Location-based selection of the surgical approach to preserve the hippocampus in lesion-associated temporal lobe epilepsy.

BACKGROUND AND OBJECTIVES: Surgical resections for lesions associated with intractable temporal lobe epilepsy (TLE) offers good seizure outcomes.However, the necessity of hippocampectomy in addition to lesionectomy is controversial, especially when the hippocampus is not involved by the lesion. Lesionectomy alone, preserving the hippocampus by an appropriate surgical approach, might offer good seizure outcomes while maintaining neurocognitive function. In the present study, the aims were to examine the surgical strategy for lesions associated with TLE and to present how to select surgical approaches to preserve the hippocampus. METHODS: A total of 22 consecutive lesion-associated TLE patients who underwent lesionectomy alone were retrospectively reviewed. The surgical approach, transsylvian, transorbital, subtemporal, supracerebellar transtentorial, or transcortical approach, was selected based on the location of the lesion. Postoperative seizure outcomes were classified by the Engel classification. Neurocognitive outcomes were assessed before and after surgery if possible. The pathology, the extent of resection, and lesion recurrence were reviewed. RESULTS: The transsylvian approach was selected in six patients, the transorbital approach in one patient, the subtemporal approach in three patients, the supracerebellar transtentorial approach in five patients, and the transcortical approach in seven patients. Eighteen of 22 (81.8 %) patients achieved Engel's class I or II good seizure outcomes. No patients had neurocognitive deterioration after surgery. Twelve patients had various types of brain tumors, and ten patients had non-tumorous lesions. Gross total resection was achieved in 21 patients. All patients had no recurrence. CONCLUSION: For patients with lesion-associated TLE, lesionectomy alone by the appropriate surgical approach offers satisfactory seizure outcomes while preserving hippocampus.

Higher incidence of acute symptomatic seizures in probable antibody-negative pediatric autoimmune encephalitis than in major antibody-positive autoimmune encephalitis.

Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p < 0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings.

Characteristics of malignant brain tumor-associated epileptic spasms.

Although epilepsy is the most common comorbidity of brain tumors, epileptic spasms rarely occur. Brain tumors associated with epileptic spasms are mostly low-grade gliomas. To date, few studies in the literature have reported on malignant (Grades 3-4) brain tumors associated with epileptic spasms. Thus, we aimed to investigate the characteristics of malignant brain tumor-associated epileptic spasms. We retrospectively reviewed patients with malignant brain tumors and epileptic spasms in our institution. Data on demographics, tumor histology, magnetic resonance imaging, epileptic spasm characteristics, electroencephalography, and treatment responsiveness were also collected. Six patients were included. In all cases, the brain tumors occurred in infancy in the supratentorial region and epileptic spasm onset occurred after the completion of brain tumor treatment. Anti-seizure medication did not control epileptic spasms; two patients were seizure-free after epileptic surgery. Although all patients had developmental delays caused by malignant brain tumors and their treatment, developmental regression proceeded after epileptic spasm onset. Two patients who achieved seizure-free status showed improved developmental outcomes after cessation of epileptic spasms. This is the first report of the characteristics of malignant brain tumor-associated epileptic spasms. Our report highlights a difficulties of seizure control and possibillity of efficacy of epileptic surgery in this condition. In malignant brain tumor-associated epileptic spasms, it is important to proceed with presurgical evaluation from an early stage, bearing in mind that epileptic spasms may become drug-resistant.

Total callosotomy ameliorates epileptic activity and improves cognitive function in a patient with Miller-Dieker syndrome.

Miller-Dieker syndrome (MDS) is characterized by facial abnormalities and lissencephaly and is caused by a microdeletion in the region containing the LIS1 gene at chromosome 17p13.3. We report a case in which postnatal neuroimaging revealed severe lissencephaly. A 9-month-old boy presented with infantile spasms syndrome. Because of the refractory course of seizures and continued poor vitality, total corpus callosotomy was performed at 28 months of age. Intraoperative electroencephalogram (EEG) showed that the bilateral synchronous epileptiform discharges disappeared immediately after the disconnection. Postoperatively, the epileptic spasms (ES) in clusters disappeared, and single ES followed by focal seizures became the main symptom. The patient smiled more and became more responsive to stimuli. Postoperative scalp interictal EEG showed desynchronized multifocal spike and wave discharges with a marked decrease in the bilateral synchronous spike and wave discharges. Our findings suggest that the corpus callosum is involved in the mechanism ES in clusters in MDS-associated lissencephaly, and total callosotomy could be a therapeutic option.

