Homozygous variant of MLC1 results in megalencephalic leukoencephalopathy with subcortical cysts.

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, inherited disorder that causes epilepsy, intellectual disorders, and early onset macrocephaly. MLC1 has been identified as a main pathogenic gene. METHODS: Clinical data such as magnetic resonance imaging (MRI), routine blood tests, and physical examinations were collected from proband. Trio whole-exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (<0.01) in the exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated using Sanger sequencing. RESULTS: Here, we report a new homozygous variant identified in two children from the same family in the MLC1 gene [NM_015166.4: c.838_843delinsATTTTA, (p.Ser280_Phe281delinsIleLeu)]. This variant is classified as variant of uncertain significance (VUS) according to the ACMG guidelines. Further experiments demonstrate that the newly identified variant causes a decrease of MLC1 protein levels when expressed in a heterologous expression system. CONCLUSION: Our case expands on this genetic variation and provides new evidence for the clinical diagnosis of MLC1-related MLC.

Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.

[Clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis: a retrospective analysis]. / å„¿ç«¥çœ¼è‚Œåž‹é‡ç—‡è‚Œæ— åŠ›ä¸åŒå ç–«æŠ‘åˆ¶å‰‚æ²»ç–—æ–¹æ¡ˆçš„å›žé¡¾æ€§åˆ†æž.

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS: For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.

Reversible splenial lesion syndrome in children: a retrospective study of 130 cases.

Background: Reversible splenial lesion syndrome (RESLES) is a new clinico-radiological syndrome. We retrospectively analyzed the clinical features of 130 children with RESLES in China, which is the largest case series available in the literature. Methods: The clinical data of children diagnosed as RESLES in Jiangxi Provincial Children's Hospital between 2017 and 2023 were retrospectively analyzed. The 130 cases were divided into two groups: ≤ 3 years old group (group A) (n = 83) and > 3 years old group (group B) (n = 47). The chi-squared test or Fisher's test was used to evaluate the data. Results: The vast majority of patients (127/130 cases, 97.7%) had prodromal symptoms of infection. Preceding infections of the gastrointestinal tract were statistically more significant in group A (60/83, 72.3%) than in group B (11/47, 23.4%) (P < 0.05). Preceding infections of the respiratory tract were statistically more significant in group B (33/47, 70.2%) than in group A (17/83, 20.5%) (P < 0.05). Seizures were statistically more significant in group A (82/83, 98.8%) than in group B (24/47,51.1%) (P < 0.05). The disturbance of consciousness and headache/dizziness were statistically more significant in group B (27/47, 57.4%; 37/47, 78.7%) than in group A (3/83, 3.6%; 1/83, 1.2%), respectively (P < 0.05). Convulsions with mild gastroenteritis (CwG) were statistically more significant in group A (50/83, 60.2%) than in group B (8/47, 17.0%) (P < 0.05). However, encephalitis/encephalopathy was statistically more significant in group B (20/47, 42.6%) than in group A (10/83, 12.0%) (P < 0.05). MRI showed cytotoxic edema in typical locations (RESLES type-1 limited to the splenium of the corpus callosum and RESLES type-2 spread to the entire corpus callosum, adjacent white matter, or both). There was full recovery of the lesions of MRI in all cases from 3 days to 50 days after the initial examinations. All the children showed normal neurodevelopment. Conclusion: Infection was the most common cause of RESLES. Infections of the gastrointestinal tract are common in ≤ 3 years old children, while infections of the respiratory tract are common in >3 years old children. Younger patients are more likely to develop convulsions, and older children were more likely to have symptoms with disturbance of consciousness and headache/dizziness. RESLES has characteristic MRI manifestations and a good prognosis.

De novo variants in PHF21A cause intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures: A case report and literature review.

