year-old African American male brought to the emergency department with a witnessed syncopal episode, abdominal pain, right sided gaze preference, and left side weakness. Upon initiation of the hospital’s “Code Stroke” response protocol, a computed tomography angiogram of the neck incidentally identified Stanford type A aortic dissection with extension into and occlusion of the brachiocephalic artery, occlusion of the right common carotid artery and right internal carotid artery, and dissection flap propagation into the origin of the left common carotid artery. Postoperative magnetic resonance imaging of the brain and the entire spine demonstrated multifocal cerebral infarcts, as well as T10 - L1 spinal infarct. Despite provision of multidisciplinary intensive care unit level of care, the patient failed to demonstrate clinically significant neurological recovery and was transitioned to comfort care after 3 weeks of hospitalization. This case highlights the importance of considering acute aortic dissection as a potential etiology of acute ischemic stroke through the use of computed tomography angiography, as this diagnosis carries profoundly different implications for the consideration of thrombolytic agents and other emergent treatment modalities. J Neurol Res. 2020;10(6):248-252 doi: https://doi.org/10.14740/jnr638

Sudden Onset Hemiplegia and Neglect: A Case Report of Type A Aortic Dissection Presenting as a Code Stroke

Stanford type A acute aortic dissection with ischemic stroke is a rare yet highly morbid presentation of sudden onset neurological symptoms. We present a case of a 57-year-old African American male brought to the emergency department with a witnessed syncopal episode, abdominal pain, right sided gaze preference, and left side weakness. Upon initiation of the hospital’s “Code Stroke” response protocol, a computed tomography angiogram of the neck incidentally identified Stanford type A aortic dissection with extension into and occlusion of the brachiocephalic artery, occlusion of the right common carotid artery and right internal carotid artery, and dissection flap propagation into the origin of the left common carotid artery. Postoperative magnetic resonance imaging of the brain and the entire spine demonstrated multifocal cerebral infarcts, as well as T10 - L1 spinal infarct. Despite provision of multidisciplinary intensive care unit level of care, the patient failed to demonstrate clinically significant neurological recovery and was transitioned to comfort care after 3 weeks of hospitalization. This case highlights the importance of considering acute aortic dissection as a potential etiology of acute ischemic stroke through the use of computed tomography angiography, as this diagnosis carries profoundly different implications for the consideration of thrombolytic agents and other emergent treatment modalities. J Neurol Res. 2020;10(6):248-252 doi: https://doi.org/10.14740/jnr638

Novel E815K knock-in mouse model of alternating hemiplegia of childhood

De novo mutations causing dysfunction of the ATP1A3 gene, which encodes the α3 subunit of Na+/K+-ATPase pump expressed in neurons, result in alternating hemiplegia of childhood (AHC). AHC manifests as paroxysmal episodes of hemiplegia, dystonia, behavioral abnormalities, and seizures. The first aim of this study was to characterize a novel knock-in mouse model (Atp1a3E815K+/−, Matoub, Matb+/−) containing the E815K mutation of the Atp1a3 gene recognized as causing the most severe and second most common phenotype of AHC with increased morbidity and mortality as compared to other mutations. The second aim was to investigate the effects of flunarizine, currently the most effective drug used in AHC, to further validate our model and to help address a question with significant clinical implications that has not been addressed in prior studies. Specifically, many E815K patients have clinical decompensation and catastrophic regression after discontinuing flunarizine therapy; however, it is not known whether this is congruent with the natural course of the disease and is a result of withdrawal from an acute beneficial effect, withdrawal from a long-term protective effect or from a detrimental effect of prior flunarizine exposure. Our behavioral and neurophysiological testing demonstrated that Matb+/− mice express a phenotype that bears a strong resemblance to the E815K phenotype in AHC. In addition, these mice developed spontaneous seizures with high incidence of mortality and required fewer electrical stimulations to reach the kindled state as compared to wild-type littermates. Matb+/− mice treated acutely with flunarizine had reduction in hemiplegic attacks as compared with vehicle-treated mice. After withdrawal of flunarizine, Matb+/− mice that had received flunarizine did neither better nor worse, on behavioral tests, than those who had received vehicle. We conclude that: 1) Our mouse model containing the E815K mutation manifests clinical and neurophysiological features of the most severe form of AHC, 2) Flunarizine demonstrated acute anti-hemiplegic effects but not long-term beneficial or detrimental behavioral effects after it was stopped, and 3) The Matb+/− mouse model can be used to investigate the underlying pathophysiology of ATP1A3 dysfunction and the efficacy of potential treatments for AHC.

