Sporadic Hemiplegic Migraine Research Articles

Expanding the Genetic and Clinical Spectrum of SCN1A-Related Hemiplegic Migraine: Analysis of Mutations in Japanese.

Familial hemiplegic migraine (FHM) is characterized by repeated episodes of reversible localized neurological deficits, in addition to headache. The aura of HM includes visual, sensory, motor, and verbal symptoms. Hemiplegic migraine (HM) is classified into non-familial sporadic HM (SHM) and familial HM (FHM). Here, we analyzed the clinical symptoms and their relevance in four Japanese patients considered to have SCN1A mutations as a cause. Sequencing of SCN1A was performed using a whole exome sequence method in 48 blood samples from clinically suspected patients with FHM. Subsequently, algorithm analysis, allele frequency determination, and three-dimensional structure analysis of the recognized variants were performed, and the recognized variants were evaluated. We found five heterozygous missense mutations (p.A23E, p.V250L, p.T398M, p.R1575C, p.L1660I) in SCN1A, three of which had not been reported. These five mutations may also affect the structure of the protein products, as assessed using a three-dimensional structural analysis. In all cases, the clinical symptoms included visual, sensory, motor, and verbal symptoms, which are forms of aura. Similarities were detected, such as the appearance of symptoms at a young age and other symptoms, such as hemiplegia after a headache attack. We report five missense mutations in SCN1A of Japanese cases.

Moyamoya Disease Masquerading as Hemiplegic Migraine in a Child: A Case Report From India

Moyamoya disease (MMD) is a chronic progressive steno-occlusive disease of the intracranial arterial vessels and their branches characterized by puff smoke appearance on angiography. Multifocal neurological insults and deficits are commonly observed in children with MMD. A 7-year-old boy presented with multiple episodes of transient hemiparesis preceded by headache, vomiting, and visual auras was initially labeled as sporadic hemiplegic migraine according to the International Headache Society criteria. However, the rare association of hemiplegic migraine with MMD compelled us to perform magnetic resonance imaging and digital subtraction angiography, which revealed MMD as the underlying cause for the alternating hemiplegia and headaches in the child.

A novel mutation in the ATP1A2 gene associated with a sporadic hemiplegic migraine and multiple supraventricular arrhythmias: A case report

Introduction ATP1A2 mutations are identified as a genetic cause of type 2 hemiplegic migraine, but to date, no ATP1A2 gene variant has been linked to heart rhythm disorders Case presentation A 37-year-old woman presented with sporadic hemiplegic migraine and multiple supraventricular arrhythmias refractory to medical treatment and electrophysiological interventions. Genetic workup revealed a mutation in the ATP1A2 gene (c.1827 + 10delT) which was not previously described. The co-segregation study supported the causal participation of the variant since it was found in the migrainous sister but not in the non-migrainous father. Conclusions We suggest that the c.1827 + 10delT mutation in the ATP1A2 gene is a novel pathogenic mutation linked to both hemiplegic migraine and supraventricular arrhythmias.

Sporadic Hemiplegic Migraine: Hypoperfusion Demonstrated by Susceptibility-Weighted Magnetic Resonance Imaging and Computed Tomography Perfusion Study

Sporadic Hemiplegic Migraine: Hypoperfusion Demonstrated by Susceptibility-Weighted Magnetic Resonance Imaging and Computed Tomography Perfusion Study

Hemiplegic Migraine in Children and Adolescents.

Only a few studies have focused on hemiplegic migraine (HM) in children despite its early age of onset. The aim of this review is to describe the peculiar characteristics of pediatric HM. This is a narrative review based on 14 studies on pediatric HM selected from 262 papers. Different from HM in adults, pediatric HM affects both genders equally. Early transient neurological symptoms (prolonged aphasia during a febrile episode, isolated seizures, transient hemiparesis, and prolonged clumsiness after minor head trauma) can precede HM long before its onset. The prevalence of non-motor auras among children is lower than it is in adults. Pediatric sporadic HM patients have longer and more severe attacks compared to familial cases, especially during the initial years after disease onset, while familial HM cases tend to have the disease for longer. During follow-up, the frequency, intensity, and duration of HM attacks often decrease. The outcome is favorable in most patients; however, neurological conditions and comorbidities can be associated. Further studies are needed to better define the clinical phenotype and the natural history of pediatric HM and to refine genotype-phenotype correlations in order to improve the knowledge on HM physiopathology, diagnosis, and outcome.