PURPOSE: PHF21A has been associated with intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Here, we report a new patient with IDDBCS and review previously reported patients. METHODS: We reviewed the phenotypic and genetic spectrum of the newly diagnosed patient and previously reported patients with IDDBCS. RESULTS: Among 12 patients (11 whose cases were previously reported and the patient whose case we report here), all patients (100%) had intellectual disability (ID) and motor development delay. Three of 8 patients (37.5%) for whom information on cognition was available had severe ID; ID was moderate in two patients (25%) and mild in three patients (37.5%). Seven of the 12 patients (58.33%) had an epileptic phenotype, and the majority (5/7, 71.42%) of affected individuals developed developmental and epileptic encephalopathy (DEE). Of the 5 patients with DEE, three developed infantile epileptic spasm syndrome (IESS). The seizures of 2 patients (2/5, 40%) were controlled by antiseizure medications. Overgrowth, ADHD, hypotonia, ASD, and sleep disorders were observed in 100%, 77.78%, 70%, 50%, and 33.33% of patients, respectively. All of the variants (100%) were de novo heterozygous variants. Three of the 12 patients (25%) had the same variant (p.Arg580*). The most common types of variants were frameshift variants (7/12, 58.33%), followed by nonsense variants (4/12, 33.33%) and missense variants (1/12, 8.33%). Genotype-phenotype relationships for IDDBCS were uncertain, as phenotypic variability was observed among patients with the same variant (p.Arg580*). The patient whose case we report here had a novel PHF21A gene variant (p.Gln97fs*20), which caused neurodevelopmental delay, macrocephaly, and IESS. CONCLUSION: The core phenotypes of IDDBCS include neurodevelopmental delay (intellectual disability and impaired motor skills), craniofacial abnormalities, and overgrowth. ADHD, hypotonia, epilepsy, ASD, and sleep disorders are common symptoms of IDDBCS. Notably, DEE is the dominant phenotype of epilepsy, especially IESS. PHF21A may be a candidate gene for DEE. De novo variants are the main mode of inheritance. The most common types of variants are frameshift variants, and the variant p.Arg580* in PHF21A is located at a mutation hot spot.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

[Prevalence, risk factors and characteristics of delirium in intensive care unit patients: a prospective observational study].

OBJECTIVE: To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients. METHODS: A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO2/FiO2), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis. RESULTS: A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO2/FiO2 at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU. CONCLUSIONS: The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.

Functional analysis of Rickettsia monacensis strain humboldt folA dihydrofolate reductase gene via complementation assay.

Nutritive symbiosis between bacteria and ticks is observed across a range of ecological contexts; however, little characterization on the molecular components responsible for this symbiosis has been done. Previous studies in our lab demonstrated that Rickettsia monacensis str. Humboldt (strain Humboldt) can synthesize folate de novo via the folate biosynthesis pathway involving folA, folC, folE, folKP, and ptpS genes. In this study, expression of the strain Humboldt folA gene within a folA mutant Escherichia coli construct was used to functionally characterize the strain Humboldt folA folate gene in vivo. The strain Humboldt folA folate gene was subcloned into a TransBac vector and transformed into a folA mutant E. coli construct. The mutant containing strain Humboldt folA subclone and a pFE604 clone of the knocked-out folA gene was cured of pFE604. Curing of the folA mutant E. coli construct was successful using acridine orange and 43.5 °C incubation temperature. The plasmid curing assay showed curing efficiency of the folA mutant at 100%. Functional complementation was assessed by growth phenotype on minimal media with and without IPTG between strain Humboldt folA and E. coli folA. Large and homogenous wild-type colony growth was observed for both strain Humboldt and E. coli folA on minimal media with 0.1 mM IPTG, wild-type growth for strain Humboldt folA and pin-point growth for E. coli folA on 0.01 mM IPTG, and pin-point growth without IPTG for both strain Humboldt and E. coli folA. This study provides evidence substantiating the in vivo functionality of strain Humboldt folA in producing functional gene products for folate biosynthesis.

The PaO2/FiO2 is independently associated with 28-day mortality in patients with sepsis: a retrospective analysis from MIMIC-IV database.

