Stimulus-induced focal motor seizure in a pediatric patient with carbamazepine overdose

IntroductionCarbamazepine (CBZ) is a common antiepileptic drug that may cause overdoses with seizures as a common neurological manifestation. In previous reports, patients with CBZ overdose exhibited stimulus-induced generalized clinical or electrical seizures. To date, no previous cases of focal motor seizures have been reported.Case reportWe report the case of an 11-year-old girl with spontaneous and stimulus-induced clustering of focal motor seizures following CBZ overdose. The patient had been treated with CBZ (150 mg daily) for focal epilepsy since the age of six years. At the age of 11, she forgot to take a morning dose, took ten CBZ pills (CBZ 1000 mg) as compensation, and presented with generalized seizures. The patient arrived at the hospital in a coma. She demonstrated clustering of focal-to-bilateral tonic-clonic seizures induced by pain stimulus or spontaneously, with focal epileptiform discharges observed on EEG. Her CBZ blood concentration measured 40.4 μg/mL and she was diagnosed with CBZ overdose. The patient showed improvement without any specific treatment, and was later discharged without neurological sequelae.ConclusionPrevious cases of CBZ overdose with stimulus-induced generalized seizures resulted in death or required intensive care. Stimulus-induced focal seizures may indicate a favorable prognosis for CBZ overdose.     

Association Between Prolonged Seizures and Malignant Middle Cerebral Artery Infarction in Children With Acute Ischemic Stroke

BackgroundMalignant middle cerebral artery infarct syndrome is a potentially fatal complication of stroke that is poorly understood in children. We studied the frequency, associated characteristics, and outcomes of this condition in children.MethodsChildren, aged two months to 18 years with acute middle cerebral artery infarct diagnosed at our center between January 2005 and December 2012 were studied. Associations with malignant middle cerebral artery infarct syndrome were sought, including age, seizures, neurological deficit severity (Pediatric National Institute of Health Stroke Severity Score), stroke etiology, fever, blood pressure, blood glucose, infarct location, infarct volume (modified pediatric Alberta Stroke Program Early Computed Tomography Score), and arterial occlusion. Death and neurological outcomes were determined.ResultsAmong 66 children with middle cerebral artery stroke, 12 (18%) developed malignant middle cerebral artery infarct syndrome, fatal in three. Prolonged seizures during the first 24 hours (odds ratio, 25.51; 95% confidence interval, 3.10 to 334.81; P = 0.005) and a higher Pediatric National Institute of Health Stroke Severity Score (odds ratio, 1.22; 95% confidence interval, 1.08 to 1.45; P = 0.006) were independently associated with malignant middle cerebral artery infarct syndrome. All children aged greater than two years with a Pediatric National Institute of Health Stroke Severity Score ≥8 and initial seizures ≥5 minutes duration developed malignant middle cerebral artery infarct syndrome (100%).ConclusionsMalignant middle cerebral artery infarct syndrome affects nearly one in five children with acute middle cerebral artery stroke. Children with higher Pediatric National Institute of Health Stroke Severity Scores and prolonged initial seizures are at greatly increased risk for malignant middle cerebral artery infarct syndrome. Children with middle cerebral artery infarcts warrant intensive neuroprotective management and close monitoring to enable early referral for hemicraniectomy surgery.     

Involuntary movements as a prognostic factor for acute encephalopathy with biphasic seizures and late reduced diffusion