Clinical features and genetic analysis of two Chinese ATP1A2 gene variants pedigrees of familial hemiplegic migraine

Clinical features and genetic analysis of two Chinese ATP1A2 gene variants pedigrees of familial hemiplegic migraine

EEG changes during left- and right-sided weakness in patient with sporadic hemiplegic migraine.

EEG changes during left- and right-sided weakness in patient with sporadic hemiplegic migraine.

Diagnostic challenges in sporadic hemiplegic migraine: a case report

Case Presentation
 Female, 62 years old, history previous of hypertension and multiple cavernomatosis, admitted to our service emergency room with hypothesis of stroke. The patient presented headache associated with nausea and phosphenes in the right eye, with evolution for right hemiplegia. However, she showed complete and spontaneous reversal of symptoms, in a few minutes. The patient presented similar symptoms with annual recurrence since 2019, always following migraine attack. She denied familiar history of migraine. Brain MRI showed multiple cavernomatosis, with no signs of old or recent ischemia. Brain and cervical CT angiography and laboratorial tests were normal. She was then diagnosed with sporadic hemiplegic migraine, with no family report of the disease. She received treatment with Amitriptyline 50 mg per day, without further recurrences.
 Discussion
 Hemiplegic migraine (HM) is a rare form of migraine with motor aura, which includes fully reversible motor weakness. The aura of HM is most probably caused by cortical spreading depression, a self-propagating wave of neuronal and glial depolarization that spreads across the cerebral cortex. Patients who are the first member of their family to have hemiplegic migraine are classified as having sporadic hemiplegic migraine. Some cases of sporadic hemiplegic migraine are caused by one of the genetic variants that cause familial hemiplegic migraine. The treatment of HM is empirical and mainly relies on principles of management of the common types of migraine, except for triptans use, medication historically contraindicated because of vasoconstrictor properties.
 Final comments
 Hemiplegic migraine is an important differential diagnosis with stroke in patients with migraine. Correct recognition of this condition can be a crucial factor in the treatment and prognosis of the patient in the emergency room.
 
 Keywords: hemiplegic migraine, motor aura, stroke mimics.

Sporadic hemiplegic migraine due to a missense variation in ATP1A2 gene in 2 children

2例散发性偏瘫性偏头痛患儿，例1，男，5岁10月龄，因“反复惊厥发作5年余，行为异常20 d”入院。例2，男，4岁6月龄，因“反复惊厥发作3年余，发热伴右侧肢体活动受限1 d”入院。2例患儿均无相关家族史，早期表现为热性惊厥，随年龄增长，在发热等诱因下出现先兆头痛伴急性脑病发作。基因检测均为ATP1A2基因错义变异，分别为c.2143G>A（p.Gly715Arg）、c.2563G>A（p.Gly855Arg）。.

Sporadic Hemiplegic Migraine with CACNA1A Mutation Masquerading as Acute Meningoencephalitis

Sporadic Hemiplegic Migraine with CACNA1A Mutation Masquerading as Acute Meningoencephalitis

Sporadic hemiplegic migraine (rare case in clinical practice)

The article describes the peculiarities of a rare disease – hemiplegic migraine in three patients (two boys aged 7 and 15 and a girl of 12 years old). The family history of migraine was not burdened. Attack symptoms were almost identical: hemiparesis, dysphasia, and headache. The electroencephalograms, magnetic resonance imaging in all patients not presented signs brain dysfunction. Analysis of the literature data has been carried out. Thediagnostic criteria for hemiplegic migraine, its differential diagnosis is described. The considered description increases the awareness of doctors on the issue, which is very rare in the practice of pediatrician and neurologist.

Sporadic Hemiplegic Migraine Presenting ATP1A2 Mutation in Korea

Hemiplegic migraine (HM) is a rare form of migraine, characterized by migraine with reversible motor weakness. HM can be divided into sporadic and familiar HM based on familiarity. Mutations in CACNA1A, ATP1A2 and SCN1A were identified in familiar HM. We present a patient with sporadic HM exhibiting recurrent hemiplegia, mental change and fever along with headache attacks. During the hemiplegia, he showed perfusion delay in left middle cerebral artery territory. Genetic panel test revealed a likely pathogenic varia nt in ATP1A2.