Changes in interhemispheric coherence after total corpus callosotomy: a scalp EEG study in children with non-lesional generalized epilepsy.

PURPOSE: Coherence analysis in electroencephalography (EEG) allows measurement of the degree of consistency of amplitude between pairs of electrodes. Theoretically, disconnective epilepsy surgery should decrease coherence between corresponding areas. The study aimed to evaluate postoperative changes in interhemispheric coherence values after corpus callosotomy (CC). METHODS: Non-lesional, drug-resistant, generalized epilepsy patients who underwent total CC were retrospectively collected. To evaluate coherence, we divided the scalp interictal EEG into "baseline" and "discharge" states after excluding periods with artifacts. Interhemispheric coherence values were obtained between eight pairs of symmetrically opposite scalp electrodes in six different frequency bands. We analyzed both pre- and postoperative EEG sessions and calculated the percentage of difference (POD) in coherence values. RESULTS: We collected 13 patients and analyzed 2496 interhemispheric coherence values. Preoperative coherence values differed significantly between baseline and discharge states (p = 0.0003), but postoperative values did not (p = 0.11). For baseline state, coherence values were decreased after CC and median POD was - 22.3% (p < 0.0001). Delta frequency showed the most decreased POD (-44.3%, p = 0.0009). Median POD was lowest in the Fp1-Fp2 pair of electrodes. For discharge state, coherence values were decreased after CC and median POD was - 24.7% (p < 0.0001). Delta frequency again showed the most decreased POD (-55.9%, p = 0.0016). Median POD was lowest in the F7-F8 pair. CONCLUSION: After total CC, interhemispheric coherence decreased significantly in both baseline and discharge states. The most decreased frequency band was the delta band, which may be used as a representative frequency band in future studies.

Efficacy and safety of ketamine for pediatric and adolescent super-refractory status epilepticus and the effect of cerebral inflammatory conditions.

OBJECTIVE: To investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology. METHODS: This retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups. RESULTS: The median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8-15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration. CONCLUSIONS: Ketamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.

Abnormal axonal development and severe epileptic phenotype in Dynamin-1 (DNM1) encephalopathy.

Dynamin-1 (DNM1) is involved in synaptic vesicle recycling, and DNM1 mutations can lead to developmental and epileptic encephalopathy. The neuroimaging of DNM1 encephalopathy has not been reported in detail. We describe a severe phenotype of DNM1 encephalopathy showing characteristic neuroradiological features. In addition, we reviewed previously reported cases who have DNM1 pathogenic variants with white matter abnormalities. Our case presented drug-resistant seizures from 1 month of age and epileptic spasms at 2 years of age. Brain MRI showed no progression of myelination, progression of diffuse cerebral atrophy, and a thin corpus callosum. Proton magnetic resonance spectroscopy showed a decreased N-acetylaspartate peak and diffusion tensor imaging presented with less pyramidal decussation. Whole-exome sequencing revealed a recurrent de novo heterozygous variant of DNM1. So far, more than 50 cases of DNM1 encephalopathy have been reported. Among these patients, delayed myelination occurred in two cases of GTPase-domain DNM1 encephalopathy and in six cases of middle-domain DNM1 encephalopathy. The neuroimaging findings in this case suggest inadequate axonal development. DNM1 is involved in the release of synaptic vesicles with the inhibitory transmitter GABA, suggesting that GABAergic neuron dysfunction is the mechanism of refractory epilepsy in DNM1 encephalopathy. GABA-mediated signaling mechanisms play important roles in axonal development and GABAergic neuron dysfunction may be cause of white matter abnormalities in DNM1 encephalopathy.

Localized focal cortical dysplasia type II: seizure freedom with lesionectomy guided by MRI and FDG-PET.

