Adult-onset type II citrullinemia (CTLN2) is a rare urea cycle disorder caused by SLC25A13 mutations, often misdiagnosed due to fluctuating neuropsychiatric and metabolic symptoms. Hyperammonemia is its defining feature and can be fatal if unrecognized. A 30-year-old woman with intellectual disability presented with recurrent seizure-like episodes and behavioral changes. Brain MRI showed bilateral temporal lobe abnormalities suggestive of encephalitis or metabolic encephalopathy. Despite antiviral and antiseizure therapy, her consciousness deteriorated. On the sixth hospital day, valproic acid (VPA) was administered for seizure control, after which she rapidly progressed to coma and respiratory failure. Serum ammonia levels were markedly elevated (>615 & micro;mol/L), and metabolic studies revealed increased citrulline and arginine levels. Genetic testing confirmed compound heterozygous SLC25A13 mutations consistent with CTLN2. Despite aggressive management, the patient died 23 days after admission. This case underscores the diagnostic difficulty of CTLN2 and highlights the fatal risk of VPA-induced hyperammonemia in patients with unrecognized urea cycle disorders. Early metabolic screening should be considered in unexplained encephalopathy, especially when imaging and EEG findings are nonspecific, and VPA should be avoided to prevent catastrophic outcomes.

RATIONALE:Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a severe autoimmune encephalitis that can result in prolonged coma, ventilator dependence, and long-term disability. Although immunotherapy is well established, the optimal timing and intensity of rehabilitation remain poorly defined. This report describes a rare case of adult anti-NMDAR encephalitis with profound neurological impairment who achieved remarkable functional and cognitive recovery following intensive, goal-oriented rehabilitation initiated while still in the intensive care unit (ICU). PATIENT CONCERNS:A 35-year-old woman with prior thyroid carcinoma and ovarian teratoma presented with fever, confusion, and behavioral changes progressing to decreased consciousness. She remained comatose for months despite extensive immunotherapy and supportive care. DIAGNOSES:Anti-NMDAR encephalitis was confirmed by the detection of anti-NMDAR antibodies in both serum and cerebrospinal fluid. Neuroimaging excluded other causes of encephalopathy. INTERVENTIONS:The patient underwent sequential immunotherapy including high-dose corticosteroids, intravenous immunoglobulin, and plasma exchange, followed by rituximab, tocilizumab, and cyclophosphamide. After nearly 20 months of medical instability, she began intensive multidisciplinary rehabilitation-five sessions per week, 2 hours daily-while still in the ICU. Therapy targeted progressive mobilization, upper-limb activation, and communication training, delivered under continuous cardiorespiratory monitoring. OUTCOMES:Over 3 months, substantial improvement was observed: Modified Barthel Index increased from 0 to 72, Berg Balance Scale to 42, Mini-Mental State Examination to 9, and Manual Function Test to over 80 bilaterally. She achieved independent ambulation and daily self-care, with significant gains in language function. The patient reported high satisfaction with her regained independence and ability to resume normal activities, and no adverse events occurred during rehabilitation. LESSONS:This case demonstrates that active, structured rehabilitation can be safely implemented even in medically complex, prolonged cases of autoimmune encephalitis. Intensive, goal-directed therapy under ICU monitoring may promote late neuroplasticity and yield meaningful recovery long after disease onset. Rehabilitation should be considered an an integral therapeutic component alongside immunotherapy in the long-term management of severe anti-NMDAR encephalitis.

BACKGROUND:Although cytokines are contributors to febrile seizures, previous studies have largely involved pathogen-heterogeneous populations. Human herpesvirus 6 (HHV-6) is a common cause of febrile seizures and is useful for studying pathogen-specific inflammatory responses. METHODS:This retrospective study included children with polymerase chain reaction-confirmed HHV-6 infection using stored plasma samples obtained within 72 h of hospital presentation, classified according to seizure status. Plasma cytokine levels were measured using a multiplex immunoassay. Multivariable linear regression was used to identify the cytokines associated with seizures, with Benjamini-Hochberg false discovery rate (FDR) correction across 15 cytokines. Correlations between cytokine levels and hematologic parameters were evaluated. Cerebrospinal fluid (CSF)-to-plasma cytokine ratios were analyzed. RESULTS:Sixty patients were included (37, without seizures; 23, seizures), with no significant differences in baseline characteristics between the groups. Plasma interleukin-8 (IL-8) showed an association with seizures (adjusted fold change 1.84, p = 0.03), but this association did not remain statistically significant after FDR correction (q = 0.45). Inverse correlations between IL-8 (and to a lesser extent macrophage inflammatory protein-1 alpha) and neutrophil and platelet counts were observed in the non-seizure group only. In the paired analyses (n = 8), the CSF-to-plasma ratios of IL-8 and monocyte chemoattractant protein-1 exceeded 1.0, with a trend toward higher IL-8 ratios in the seizure group after adjusting for age. CONCLUSIONS:Although exploratory, findings from this pathogen-homogeneous cohort suggest that IL-8 is a candidate cytokine associated with both seizure occurrence and an altered relationship with neutrophil and platelet counts, warranting further study.

