Genetic and pathological features encipher the phenotypic heterogeneity of Gerstmann-Sträussler-Scheinker disease.

OBJECTIVES: To elucidate and compare the genetic, clinical, ancillary diagnostic, and pathological characteristics across different Gerstmann-Sträussler-Scheinker disease (GSS) phenotypes and explore the underlying causes of the phenotypic heterogeneities. METHODS: The genetic, clinical, ancillary diagnostic, and pathological profiles of GSS patients reported in the literature were obtained and analyzed. Additionally, 3 patients with genetically confirmed GSS from our unit were included. Based on clinical presentation, patients were classified into typical GSS, Creutzfeldt-Jakob disease (CJD)-like GSS, GSS with dementia, and other categories. RESULTS: A total of 329 GSS cases were included with a 1.13:1 female-to-male ratio, median onset age 44, and median duration 4 years. Of the 294 categorized patients, 50.7% had typical GSS, 24.8% showed CJD-like GSS, and 16.3% presented with GSS with dementia. Clinical classification varied significantly based on genotype, with P102L more common in typical GSS and A117V prevalent in CJD-like GSS. Polymorphism at codon 129 has no effect on GSS phenotype, but the 129 M allele acts as a protective factor in GSS patients in Asia and North America. Moderate to severe spongiform degeneration and the presence of PK-resistant small fragments migrating at <11 kDa on electrophoretic gels along with PrP27-30 fragments were more prevalent in CJD-like GSS phenotype, while hyperphosphorylated tau protein co-deposition tends to be characteristic of typical GSS and GSS with dementia. CONCLUSION: This study reveals GSS's intricate nature, showing significant variations in clinical presentations, diagnostic findings, and pathological features. Mutation sites and pathological changes play crucial roles in determining the GSS clinical heterogeneity.

Regional Glymphatic Abnormality in Behavioral Variant Frontotemporal Dementia.

OBJECTIVES: Glymphatic function has not yet been explored in behavioral variant frontotemporal dementia (bvFTD). The spatial correlation between regional glymphatic function and bvFTD remains unknown. METHOD: A total of 74 patients with bvFTD and 67 age- and sex-matched healthy controls (HCs) were selected from discovery dataset and replication dataset. All participants underwent neuropsychological assessment. Glymphatic measures including choroid plexus (CP) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling between blood-oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling), were compared between the two groups. Regional glymphatic function was evaluated by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, and posterior regions. The bvFTD-related metabolic pattern was identified using spatial covariance analysis based on l8 F-FDG-PET. RESULTS: Patients with bvFTD showed higher CP volume (p < 0.001); anterior and middle DTI-ALPS (p < 0.001); and weaker anterior BOLD-CSF coupling (p < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI-ALPS was negatively associated with the expression of the bvFTD-related metabolic pattern (r = -0.52, p = 0.034) and positively related with regional standardized uptake value ratios of l8 F-FDG-PET in bvFTD-related brain regions (r range: 0.49 to 0.62, p range: 0.017 to 0.047). Anterior and middle glymphatic functions were related to global cognition and disease severity. INTERPRETATION: Our findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD. ANN NEUROL 2023;94:442-456.

Application of the mild behavioral impairment checklist in Chinese patients with the behavioral variant of frontotemporal dementia.

BACKGROUND: The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). METHODS: Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI-C, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI-C, NPI-Q, and FBI, and cutoff points were determined using the Youden index. RESULTS: The MBI-C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI-C score was positively correlated with the NPI-Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI-C cutoff point was 5.5 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI-Q and FBI. CONCLUSION: The MBI-C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.

Clinical features of COVID-19-related encephalitis: comparison with the features of herpes virus encephalitis and autoimmune encephalitis.

INTRODUCTION: Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types. METHODS: Adult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8). RESULTS: The predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis. DISCUSSION: COVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.

Octapeptide repeat alteration mutations of the prion protein gene in clinically diagnosed Alzheimer's disease and frontotemporal dementia.