OBJECTIVE: The authors perform thorough, noninvasive presurgical evaluations for intractable epilepsy at their center and avoid unnecessary intracranial EEG when possible. The purpose of this study was to clarify the appropriateness of their lesion-oriented surgical strategy for localized focal cortical dysplasia (FCD) type II. METHODS: Fifty-one patients with pathologically proven localized FCD type II who were followed for at least 1 year after surgery were included. Patients with FCD type II with lobar or multilobar distribution were excluded. The results of presurgical evaluations, including thin-slice 3-T MRI, FDG-PET, and ictal SPECT, as well as surgical procedures and postoperative seizure and functional outcomes, were examined retrospectively. RESULTS: MRI was positive in 46 (90%) of 51 patients, and FDG-PET revealed localized hypo- or hypermetabolism in 47 (92%) of 51 patients. Ictal SPECT revealed concordant hyperperfusion in 37 of 42 patients examined. Intracranial EEG was used in only 13 patients (25%), including 5 with negative MRI results and 4 with subtle MRI findings. Of the 15 patients with FCD in the vicinity of eloquent (sensorimotor and language) areas, intracranial EEG was used in 4. Lesionectomy was performed in all 51 patients. Intraoperative electrocorticography (ECoG) was performed in 8 patients, but the findings were not used to tailor the extent of resection. Postoperative seizure outcomes were Engel class I in 47 patients (92%) and Ia in 45 (88%). In the 15 patients with FCD in the vicinity of eloquent areas, 13 (87%) achieved a class I outcome. Predictive factors for favorable seizure outcome were complete resection of the MRI lesion (p = 0.006) and frontal lobe surgery (p = 0.012). Postoperative neurological deficits were noted in only 4 (27%) of 15 patients with FCD in the vicinity of eloquent areas. All 5 MRI-negative patients achieved an Engel class I outcome. CONCLUSIONS: In most of the patients with localized FCD type II, MRI and/or FDG-PET detected the localized abnormality. Lesionectomy without intracranial EEG led to seizure freedom in most cases. Even when lesions were in the vicinity of eloquent areas, seizure and functional outcomes were favorable. Intraoperative ECoG may thus be unnecessary. Complete resection of the lesion is essential for favorable seizure outcome in MRI-positive patients. In MRI-negative patients, surgery with intracranial EEG guided by FDG-PET provided seizure-free outcomes.

CDKL5 deficiency causes epileptic seizures independent of cellular mosaicism.

OBJECTIVE: In a study using a mouse model of CDKL5 deficiency disorder (CDD), seizures are specific to female mice heterozygous for Cdkl5 mutations and not observed in hemizygous knockout males or homozygous knockout females. The aim of this study was to examine whether the clinical phenotype of patients with CDD can be impacted by the type of genetic variant. METHODS: Eleven CDD patients (six females and five males) were included in this study. The molecular diagnosis of hemizygous male patients was performed using digital PCR and their clinical phenotypes were compared with those of patients with mosaic or heterozygous CDKL5 variants. The severity of clinical phenotypes was graded by using CDKL5 Developmental Score and the adapted version of the CDKL5 Clinical Severity Assessment. The effect of cellular mosaicism on the severity of CDD was studied by comparing the clinical characteristics and comorbidities between individuals with hemizygous and mosaic or heterozygous CDKL5 variants. RESULTS: One of the five male patients was mosaic for the CDKL5 variant. All patients developed seizures irrespective of their genetic status of the pathogenic variant. However, cellular mosaicism of CDKL5 deficiency was associated with lesser severity of other comorbidities such as feeding, respiratory, and visual functional impairments. SIGNIFICANCE: This study provided evidence that cellular mosaicism of CDKL5 deficiency was not necessarily required for developing epilepsy. CDD patients not only exhibited clinical features of epilepsy but also exhibited the developmental consequences arising directly from the effect of the CDKL5 pathogenic variant.

A case of focal cortical dysplasia type IIa with pathologically suspected bilateral Rasmussen syndrome.