Background Cerebral air embolism (CAE) is a rare but potentially devastating complication of concentrated hydrogen peroxide (H₂O₂) ingestion. Distinguishing CAE from other embolic sources is critical for appropriate acute management, especially when alternative etiologies coexist. Case Description An 82-year-old woman presented with acute left-sided weakness after accidentally ingesting 50 mL of 35% H₂O₂. While 48-hour Holter monitoring incidentally detected paroxysmal atrial fibrillation (AFib) during the workup, brain MRI revealed a characteristic "scattered cortical pattern" of punctate diffusion restrictions across bilateral hemispheres. This non-territorial distribution, combined with a 16-mm pulmonary air cyst on CT and corrosive gastritis on endoscopy, facilitated the identification of CAE over AFib-related cardioembolism. Anticoagulation was deferred to avoid exacerbating gastrointestinal bleeding, and the patient improved with oxygen-based supportive care. Conclusion In patients with incidental embolic sources like AFib, recognizing the non-territorial punctate cortical pattern on MRI is a pivotal diagnostic clue for CAE. This distinction is essential to prevent inappropriate anticoagulation in the setting of acute corrosive mucosal injury.

Background and Purpose The Generalized Anxiety Disorder 7-item (GAD-7) is a self-report questionnaire assessing anxiety-related symptoms experienced over the past two weeks. The GAD-7 is widely used to screen for generalized anxiety disorder (GAD), and reported optimal cutoff scores for detecting GAD in people living with epilepsy (PLWE) range between >6 and >9. This meta-analysis aims to determine the most appropriate GAD-7 cutoff score for PLWE. Methods We identified relevant studies through comprehensive searches in MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus. Studies included original research examining GAD-7 accuracy for detecting GAD in adult PLWE, using structured diagnostic interviews including the Mini International Neuropsychiatric Interview as a reference standard. Only studies providing sufficient data for meta-analysis were included, including the number of PLWE with GAD, the total participant number, sensitivity, and specificity. We performed summary receiver operating characteristic curve analyses. Results Seven studies conducted in outpatient epilepsy clinics were included. The area under the curve (AUC) ranged between 0.91 and 0.96 across cutoff scores from >5 to >9. The cutoff score of >6 provided the best balance of diagnostic accuracy, with an AUC of 0.96, sensitivity of 0.95, and specificity of 0.83. Conclusions The GAD-7 cutoff score of >6 has optimal diagnostic performance for screening GAD in PLWE. These results offer valuable guidance for clinicians and researchers applying the GAD-7 questionnaire to detect GAD among PLWE, especially in geographic areas without previously validated language-specific versions.

We previously conducted a retrospective analysis of polysomnography (PSG) electrocarttiography (ECG) data to classify obstructive sleep apnea (OSA) using deep learning analysis (DLA). The study achieved a ROC AUC score of 0.7077 and an F1 score of 0.67, demonstrating its potential as a screening tool for OSA. In this study, we further analyzed oximetry data extracted from PSG and explored the integration of ECG- and oximetry-based screening tools into vital sign monitoring devices within the stroke intensive care unit (SU) to evaluate their clinical utility in real-world settings. We retrospectively analyzed PSG data collected between 2015 and 2023. OSA was classified into two categories: normal/mild and moderate/severe, based on the apnea-hypopnea index (AHI). For DLA, oximetry data were converted into Mel-spectrograms and analyzed using a Convolutional Neural Network, generating a confusion matrix. Additionally, we assessed the utility of the screening tool in patients admitted to the SU between January and October 2024. PSG was conducted for patients meeting the following criteria: STOP-BANG score ≥3, witnessed snoring or apnea, and a Modified Mallampati Score ≥3. Out of 1,806 PSG records, 252 cases with arrhythmias were excluded, leaving 1,554 records for analysis. OSA was classified as normal/mild in 616 cases and moderate/severe in 938 cases. The DLA results for oximetry yielded a ROC AUC score of 0.7814 and an F1 score of 0.79. In the SU cohort, 211 patients were evaluated. After excluding 34 cases with arrhythmias and 67 instances of data loss, 110 patients remained. Among these, 49.5% had a STOP-BANG score ≥3, 40.4% were suspected of having OSA based on oximetry data, and 60.6% based on ECG data. Among the five patients who underwent final PSG testing, oximetry demonstrated an accuracy of 80%, while ECG achieved 100%. Our findings suggest that DLA using oximetry showed higher accuracy in retrospective PSG data compared to ECG. However, in the SU setting, oximetry faced challenges due to variations in sampling rates across devices. In contrast, ECG data demonstrated more consistent sampling rates, providing a clinical advantage. Further studies are warranted to validate and optimize both approaches for widespread application.