BACKGROUND: To clarify the relationship between the PaO2/FiO2 and 28-day mortality in patients with sepsis. METHODS: This was a retrospective cohort study regarding MIMIC-IV database. Nineteen thousand two hundred thirty-three patients with sepsis were included in the final analysis. PaO2/FiO2 was exposure variable, 28-day mortality was outcome variable. PaO2/FiO2 was log-transformed as LnPaO2/FiO2. Binary logistic regression was used to explore the independent effects of LnPaO2/FiO2 on 28-day mortality using non-adjusted and multivariate-adjusted models. A generalized additive model (GAM) and smoothed curve fitting was used to investigate the non-linear relationship between LnPaO2/FiO2 and 28-day mortality. A two-piecewise linear model was used to calculate the OR and 95% CI on either side of the inflection point. RESULTS: The relationship between LnPaO2/FiO2 and risk of 28-day death in sepsis patients was U-shape. The inflection point of LnPaO2/FiO2 was 5.30 (95%CI: 5.21-5.39), which indicated the inflection point of PaO2/FiO2 was 200.33 mmHg (95%CI: 183.09 mmHg-219.20 mmHg). On the left of inflection point, LnPaO2/FiO2 was negatively correlated with 28-day mortality (OR: 0.37, 95%CI: 0.32-0.43, p < 0.0001). On the right of inflection point, LnPaO2/FiO2 was positively correlated with 28-day mortality in patients with sepsis (OR: 1.53, 95%CI: 1.31-1.80, p < 0.0001). CONCLUSIONS: In patients with sepsis, either a high or low PaO2/FiO2 was associated with an increased risk of 28-day mortality. In the range of 183.09 mmHg to 219.20 mmHg, PaO2/FiO2 was associated with a lower risk of 28-day death in patients with sepsis.

The ketogenic diet for Dravet syndrome: A multicenter retrospective study.

OBJECTIVE: The ketogenic diet (KD) is one of the main treatments for drug-resistant epilepsy. However, there have been few multicenter reports on the use of the KD for the treatment of Dravet syndrome (DS). The aim of this study was to analyze the efficacy and safety of this approach based on a large number of multicenter cases. METHODS: This was a retrospective, multicenter cohort study from 14 centers in China. All patients were treated with the KD. We compared the effects of KD intervention time, age, and other factors. RESULTS: From March 2014 to March 2020, we treated 114 patients with DS with the KD. The male-to-female ratio was 67:47. The KD median initiation age was 3 y and 4 mo, and the median number of antiseizure medications (ASMs) was 2.4. KD therapy was the first choice for three patients. Exactly 10.5% of the patients started KD therapy after failure of the first ASM therapy, with 35.1% after failure of the second, 44.7% after the third, and 7% after the fourth or more. After KD therapy for 1, 3, 6, and 12 mo, the seizure-free rates were 14%, 32.5%, 30.7%, and 19.3%, respectively; KD efficacy (≥50% reduction in seizure frequency) were 57.9%, 76.3%, 59.6%, and 43%, respectively; the retention rates were 97.4%, 93%, 71.9%, and 46.5%, respectively; and the rates of adverse events were 25.2%, 19.9%, 11%, and 5.7%, respectively. CONCLUSIONS: Real-world, multicenter data analysis showed that the KD is effective for patients with DS and has a low incidence of side effects.

A newborn with convulsions 12 days after birth was misdiagnosed as neonatal intracranial hemorrhage: Case report.

INTRODUCTION: Cases with early diagnosis of neonatal tuberous sclerosis syndrome (TSC) are relatively seldom seen, and misdiagnosis of intracranial hemorrhage is even more rare. We retrospectively analyzed the clinical data of a case of neonatal tuberous sclerosis with atypical early symptoms and misdiagnosed as more common intracranial hemorrhage of the newborn. PATIENT CONCERNS: The child was female and had no obvious cause of convulsion 12 days after birth. The local hospital was initially diagnosed as "neonatal intracranial hemorrhage, congenital heart disease," and still had convulsions after 5 days of treatment, so it was transferred to neonatal intensive care unit of our hospital. DIAGNOSIS: After admission, cardiac color ultrasound, magnetic resonance imaging, and electroencephalogram were performed, and TSC was diagnosed in combination with clinical symptoms. However, no known pathogenic mutations such as TSC1 and TSC2 were detected by peripheral blood whole exon sequencing. INTERVENTION: After a clear diagnosis, sirolimus, and vigabatrin were given. But there were still convulsions. Topiramate, valproic acid, and oxcarbazepine were successively added to the outpatient department for antiepileptic treatment, and vigabatrin gradually decreased. OUTCOME: Up to now, although the seizures have decreased, they have not been completely controlled. CONCLUSIONS: The TSC of neonatal tuberous sclerosis is different from that of older children. It is usually characterized by respiratory distress and arrhythmia, and may be accompanied by convulsions, but the activity between attacks is normal. However, neonatal intracranial hemorrhage can be caused by premature delivery, birth injury, hypoxia, etc. Its characteristics are acute onset, severe illness, and rapid progression. Consequently, the diagnosis of these 2 diseases should not only be based on medical imaging, but also be combined with their clinical characteristics. When the imaging features are inconsistent with the clinical diagnosis, a comprehensive evaluation should be made again. The timing and pattern of onset of neonatal convulsions can help in differential diagnosis. If there is cardiac rhabdomyoma, subependymal or cortical nodule, skin low melanoma, etc, the possibility of neonatal TSC should be considered, and the diagnosis should be made according to its diagnostic criteria to avoid or reduce misdiagnosis.

