Recurrent Hemiplegia Research Articles

Alternating hemiplegia of childhood misdiagnosed as hysteria: a case report

BackgroundAlternating hemiplegia of childhood (AHC) is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia, and frequently accompanied by dystonic posturing, choreoathetosis movements, anomalous ocular motions, and a gradual deterioration in cognitive function. The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.Case presentationHere, we report a 16-year-old girl with recurrent hemiplegia since her infancy. This patient has experienced paroxysmal limb weakness and aphasia for over 15 years, and has kept seeking medical attention but without receiving effective treatment. A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital. Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C (p.Leu757Pro) mutation in her ATP1A3 gene. Notably, her clinical manifestations, including pathological emotional responses and autonomic dysfunction, differed from the established profile associated with the same ATP1A3 mutation, which typically present with intellectual disability, a rostrocaudal symptom gradient, choreoathetosis, and dysarthria. The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.ConclusionsThis case enhances our understanding of the intricate clinical manifestations of AHC, which require careful differentiation from various diseases such as epilepsy, hysteria, and paroxysmal dyskinesias. In the diagnosis of patients presenting with suspected symptoms, adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments. Additionally, when AHC is suspected in a patient, genetic testing should be considered as part of the diagnostic approach.

Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability

BackgroundAlternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability.Case presentationClinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature.ConclusionsHemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.

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.

An Infant With Epilepsy and Recurrent Hemiplegia due to Compound Heterozygous Variants in ATP1A2

BackgroundPathogenic heterozygous variants in the ATP1A2 gene have most commonly been associated with familial hemiplegic migraine. However, a wide spectrum of phenotypes that include alternating hemiplegia of childhood and epilepsy have been described. Patient DescriptionWe describe a boy who presented at age three months with a complex phenotype that included epilepsy, nonepileptic paroxysmal events, and recurrent hemiplegia. Magnetic resonance imaging demonstrated unilateral cortical edema during a severe episode of hemiplegia that was followed by a persistent mild hemiparesis. ResultsWhole-exome sequencing identified a previously reported ATP1A2 missense variant (p.Arg548Cys) classified as pathogenic and a novel missense variant (p.Arg1008Trp) classified as a variant of uncertain significance. After this genetic diagnosis, treatment with flunarizine was initiated and no further episodes of hemiplegia have occurred. ConclusionsThis is only the second report of compound heterozygosity of the ATP1A2 gene. It demonstrates the spectrum of paroxysmal neurological events that can arise as a result of ATP1A2 variants, with unique features overlapping alternating hemiplegia of childhood, hemiplegic migraine, and epilepsy. This child illustrates the diagnostic challenges that these disorders can present and the importance of genetic diagnosis in guiding management.

Child Neurology: Benign nocturnal alternating hemiplegia of childhood

Alternating hemiplegia of childhood (AHC) is a disorder of recurrent hemiplegia beginning before age 18 months and is associated with dystonia, nystagmus, and progressive cognitive and motor impairment. This disorder was first recognized by Verret and Steele1 in 1971. Benign nocturnal alternating hemiplegia of childhood, which differs from AHC by its absence of decline in neurologic or cognitive impairment, is very rare or possibly only rarely recognized. We describe 2 children diagnosed with this syndrome and review the literature published. In contrast to the severe prognosis of the much more known syndrome of AHC,1,2 the prognosis of benign nocturnal alternating hemiplegia of childhood is excellent. In August 2008, a 2-year-old boy visited our outpatient department because of possible psychomotor delay. He had started walking at age 23 months and was only talking in single words. He was the second child of healthy, nonrelated parents. His paternal grandmother had migraine without aura. Neurologic examination revealed no abnormalities. We diagnosed benign delay in gross motor function and advised no further analysis. Just by chance, his parents mentioned that a few weeks earlier, they had noted that their son cried loudly while asleep. When they arrived, they found him in bed. He was unable to lift his head. When his parents took him out of bed, he seemed to be completely flaccid. In their opinion, he was fully conscious during this attack. After 20–30 minutes the symptoms gradually disappeared. According to his parents, the left side of …

The remarkably variable expressivity of CADASIL: report of a minimally symptomatic man at an advanced age