Studies focusing on octapeptide repeat alteration mutations in PRNP in Alzheimer's disease (AD) and frontotemporal dementia (FTD) cohorts have been rare. We aim to screen sporadic AD and FTD patients with unknown etiology for the octapeptide repeat insertions and deletions in PRNP. Two hundred and six individuals were screened for alterations to the repeat region in the PRNP gene, including 146 sporadic AD and 60 sporadic FTD patients. Our study showed a 1.5% (3/206) occurrence of the octapeptide repeat alteration mutations in PRNP in a Chinese cohort of sporadic dementia. One late-onset FTD patient and one early-onset AD patient each had a two-octapeptide repeat deletion in PRNP, while one early-onset AD patient had a five-octapeptide repeat insertion mutation. PRNP octapeptide repeat alteration mutations are present in sporadic AD and FTD patients. The genetic investigation for PRNP octapeptide repeat alteration mutations in sporadic dementia patients should be carried out in future clinical studies.

Two-photon fluorescence imaging using a tunable spectral window based on fiber supercontinuum.

Two-photon excitation fluorescence (TPEF) microscopy has evolved into a versatile tool in biological research. However, the multiplexing capability of TPEF microscopy is limited by the narrow spectral bandwidth of the light source. In this study, we apply a photonic crystal fiber in TPEF microscopy to broaden the excitation source bandwidth. We tuned the spectral window using a spatial light modulator as a programmable diffraction grating that was placed behind a prism pair. In addition, we combined a grating pair to compensate for dispersion to improve the two-photon excitation efficiency. The combination of a broad spectrum and a programmable grating enabled fast spectral window tuning rate on a time scale of tens of milliseconds. We demonstrate the performance of our method by imaging live B16 cells labeled with four emission spectrum overlapped fluorescent proteins.

Involvement of specific striatal subregion contributes to executive deficits in Alzheimer disease.

BACKGROUND: There is growing evidence that the striatum plays a central role in cognitive dysfunction. However, it remains unclear whether and how the striatum contributes specifically to executive deficits in Alzheimer disease (AD). We sought to elucidate aberrations in the striatal subregion associated with executive function and its metabolic connectivity with the cortical regions to investigate its role in the pathogenesis of executive deficits in patients with AD. METHODS: Patients with AD and healthy controls underwent a neuropsychological assessment battery, including assessment of executive function, and a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) scan. We performed voxel-wise analyses of cerebral metabolism between patients and controls, focusing on the executive subregion of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. We assessed the correlation between the [18F]-fluorodeoxyglucose standardized uptake value ratio of the striatal executive subregion and clinical variables, and we analyzed seed-based metabolic connectivity of the striatal executive subregion with the dorsolateral prefrontal cortex (DLPFC) using [18F]-fluorodeoxyglucose PET. RESULTS: We included 50 patients with AD and 33 controls in our analyses. The patterns of striatal hypometabolism in patients with AD were specific to executive and caudal motor subregions. Metabolic activity in the executive subregion of the striatum correlated negatively with the severity of executive dysfunction, as measured with the Trial-Making Test (TMT) part B and the difference score TMT B-A, and correlated positively with Digit Span (backward) and Verbal Fluency Test scales, particularly on the left side. Compared with controls, patients with AD showed reduced metabolic connectivity between striatal executive subregions and the dorsolateral prefrontal cortex (DLPFC). LIMITATIONS: Our study was limited by small sample sizes and cross-sectional findings. CONCLUSION: Our findings show that patients with AD have impairments in the executive subregion of the striatum, and these deficits may be associated with a disconnection between the executive striatum and DLPFC, providing valuable insight into the pathogenesis of this disease.

Clinical profiles and ethnic heterogeneity of sporadic fatal insomnia.