BACKGROUND: Rasmussen syndrome (RS) is a rare neurological disorder characterized by unilateral chronic inflammation, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. There has been no detailed pathological evaluation or finding, including focal cortical dysplasia, for bilateral RS. CASE REPORT: A 13-year-old boy presented with status epilepticus with focal to bilateral tonic clonic seizure starting from the left upper limb. At the age of 15, epilepsia partialis continua of the right face and upper extremities appeared, and MRI showed hemispheric abnormal signal intensities with left frontal lobe predominance. Three months later, MRI showed extensive abnormal signal intensities in the right occipitoparietal and left temporal lobes. Tacrolimus was useful in preventing recurrence. Because the seizures were intractable, a corpus callosotomy was performed at 16 years along with a concurrent brain biopsy from the bilateral lateral frontal cortices. We detected dysmorphic neurons in addition to inflammatory changes suspicious for RS, leading to a diagnosis of focal cortical dysplasia (FCD) type Ⅱa and suspected bilateral RS. Total callosotomy and vagus nerve stimulation were not sufficiently effective. CONCLUSIONS: In bilateral RS, FCD may be present in both cerebral hemispheres. In the current case, an autoimmune response to dysmorphic neurons may have contributed to the pathogenesis of intense inflammation.

De novo ATP1A3 variants cause polymicrogyria.

Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo ATP1A3 variants in eight patients. Mutated ATP1A3 causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS). However, our patients showed no clinical features of AHC, RDP, or CAPOS and had a completely different phenotype: a severe form of polymicrogyria with epilepsy and developmental delay. Detected variants had different locations in ATP1A3 and different functional properties compared with AHC-, RDP-, or CAPOS-associated variants. In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis. We propose a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.

Preliminary report for Epilepsia Open A case of West syndrome with severe global developmental delay and confirmed KIF5A gene variant.

Objective: Kinesin family member 5A (KIF5A) is a molecular motor protein responsible for intracellular transport, specifically in neurons. While abnormalities in the KIF5A gene have been reported in the onset of various neurological diseases, there are no studies demonstrating an association between this gene and West syndrome. Methods: In the case presented here, epileptic spasms appeared at 7 months; electroencephalogram (EEG) investigation confirmed hypsarrhythmia, resulting in a diagnosis of West syndrome. The patient exhibited peculiar facies, hypotonia, failure to thrive, and severe global developmental delay. Results: Cranial magnetic resonance imaging (MRI) revealed severe delayed myelination. 123I-iomazenil SPECT image at 7 months demonstrated decreased accumulation in bilateral areas, including the primary somatosensory and motor cortices, and the primary and association visual areas compared to an age-matched control. Whole exome sequencing analysis demonstrated a novel de novo heterozygous missense variant in KIF5A, (NM_004984.4:c.710A>T: p. Glu237Val). Significance: It was concluded that the KIF5A variant impaired the transport of GABAA receptors to the cell membrane surface, thus leading to an imbalance of these receptors between regions of the cerebrum and resulting in the onset of epilepsy.

Characteristics of internalization of NMDA-type GluRs with antibodies to GluN1 and GluN2B.

To characterize internalization of NMDA-type glutamate receptors (GluRs) by antibodies to NMDA-type GluRs, we produced rabbit antibodies to N-terminals of human GluN1 and GluN2B, and examined internalization of NMDA-type GluRs in HEK293T cells using confocal microscopy. Internalization of NMDA-type GluRs occurred from at least 10 min after incubation with antibodies to GluN1 and or GluN2B and was temperature-dependent. These findings confirm that antibodies to N-terminals of GluN1 and GluN2B present in the cerebrospinal fluid of patients with NMDAR encephalitis can mediate prompt internalization of NMDA-type GluR complexes.

Clinical and genetic characteristics of patients with Doose syndrome.

OBJECTIVE: To elucidate the genetic background and genotype-phenotype correlations for epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy (MAE) or Doose syndrome. METHODS: We collected clinical information and blood samples from 29 patients with MAE. We performed whole-exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant. RESULTS: We newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic-atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention-deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology. SIGNIFICANCE: MAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic-atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.

Chronological dynamic changes in cortico-subcortical imbalance of cerebral blood flow in a boy with CAPOS syndrome.