Sir, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset, dominantly inherited disorder caused by NOTCH3 mutations. It is characterized by recurrent subcortical infarctions, dementia, and less frequently, migraine and psychiatric symptoms. NOTCH3 has 33 exons, and most CADASIL-associated NOTCH3 mutations result in a gain or loss of one cysteine residue within a given extracellular epidermal growth factor (EGF)-like repeat domain and, in Caucasians, with a strong cluster in exon 3–6 encoding the first five EGF-like repeats [1]. The typical MRI features in CADASIL include multi-focal lacunar infarcts and diffuse T2-weighted hyperintensity of cerebral white matter with involvement of the anterior temporal lobes [1]. The presence of granular osmiophilic material (GOM), which is seen in close vicinity to the basement membrane of the smooth muscle cells of the arterioles on electron microscopy (EM), is pathognomonic for CADASIL [1]. Although the penetrance of MRI changes has been reported to be complete by 40 years of age [2], the spectrum of clinical phenotypes has remained elusive. Herein, we report the case of an 86-year-old minimally symptomatic male with CADASIL mutation, representing one extreme of the remarkably variable expressivity of CADASIL. The 86-year-old man had been doing very well before. His past history is only remarkable for heavy cigarette smoking without migraine or psychiatric symptoms. He came to our attention because of a mild numbness in the left hand following two falls 2 months earlier. The neurological examinations revealed only subtly increased deep tendon reflexes in the right biceps and brachioradialis. The brain MRI with gadolinium-enhanced magnetic resonance angiography (MRA) revealed a diffuse leukoencephalopathy without anterior temporal lobe involvement, one single and small lacunar infarct in the left putamen (Fig. 1a), and patent cerebral vessels. Subsequent mutational analysis of NOTCH3 uncovered a missense mutation, c. 1708C [ T, in exon 11, which putatively may result in a substitution of cysteine for arginine at amino acid 544 (R544C). The EM exam of a skin biopsy demonstrated the presence of characteristic GOM (Fig. 1b, c). His family history was unclear because of his early separation, at teenage, from the family and he has no children. He had received 7 years of education. His score of Mini-Mental State Examination (MMSE) was 27 out of 30 and the Cognitive Abilities Screening Instruments (CASI) was 81 out of 100. The cutoff scores of CASI in our population for the diagnosis of dementia in those who received 6 or more years of education is 79/80 [3]. NOTCH3 R544C has previously been reported manifesting typical CADASIL features [4, 5]. In the literature, the clinical manifestations of NOTCH3 mutations are enormously variable [6], with another report of a 14-yearold boy presenting with recurrent hemiplegia [7]. The observation in this patient highlights that, because the clinical manifestations may be extremely subtle, NOTCH3 Y.-C. Lee B.-W. Soong (&) Department of Neurology, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, #155, Sec.2, Li-Nung Street, Peitou District, Taipei 11217, Taiwan, ROC e-mail: bwsoong@vghtpe.gov.tw

Recurrent hemiplegia associated with cerebral vasculopathy following third trimester maternal herpes zoster infection

The chickenpox virus (varicella zoster virus; VZV) is known to cause large and small vessel central nervous system vasculopathies that may be associated with strokes in both adults and children. We present the case of a female aged 2 years 6 months who developed a chronic progressive small‐vessel vasculopathy with radiological features of moyamoya disease as a manifestation of congenital varicella syndrome. Clinically, the condition was characterized by recurrent ischaemic strokes, which were brought under control using intravenous acyclovir. The case is unique in that it is the first report of congenital varicella syndrome to occur after a maternal herpes zoster infection. Furthermore, it is the first case of symptomatic VZV infection in a child to occur after a maternal infection occurring in the third trimester of pregnancy.

Recurrent hemiplegia associated with cerebral vasculopathy following third trimester maternal herpes zoster infection

The chickenpox virus (varicella zoster virus; VZV) is known to cause large and small vessel central nervous system vasculopathies that may be associated with strokes in both adults and children. We present the case of a female aged 2 years 6 months who developed a chronic progressive small-vessel vasculopathy with radiological features of moyamoya disease as a manifestation of congenital varicella syndrome. Clinically, the condition was characterized by recurrent ischaemic strokes, which were brought under control using intravenous acyclovir. The case is unique in that it is the first report of congenital varicella syndrome to occur after a maternal herpes zoster infection. Furthermore, it is the first case of symptomatic VZV infection in a child to occur after a maternal infection occurring in the third trimester of pregnancy.

Ventricular myxoma associated with cerebral embolism

Cardiac tumor emboli to the brain are rare. Previously reported cases have all been associated with myxoma of the left atrium, and, to our knowledge, an embolus associated with a myxoma of the ventricle has not been previously reported. The patient had two episodes of recurrent hemiplegia following periods of excessive exertion. Carotid angiography demonstrated a complete occlusion of the left middle cerebral artery. Echocardiography also proved valuable in diagnosis. Microscopic examination of this vessel revealed the lesion to be a myxoma which had originated from a myxoma of the apex of the left ventricle. This etiologic factor should be considered in the occurrence of cerebrovascular occlusive disease in the young adult.

Ventricular Myxoma Associated With Cerebral Embolism

Cardiac tumor emboli to the brain are rare. Previously reported cases have all been associated with myxoma of the left atrium, and, to our knowledge, an embolus associated with a myxoma of the ventricle has not been previously reported. The patient had two episodes of recurrent hemiplegia following periods of excessive exertion. Carotid angiography demonstrated a complete occlusion of the left middle cerebral artery. Echocardiography also proved valuable in diagnosis. Microscopic examination of this vessel revealed the lesion to be a myxoma which had originated from a myxoma of the apex of the left ventricle. This etiologic factor should be considered in the occurrence of cerebrovascular occlusive disease in the young adult.

On Recurrent Motor Paralysis in Migraine, with Report of a Family in which Recurrent Hemiplegia Accompanied the Attacks

On Recurrent Motor Paralysis in Migraine, with Report of a Family in which Recurrent Hemiplegia Accompanied the Attacks