Efficacy and safety of phenobarbital for benign convulsions with mild gastroenteritis: A prospective randomized controlled study.

BACKGROUND: previous studies have shown that phenobarbital (PB) is a effective and safe drug in the treatment of benign convulsions with mild gastroenteritis (CwG), but there is a lack of large sample prospective randomized controlled study of different doses. This study was a prospective randomized controlled study on the efficacy and safety of different doses of phenobarbital for CwG. There has been no similar study. METHODS: One hundred twenty CwG cases were included in this study. All of them were hospitalized in the Department of Neurology of Jiangxi Provincial Children's Hospital from January 2019 to August 2021. They were randomly divided into 10 mg/kg single dose group (Group A, n = 60) and 5 mg/kg single dose group (Group B, n = 60). The criteria for judging the efficacy of PB in our study were there was no convulsion in the course of acute gastroenteritis within 2 weeks after using PB. RESULTS: The effective rate was 93.33% in group A and 80.00% in group B. There was significant difference between the 2 groups (P < .05). Drowsiness was the most frequent adverse reaction. 14 cases in group A and 7 cases in group B had drowsiness. There was no significant difference between the 2 groups in the incidence of adverse events such as somnolence, ataxia, abnormal liver function, anemia, abnormal leukocyte, respiratory depression, cognitive impairment, rash, abnormal platelet and abnormal renal function (P > .05). All side reaction were transient. CONCLUSION: it is suggested that PB 10 mg/kg intravenously should be used as soon as possible for CwG, which has high effectiveness and safety.

Case report: A novel de novo variant of SCN8A in a child with benign convulsions with mild gastroenteritis.

Benign convulsions with mild gastroenteritis (CwG) is characterized by afebrile convulsions accompanied by mild gastroenteritis, and it can be considered after central nervous system infection, hypoglycemia, electrolyte disturbance, and moderate and severe dehydration are excluded. Previous studies have suggested that genetics may be involved in CWG. Herein, we reported a novel de novo variant of SCN8A in a child with CwG. This is the first report that SCN8A may be associated with CwG. Our report may provides evidence for the genetic etiology of CwG and expands the phenotypic and genetic spectrum of SCN8A-related disorders, which previously included severe developmental and epileptic encephalopathy (DEE) phenotype, benign epilepsy phenotype, spectrum of intermediate epilepsies, and patients with cognitive and/or behavioral disturbances without epilepsy. Phenotype of CwG has a good prognosis, and it does not require long-term antiepileptic therapy. Overtreatment should be avoided clinically. However, the conclusion needs to be further defined by long-term follow-up and similar clinical reports. In spite of this, our clinical observation provides possible evidence for future studies on the relationship between SCN8A and CwG.

Case report of two affected siblings in a family with thiamine metabolism dysfunction syndrome 5: a rare, but treatable neurodegenerative disease.

BACKGROUND: Thiamine metabolism dysfunction syndrome 5 (THMD5) is a rare inherited metabolic disorder due to thiamine pyrophosphokinase 1(TPK1) deficiency, caused by mutations in TPK1. The core symptoms of the disease is acute or subacute onset encephalopathy, ataxia, muscle hypotonia, and regression of developmental milestones in early infancy, repeatedly triggered by acute infectious illness. However, we report two brothers of THMD5 with compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn), but the prognosis is quite different if thiamine suppled. According to our current knowledge, the missense variant c.224 T > A p.(Ile75Asn) was not published previously. CASE PRESENTATION: Here, we describe two affected siblings in a Chinese family, after an uneventful pregnancy to non-consanguineous and healthy parents. The older brother presented with normal development during the first 6 months of life, but developed regression of developmental milestones after, accompanied with muscle hypotonia, and chronic encephalopathy, and died at 1 year and 6 months old. The younger brother presented with acute onset encephalopathy, ataxia, muscle hypotonia, repeatedly triggered by acute infectious illness. He was compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn) identified by whole exome sequencing. He was diagnosed of THMD5 when he was 11 month. Oral supplementation of thiamine 100 mg/day, the symptoms gradually disappeared. At the age of 2 years and 4 months, he stoped thiamine, his symptoms returned and were once again relieved by oral supplementation of thiamine 100 mg/day. CONCLUSIONS: THMD5 is a rare, but treatable neurodegenerative disease, the clinical phenotype ranges from mild to severe. Massive-dose of thiamine supplementation may ameliorate the course of TPK1 deficiency. When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis. Treatment with thiamine while awaiting the outcome of diagnostic tests may be a good choice.