BACKGROUND:Human herpesvirus 6 (HHV-6) is occasionally detected in the cerebrospinal fluid (CSF) of young children, but its clinical significance remains uncertain. This study aimed to describe HHV-6-positive cases and to explore features that may help distinguish presumed infection from bystander detection. METHODS:We retrospectively reviewed pediatric patients with CSF HHV-6 detected by multiplex polymerase chain reaction or the FilmArray Meningitis/Encephalitis (FA-ME) panel between January 2015 and March 2025 at a single tertiary hospital. Cases were categorized as presumed HHV-6 infection or bystander detection based on clinical features and the presence of alternative pathogens or diagnoses. Clinical and laboratory findings were compared between the two groups. RESULTS:Among 1,865 children tested, HHV-6 was detected in 25 (1.3%; median age, 6 months), all of whom presented with fever. Seizures occurred in seven (28%) and ataxia in one (4%). Two patients developed encephalitis; one had abnormal imaging and later developed epilepsy. Seventeen patients were classified as presumed infection. In this group, rash was more prevalent (59% vs. 13%, p = 0.04), neutrophil and platelet counts were lower at admission and declined further at follow-up (p < 0.05), and aspartate aminotransferase (AST) levels were higher (p < 0.01) than those in the bystander infection group. CSF pleocytosis did not differ significantly between groups. Two patients received ganciclovir; both had HHV-6 detected early by the FA-ME panel, and one was subsequently diagnosed with bacterial sepsis. CONCLUSIONS:HHV-6 encephalitis was uncommon. Rash, changes in neutrophil and platelet counts, along with elevated AST levels may help interpret CSF HHV-6 detection, but these findings require validation in larger studies incorporating virologic confirmation.

OBJECTIVE:This study aimed to assess the long-term outcome and prognostic factors of vagus nerve stimulation (VNS) for drug-resistant epilepsy (DRE) using real-world data. METHOD:We included 189 DRE patients who underwent VNS implantation between 2005 and 2018 at nine national hospitals in Korea. Seizure-frequency data obtained quarterly one year before and after surgery and annually up to four years after surgery were collected from medical records. Health resource utilization trends over the four years preceding and following surgery were assessed through linkage with national health insurance data. We performed interrupted time series analysis to examine the trend in seizure frequency before and after one year following surgery. RESULTS:The seizure frequency exhibited a decreasing trend in 27.5 % and an increasing trend in 3.8 % during the first year following VNS implantation without a significant change in efficacy over the subsequent three years. Patients with focal spikes with secondary bilateral synchrony (SBS) in electroencephalography had a higher responder rate (adjusted odds ratio (aOR)= 3.06 [1.36-6.90]), whereas those with Lennox-Gastaut syndrome had a lower responder rate (aOR=0.38 [0.15-0.94]). One-year seizure-freedom was achieved in 6.0 % of patients at some point during the four-year follow-up. Over an eight-year period, the number of antiseizure medications (ASMs) tended to increase before surgery and remained at a median of 5 [4-6] after surgery. While the total medical and epilepsy-related costs tended to decrease after surgery, the ASM cost continued to increase. CONCLUSION:VNS was substantially beneficial for one in four patients with DRE, offering the chance of seizure-freedom. However, the efficacy of VNS fell within the efficacy range of recently introduced medical treatments and did not lead to a decrease in the ASM burden. Focal spike with SBS is a potential biomarker for a favorable response to VNS.