Vestibular Migraine With Brainstem Auras: A Review of Pathogenesis, Clinical Varieties, Abortive and Prophylactic Treatment

Vestibular migraine (VM) is the most common etiology of vertigo in the adults. VM accompanied by brainstem symptoms is not uncommon, but underrecognized so far. It is often misdiagnosed as brainstem infarction. Earlier correct diagnosis could help avoid thrombolysis, intravascular intervention, excessive auxiliary examination, panic and fear, repeated hospitalization, waste of medical resources, early and short-term use of steroid hormone, and antioxidant. Family or sporadic hemiplegic migraine (HM) is a kind of encephalopathy instead of simple hypoperfusion; the pathogenesis, which was not well described, might also account for the neurological symptoms in VM patients. The genomic identification of the migraine could facilitate better understanding on molecular pathogenesis of familial HM. Genetic mutations are believed to be associated with more susceptible alterations of cortical spreading depression in the brain. J Neurol Res. 2021;11(5):77-86 doi: https://doi.org/10.14740/jnr651

Vestibular Migraine With Brainstem Auras: A Review of Pathogenesis, Clinical Varieties, Abortive and Prophylactic Treatment

Vestibular migraine (VM) is the most common etiology of vertigo in the adults. VM accompanied by brainstem symptoms is not uncommon, but underrecognized so far. It is often misdiagnosed as brainstem infarction. Earlier correct diagnosis could help avoid thrombolysis, intravascular intervention, excessive auxiliary examination, panic and fear, repeated hospitalization, waste of medical resources, early and short-term use of steroid hormone, and antioxidant. Family or sporadic hemiplegic migraine (HM) is a kind of encephalopathy instead of simple hypoperfusion; the pathogenesis, which was not well described, might also account for the neurological symptoms in VM patients. The genomic identification of the migraine could facilitate better understanding on molecular pathogenesis of familial HM. Genetic mutations are believed to be associated with more susceptible alterations of cortical spreading depression in the brain. J Neurol Res. 2021;11(5):77-86 doi: https://doi.org/10.14740/jnr651

Modeling NaV1.1/SCN1A sodium channel mutations in a microcircuit with realistic ion concentration dynamics suggests differential GABAergic mechanisms leading to hyperexcitability in epilepsy and hemiplegic migraine.

Loss of function mutations of SCN1A, the gene coding for the voltage-gated sodium channel NaV1.1, cause different types of epilepsy, whereas gain of function mutations cause sporadic and familial hemiplegic migraine type 3 (FHM-3). However, it is not clear yet how these opposite effects can induce paroxysmal pathological activities involving neuronal networks’ hyperexcitability that are specific of epilepsy (seizures) or migraine (cortical spreading depolarization, CSD). To better understand differential mechanisms leading to the initiation of these pathological activities, we used a two-neuron conductance-based model of interconnected GABAergic and pyramidal glutamatergic neurons, in which we incorporated ionic concentration dynamics in both neurons. We modeled FHM-3 mutations by increasing the persistent sodium current in the interneuron and epileptogenic mutations by decreasing the sodium conductance in the interneuron. Therefore, we studied both FHM-3 and epileptogenic mutations within the same framework, modifying only two parameters. In our model, the key effect of gain of function FHM-3 mutations is ion fluxes modification at each action potential (in particular the larger activation of voltage-gated potassium channels induced by the NaV1.1 gain of function), and the resulting CSD-triggering extracellular potassium accumulation, which is not caused only by modifications of firing frequency. Loss of function epileptogenic mutations, on the other hand, increase GABAergic neurons’ susceptibility to depolarization block, without major modifications of firing frequency before it. Our modeling results connect qualitatively to experimental data: potassium accumulation in the case of FHM-3 mutations and facilitated depolarization block of the GABAergic neuron in the case of epileptogenic mutations. Both these effects can lead to pyramidal neuron hyperexcitability, inducing in the migraine condition depolarization block of both the GABAergic and the pyramidal neuron. Overall, our findings suggest different mechanisms of network hyperexcitability for migraine and epileptogenic NaV1.1 mutations, implying that the modifications of firing frequency may not be the only relevant pathological mechanism.