BACKGROUND AND PURPOSE: This study was undertaken to elucidate the clinical profile of sporadic fatal insomnia (sFI), assess the similarities and differences between sFI and fatal familial insomnia (FFI), and evaluate the influence of ethnicity on the phenotype of sFI patients. METHODS: The data of sFI and FFI patients were retrieved from our case series and through literature review. The clinical and diagnostic features of sFI and FFI were compared, as were the phenotypes of Asian and Caucasian sFI patients. RESULTS: We identified 44 sFI and 157 FFI cases. The prevalence of sleep-related, neuropsychiatric, and autonomic symptoms among the sFI patients were 65.9%, 100.0%, and 43.2%, respectively. Compared to FFI, sFI exhibited longer disease duration and a higher proportion of neuropsychiatric symptoms, whereas FFI was characterized by a higher incidence of sleep-related and autonomic symptoms in the early stages of the disease or throughout its course. In addition, a higher proportion of the sFI patients showed hyperintensity on magnetic resonance imaging (MRI) and periodic sharp wave complexes on electroencephalography compared to the FFI patients, especially those presenting with pathological changes associated with MM2-cortical type sporadic Creutzfeldt-Jakob disease. The Asian sFI patients had a higher proportion of males and positivity for cerebrospinal fluid 14-3-3 protein, and fewer sleep-related symptoms compared to Caucasian sFI patients. The age at onset and duration of sFI differed between ethnic groups, but the difference failed to reach statistical significance. CONCLUSIONS: Despite its similarities to FFI, sFI is characterized by longer disease duration, higher proportion of neuropsychiatric symptoms, and hyperintensity on MRI, along with differences in the clinical characteristics based on ethnicity.

Neutrophil to High-density Lipoprotein ratio (NHR) as a potential predictor of disease severity and survival time in Creutzfeldt-Jakob disease.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a fatal and irreversible neurodegenerative disease. Identification of inexpensive and easy-to-implement biomarkers of CJD which could predict disease severity and patient survival is important for improving disease management. The aim of this study was to assess the predictive value of peripheral neutrophil to lymphocyte ratio (NLR), high-density lipoprotein (HDL), monocyte to HDL ratio (MHR) and neutrophil to HDL ratio (NHR) for CJD. METHODS: Patients with definite or probable CJD admitted to the Neurology Department of Xuanwu Hospital from 2014 to 2021 were enrolled and followed up until April 2022. Clinical information including sex, age, Barth Index, survival time and results of auxiliary examination were collected, and NLR, HDL, NHR and MHR were measured for all enrolled patients. The associations between NLR, HDL, NHR and MHR, and disease severity (evaluated by Barth Index), survival time and auxiliary examinations were evaluated. RESULTS: A total of 88 CJD patients were enrolled and all were deceased. NLR (r = -0.341, p = 0.001), NHR (r = -0.346, p = 0.001) and MHR (r = -0.327, p = 0.002) were significantly associated with disease severity. Higher NHR (HR = 2.344, 95% CI = 1.277-4.303 p = 0.006) and lower HDL (HR = 0.567, 95% CI = 0.346-0.930, p = 0.025) were associated with shorter survival time in the CJD patients. CONCLUSIONS: Peripheral inflammatory biomarkers, especially NHR, were associated with disease severity and survival duration. These findings provide new insights into the mechanisms and treatment strategies of CJD.

Femtosecond laser trapping nanoprinting of silver micro/nanostructures.

In this paper, silver micro/nanostructures composed of sintered nanoparticles were printed by capturing silver nanoparticles in water with 800 nm femtosecond laser trapping. Relationships of laser power, scanning speed, nanoparticle concentration, and the width and morphology of fabricated silver wire were systematically investigated. It is found that low scanning speed and high nanoparticle concentration favor the printing of silver wire with good morphology. A silver wire with width of 305 nm was printed. Electrical resistivities of printed wires are about 24 times that of bulk silver. Silver grid structures and dot arrays were printed by using this technology. Several three-dimensional silver cuboid structures were also printed. This work provides a protocol for printing of three-dimensional metallic micro/nanostructures using laser trapping. These printed structures have great application prospects in metamaterials, flexible electronics, and SERS.

Controlling Blood Pressure Under Transcranial Doppler Guidance after Endovascular Treatment in Patients with Acute Ischemic Stroke.

