A case of mild CADASIL patient with a novel heterozygous NOTCH3 variant

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease caused by mutations in the neurogenic locus notch homolog protein 3 (NOTCH3) gene. The spectrum of clinical manifestations is broad, ranging from asymptomatic to typical ischemic stroke, and mainly depends on the location of the mutations. We describe the case of a 76-year-old female without apparent neurological deficits. However, brain magnetic resonance imaging revealed confluent lesions in the white matter. Direct sequencing of the NOTCH3 gene revealed a novel pathogenic mutation, c.811T>A, which results in a mild phenotype. Therefore, this report will expand the current knowledge in regards to the mutations that can cause CADASIL.

Neuronal Intranuclear Inclusion Disease with Abnormal Peripheral Nerve Conduction

A 70-year-old female presented with progressive gait disturbance. Neurologic examination revealed sensory impairment, hyporeflexia, and sensory ataxia. Nerve conduction study demonstrated mildly decreased velocity in motor nerves. Brain magnetic resonance imaging showed high signal intensities in the corticomedullary junction on diffusion weighted imaging. Neurocognitive function test implied mild cognitive impairment. Based on eosinophilic intranuclear inclusions in pathology, neuronal intranuclear inclusion disease was confirmed. Neuronal intranuclear inclusion needs to be considered when abnormal nerve conduction studies are consistent with abnormal brain imaging findings.

Two Korean siblings with autosomal recessive spinocerebellar ataxia 20 caused by homozygous variants in SNX14

Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by ataxia, intellectual disability, cerebellar atrophy, macrocephaly, coarse face, and absent speech. It is caused by lossof-function mutations in SNX14. To date, all cases with homozygous pathogenic variants have been identified in consanguineous families. This report describes the first Korean cases of SCAR20 family caused by homozygous variants in SNX14. Two siblings were referred to our clinic because of severe global developmental delay. They presented similar facial features, including a high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose. Because the older sibling was unable to walk and newly developed ataxia, repeated brain magnetic resonance imaging (MRI) was performed at the age of 4 years, revealing progressive cerebellar atrophy compared with MRI performed at the age of 2 years.The younger sibling’s MRI revealed a normal cerebellum at the age of 2 years. Whole-exome sequencing was performed, and homozygous variants, such as c.2746-2A>G, were identified in SNX14 from the older sibling. Sanger sequencing confirmed homozygous SNX14 variants in the two siblings as well as a heterozygous variant in both parents. This report extends our knowledge of the phenotypic and mutational spectrum of SCAR20. We also highlight the importance of deep phenotyping for the diagnosis of SCAR20 in individuals with developmental delay, ataxia, cerebellar atrophy, and distinct facial features.

Practical Diagnostic Approach to Myopathy / 대한신경근육질환학회지

Hereditary myopathy is characterized by the weakness of skeletal muscles and is associated with various genetic defects. The efficiency of a genetic diagnosis has been archived with wide application of next-generation sequencing (NGS) recently. However, the establishment of the correct diagnosis of hereditary myopathy is still challenging and sometimes requires other methods of genetic analysis besides NGS. Therefore, clinicians still have crucial roles in analyzing the causative genes. In this article, we introduced the genetic analysis approach in the clinical field.

Pathologically and Genetically Diagnosed Subclinical Symptomatic Duchenne Muscular Dystrophy Carrier: Broadened Spectrum of Clinical Phenotype

A 29-year-old female presented with an elevated level of serum creatine kinase without subjective weakness. Neurologic examination showed the subtle motor weakness of the right arm. Muscle biopsy showed dystrophic changes and a mosaic pattern of dystrophin expression. The diagnosis was confirmed by multiplex ligation-dependent probe amplification and whole-exome sequencing, revealing heterozygous deletion of exon 44 in the DMD gene. Here, we introduce a subclinical symptomatic Duchenne muscular dystrophy carrier, which broadens the clinical spectrum of phenotype.