Early-onset encephalopathy with paroxysmal movement disorders and epileptic seizures without hemiplegic attacks: About three children with novel ATP1A3 mutations

ObjectiveHeterozygous mutations in the ATP1A3 gene are responsible for various neurological disorders, ranging from early-onset alternating hemiplegia of childhood to adult-onset dystonia-parkinsonism. Next generation sequencing allowed the description of other phenotypes, including early-onset epileptic encephalopathy in two patients. We report on three more patients carrying ATP1A3 mutations with a close phenotype and discuss the relationship of this phenotype to alternating hemiplegia of childhood. MethodsThe patients’ DNA underwent next generation sequencing. A retrospective analysis of clinical case records is reported. ResultsEach of the three patients had an unreported heterozygous de novo sequence variant in ATP1A3. These patients shared a similar phenotype characterized by early-onset attacks of movement disorders, some of which proved to be epileptic, and severe developmental delay. (Hemi)plegic attacks had not been considered before genetic testing. SignificanceTogether with the two previously reported cases, our patients confirm that ATP1A3 mutations are associated with a phenotype combining features of early-onset encephalopathy, epilepsy and dystonic fits, as in the most severe forms of alternating hemiplegia of childhood, but in which (hemi)plegic attacks are absent or only suspected retrospectively.

Clinical efficacy of Flunarizine in treating alternating hemiplegia in children and the influencing factors

Objective To investigate the effective rate of Flunarizine in treating alternating hemiplegia during childhood (AHC) kids, and to analyze the related factors influencing efficacy. Methods The clinical data and peripheral blood DNA of AHC patients at the Outpatient and Inpatient Ward of Department of Pediatrics, Peking University First Hospital from August 2005 to May 2016 were collected, and the ATP1A3 gene mutations were screened.Clinical efficacy of oral administration of Flunarizine for improving paroxysmal symptoms such as alternating hemiplegia in AHC patients was followed up. Results A total of 96 AHC patients were collected, and among them, 75 cases received oral administration of flunarizine were followed up for 1-11 years.The age of last follow-up was 1-21 years old (the median age was 5 years old). Fifty of these 75 patients (66.7%) were improved, while 25 patients were not alleviated (33.3%). In 50 improved patients, 43 patients (86.0%) reduced the frequency of hemiplegia attacks, 28 patients (56.0%) reduced the duration, and 3 patients (6.0%) alleviated the severity.Univariate analysis between the effective group and ineffective group showed that differences in age of onset, age of initial treatment, dose and carrying D801N, E815K or G947R mutation of ATP1A3 gene were not statistically significant(all P>0.05). The findings by multivariate analysis indicated that age of onset, age of initial treatment, dose and carrying D801N, E815K or G947R mutation of ATP1A3 gene were not related to the efficacy of Flunarizine. Conclusion Flunarizine is effective for most AHC children, which can reduce the frequency of hemiplegia attacks, shorten the duration, and alleviate the severity of attacks.Age of onset, age of initial treatment, dose and carrying D801N, E815K or G947R mutation of gene ATP1A3 are not factors influencing efficacy. Key words: Alternating hemiplegia of childhood; Flunarizine; Treatment