OBJECTIVE: This study aimed to control blood pressure (BP) under transcranial Doppler (TCD) guidance in patients with anterior circulation acute ischemic stroke after endovascular treatment (EVT) to reduce the incidence of early neurological deterioration (END) and improve neurological prognosis. METHODS: This prospective randomized controlled study included 95 patients who were randomly divided into a TCD-guided BP control (TBC) group and a non-TCD-guided BP control (NBC) group. The patients were monitored by TCD within 72 h after EVT. In the TBC group, BP decreased, BP increased, or intracranial pressure decreased when TCD showed blood flow acceleration, deceleration, or intracranial hypertension respectively. The BP of the NBC group was controlled according to the guidelines. The incidence of END and the prognosis was compared between the 2 groups. RESULTS: TCD identified 18 patients with blood flow acceleration, but the prognosis of the 2 groups was not significantly different. TCD identified 23 patients with blood flow deceleration, and the poor prognosis rate at discharge was lower in the TBC group than in the NBC group (45.5 vs. 91.7%, p = 0.027). TCD identified 34 patients with intracranial hypertension, and the 3-month mortality rate of the TBC group was lower than that of the NBC group (0 vs. 36.8%, p = 0.011). The incidence rates of END and 3-month mortality in the TBC group were lower than those in the NBC group (13.8 vs. 37.5%, p = 0.036; 0 vs. 25.0%, p = 0.012) when TCD parameters were abnormal. Multivariable logistic regression analysis showed that the TBC group (adjusted OR 0.267, 95% CI 0.074-0.955; p = 0.042) was an independent protective factor against the incidence of END when TCD parameters were abnormal. CONCLUSION: These findings indicated that TCD-guided BP and intracranial pressure control improved the prognosis of patients with blood flow deceleration and intracranial hypertension.

Low TSH level predicts a poor clinical outcome in patients with anterior circulation ischemic stroke after endovascular thrombectomy.

OBJECTIVE: To determine the correlation of thyroid hormone status with hemorrhagic transformation (HT) and short-term clinical outcomes in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT) METHODS: A retrospective analysis was conducted on AIS patients who underwent EVT at our hospital from 2016 to 2019. Thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), and free thyroxine (FT4) levels were assessed, and logistic regression analyses were performed with HT incidence and functional outcome at 3 months. RESULTS: A total of 199 patients (148 males; mean age 62.9 ± 13.1 years) were included in the study. The number of patients with HT and unfavorable functional outcomes at 3 months were 74 (37.2%) and 129 (64.8%), respectively. Multiple logistic regression analysis showed that low TSH level (OR = 0.609; 95% CI 0.402-0.920, 푃 = 0.019) was an independent risk factor of poor functional outcome, while none of the thyroid hormones were significantly associated with HT risk. The optimal cutoff value of TSH that best distinguished both unfavorable outcome (sensitivity 31%, specificity 88.6%, area under the curve (AUC) 0.586) and mortality at 3 months (sensitivity 47.4%, specificity 78.3%, AUC 0.606) was 0.485 uIU/ml. CONCLUSION: A lower TSH value upon admission may predict an unfavorable functional outcome in AIS patients after EVT, but thyroid hormone levels have no bearing on the risk of HT.

Lower uric acid level may be associated with hemorrhagic transformation but not functional outcomes in patients with anterior circulation acute ischemic stroke undergoing endovascular thrombectomy.