Depression is a significant comorbidity of epilepsy that affects both quality of life and seizure control. Selective serotonin reuptake inhibitors (SSRIs) are the recommended first-line treatment for depression in patients with epilepsy; however, the optimal management strategies for SSRI-resistant depression in this population remain unclear. We conducted a 10-year retrospective analysis of epilepsy patients with SSRI-resistant depression who were treated by either switching to a serotonin norepinephrine reuptake inhibitor (SNRI) or augmenting with aripiprazole. We compared demographic factors, seizure characteristics, and treatment outcomes between the two groups. Our study included 33 epilepsy patients with SSRI-resistant depression who switched to SNRIs and 36 patients who were treated with aripiprazole augmentation. There were no significant differences in demographic factors, seizure characteristics, mean initial depression scores, or seizure freedom between the groups. However, patients receiving aripiprazole augmentation showed higher retention rates than those switching to SNRIs at their last follow-up (28/36 vs. 13/33, p = .001). Our study suggests that aripiprazole augmentation may be a more favorable option than switching to SNRIs for epilepsy patients with SSRI-resistant depression. Further prospective studies are needed to investigate effective treatment strategies for epilepsy patients with SSRI-resistant depression.

OBJECTIVE:To compare parenting stress between parents of children with autism spectrum disorder (ASD) and other developmental disabilities (DDs) and to examine ASD's influence on parenting stress through mediation analysis. METHODS:We retrospectively analyzed 48 children with ASD (ASD group) and 77 with non-ASD DDs (non-ASD group), along with one of their parents, at the Gyeongsang National University Hospital between May 2021 and August 2024. All underwent developmental assessments and completed the Korean version of the Parenting Stress Index-4 and the Child Interactive Behavior Test (CIBT). RESULTS:The ASD group's median age was 37.5 months, with 37 boys (77.1 %). No significant difference was found in child age, sex, or parental demographics between the groups. Total parenting stress was significantly higher in the ASD group (p = 0.01), primarily due to higher child domain scores (p<0.01) than in the non-ASD group. Among the child domain subscales, Distractibility/Hyperactivity, Adaptability, Reinforces Parent, and Acceptability were significantly higher in the ASD group, while only the Attachment subscale differed in the parent domain. For high parenting stress (>85th percentile), Initiative Interaction-a CIBT subscale-was the only independent predictor, rather than ASD diagnosis. Mediation analysis showed no direct effect of ASD on parenting stress (β = 4.28, p = 0.42) but an indirect effect via reduced initial interaction (β = 3.68, p<0.05). CONCLUSIONS:Parenting stress was higher in the ASD group, mainly due to child-related factors. ASD influenced parenting stress indirectly through reduced initiative interaction. These findings provide further insight into parenting stress in families of children with ASD.

Obstructive sleep apnea (OSA) presents an elevated risk to patients with stroke, especially during the acute phase when prolonged bed rest in the supine position is common in stroke unit (SU). Recent studies suggest that rostral fluid shifts may worsen OSA severity. This study aimed to compare OSA severity between patients with acute stroke in a SU and outpatients with OSA using in-laboratory polysomnography (iPSG) to gain further insight into this relationship. This cross-sectional study was conducted at Samsung Changwon Hospital between April 2021 and October 2022. Patients with acute stroke and outpatients who underwent iPSG were included. SU patients were screened for OSA symptoms and selected based on modified Mallampati score ≥ 3. SU patients were assessed using iPSG during their hospital stay after bed rest periods. Propensity score matching (PSM) was used to control for confounding variables. Among 530 SU patients, 30 completed iPSG. SU patients exhibited significantly higher supine apnea-hypopnea index (AHI) than outpatients (60.1 vs 28.4, P = .004). The stroke group showed increased odds of elevated supine AHI (OR = 4.99, 95% CI: 1.90-13.11, P = .001). After PSM adjustment, the association remained significant (OR = 18.47, 95% CI: 1.53-222.20, P = .022). Eighty percent of SU patients had moderate-to-severe OSA (AHI ≥ 15) compared to 60% of outpatients. Patients with acute stroke in a SU demonstrate significantly higher supine AHI compared to outpatients with OSA. These findings suggest that prolonged bed rest and supine positioning during acute stroke management may contribute to OSA severity.