Pathologically and Genetically Diagnosed Subclinical Symptomatic Duchenne Muscular Dystrophy Carrier: Broadened Spectrum of Clinical Phenotype

A 29-year-old female presented with an elevated level of serum creatine kinase without subjective weakness. Neurologic examination showed the subtle motor weakness of the right arm. Muscle biopsy showed dystrophic changes and a mosaic pattern of dystrophin expression. The diagnosis was confirmed by multiplex ligation-dependent probe amplification and whole-exome sequencing, revealing heterozygous deletion of exon 44 in the DMD gene. Here, we introduce a subclinical symptomatic Duchenne muscular dystrophy carrier, which broadens the clinical spectrum of phenotype.

A Vanishing White Matter Disease Case with a Homozygous Point Mutation in the EIF2B2 Gene Assessed by the Whole-Exome Sequencing

A 30-year-old female patient presented with a progressive gait disturbance, who had been previously diagnosed for cataract and ovarian failure. Brain magnetic resonance imaging showed a high signal intensity of white matter in fluid attenuated inversion recovery and low signal intensity in brain volume imaging, suggesting demyelinating leukodystrophy. Genetic analysis confirmed the pathogenic homozygous mutations c.245T>A in the EIF2B2 gene, which is associated with vanishing white matter disease.

Practical Diagnostic Approach to Myopathy / 대한신경근육질환학회지

Hereditary myopathy is characterized by the weakness of skeletal muscles and is associated with various genetic defects. The efficiency of a genetic diagnosis has been archived with wide application of next-generation sequencing (NGS) recently. However, the establishment of the correct diagnosis of hereditary myopathy is still challenging and sometimes requires other methods of genetic analysis besides NGS. Therefore, clinicians still have crucial roles in analyzing the causative genes. In this article, we introduced the genetic analysis approach in the clinical field.

Olfactory and Gustatory Dysfunction in a COVID-19 Patient with Ankylosing Spondylitis Treated with Etanercept: Case Report

The neurologic manifestations concerning coronavirus disease 2019 (COVID-19) are highly penetrated. Anosmia and ageusia are one of the common acute neurologic symptoms, which develop in the early stage of COVID-19. However, it is not reported that how immunosuppressive agents affect these symptoms. We report olfactory and gustatory dysfunctions in a patient with ankylosing spondylitis (AS) treated with etanercept during COVID-19. A 53-year-old female showing AS controlled with tumor necrosis factor-α inhibitor, etanercept, had been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, presenting cough and rhinorrhea. One month after diagnosis, she complained about hyposmia and hypogeusia two days before the seronegative conversion of SARS-CoV-2, which were confirmed by a neurological examination. We speculate that the etanercept may have delayed the development of olfactory and gustatory dysfunction in the patient.

Axonal Charcot-Marie-Tooth case with a novel heterozygous variant in MFN2 assessed by the MutationDistiller

Charcot-Marie-Tooth (CMT) disease can be divided mainly into demyelination and axonopathy based on the results of the electrophysiological study. Mitofusin 2, encoded by MFN2 gene, has a crucial role in the fusion of mitochondria, which is known to associate with CMT type 2A as one of the axonal forms. We describe a 44-year-old man with progressive weakness on bilateral legs after noticing foot drop in his early teen. When we examined him at 45 years of age, he presented atrophy on entire legs and with distal muscle weakness on limbs. The nerve conduction study revealed severely decreased amplitude on motor nerve ranging from 0.2 to 4.5 mV, while conduction velocity remained more than 30.4 m/s. The whole-exome sequencing revealed a novel variant c.2228G>T in MFN2 by efficient genetic analysis tool, MutationDistiller. This report will not only expand the mutation spectrum of CMT2A but also introduce a time-saving genetic analysis tool.