BackgroundAcute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and white matter lesions with reduced diffusion, which are often accompanied by involuntary movements. The neurological outcomes of AESD vary from normal to mild or severe sequelae, including intellectual disability, paralysis, and epilepsy. The present study aimed to clarify the prognostic factors of AESD, including involuntary movements.MethodsWe enrolled 29 patients with AESD admitted to Tottori University Hospital from 1991 to 2020 and retrospectively analyzed their clinical data. Neurological outcomes were assessed by the Pediatric Cerebral Performance Category score and cerebral paralysis as neurological sequelae.ResultsOf the 29 patients, 12 had favorable outcomes and 17 had unfavorable outcomes. Univariate analysis revealed that the presence of underlying diseases, a decline in Glasgow Coma Scale (GCS) score 12–24 h after early seizures, and involuntary movements were associated with unfavorable outcomes. In multivariate analysis, a decline in GCS score and involuntary movements were associated with unfavorable outcomes. The sensitivities and specificities of underlying diseases, a decline of ≥ 3 points in GCS score 12–24 h after early seizures, and involuntary movements for unfavorable outcomes were 53% and 92%, 92% and 65%, and 59% and 92%, respectively.ConclusionsThe appearance of involuntary movements may be associated with unfavorable outcomes of AESD. The prognostic factors identified herein are comparable with previously known prognostic factors of consciousness disturbances after early seizures.     

Forearm compartment syndrome following intravenous thrombolytic therapy for acute ischemic stroke

Introduction: Minor and major bleeding complications have occurred following thrombolysis in acute ischemic stroke. However, compartment syndrome has not been reported among these incidences. Methods and Results: This article presents a case of a forearm compartment syndrome in a patient with stroke who had fallen at the time of the infarction and was treated with tissue plasminogen activator. We wish to forewarn clinicians who may encounter similar cases. Conclusion: Patients suffering from stroke who fall are at risk of developing a compartment syndrome; the early diagnosis is often difficult, the sequelae can be devastating, and wrestling with the benefits and risks of reversing the coagulopathy in the acute phase of a cerebral infarction is a challenge.     

An exploratory study to identify neonatal arterial ischemic stroke: A single-center study

BackgroundNeonatal arterial ischemic stroke (NAIS) presents as seizures, including convulsions, subtle seizures, and apnea, and most patients experience neurological sequelae. Diagnosis is often delayed owing to low test sensitivity. The present study aimed to identify the early clinical diagnostic factors for NAIS in neonates with seizures.MethodsThe present study included 54 patients born at ≥36 weeks of gestation during the last 15 years who presented to the neonatal intensive care unit with neonatal seizures and underwent brain magnetic resonance imaging (MRI), 6 of whom were diagnosed with NAIS. Maternal background, clinical characteristics, and transcranial pulsed Doppler sonography results were retrospectively reviewed.ResultsOf the 24 patients who presented with convulsions or subtle seizures, 3 (13%) were diagnosed with NAIS and 3 of 30 patients (10%) presented with apnea. Maternal premature ventricular contraction complications were higher in the NAIS group than in the non-NAIS group (p = 0.01). NAIS group showed lower mean middle cerebral artery (MCA) resistance index (RI) was lower the non-NAIS group (p = 0.009), while the left–right RI difference (p = 0.019), mean MCA blood velocity (MnV; p = 0.04), and left–right MnV difference (p < 0.001) in cerebral blood flow velocities (CBFVs) were higher in the NAIS group.ConclusionsOur results revealed that maternal arrhythmia may be a diagnostic factor for NAIS in neonates with seizures. Early brain MRI is essential in neonates with seizures and findings of low MCA-RI, high MCA-MnV, or high left–right difference in CBFVs to distinguish between NAIS and non-NAIS.     

Postictal Subcortical Restricted Diffusion in a Child With Focal Symptomatic Epilepsy

BackgroundDiffusion abnormalities on MRI are well described after prolonged seizures. However, isolated, focal, subcortical restricted diffusion is uncommon.PatientA girl of Kurdish descent experienced focal-onset epilepsy secondary to a left thalamic infarction at age 3 years. At age 6 years, she developed status epilepticus in the context of a febrile illness.ResultsFour days after the seizure, she had neurological deterioration including involuntary posturing movements and irritability. A brain MRI revealed left hemisphere subcortical restricted diffusion, predominantly in the frontal and occipital regions. She experienced persistent right hemiparesis for 2 months after the initial seizure.ConclusionsThis presentation is reminiscent of acute encephalopathy with biphasic seizures and late reduced diffusion, a syndrome thus far reported almost exclusively in Japan. This represents one of the few documented examples of acute encephalopathy with biphasic seizures and late reduced diffusion in an individual not of east Asian descent.     

Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis

BackgroundThe MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients’ quality of life.CaseA 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient’s clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient’s refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death.ConclusionThe pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and β-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered.     

Neurological prognostic factors for human herpes virus 6/7-associated acute encephalopathy in children: A single-center study

AimTo identify prognostic factors for severe neurological sequelae and epileptic seizures in children with human herpes virus (HHV) 6/7-associated acute encephalopathy (AE).MethodsWe retrospectively studied pediatric cases of HHV6/7-associated AE between April 2011 and March 2021. Neurological sequelae were assessed using the Pediatric Cerebral Performance Category scale (PCPC) and the presence of epileptic seizures 1 year after onset. We investigated the prognostic factors between the non-severe sequelae group (PCPC scores ≤ 2) and severe sequelae group (PCPC scores ≥ 3) in patients without severe neurological complications before onset.ResultsForty patients, ranging from 4 to 95 months old, were included. AE with biphasic seizures and late reduced diffusion were the most common types of encephalopathy (n = 28). Among the 36 patients evaluated neurological sequelae, 17, nine, eight, and two were categorized as PCPC 1, 2, 3 and 4, respectively. Epileptic seizures were observed in nine patients. In the severe sequelae group, significantly more cases with coma in the acute phase and thalamic lesions on MRI and higher serum aspartate aminotransferase, alanine aminotransferase (ALT), and lactate dehydrogenase levels were observed. Multivariate analysis showed a significant between-group difference in the rate of coma (p = 0.0405). Patients with epileptic seizures had a higher rate of coma and thalamic lesions and higher serum ALT and urinary beta 2-microglobulin levels, but there was no significant difference in the multivariate analysis.ConclusionsIn HHV6/7-associated AE, coma was a significant prognostic factor for severe neurological sequelae.     

Seizures and cerebral infarction in the full-term newborn

Cerebral arterial infarction is a more common cause of neonatal seizures than has been previously appreciated. In 50 full-term newborns with seizures studied, 7 had cerebral infarction which was the second most common definable cause of seizures. We describe these 7 full-term infants with cerebrovascular accidents who presented with focal or generalized seizures. Obstetrical histories were normal in 5 of these patients. Their neurological examinations demonstrated lethargy and generalized hypotonia. Electroencephalograms demonstrated focal abnormalities in 4 infants. Computed tomographic scans in the first week of life showed infarctions in 6 newborns and in another at age 6 months. Neonatal stroke should be considered as a cause of seizures in a full-term newborn in spite of a normal obstetrical history and a nonfocal neurological examination.     

Two types of early epileptic encephalopathy in a Pitt-Hopkins syndrome patient with a novel TCF4 mutation

IntroductionPitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by mutations in TCF4. Seizures have been found to vary among patients with PTHS. We report the case of a PTHS patient with a novel missense mutation in the gene TCF4, presenting with two types of early epileptic encephalopathy.Case reportThe patient was a Japanese boy. His first seizure was reported at 17 days of age, with twitching of the left eyelid and tonic-clonic seizures on either side of his body. An ictal electroencephalogram (EEG) showed epileptic discharges arising independently from both hemispheres, occasionally resembling migrating partial seizures of infancy (MPSI) that migrated from one side to the other. Brain magnetic resonance imaging revealed agenesis of the corpus callosum. His facial characteristics included a distinctive upper lip and thickened helices. His seizures were refractory, and psychomotor development was severely delayed. At the age of 10 months, he developed West syndrome with spasms and hypsarrhythmia. After being prescribed topiramate (TPM), his seizures and EEG abnormalities dramatically improved. Also, psychomotor development progressed. Whole-exome sequencing revealed a novel de novo missense mutation in exon 18 (NM_001083962.2:c.1718A > T, p.(Asn573Ile)), corresponding to the basic region of the basic helix-loop-helix domain, which may be a causative gene for epileptic encephalopathy.ConclusionsTo our knowledge, this is the first report of a patient with PTHS treated with TPM, who presented with both MPSI as well as West syndrome. This may help provide new insights regarding the phenotypes caused by mutations in TCF4.     