Purpose: We used arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging to evaluate cerebral perfusion abnormalities in patients with seizures within 24 hours of symptom onset. Materials and Methods: A retrospective search of our institutional database identified 27 patients who had undergone ASL perfusion studies for seizures or seizure-like symptoms. The inclusion criteria were as follows: 1) history of seizure, 2) MR examination performed within 24 hour of seizure onset, and 3) localized perfusion abnormality on ASL. We evaluated the presence, location, and extent of perfusion abnormalities on ASL and signal abnormalities on fluid-attenuated inversion recovery (FLAIR), diffusion-weighted image (DWI), and susceptibility-weighted image (SWI), respectively. All pathological MR findings, accompanying focal neurological symptoms, and electroencephalogram (EEG) findings were compared. Results: The mean time from symptom onset to MR examination was 5 h 54 min. All patients (n = 27) showed localized increased perfusion on ASL perfusion imaging. On FLAIR imaging, 20 patients (74.1%) showed hyperintensity in the area of perfusion abnormality. In 19 patients (70.4%), DWI showed hyperintensity of the lesion with decreased apparent diffusion coefficient value (ADC). Seven patients (25.9%) showed a focal parenchymal area of pseudo-narrowed cortical veins on SWI, associated with focal hyperperfusion. In 20 patients (74.1%), the extent of perfusion abnormalities on ASL was greater than that of signal abnormalities on FLAIR or DWI. In 14/16 patients (87.5%) with abnormal EEG findings, the area with EEG findings and the location of the hyperperfusion abnormality on ASL corresponded. Conclusion: In patients with seizures within 24 hours of symptom onset, ASL perfusion imaging revealed localized hyperperfusion, which was more frequent than signal intensity abnormalities on FLAIR or DWI. The locations of hyperperfusion areas correlated with EEG abnormalities. Thus, the ASL sequence may be a useful clinical assessment protocol for evaluating patients with seizures.

Super refractory status epilepticus (SRSE) is a condition in which status epilepticus persists despite 48 hours of anesthetic treatment. Nonconvulsive status epilepticus (NCSE) is characterized by seizures lasting more than 30 min on an electroencephalogram, with accompanying changes in behavior or consciousness without convulsions. Prompt treatment of NCSE is crucial, as delayed treatment may lead to additional brain damage and progression to convulsive status epilepticus. Although vagus nerve stimulation (VNS) has been approved as an adjunct treatment for drug-resistant epilepsy, it is rarely used to treat refractory status epilepticus. To the best of our knowledge, only two cases of NCSE treated with VNS have been reported to date, and these patients were successfully treated with VNS for NCSE caused by anti-NMDAR encephalitis. We report the case of a patient with posttraumatic epilepsy who developed super refractory-NCSE after convulsive status epilepticus and was successfully treated with VNS.

Abstract Introduction Previous studies suggested that obstructive sleep apnea (OSA) can affect the autonomic nervous system. Patients with OSA appear to have a higher sympathetic component, a lower parasympathetic component, and greater autonomic nervous system (ANS) imbalance. We compared heart rate variability (HRV) with existing studies and confirmed classification accuracy through deep learning analysis (DLA), using electrocardiogram (ECG) data extracted from polysomnography (PSG). Methods We retrospectively surveyed people who underwent PSG at our hospital from January 2015 to March 2023. The diagnosis of OSA was classified into normal, mild, moderate, and severe based on AHI, and whether arrhythmia was identified during the test was also investigated. HRV analysis performed by frequency domain analysis of the tachogram. For DLA, the tachogram was converted to a Mel-spectrogram and a Convolutional Neuronal Network (CNN) was used to confirm the confusion matrix. Results Of a total of 1,806 PSG, 1,554 cases were selected, excluding 252 cases of arrhythmia. OSA confirmed by PSG was normal in 282 patients, mild in 334, moderate in 293, and severe in 645. When comparing the results of HRV divided into AHI below 15 and above, VLF power (ms2/Hz) was 940.78 ± 763.72 vs 1132.75 ± 1104.50 (p < 0.001), LF power (ms2/Hz) was 719.26 ± 734.71 vs. 724.46 ± 945.26 (p = 0.908), HF power (ms2/Hz) was 763.61 ± 1058.92 vs 595.53 ± 1386.75 (p = 0.011), and LF/HF ratio was 1.27 ± 0.74 vs 1.63 ± 1.02 (p < 0.001). As a result of DLA, the ROC AUC Score was confirmed to be 0.7077 and the F1 Score was 0.67. Conclusion As a result of HRV using ECG from PSG, OSA patients were found to have low HF power and high LF/HF ratio, similar to previous studies. Additionally, if tachogram's DLA accuracy can be improved through preprocessing and deep learning model improvements, it is expected that it can be used as a screening tool in various place. Support (if any) This work was partly supported by Institute of Information & Communications Technology Planning & Evaluation grant funded by the Korea government No.RS_2023_00227552, Development of artificial intelligence video background removal SaaS service using domestic semiconductor 64 TOPS.