Axonal Charcot-Marie-Tooth case with a novel heterozygous variant in MFN2 assessed by the MutationDistiller

Charcot-Marie-Tooth (CMT) disease can be divided mainly into demyelination and axonopathy based on the results of the electrophysiological study. Mitofusin 2, encoded by MFN2 gene, has a crucial role in the fusion of mitochondria, which is known to associate with CMT type 2A as one of the axonal forms. We describe a 44-year-old man with progressive weakness on bilateral legs after noticing foot drop in his early teen. When we examined him at 45 years of age, he presented atrophy on entire legs and with distal muscle weakness on limbs. The nerve conduction study revealed severely decreased amplitude on motor nerve ranging from 0.2 to 4.5 mV, while conduction velocity remained more than 30.4 m/s. The whole-exome sequencing revealed a novel variant c.2228G>T in MFN2 by efficient genetic analysis tool, MutationDistiller. This report will not only expand the mutation spectrum of CMT2A but also introduce a time-saving genetic analysis tool.

Presenting Internuclear Ophthalmoplegia with Peripheral Type Facial Palsy: Seven-and-a-Half Syndrome

A 49-year-old male presented with horizontal binocular diplopia without facial pain or skin lesion. Limitation of medial gaze in the left eye was revealed on neurological examination, which is accompanied by peripheral facial nerve palsy ipsilaterally. The diagnosis had been made based on the diffusion restriction lesion of left pontine tegmentum. We may denominate a “seven-and-a-half syndrome” and clinician should maintain a high level of awareness of the various syndromes associated with pontine lesions.

Optic Neuropathy with Diffusion Weighted High Signal Changes in Optic Nerve

No abstract available.

An Anti-aquaporin 4 Positive Longitudinally Extensive Transverse Myelitis with Antecedent Necrotizing Pneumonia Associated with S. aureus

A 53-year-old male patient presented with quadriparesis during pulmonological hospitalization for the treatment of S. aureus associated necrotizing pneumonia. He was diagnosed with the aquaporin-4 (AQP4) positive longitudinally extensive transverse myelitis from pons to T3 level. Despite the administration of intravenous methylprednisolone and plasma exchange with appropriate antibiotics, the patient's neurological condition deteriorated and he died. Our case implies that an S. aureus associated necrotizing pneumonia can trigger an AQP4 positive neuromyelitis optica spectrum disorder and contribute to the devastating course.

X-linked Charcot-Marie-Tooth disease case with a novel missense mutation in GJB1 gene

X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is caused by the mutation in GJB1 gene, characterized by the transient central nervous system involvement and long standing peripheral polyneuropathy which does not fulfill the criteria of demyelination or axonopathy. We describe a 37-year-old man with progressive bilateral leg weakness since his early teen. He suffered transient right hemiparesis, followed by quadriparesis at 14 years of age. When we examined him at 37 years of age, he presented a distal muscle weakness on lower extremities with a sensory symptom. The nerve conduction study demonstrated a motor conduction velocity between 26 and 49 m/s. The whole exome sequencing revealed a novel variant c.136 G>A in GJB1. This report will raise awareness in this rare disease, which is frequently misdiagnosed early in its course.

Stigma in Patients with Drug Refractory Epilepsy: the Risk Factor, Psychiatric Comorbidities, and Quality of Life / 대한간질학회지