Refractory status epilepticus with fever due to mumps vaccine-induced encephalitis caused secondary encephalopathy mimicking acute encephalopathy with biphasic seizures and late reduced diffusion

BackgroundEncephalitis due to vaccination for mumps is a rare complication that occurs in 0.00004% of recipients, and there has been no report of serious neurological sequelae. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported as the most frequent type among acute encephalopathy syndromes in the pediatric population in Japan. There has been no report of AESD caused by vaccinations.Case presentationWe present the clinical course of a 1-year and 10-month-old boy who had no preexisting condition, and developed mumps vaccine-induced severe primary encephalitis. Refractory status epilepticus due to encephalitis persisted for 16 h and resulted in secondary encephalopathy as a form of AESD mimic. He had serious neurological sequelae, such as West syndrome, transient spastic tetraplegia, and intellectual disability, despite intensive treatments.DiscussionThe presented boy is the first patient to develop mumps vaccine-induced primary encephalitis with severe central nervous system (CNS) damage. Screening of the immunological background in the presented patient revealed no abnormalities; therefore, it is unclear why he developed such severe adverse events. In patients with acute encephalitis caused by the herpes simplex virus 1, inborn immune errors in CNS based on mutations in single genes are involved in its pathophysiology. Consequently, some immunogenetic alterations could be found by further analysis in the presented patient.     

Age at onset of seizures in young children

Age at onset of seizures in young children and its relationship to factors such as prior neurological status and neurological outcome were examined. Of 52,360 children, 39,270 of whom were followed for the full 7 years, a total of 2,635 experienced one or more seizures between birth and 7 years of age. The incidence of nonfebrile convulsions was highest in the first year of life, especially in the first month. Children with neonatal seizures who later developed nonfebrile seizures did so early, two-thirds by 6 months and three-quarters by 1 year of age. Children with neurological or developmental abnormality assessed in the first year of life did not have their first seizure earlier than children without abnormality. Neurological abnormality in the first year of life before any seizure, and the presence of minor motor seizures, were associated with an increased rate of mental retardation and cerebral palsy at age 7, but early age at onset appeared to have little prognostic value regarding intellectual function, cerebral palsy, and epilepsy.     

The results of checking a scoring system for neonatal seizures

We report the result of checking a scoring system for neonatal seizures in which information from the EEG, etiology, neurological examination, seizure type and birth weight are combined to predict neurological sequelae and to make decisions about treatment. The results for two samples are presented and compared. The first sample included 96 neonates; 103 neonates were evaluated in the second sample, yielding data from 199 neonates in the combined samples. The scoring system served to separate neonates who had neurological sequelae at age 10 months or more from those who did not. In addition, the scoring system provided an excellent guide for treatment of neonatal seizures. Neonates with scores less than or equal to 4 can be safely discharged from the hospital without anticonvulsant therapy. At age three months a score of less than or equal to 5 can be used as a guideline for discontinuing anticonvulsant therapy.     

Cerebral dominance for speech and handwriting of patients with cortical vascular malformations

Abstract

Lateralization of speech dominance was established using amobarbital for 22 patients with vascular malformations lateralized to the left cerebral hemisphere. Patients' histories were negative for clinically evident neurological events (e.g., seizures or hemorrhage) prior to adulthood. The vascular lesions were categorized as high flow arteriovenous malformations (AVMs) (n = 4), low flow AVMs (n = 6), cavernous hemangiomas (n = 10), or venous angiomas (n = 2) by reviewing angiographic findings and surgical pathology for those patients whose lesions were excised. Three of the malformations encroached upon primary language areas. The frequency of right hemisphere speech dominance was not significantly elevated in comparison with the normal population, even though the incidence of nonright-handedness was. Ninety-five percent of the patients were left hemisphere dominant for speech: only one patient, with a parietal lobe cavernous hemangioma, was found to be right hemisphere dominant for speech. This malformation did not involve the primary language areas. These findings suggest that vascular malformations do not affect speech dominance as readily as other neurological diseases, but frequently affect manual dominance.     