Alternating Hemiplegia of Childhood: Report of Two Cases

Alternating hemiplegia of childhood (AHC) is a rare disorder which presents before 18 months of age characterized by repeated attacks of hemiplegia involving either side of the body, paroxysmal disturbances,developmental delay and learning disability. The cause of AHC remains largely unknown and treatment evidence is less available. AHC is unreported in Bangladeshi literature. We report two cases of AHC. Our first case is a 16-month-old girl who presented with hemiplegia in alternate side for four episodes. She also had abnormal body movement and irritability during awakening. Every episode subsided spontaneously after 2 to 5 days. All investigations were normal except iron deficiency anemia. She was treated with flunarizine. Our second case, a 7 year and 10 month-old boy presented with recurrent alternate hemiplegia since 3½ years of age with epilepsy. His attacks were precipitated in high temperature. His EEG was abnormal. He was treated with multiple antiepileptic drugs and flunarizine. These are first two cases reported from Bangladesh. AHC remains undiagnosed in many cases. So a detailed history and diagnostic evaluation is very important for early counseling and treatment.J Enam Med Col 2018; 8(1): 46-49

Hypoglycemic Hemiplegia

Hypoglycemia may cause acute hemiplegia. The most common diffusion-weighted MR imaging finding in patients with hypoglycemic hemiplegia is the hyperintense lesion involving the internal capsule, mimicking acute ischemic stroke. Thus, in patients with acute onset hemiplegia, it is important to differentiate hypoglycemia on arrival by immediate blood glucose measurement. It has recently been shown that hypoglycemic brain injury start in large white matter tracts such as internal capsule and spread throughout the whole brain, including the gray matter. However, it is still unclear why focal signs such as hemiplegia develope in metabolic disorders affecting the whole brain.

Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study.

BackgroundAlternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities.MethodsWe used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used.ResultsOne person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls.ConclusionsWe report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity.

1. Alternating hemiplegia of childhood into adulthood (AHCA): Case series and literature update

Objective To describe the clinical and electrophysiological characteristics of 3 cases of AHC, including novel treatment (off-label use). Study design We report three patients with AHCA. The clinical phenotype comprises of episodes of hemiplegia that moves from one side of the body to the other. The onset of the weakness usually occurs in the first few months of life. Movement disorder such as dystonia can also accompany the hemiplegic attacks in 2/3 cases. Intellectual impairment and epilepsy have been reported in these patients. However, the onset of seizures is usually in the age range between 3 and 4 years. Half the children with AHC have epilepsy, and these seizures are usually quite distinct from AHC attacks in their manifestations, although they may occur simultaneously. If an EEG is recorded during the seizure it usually shows an appropriate abnormality, but between seizures the EEG is normal. Seizures may be prolonged in two forms: epilepsia partialis continua or a more generalized convulsive status epilepticus. There is no agreed specific drug for seizure prevention in AHCA, and indeed, the epilepsy is often resistant to treatment. It is usual to give antiepilepsy drugs (AEDs) if the child has epilepsy, but one should monitor their effect and not continue in the face of side effects and poor efficacy. The management of these cases is challenging. The only drug with some efficacy is flunarizine and AEDs for seizure control. A trial of gamma-hydroxy butyrate (GHB) in N = 1 study had some efficacy and lateralised EEG changes contralateral to the side of hemiplegia, reversing with GHB. Results The diagnosis of AHCA was confirmed by the finding of ATP1A3 gene mutation in all 3 patients. In 2/3 cases the disorder extended into adulthood necessitating a name change: AHCA for the same genotype. Discussion The mutation found to be associated with AHCA is the ATP1A3 gene in 3/3 cases, reported in a majority of AHCA patients, with some familial cases. Conclusion AHCA is very uncommon, likely underdiagnosed clinically but with a high index of suspicion for early diagnosis and appropriate therapy, may ameliorate outcome and long-term prognosis in a larger RCT study.

Alternating hemiplegia of childhood

(1) Onset of AHC before 18 months of age. (2) Repeated attacks of hemiplegia involving either side of the body. (3) Other paroxysmal disturbances including tonic or dystonic spells, nystagmus, strabismus, dyspnea and autonomic phenomena occurring during hemiplegic episodes or in isolation. (4) Episodes of bilateral hemiplegia either during attacks that start unilaterally or from the beginning of attacks. (5) Sleep consistently produces disappearance of all symptoms, which reappear on awakening after 10 to 20 min in children having long attacks. (6) Evidence of developmental delay, learning disability and neurologic abnormalities including choreoathetosis, dystonia or ataxia.