BACKGROUND: Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS) syndrome is a known ATP1A3-related disorder, but little has been elucidated regarding its pathophysiology. We now report two new patients, a Japanese boy and his mother with a pathogenic mutation (c.2452G>A) in ATP1A3, who were diagnosed with CAPOS syndrome. METHODS: After febrile illnesses at 7 months of age, and again at 22 months of age, the boy had a reduced level of consciousness, truncal ataxia and eye movement-disorders. The patient's 32-year-old mother may have experienced an episode of acute encephalopathy in her childhood and sustained sensorineural hearing loss. In the present study, we demonstrated chronological dynamic changes in cerebral blood flow (CBF) in the son, using serial single-photon emission computed tomography (SPECT). RESULTS: The serial CBF-SPECT findings using statistical methods showed progressive hyperperfusion in the frontal lobes, basal ganglia and thalamus, and hypoperfusion in the occipital and temporal lobes during the acute and subacute phases. Thereafter, the dynamic changes of CBF improved in the chronic but hypoperfusion in thalamus appeared to the chronic phase. CONCLUSION: The abnormal cortico-subcortical CBF may contribute to an acute encephalopathy-like condition in the acute stage of CAPOS syndrome. CAPOS syndrome is not often reported, and is possibly an under-recognized syndrome in clinically mild cases.

An unusual manifestation of Sjögren syndrome encephalitis.

Sjögren syndrome (SS) is a systemic inflammatory and autoimmune disease characterized by systemic disorders of the exocrine glands, predominantly the salivary and lacrimal glands. Here, we report a 4-year-old boy who presented with the repetition of generalized tonic-clonic seizures for 1-2 min. Initially, he was diagnosed with idiopathic autoimmune encephalitis and was treated with steroids. He was eventually diagnosed with SS based on the examination results, such as inflammatory cell infiltration into the minor salivary glands and positive serum anti-SSA/Ro antibody. Although central nervous system complications are rare in pediatric SS, this condition should be considered in the differential diagnosis when a patient presents with idiopathic autoimmune encephalitis of unknown cause. Furthermore, SS can occur in relatively young children and can present without imaging abnormalities.

Seizure freedom from temporal lobe epilepsy with mesial temporal lobe tumor by tumor removal alone without hippocampectomy despite remaining abnormal discharges on intraoperative electrocorticography: Report of two pediatric cases and reconsideration of the surgical strategy.

BACKGROUND: In the surgical treatment of temporal lobe epilepsy with mesial temporal lobe tumor, whether to remove the hippocampus aiming for a better seizure outcome in addition to removing the tumor is a dilemma. Two pediatric cases treated successfully with tumor removal alone are presented. CASE DESCRIPTION: The first case was an 11-year-old girl with a ganglioglioma in the left uncus, and the second case was a 9-year-old girl with a pleomorphic xanthoastrocytoma in the left parahippocampal gyrus. In both cases, the hippocampus was not invaded, merely compressed by the tumor. Tumor removal was performed under intraoperative electrocorticography (ECoG) monitoring. After tumor removal, abnormal discharges remained at the hippocampus and adjacent temporal cortices, but further surgical interventions were not performed. The seizures disappeared completely in both cases. CONCLUSIONS: When we must decide whether to remove the hippocampus, the side of the lesion, the severity and chronicity of the seizures, and the presence of invasion to the hippocampus are the factors that should be considered. Abnormal discharges on ECoG at the hippocampus or adjacent cortices are one of the factors related to epileptogenicity, but it is simply a result of interictal irritation, and it is not an absolute indication for additional surgical intervention.

A child with acute transverse myelitis requiring permanent pacemaker implantation.

We diagnosed a 3-year-old girl with acute transverse myelitis (ATM). She presented with weakness of the limbs and developed urination difficulty and respiratory disturbance. Magnetic resonance imaging revealed a symmetric area of high signal intensity on T2-weighted images involving the lower end of the medulla oblongata to the level of the fourth thoracic vertebra. Anti-aquaporin-4 antibody was negative. She was treated with intravenous methylprednisolone pulse therapy, immunoglobulin therapy, and plasmapheresis; however, her clinical symptoms did not change. At 10 and 20days after symptom onset, cardiac arrest occurred on postural change, requiring cardiopulmonary resuscitation. A permanent pacemaker was implanted 23days after onset. In the presence of sympathetic nerve hypofunction, relative hyperactivity of the parasympathetic nerves may have led to severe bradycardia and cardiac arrest in the presence of an inducer, such as a postural change. This is the first reported case of pacemaker implantation for management of ATM.