Efficacy and Safety of the Ketogenic Diet for Mitochondrial Disease With Epilepsy: A Prospective, Open-labeled, Controlled Study.

Background: The ketogenic diet (KD) is increasingly used to treat drug-resistant epilepsy because of its favorable effect on seizure reduction. Patients with mitochondrial diseases tend to experience seizures. Therefore, this study aimed to test the efficacy of the KD on participants with mitochondrial diseases in a controlled trial. Methods: Participants from fourteen clinical centers who were diagnosed with mitochondrial disease were semi-randomized to either the intervention (KD) or control group. The KD group followed a 3-month KD intervention, while the control group received a 1-month normal diet initially and then a 3-month KD intervention. The primary outcome measure was seizure reduction. Biomarker changes, cognitive impairments, and side effects were also recorded, if available. Result: A total of 33 participants were assigned to the KD (n = 22) and control groups (n = 11). In the KD group, 31.8% (7/22) of participants achieved ≥50% seizure reduction after 1 month of diet intervention, which increased to 40.9% (9/22) at 3 months. In the control group, only 18.2% (2/11) of the participants had ≥50% seizure reduction during the normal diet period. After the control group was transferred to the KD, 63.6% (7/11) of participants had >50% seizure reduction, and this rate increased to 72.7% (8/11) at 3 months. The KD also showed high efficacy in participants with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) or pathogenic variants in mitochondrial DNA (mtDNA) (90% and 93.3% response rates, respectively). The most frequent side effects reported at the 3-month review were vomiting, cold, hyperlipidemia, and bloating. Conclusion: The KD is a safe and effective therapy for seizure control in mitochondrial diseases, especially MELAS and pathogenic variants of mtDNA. KD intervention can be considered in the management of these patients.

Intensivists' cognizance of nutrition management and its determinants in ICUs in Guizhou province, China.

BACKGROUND AND OBJECTIVES: To investigate the Intensivists' cognizance of nutritional management and its determinants, and to provide evidence for standardizing nutritional therapy with protocols. METHODS AND STUDY DESIGN: From April to July 2021, a multi-stage sampling method was used to investigate the nutritional cognizance of critical care physicians in secondary and tertiary hospitals in Guizhou Province, China; Questionnaires and scales were used as survey tools. The questionnaires sought general information about the respondents and documented their nutrition cognizance and practice. Five scalar dimensions explored nutritional management, with answers scored for 1-5 points, 3 points being the pass score. RESULTS: 322 respondents from 147 hospitals were surveyed. The average score was passable, but not good at 3.37±0.71 (p<0.01 with 3.0 as reference). Among the five dimensions, evaluation and monitoring of nutritional status had the highest score (3.79±0.67, p<0.01), the understanding of nutritional preparations had the lowest (3.09±0.86, p>0.05), and the scores of other dimensions ranged from 3.21 to 3.49. Almost 70% of intensivists said that they would give priority to other than nutritional therapeutic measures in actual clinical practice. But 96% thought it necessary to strengthen and emphasise nutritional management. CONCLUSIONS: Critical care physicians' knowledge and understanding of nutritional therapy are limited, especially in the use of supportive preparations; Recourse to protocols and standardized nutritional management of assistance may depend on training, assigned role, peer expectations and health system policy, each of which has the potential for advancement in the interest of better nutritional care in provincial Guizhou.

Detection and Isolation of Rickettsia tillamookensis (Rickettsiales: Rickettsiaceae) From Ixodes pacificus (Acari: Ixodidae) From Multiple Regions of California.