Alternating hemiplegia of childhood

We reviewed the etiologic aspects, clinical symptoms, complementary studies, differential diagnosis and treatment of alternating hemiplegia of childhood (AHC). AHC is an uncommon illness of uncertain pathophysiology that provokes crisis of transient hemiplegia affecting one hemibody or occasionally both at the same time. Clinical symptoms of AHC usually begin before the age of 18 months and in some cases may present in the neonatal period. Clinical symptoms include abnormal ocular movements such as nystagmus and dystonic or tonic posturing. Hemiplegic attacks are not associated with alteration of consciousness. Hemiplegia may disappear after arousal and may reappear 10 to 20 minutes after arousal in children with AHC. The diagnosis of AHC is clinically made, and most of the clinically used diagnostic tests result in negative. The treatment of AHC includes flunarizine. It is necessary to suspect this diagnosis to identify patients with AHC.

Hemiplegia and headache: a review of hemiplegia in headache disorders.

The most common scenario wherein the practicing neurologist is likely to encounter a patient with headache and hemiplegia will vary depending on his/her specific type of practice. A neurologist providing consultative service to an emergency department is far more likely to see patients with "secondary" headache and hemiplegia in the setting of either ischemic or hemorrhagic stroke than hemiplegia as a transient feature of a primary headache disorder. Neurologists subspecializing in headache medicine who practice in a tertiary referral headache clinic are more likely to encounter hemiplegic migraine, but even in that clinical setting hemiplegic migraine is by no means a frequent diagnosis. The acute onset of hemiplegia can be very frightening not only to the patient but also to the medical personnel. Given the abundance of mimicry, practitioners must judiciously ascertain the correct diagnosis as treatment may greatly vary depending on the cause of both headache and hemiplegia. In this review, we will address the most common causes of hemiplegia associated with headache.

7. EEG findings in three patients with Alternating Hemiplegia of childhood (AHC)

Aim First reported by Verret and Steele in 1971, Alternating hemiplegia of childhood (AHC) is a rare disorder. The incidence is reported at 1 in 1,000,000 but this is most likely higher as AHC is often misdiagnosed. Infants often present with recurrent attacks of hemiplegia affecting either side of the body, abnormalities of ocular movement, movement disorders, and progressive developmental delay. It has been reported to be associated with mutations in CACNA1A, a calcium channel gene, and ATP1A2, a sodium potassium ATPase gene. It has been reported in large cohort studies that close to 50% of children with AHC will develop epilepsy. The purpose of this study is to examine the EEG finding with patient with AHC to further help clarify diagnosis. Methods This paper will explore 3 patients, chart review, with confirmed genetic testing of the APT1A2 gene mutation, EEG findings. Results Patient 1(R.G) low background activity in left temporal region, irregular sharp slow ave complex at 2 Hz, mild epileptiform focus in right posterior T6, T4 (temporal region. Patient 2 (A.K). slow wave at 4 Hz over both hemispheres that progressed to vertex waves and hypnagogic hypersynchrony after gamma hydroxbutyrate administration. Patient 3 (A.B), normal EEG. Summary Although the findings seen in patient with AHC are not pathognomonic, EEG is still a powerful tool in diagnosing patients especially in situations where genetic testing is not available.

Clinical manifestations and advances in hereditary research of alternating hemiplegia of childhood

Alternating hemiplegia of childhood(AHC) is a hereditary disease characterized by hemiplegia spells,abnormal eye movements,dystonia and cognitive impairment.There are three phases of the disease.Each phase has its unique clinical symptoms:phase 1-abnormal eye movements and dystonia;phase 2-hemiplegia spells; phase 3-permanent cognitive impairment.The severity of cognitive impairment depends on the time of onset of hemiplegia spells:the earlier the onset is,the worse outcome will be.No effective treatment has been established.Thetreatments currently include:avoiding predisposing factors and taking drugs such as flunarizine to prevent hemiplegia attacks,in the inter-ictal stage;and sedation during hemiplegia attacks.According to the latest research,AHC is caused by the de novo mutation of gene ATP1A3. Key words: Alternating hemiplegia of childhood; ATP1 A3 ; Abnormal ocular movements; Dystonia