To determine the correlation of uric acid (UA) with hemorrhagic transformation (HT) and poor short-term functional outcomes in anterior circulation acute ischemic stroke (AIS) patients after endovascular thrombectomy (EVT). A retrospective analysis was conducted for anterior circulation AIS patients who underwent EVT at our hospital from 2015 to 2019. HT within 72 h was documented according to the European Cooperative Acute Stroke Study II Classification. Baseline demographic, clinical and laboratory data were compared between the HT and non-HT groups, and between patients with favorable and unfavorable outcomes on 90-day. A total of 247 AIS patients were enrolled, of which 92 (37.2%) and 85 (34.4%) experienced HT and had favorable functional outcomes at 3 months respectively. Patients with HT had significantly lower UA levels compared to those without HT (322.60 ± 94.49 vs. 350.25 ± 99.28 µmol /L, P = 0.032). In contrast, UA levels were similar in patients with good or poor outcomes (345.67 ± 103.55 vs. 336.95 ± 95.5 µmol /L, P = 0.509). Compared to the patients with UA levels in the first quartile, those in the fourth quartile were at a higher risk of HT in univariate logistic regression analysis (OR = 0.383, 95% CI = 0.173-0.848, P = 0.018). The association remained significant after multivariable adjustment for potential confounders. A lower UA level is an independent risk factor of HT post-EVT in anterior circulation AIS patients, but is not associated with the short-term functional outcomes.

Contrast Extravasation is Predictive of Poor Clinical Outcomes in Patients Undergoing Endovascular Therapy for Acute Ischemic Stroke in the Anterior Circulation.

OBJECTIVE: To investigate whether contrast extravasation on dual-energy computed tomography (DECT) in patients with acute ischemic stroke (AIS) after endovascular therapy (EVT) are related to hemorrhagic transformation (HT) and poor short-term clinical outcomes. METHODS: A retrospective analysis was conducted on AIS patients who underwent EVT at Xuanwu hospital between November 2016 and January 2019. DECT was performed on all patients within 24 hours after EVT. Baseline demographic and clinical data were analyzed between patients with and without contrast extravasation and between patients with HT and non-HT, good and poor outcomes at 3 months post-EVT. RESULTS: A total of 166 patients were included in the study with 51 (30.7%) patients experiencing contrast extravasation. Compared to patients without contrast extravasation, patients with contrast extravasation had longer onset to reperfusion time (444.8 minutes versus 374.0 minutes, P = .044) and higher percentages of greater than 3 retriever passes (16.7% versus 31.4%, P = .030). Contrast extravasation was associated with higher risk of HT (P = .038), poor outcome after discharge (P = .030), and longer hospital stay (P = .034). Multivariate analysis showed that contrast extravasation occurrence was an independent factor for HT (OR = 2.150, 95% CI 1.060-4.360, P = .034) and poor short-term outcome (OR = 2.936; 95% CI 1.147-7.518, P = .025). CONCLUSIONS: The presence of contrast extravasation within 24 hours of EVT may be associated with higher risks of HT and may be predictive of unfavorable functional outcomes in AIS patients.

The impact of UV treatment on microbial control and DBPs formation in full-scale drinking water systems in northern China.

To manage potential microbial risks and meet increasingly strict drinking water health standards, UV treatment has attracted increasing attention for use in drinking water systems in China. However, the effects of UV treatment on microbial control and disinfection by-products (DBPs) formation in real municipal drinking water systems are poorly understood. Here, we collected water samples from three real drinking water systems in Beijing and Tianjin to investigate the impacts of UV treatment on microbial control and DBP formation. We employed heterotrophic plate count (HPC), flow cytometry (FCM), quantitative PCR analysis, and high-throughput sequencing to measure microorganisms in the samples. Different trends were observed between HPC and total cell count (measured by FCM), indicating that a single indicator could not reflect the real degree of biological re-growth in drinking water distribution systems (DWDSs). A significant increase in the 16S rRNA gene concentration was observed when the UV system was stopped. Besides, the bacterial community composition was similar at the phylum level but differed markedly at the genera level among the three DWDSs. Some chlorine-resistant bacteria, including potential pathogens (e.g., Acinetobacter) showed a high relative abundance when the UV system was turned off. It can be concluded that UV treatment can mitigate microbial re-growth to some extent. Finally, UV treatment had a limited influence on the formation of DBPs, including trihalomethanes, haloacetic acids, and nitrogenated DBPs. The findings of this study may help to understand the performance of UV treatment in real drinking water systems.

Changes in Event-Related Potentials Underlying Coma Recovery in Patients with Large Left Hemispheric Infarction.

