Novel missense mutation in the ATP1A2 gene associated with atypical sporadic hemiplegic migraine

Rispoli, Marianna Gabriella; Stefano, Vincenzo Di; Mantuano, Elide; Angelis, Maria Vittoria De

doi:10.1136/bcr-2019-231129

Cited by 10 publications

(10 citation statements)

References 23 publications

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“…Table 1 includes clinical presentations, imaging findings, and genetic testing if performed for patients with hemiplegic migraines with an ATP1A2 mutation undergoing severe attacks published in the last ten years [6,9,10,15,[17][18][19][20][21][22][23][24]. Perfusion studies on FHM2 patients have demonstrated both hypo-and hyperperfusion.…”

Section: Discussionmentioning

confidence: 99%

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

2021

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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 presentation We 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). Conclusions We 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.

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Section: Discussionmentioning

confidence: 99%

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

2021

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“…Indeed, cerebellar involvement with a gaze-evoked nystagmus and progressive ataxia has been associated with in FHM type 1 (FHM1) in about 60% of cases, but is rare in FHM type 2 (FHM2). 1 8 18 19 Moreover, some mutations of CACNA1A or ATP1A2 have been associated with mental retardation and cognitive impairment after severe and recurrent episodes [20][21][22][23] ; early onset attacks, coma and seizure are considered the main risk factors for this kind of complication. 1 24 More recently, 50% of children (aged 3-18 years) with a pathogenic CACNA1A mutation associated with HM and other benign paroxysmal events (torticollis, vertigo or tonic upgaze) showed an heterogeneous cognitive dysfunction without a specific cognitive profile, mainly associated with vermian cerebellar atrophy for these early onset CACNA1A-associated phenotype was proposed a classification as 'neurodevelopmental disorders', suggesting thus a close follow-up of psychomotor development and academic performances.…”

Section: Chronic Symptomsmentioning

confidence: 99%

“…We previously described the case of a patient with late-onset SHM (missense mutation of the ATP1A2 gene) with hypertension and severe carotid stenoses. 21 Conversely, recurrent TIAs can be evocative of SHM in patients with rare syndromes who fulfil criteria for HM. 61 Nevertheless, TIAs and strokes have a sudden onset, while HM typically shows gradual progressive spread with aura 1 ; the neuroimaging can be helpful to distinguish among these conditions, but the timing of the headache also provides relevant information, because the headache usually follows the motor weakness in HM and precedes the weakness in haemorrhagic strokes.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and therapeutic aspects of hemiplegic migraine

Stefano

Rispoli

Pellegrino

et al. 2020

J Neurol Neurosurg Psychiatry

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Hemiplegic migraine (HM) is a clinically and genetically heterogeneous condition with attacks of headache and motor weakness which may be associated with impaired consciousness, cerebellar ataxia and intellectual disability. Motor symptoms usually last <72 hours and are associated with visual or sensory manifestations, speech impairment or brainstem aura. HM can occur as a sporadic HM or familiar HM with an autosomal dominant mode of inheritance. Mutations in CACNA1A, ATP1A2 and SCN1A encoding proteins involved in ion transport are implicated. The pathophysiology of HM is close to the process of typical migraine with aura, but appearing with a lower threshold and more severity. We reviewed epidemiology, clinical presentation, diagnostic assessment, differential diagnosis and treatment of HM to offer the best evidence of this rare condition. The differential diagnosis of HM is broad, including other types of migraine and any condition that can cause transitory neurological signs and symptoms. Neuroimaging, cerebrospinal fluid analysis and electroencephalography are useful, but the diagnosis is clinical with a genetic confirmation. The management relies on the control of triggering factors and even hospitalisation in case of long-lasting auras. As HM is a rare condition, there are no randomised controlled trials, but the evidence for the treatment comes from small studies.

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“…The duration of symptoms is usually 20–60 min. In some cases, the aura and hemiplegia may onset quickly and simulate an ischaemic attack [ 17 ]. Complete recovery from attacks is the rule, but in severe HM, hemiplegia and altered consciousness may persist for weeks until normal [ 3 ].…”

Section: Resultsmentioning

confidence: 99%

A case report of atypical hemiplegic migraine with nonheadache onset in a Chinese child

et al. 2021

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Background Hemiplegic migraine (HM) is an uncommon subtype of migraine with aura including motor weakness. The core symptoms of HM are headache and motor weakness. However, we report a rare case of atypical HM with nonheadache onset in a Chinese child who was misdiagnosed several times. Case presentation We report a Chinese boy whose onset was sudden when he was 3 years old. He presented with a variety of phenotypes, including fever, vomiting, alternating hemiplegia, and drowsiness, but no headache in the initial stages. Magnetic resonance imaging (MRI) demonstrated unilateral cerebral oedema during the initial episode of hemiplegia. These symptoms recurred many times. As the disease progressed, the patient developed episodic headache. The patient was misdiagnosed several times with encephalitis, alternating hemiplegia of childhood (AHC) and mitochondrial encephalopathy. Whole-exome next-generation sequencing revealed a de novo heterozygous missense mutation in the ATP1A2 gene(p.Gly715Arg) classified as pathogenic and eventually led to a diagnosis of HM when he was 11 years old. Flunarizine was subsequently administered, and no recurrence was found during follow-up. Conclusions HM in children may be atypical in the initial stage of the disease, which could manifest as fever, alternating hemiplegia and drowsiness but no headache at the onset. This could easily lead to misdiagnosis. With age, it may eventually manifest as typical HM. Therefore, attention should be given to differentiation in clinical practice.When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment.

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Novel missense mutation in the ATP1A2 gene associated with atypical sporadic hemiplegic migraine

Cited by 10 publications

References 23 publications

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

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

Diagnostic and therapeutic aspects of hemiplegic migraine

A case report of atypical hemiplegic migraine with nonheadache onset in a Chinese child

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