颅内成血管细胞瘤术前栓塞术的有效性和安全性评价

目的评价颅内成血管细胞瘤栓塞剂术前栓塞术的有效性和安全性。方法选取2009年10月~2013年10月颅内成血管细胞瘤患者54例,行术前栓塞剂栓塞术治疗的患者24例作为观察组,另外30例采用传统手术进行治疗的患者作为对照组。结果观察组与对照组患者基本情况无统计学意义,具有可比性;观察组术中出血量为335±21 ml,对照组为540±32 ml,两组比较差异具有统计学意义(P=0.0010.05);观察组手术时间为8.35h,对照组手术时间为11.2 h,两组比较差异无统计学意义(P0.05);观察组患者23(95%)例为部分栓塞;观察组术后并发症脑梗塞、再出血、神经功能缺失各1例,发生率为12.5%,对照组术后并发症脑水肿、神经功能缺失各1例,发生率为6.7%,两组相比较差异无统计学意义(P=0.230.05)。结论使用术前栓塞术治疗颅内成血管细胞瘤的患者栓塞程度较高,手术中出血量显著减少;术后再出血、脑梗塞、神经功能缺失、脑水肿等并发症无显著性增加,具有较好的有效性和安全性,可能作为治疗成血管细胞瘤的一种方式。     

Reversible cerebral vasoconstriction syndrome identification of prognostic factors

Object

: Reversible cerebral vasoconstriction syndrome (RCVS) is described as a clinical and radiological entity characterized by thunderclap headaches, a reversible segmental or multifocal vasoconstriction of cerebral arteries with or without focal neurological deficits or seizures. The purpose of this study is to determine risk factors of poor outcome in patients presented a RCVS.

Methods

A retrospective multi-center review of invasive and non-invasive neurovascular imaging between January 2006 and January 2011 has identified 10 patients with criterion of reversible segmental vasoconstriction syndrome. Demographics data, vascular risks and evolution of each of these patients were analyzed.

Results

Seven of the ten patients were females with a mean age of 46 years. In four patients, we did not found any causative factors. Two cases presented RCVS in post-partum period between their first and their third week after delivery. The other three cases were drug-induced RCVS, mainly vaso-active drugs. Cannabis was found as the causative factor in two patient, Sumatriptan identified in one patient while cyclosporine was the causative agent in also one patient. The mean duration of clinical follow-up was 10.2 months (range: 0–28 months). Two patients had neurological sequelae: one patient kept a dysphasia and the other had a homonymous lateral hemianopia. We could not find any significant difference of the evolution between secondary RCVS and idiopathic RCVS. The only two factors, which could be correlated to the clinical outcome were the neurological status at admission and the presence of intraparenchymal abnormalities (ischemic stroke, hematoma) in brain imaging.

Conclusions

Fulminant vasoconstriction resulting in progressive symptoms or death has been reported in exceptional frequency. Physicians had to remember that such evolution could happen and predict them by identifying all factors of poor prognosis (neurological status at admission, the presence of intraparenchymal abnormalities).     

Subcortical infarction in a young adult with Hunter syndrome

IntroductionHunter syndrome (mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal storage disease caused by deficiency of iduronate-2-sulfatase. Recently, stroke caused by embolization with Hunter syndrome has been reported. Here, we report the case of a 23-year-old Japanese man with Hunter syndrome who developed subcortical infarction by the mechanism similar to branch atheromatous disease (BAD).Case presentationHe had been treated with idursulfase supplementation. He presented with left-sided weakness and conjugate eye deviation to the right, and was diagnosed with branch atheromatous disease affecting the right corona radiata, based on MRI findings. The patient was treated with argatroban and aspirin. Magnetic resonance angiography demonstrated no evidence of luminal narrowing of the cerebral arteries. T1-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging revealed thickened middle cerebral artery. The patient had markedly low flow-mediated vasodilation, suggesting impaired vasodilation in response to nitric monoxide.ConclusionThe arterial wall thickening and impaired vasodilation in the cerebral arteries related to subcortical infarction. We should clarify the mechanism of cerebral infarction in Hunter syndrome patients.