Evaluation of the neurofilament light chain as a biomarker in children with spinal muscular atrophy treated with nusinersen.

BACKGROUND: This study aimed to evaluate the neurofilament light chain (NfL) as a biomarker for treatment responses in children with a broad spectrum of spinal muscular atrophy (SMA) under nusinersen treatment. METHOD: We measured NfL levels in serum (sNfL) and cerebrospinal fluid (cNfL) in nusinersen-treated patients with SMA and children without neurologic disorders. Correlations between cNfL and sNfL levels and motor function scores were analyzed. RESULTS: sNfL and cNfL levels were measured in eight patients with SMA (SMA type 1, n = 3; SMA type 2, n = 5). sNfL levels were strongly correlated with cNfL levels regardless of the SMA subtype (r = 0.97, P < 0.001). Patients with SMA type 1 had higher baseline cNfL and sNfL levels before treatment initiation than those with SMA type 2 and neurologically healthy children. In patients with acute stage of SMA type 1 and 2, the NfL level rapidly decreased during the nusinersen treatment loading phase followed by stabilization at a lower plateau level. In contrast, in a patient with a chronic stage of SMA type 2, the NfL level remained within the normal range with no apparent downward trend. Motor function scores showed a tendency toward an inverse correlation with NfL levels in patients with acute stage although not in patients with chronic stage. CONCLUSIONS: cNfL and sNfL levels can be promising biomarkers for monitoring treatment response in patients within their acute stage, particularly in SMA type 1, although not in patients with a chronic stage of SMA type 2.

Seasonal Trends in the Prevalence and Incidence of Viral Encephalitis in Korea (2015-2019).

Viral infections are a common cause of encephalitis. This study investigated the relationship between the incidence of encephalitis and that of respiratory and enteric viral infections in all age groups from 2015 to 2019, using the Health Insurance Review and Assessment (HIRA) Open Access Big Data Platform. We identified monthly incidence patterns and seasonal trends using the autoregressive integrated moving average (ARIMA). The Granger causality test was used to analyze correlations between encephalitis incidence and the positive detection rate (PDR) at 1-month intervals. A total of 42,775 patients were diagnosed with encephalitis during the study period. The incidence of encephalitis was highest in the winter (26.8%). The PDRs for respiratory syncytial virus (HRSV) and coronavirus (HCoV) were associated with the trend in encephalitis diagnosis in all age groups, with a 1-month lag period. In addition, an association with norovirus was observed in patients aged over 20 years, and with influenza virus (IFV) in patients aged over 60 years. This study found that HRSV, HCoV, IFV, and norovirus tended to precede encephalitis by 1 month. Further research is required to confirm the association between these viruses and encephalitis.

Seasonal Trend of Viral Prevalence and Incidence of Febrile Convulsion: A Korea Public Health Data Analysis.

Febrile convulsion (FC) is the most common seizure disease in children, which occurs with a fever. We investigated the Korean Health Insurance Review and Assessment Service data of patients aged between 6 months and 5 years at the time of FC diagnosis. Diseases that can cause seizures with fever, such as neoplasms, metabolic disorders, nervous system disorders, cerebrovascular diseases, perinatal problems, and congenital abnormalities, were excluded. Weekly virus-positive detection rate (PDR) data were obtained from the Korea Disease Control and Prevention Agency for adenovirus, parainfluenza virus, respiratory syncytial virus (HRSV), influenza virus, coronavirus (HCoV), rhinovirus (HRV), bocavirus, metapneumovirus (HMPV), rotavirus, norovirus, and astrovirus. Using the Granger test, we then analyzed the monthly PDR and investigated the association between FC incidence and monthly PDR. We additionally identified monthly and seasonal FC incidence trends using the autoregressive integrated moving average. Between 2015 and 2019, 64,291 patients were diagnosed with FC. Annually, the incidence was the highest in May and the lowest in October. Most patients were diagnosed during the spring (26.7%). The PDRs for HRSV, HCoV, HRV, HMPV, and norovirus were associated with FC incidence after 1 month.

Hypertrophic cardiomyopathy as the initial presentation of mitochondrial disease in an infant born to a diabetic mother.

In contrast to hypertrophic cardiomyopathy caused by maternal diabetes, neonatal mitochondrial cardiomyopathy is rare and has a poor prognosis. We report an infant born to a mother with maternal diabetes with persistent ventricular hypertrophy, who was diagnosed with mitochondrial disease associated with m.3243A>G mutation in a mitochondrial tRNA leucine 1 gene. The hypertrophic cardiomyopathy was his initial and only clinical presentation.