The western black-legged tick (Ixodes pacificus) is the most frequently identified human-biting tick species in the western United States and the principal vector of at least three recognized bacterial pathogens of humans. A potentially pathogenic Rickettsia species, first described in 1978 and recently characterized as a novel transitional group agent designated as Rickettsia tillamookensis, also exists among populations of I. pacificus, although the distribution and frequency of this agent are poorly known. We evaluated DNA extracts from 348 host-seeking I. pacificus nymphs collected from 9 locations in five California counties, and from 916 I. pacificus adults collected from 24 locations in 13 counties, by using a real-time PCR designed specifically to detect DNA of R. tillamookensis. DNA of R. tillamookensis was detected in 10 (2.9%) nymphs (95% CI: 1.6-5.2%) and 17 (1.9%) adults (95% CI: 1.2-3.0%) from 11 counties of northern California. Although site-specific infection rates varied greatly, frequencies of infection remained consistently low when aggregated by stage, sex, habitat type, or geographical region. Four novel isolates of R. tillamookensis were cultivated in Vero E6 cells from individual adult ticks collected from Alameda, Nevada, and Yolo counties. Four historical isolates, serotyped previously as 'Tillamook-like' strains over 40 yr ago, were revived from long-term storage in liquid nitrogen and confirmed subsequently by molecular methods as isolates of R. tillamookensis. The potential public health impact of R. tillamookensis requires further investigation.

[Early identification and diagnosis of epilepsy related to fever sensitivity].

Febrile seizures are the most common nervous system disease in childhood, and most children have a good prognosis. However, some epilepsy cases are easily induced by fever and are characterized by "fever sensitivity", and it is difficult to differentiate such cases from febrile seizures. Epilepsy related to fever sensitivity includes hereditary epilepsy with febrile seizures plus, Dravet syndrome, and PCDH19 gene-related epilepsy. This article mainly describes the clinical manifestations of these three types of epilepsy and summarizes their clinical features in the early stage of disease onset, so as to achieve early identification, early diagnosis, and early intervention to improve prognosis.

A case report of atypical hemiplegic migraine with nonheadache onset in a Chinese child.

BACKGROUND: Hemiplegic migraine (HM) is an uncommon subtype of migraine with aura including motor weakness. The core symptoms of HM are headache and motor weakness. However, we report a rare case of atypical HM with nonheadache onset in a Chinese child who was misdiagnosed several times. CASE PRESENTATION: We report a Chinese boy whose onset was sudden when he was 3 years old. He presented with a variety of phenotypes, including fever, vomiting, alternating hemiplegia, and drowsiness, but no headache in the initial stages. Magnetic resonance imaging (MRI) demonstrated unilateral cerebral oedema during the initial episode of hemiplegia. These symptoms recurred many times. As the disease progressed, the patient developed episodic headache. The patient was misdiagnosed several times with encephalitis, alternating hemiplegia of childhood (AHC) and mitochondrial encephalopathy. Whole-exome next-generation sequencing revealed a de novo heterozygous missense mutation in the ATP1A2 gene(p.Gly715Arg) classified as pathogenic and eventually led to a diagnosis of HM when he was 11 years old. Flunarizine was subsequently administered, and no recurrence was found during follow-up. CONCLUSIONS: HM in children may be atypical in the initial stage of the disease, which could manifest as fever, alternating hemiplegia and drowsiness but no headache at the onset. This could easily lead to misdiagnosis. With age, it may eventually manifest as typical HM. Therefore, attention should be given to differentiation in clinical practice.When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment.

Balamuthia mandrillaris encephalitis in a child: case report and literature review.

Balamuthia mandrillaris encephalitis is a rare disease with high mortality in the children. Due to the lack of specificity in clinical manifestations, laboratory tests, and neuroimaging, the diagnosis of the disease is difficult, especially the diagnosis of etiology. Currently, the evidence shows that the diagnosis of the disease depends on local brain biopsy or autopsy, and it is difficult to detect the pathogens by traditional etiological detection methods in blood and cerebrospinal fluid. We report a 9-year-old Chinese girl with B. mandrillaris encephalitis who was diagnosed with metagenomic next-generation sequencing (mNGS). The technology of mNGS can provide rapid, early etiological diagnosis without the need for a local brain biopsy, which can buy time for the early treatment of patients. We also provide a comprehensive literature review on this disease.