BACKGROUND The aim of this study was to investigate changes in event-related potentials (ERPs) between coma and awakening in patients with large left hemispheric infarction (left LHI). MATERIAL AND METHODS Ten patients with left LHI who suffered coma and survived to awaken were enrolled in this study. The eye-opening subscore of the Glasgow Coma Scale (GCS) was used to assess the extent of patients' arousal. ERPs elicited by the passive oddball paradigm were collected during coma and awakening states, respectively. Peak latencies, peak amplitudes, topography, and time-frequency information of P1, N1, P2, and mismatch negativity (MMN) were compared between the 2 sessions. RESULTS No significant differences in the peak amplitudes and peak latencies of P1 and N1, but significantly greater P2 amplitude with shorter latency in left hemisphere and midline was shown in the awakening state compared with that in coma. A marked shift of P2 topography in response to deviant tones was also seen, from the right centro-parieto-frontal areas during coma to left frontal-midline areas during awakening. MMN waveforms were not detected in 6/10 patients during the coma state, but these 6 patients all recovered to awakening. Evoked oscillations in bilateral hemisphere were profoundly inhibited during the coma state, with poor inter-trial phase synchronization, while obvious activities with broader frequency ranges and consistent inter-trial phase synchronization were observed during awakening state, and different frequency activities were distributed in distinct brain regions. CONCLUSIONS P2 may be a central index of coma recovery and a component of the arousal system. Changes in time-frequency information could provide more information during coma recovery, perhaps including some cognitive processing of the sensory stimulus.

A patient with juvenile-onset refractory status epilepticus caused by two novel compound heterozygous mutations in FARS2 gene.

FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14. The clinical manifestation can be divided into early onset epileptic phenotype and spastic paraplegia phenotype. The purpose of this study was to report a case of juvenile manifesting refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. Microscopic and histochemical examination as well as next-generation sequencing and reconstruction of the three-dimensional structure of FARS2 protein were performed. A 17-year-old man with no developmental delays suffered from generalized tonic-clonic convulsion since 12 years of age and developed refractory status epilepticus 5 years later. No specific etiology was found following brain imaging, muscle biopsy and metabolic studies. DNA sequencing identified two novel compound heterozygous mutations in FARS2, (p.V197M and p.F402S), derived from each parents, respectively. These mutations affected the structure or thermodynamic stability of the protein. This is a case report of juvenile-onset refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. This case confirms and expands the clinicalphenotype and the genotypic spectrum of the FARS2 gene.

Association of Hyponatremia and Risk of Short- and Long-Term Mortality in Patients with Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Hyponatremia is the most common electrolyte disorder in the clinic practice and it is closely related to the prognosis of various diseases. Studies reported that hyponatremia increased the risk of stroke mortality while yielded inconsistent findings during the follow-up period. Thus, a systematic review and meta-analysis to assess the relationship between hyponatremia and the short-term (within 90 days) and long-term (more than 1 year) prognosis of stroke patients was conducted. METHODS: A computerized systematic literature search was performed before November of 2018 for relevant articles evaluating the relationship between hyponatremia and all-cause mortality risk in stroke patients. Pooled relative risk (RR) and hazard risk (HR) with 95% confidence interval (CI) were calculated using DerSimonian-Laird random-effects model. Subgroup analyses were performed according to the follow-up period, types of stroke, different controls, sample size, and sampling time. RESULTS: A total of 12 studies with 21,973 patients were identified. Compared to the nonhyponatremia patients, hyponatremia was associated with a higher risk of all-cause mortality in short-term (RR 1.61, 95% CI 1.33-1.96; HR 1.78 95% CI 1.19-2.75) and long-term follow-up (RR 1.77, 95% CI 1.27-2.47; HR 2.23,95% CI 1.30-3.82). Subgroups analysis showed the similar results in most subgroups. CONCLUSIONS: This meta-analysis concludes that hyponatremia has a significant prognostic value for short- and long-term prognosis to stroke patients.