Multiple cranial nerve palsies with small angle exotropia following COVID-19 mRNA vaccination in an adolescent: A case report.

BACKGROUND: Several vaccines against the severe acute respiratory syndrome coronavirus 2 have been approved and widely distributed, raising public concerns regarding the side effects of immunization, as the incidence of ease. Although many adverse events following the coronavirus disease 2019 (COVID-19) vaccine have been reported, neurological complications are relatively uncommon. Herein, we report a rare case of multiple cranial palsies following COVID-19 vaccination in an adolescent patient. CASE SUMMARY: A previously healthy, 14-year-old Asian girl with facial palsy presented to the emergency department with inability to close the right eye or wrinkle right side of the forehead, and pain in the right cheek. She had received second dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech) 18 days before onset of symptoms. She was diagnosed with Bell's palsy and prescribed a steroid (1 mg/kg/day methylprednisolone) based on symptoms and magnetic resonance imaging findings. However, the next day, all sense of taste was lost with inability to swallow solid food; the gag reflex was absent. Horizontal diplopia was also present. Due to worsening of her condition, she was given high-dose steroids (1 g/day methylprednisolone) for 3 days and then discharged with oral steroids. Improvement in the symptoms was noted 4 days post steroid treatment completion. At the most recent follow-up, her general condition was good with no symptoms except diplopia; ocular motility disturbances were noted. Hence, prism glasses were prescribed for diplopia relief. CONCLUSION: Small-angle exotropia was observed in the facial, trigeminal, and glossopharyngeal nerve palsies, in our patient. The etiology of this adverse effect following vaccination was thought to be immunological.

Clinical Usefulness of Simultaneous Electroencephalography and Functional Magnetic Resonance Imaging in Children With Focal Epilepsy.

BACKGROUND AND PURPOSE: The current study analyzed the interictal epileptiform discharge (IED)-related hemodynamic response and aimed to determine the clinical usefulness of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) in defining the epileptogenic zone (EZ) in children with focal epilepsy. METHODS: Patients with focal epilepsy showing IEDs on conventional EEG were evaluated using EEG-fMRI. Statistical analyses were performed using the times of spike as events modeled with multiple hemodynamic response functions. The area showing the most significant t-value for blood-oxygen-level-dependent (BOLD) changes was compared with the presumed EZ. Moreover, BOLD responses between -9 and +9 s around the spike times were analyzed to track the hemodynamic response patterns over time. RESULTS: Half (n=13) of 26 EEG-fMRI investigations of 19 patients were successful. Two patients showed 2 different types of spikes, resulting in 15 analyses. The maximum BOLD response was concordant with the EZ in 11 (73.3%) of the 15 analyses. In 10 (66.7%) analyses, the BOLD response localized the EZs more specifically. Focal BOLD responses in the EZs occurred before IEDs in 11 analyses and were often widespread after IEDs. Hemodynamic response patterns were consistent in the same epilepsy syndrome or when repeating the investigation in the same patients. CONCLUSIONS: EEG-fMRI can provide additional information for localizing the EZ in children with focal epilepsy, and also reveal the pathogenesis of pediatric epilepsy by evaluating the patterns in the hemodynamic response across time windows of IEDs.

Neuralgic Amyotrophy with Concomitant Hereditary Neuropathy with Liability to Pressure Palsy as a Cause of Dropped Shoulder in a Child after Human Papillomavirus Vaccination: A Case Report.

Hereditary neuropathy with liability to pressure palsy (HNPP) makes nerves increasingly susceptible to mechanical pressure at entrapment sites. Neuralgic amyotrophy (NA) can cause sudden regional weakness following events to which the patient is immunologically predisposed, such as vaccination. However, NA related to human papilloma virus (HPV) vaccination is seldom reported. We describe the case of a child with NA as the cause of a dropped shoulder following the administration of the HPV vaccine. Underlying asymptomatic HNPP was confirmed in this patient based on the electrodiagnostic findings and genetic analysis. We speculate that HPV vaccination elicited an immune-mediated inflammatory response, resulting in NA. Our patient with pre-existing HNPP might be vulnerable to the occurrence of an immune-mediated NA, which caused the dropped shoulder.

Atypical Presentation of Enlarged Vestibular Aqueducts Caused by SLC26A4 Variants.