Serial magnetic resonance imaging findings during severe attacks of familial hemiplegic migraine type 2: a case report

Background Hemiplegic migraines represent a heterogeneous disorder with various presentations. Hemiplegic migraines are classified as sporadic or familial based on the presence of family history, but both subtypes have an underlying genetic etiology. Mutations in the ATP1A2 gene are responsible for Familial Hemiplegic type 2 (FHM2) or the sporadic hemiplegic migraine (SHM) counterpart if there is no family history of the disorder. Manifestations include migraine with aura and hemiparesis along with a variety of other symptoms likely dependent upon the specific mutation(s) present.Case presentationWe report the case of an adult man who presented with headache, aphasia, and right-sided weakness. Workup for stroke and various infectious agents was unremarkable during the patient’s extended hospital stay. We emphasize the changes in the Magnetic Resonance Imaging (MRI) over time and the delay from onset of symptoms to MRI changes in Isotropic Diffusion Map (commonly referred to as Diffusion Weighted Imaging (DWI)) as well as Apparent Diffusion Coefficient (ADC).ConclusionsWe provide a brief review of imaging findings correlated with signs/symptoms and specific mutations in the ATP1A2 gene reported in the literature. Description of the various mutations and consequential presentations may assist neurologists in identifying cases of Hemiplegic Migraine, which may include transient changes in ADC and DWI imaging throughout the course of an attack.

Sporadic Hemiplegic Migraine Type 1 and Congenital Ataxia due to a Single Amino Acid Deletion (ΔF1502) in CACNA1A: A Challenging Diagnosis

AbstractMutations in the CACNA1A gene have been classically related to three neurologic disorders: hemiplegic migraine type 1 (both familiar and sporadic FHM1/SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). More recently, pathogenic variants in CACNA1A have been recognized as causative of an early-onset cerebellar syndrome consistent with the definition of congenital ataxia (CA), variably associated with paroxysmal symptoms. Early recognition of congenital ataxia is challenging because the presenting symptoms, such as hypotonia, weak deep tendon reflexes, and delayed motor milestones, are unspecific while clear signs of a cerebellar syndrome which are usually not seen before the second or third year. Here, we report on a case of nonepisodic ataxia of congenital onset and severe SHM1 where the diagnosis of congenital ataxia was made retrospectively after the identification of the ΔF1502 pathogenic variant in CACNA1A by an hemiplegic migraine multigene panel, conducted for the onset of hemiplegic migraine attacks associated with hemispheric swelling. A significant reduction in migraine attacks frequency was achieved with acetazolamide.

Child with Sporadic Hemiplegic Migraine: Case Report

Child with Sporadic Hemiplegic Migraine: Case Report

CACNA1A Gene Variants in Eight Chinese Patients With a Wide Range of Phenotypes.

Background: The CACNA1A gene encodes the voltage-dependent P/Q-type calcium channel subunit alpha-1A, which is widely expressed throughout the CNS. The biological roles of the P/Q channel are diverse and the phenotypic spectrum caused by CACNA1A mutations is wide. The aim of this study is to demonstrate its phenotypic diversity and analyze the genotype-phenotype correlations in a cohort of Chinese patients.Methods: Patients with hemiplegic migraine, cerebellar ataxia, developmental delay, or epilepsy without known causes were tested by trios whole-exome sequencing. Patients with pathogenic CACNA1A gene variants were recruited. The clinical information of the patients was collected, and the association between the genotype and the phenotype was investigated.Results: In total, eight patients (six females and two males) were found to have CACNA1A gene variants. All the variants were de novo including six missense variants and one frameshift variant. Four de novo missense variants were found in five patients located in the S4, S5, or S6 transmembrane segments of Domain II and III (p.R1352Q, p.G701V, p.A713T, p.V1393M). All of them were correlated with severe phenotypes, including three with sporadic hemiplegic migraine type 1 and epilepsy, and two with developmental and epileptic encephalopathy. The other two missense variants, p.Y62C and p.F1814L, located in the cytoplasmic side of the N-terminus and C-terminus, respectively. The variant p.Y62C was associated with severe hemiconvulsion-hemiplegia-epilepsy syndrome, and p.F1814L was associated with relatively mild phenotypes. All the missense variants were speculated as gain-of-function (GOF) mutations. The only frameshift variant, p.Q681Rfs*100, a lose-of-function (LOF) mutation, was found in a patient with episodic ataxia type 2. Meanwhile, all the patients had developmental delay ranging from mild to severe, as well as cerebellar ataxia including one with congenital ataxia, one with episodic ataxia, and six with non-progressive ataxia.Conclusions: CACNA1A variants could lead to a wide spectrum of neurological disorders including epileptic or non-epileptic paroxysmal events, cerebellar ataxia, and developmental delay. The variants could be both GOF and LOF mutations. There appeared to be some correlations between genotypes and phenotypes.

Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study

Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study