PURPOSE: Stigma is more likely to be reported by people with epilepsy with frequent seizures and associated with various physical and psychosocial factors. We determined risk factors associated with stigma, and investigated the impact of felt stigma on psychiatric comorbidities and quality of life (QOL) in patients with drug refractory epilepsy (DRE). METHODS: Patients with DRE of partial onset, who experienced a failure of at least two antiepileptic drugs (AEDs) and at least 1/month of seizure attack for recent 6 months, were enrolled in the study. We divided patients into two groups according to the presence of stigma. We compared demographic and clinical variables, mood, anxiety, psychiatric symptoms, and QOL between two groups. RESULTS: Among 75 patients with DRE of partial onset, 34 patients (45%) had stigma. Risk factors associated with stigma were age, history of psychiatric disease, duration of epilepsy, and duration of AEDs intake. However, seizure frequency was not associated with the occurrence of stigma. Mood, anxiety, and psychiatric symptoms were significantly higher in patients with stigma than those without stigma. QOL was significantly lower in patients with stigma than those without stigma. CONCLUSIONS: A longer duration of epilepsy with previous history of psychiatric diseases may be indispensable for the occurrence of stigma in patients with DRE. Early detection and appropriate treatment of psychiatric comorbidities can lessen the degree of stigma and improve QOL.

Callosal and Cortical Involvement in Acute Marchiafava-Bignami Disease

No abstract available.

A Case of Epilepsy Exhibiting a Severe, Dose-Dependent, Memory Deficit after Zonisamide Administration / 대한간질학회지

Zonisamide (ZNS) has been proven as a safe, effective, and well-tolerated antiepileptic drug. We report an epilepsy patient who had a severe, dose-dependent, memory deficit after ZNS administration. A 65-year-old man visited our epilepsy clinic due to the occurrence of nocturnal convulsions. Despite the absence of seizures, he developed a severe impairment of verbal and visual memory functions after the increment of ZNS dosage from 200 mg/day to 300 mg/day. We substituted 1,000 mg/day valproic acid for ZNS. His cognitive performances were returned to original levels.

Longitudinal Assessment of Cognitive Function in Patients with Juvenile Myoclonic Epilepsy / 대한간질학회지

BACKGROUND AND PURPOSE: We investigated the cognitive change of patients with juvenile myoclonic epilepsy (JME) after a long-term antiepileptic drug(s) (AED) administration to clarify the cause of cognitive impairment. METHODS: Thirty-three patients with JME who were newly diagnosed or did not take any AED for at least 6 months prior to the beginning of the study were included. We conducted neuropsychological tests at baseline and after at least 12 months of AEDs trial. Forty healthy controls were acquired according to age- and education-match to patients with JME. We compared the differences of neuropsychological outcomes among them. We tried to identify the determinants for cognitive performances after AEDs trial. RESULTS: Twenty-seven patients completed the second neuropsychological tests. Seizure frequency and EEG abnormality were significantly decreased after AEDs intake. The Number of epileptiform discharges (EDs) on EEG tended to be decreased at last visit. However, cognitive performances between baseline and follow-up period were not different. Cognitive measures of baseline and follow-up period were worse than those of controls in list learning, forward digit span, backward digit span, Trail Making Test, and verbal fluency. Cognitive performances of follow-up period in the JME group were not correlated with age at seizure onset, duration of epilepsy, seizure recurrence, EEG abnormality, and type of AEDs. CONCLUSIONS: Cognitive performances of JME were not recovered to the level of healthy controls despite the control of seizures and EDs by AEDs. Therefore, cognitive impairment of JME may be due to irreversible, disease-related characteristics.

Cognitive Profiles of Lamotrigine in Epilepsy Patients : A Comparative Study with Valproate / 대한간질학회지

PURPOSE: To identify cognitive effects of lamotrigine (LTG) compared with valproate (VPA) in epilepsy patients after 1 year of treatment. METHODS: Cognitive tests and subjective complaints of 22 patients with LTG monotherapy (50-200 mg/day) were retrospectively compared with those of 22 patients with VPA monotherapy (500-1300 mg/day) at 1 year of medication. RESULTS: LTG group did not show any significant difference in the performance of cognitive tests compared with VPA group. The incidence of cognitive complaints between two drugs were also not different. Both groups showed a better performance of list learning and Trail Making Test type A after antiepileptic drug medication. CONCLUSION: The impact of LTG and VPA monotherapy on cognitive functioning is similar. Both drugs may not be harmful or rather slightly beneficial for cognitive functions.