Enlarged vestibular aqueduct is the most common inner ear malformation in pediatric patients with sensorineural hearing loss. Here, we report a new presentation of enlarged vestibular aqueduct in a Korean family. The family consists of two parents and five daughters, and the first and second daughters were diagnosed with bilateral enlarged vestibular aqueducts. The third daughter, who showed no signs of hearing deterioration, came to medical attention with incomplete Horner syndrome. Evaluations for localization of Horner syndrome on the patient and Sanger sequencing of SLC26A4 on the family members were performed. Although auditory brainstem response and pure tone audiometry of the third daughter were normal, temporal bone computed tomography demonstrated bilateral enlarged vestibular aqueducts. Sanger sequencing of SLC26A4 revealed compound heterozygous variants c.2168A>G and c.919-2A>G in the first, second, and third daughters. Diagnosis of enlarged vestibular aqueduct is often delayed because the degree of hearing loss can vary, and a considerable phenotypic variability can be shown even in family members with the same SLC26A4 variations. Fluctuations of CSF pressure into the cochlear duct and recurrent microruptures of the endolymphatic membrane could result in damage of sympathetic nerve supplying to the inner ear, which could explain the mechanism of Horner syndrome associated with enlarged vestibular aqueduct.

Effects of carnosine and hypothermia combination therapy on hypoxic-ischemic brain injury in neonatal rats.

BACKGROUND: Carnosine has antioxidative and neuroprotective properties against hypoxic-ischemic (HI) brain injury. Hypothermia is used as a therapeutic tool for HI encephalopathy in newborn infants with perinatal asphyxia. However, the combined effects of these therapies are unknown. PURPOSE: Here we investigated the effects of combined carnosine and hypothermia therapy on HI brain injury in neonatal rats. METHODS: Postnatal day 7 (P7) rats were subjected to HI brain injury and randomly assigned to 4 groups: vehicle; carnosine alone; vehicle and hypothermia; and carnosine and hypothermia. Carnosine (250 mg/kg) was intraperitoneally administered at 3 points: immediately following HI injury, 24 hours later, and 48 hours later. Hypothermia was performed by placing the rats in a chamber maintained at 27°C for 3 hours to induce whole-body cooling. Sham-treated rats were also included as a normal control. The rats were euthanized for experiments at P10, P14, and P35. Histological and morphological analyses, in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and immunofluorescence studies were conducted to investigate the neuroprotective effects of the various interventional treatments. RESULTS: Vehicle-treated P10 rats with HI injury showed an increased infarct volume compared to sham-treated rats during the triphenyltetrazolium chloride staining study. Hematoxylin and eosin staining revealed that vehicle-treated P35 rats with HI injury had decreased brain volume in the affected hemisphere. Compared to the vehicle group, carnosine and hypothermia alone did not result in any protective effects against HI brain injury. However, a combination of carnosine and hypothermia effectively reduced the extent of brain damage. The results of in situ zymography, TUNEL assays, and immunofluorescence studies showed that neuroprotective effects were achieved with combination therapy only. CONCLUSION: Carnosine and hypothermia may have synergistic neuroprotective effects against brain damage following HI injury.

A new type of oculocutaneous albinism with a novel OCA2 mutation.

Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders, characterized by hypopigmentation of the eyes, skin, and hair, which result in ocular abnormalities and a risk of developing skin cancer. Currently, there is no ophthalmologic procedure or drug that prevents the clinical features of OCA. Here, we report a new type of OCA in two, unrelated Korean families with the same OCA2 mutation. Affected individuals in this study are different from those of previous reports in two aspects: an inheritance pattern and clinical presentation. All reported patients with OCA have shown an autosomal recessive inheritance pattern, while our patients showed an autosomal dominant inheritance pattern. Small amounts of pigment can be acquired with age in OCA, but there is no substantial variation from adolescence to adulthood in this regard. A case where the patient attained normal pigmentation levels has never been reported. However, our patients displayed completely normal pigmentation in their late twenties. Whole exome sequencing and in-silico analysis revealed a novel mutation, OCA2 c.2338G>A p.(G780S) (NM_000275) with a high likelihood of pathogenicity. Sanger sequencing of p.G780S identified the same mutation in the affected individuals, which was not found in the family members with normal phenotype. We hypothesize that OCA2 G780S not only acts as a pathogenic variant of OCA but also induces pigmentation by enhancing the melanogenesis gene expression of other modifier genes, such as SLC45A2 and TPC2. These findings may provide further understanding of melanin biosynthesis and new treatment methods for OCA.