Clinical features and outcomes in children with seronegative autoimmune encephalitis.

AIM: To characterize the presenting features and outcomes in children with seronegative autoimmune encephalitis, and to evaluate whether scores at nadir for the Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) or its paediatric-specific modification (ped-CASE) are predictive of outcomes. METHOD: This observational study included children younger than 18 years of age with seronegative autoimmune encephalitis. Demographics and clinical data were collected. The mRS and CASE/ped-CASE scores were used to evaluate disease severity. Descriptive statistics and logistic regression were used for data analysis and to evaluate associations between scale scores and outcomes. RESULTS: Sixty-three children were included (39 [62%] females, median age 7 years, interquartile range [IQR] 4 years 1 months-11 years 6 months), with follow-up available for 56 out of 63 patients (median follow-up 12.2 months, IQR 13.4-17.8). The most frequent presenting neurological manifestation was encephalopathy (81%). Median CASE/ped-CASE and mRS scores at nadir were 12.0 (IQR 7.0-17.0) and 1.0 (IQR 0-2.0) respectively. Thirty-three patients (59%) had persistent neurological deficits at follow-up. Both scoring systems suggested good functional recovery (mRS score ≤2, 95%; CASE/ped-CASE score <5, 91%). CASE/ped-CASE score was more likely than mRS to distinguish children with worse outcomes. INTERPRETATION: Children with seronegative autoimmune encephalitis are likely to have neurological deficits at follow-up. CASE/ped-CASE is more likely to distinguish children with worse outcomes than MRS.

Non-invasive neuromodulation in the acute treatment of migraine: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: A systematic review and meta-analysis was performed to determine the efficacy of non-invasive neuromodulation modalities for the treatment of acute migraine. BACKGROUND: Although pharmacological treatments are the gold standard for the management of acute migraine, some patients may require non-pharmacological treatment options. Non-invasive neuromodulation may provide an alternative, and techniques include transcranial magnetic stimulation (TMS), non-invasive vagal nerve stimulation (nVNS), non-painful remote electrical stimulation (NRES), and external trigeminal nerve stimulation (e-TNS). METHODS: This systematic review and meta-analysis was performed following PRISMA guidelines. We searched PUBMED, EMBASE, ClinicalTrials.gov, Cochrane Center Register of Controlled Trials, and LILACS databases. We included randomized controlled clinical trials studying patients with migraine treated with any form of non-invasive neuromodulation. Primary outcome was pain freedom within 2 h post-treatment. Secondary outcomes were pain relief within 2-h post-treatment and sustained pain freedom and sustained pain relief 48 h post-treatment. RESULTS: Pooled analysis demonstrated a significant effect of non-invasive neuromodulation on pain-free rates within 2 h (RR, 1.66; 95% CI, 1.35 to 2.05; P < 0.00001) and pain relief rates within 2 h (RR, 1.52; 95% CI, 1.13 to 2.05; P = 0.005) post-treatment. Non-invasive neuromodulation had no significant effect on sustained pain freedom at 48 h (RR, 1.56; 95% CI, 0.68 to 3.59; P = 0.29) or sustained pain relief at 48 h (RR, 1.47; 95% CI, 0.57 to 3.77; P = 0.43) after administration. CONCLUSION: Neuromodulation has demonstrated some efficacy in acute migraine management and may be considered in the treatment paradigm of acute migraine in patients with contraindications to pharmacological therapies.

Homozygous pathogenic variant in BRAT1 associated with nonprogressive cerebellar ataxia.

OBJECTIVE: To investigate the pathogenicity of a novel homozygous BRAT1 variant in 2 siblings with nonprogressive cerebellar ataxia (NPCA) through functional studies on primary and immortalized patient cell lines. METHODS: BRAT1 protein levels and ataxia-telangiectasia mutated (ATM) kinase activity in patient-derived and control cell lines were assessed by Western blotting. The impact of the novel BRAT1 variants on mitochondrial function was also assessed, by comparing patient and control cell lines for rates of oxygen consumption and for phosphorylation (S293) of the E1⍺ subunit of pyruvate dehydrogenase (PDH). RESULTS: Two male siblings with NPCA, mild intellectual disability, and isolated cerebellar atrophy were found to be homozygous for a c.185T>A (p.Val62Glu) variant in BRAT1 by whole exome sequencing. Western blotting revealed markedly decreased BRAT1 protein levels in lymphocytes and/or fibroblast cells from both affected siblings compared to control cell lines. There were no differences between the patient and control cells in ATM kinase activation, following ionizing radiation. Mitochondrial studies were initially suggestive of a defect in regulation of PDH activity, but there was no evidence of increased phosphorylation of the E1⍺ subunit of the PDH complex. Measurement of oxygen consumption rates similarly failed to identify differences between patient and control cells. CONCLUSIONS: Biallelic pathogenic variants in BRAT1 can be associated with NPCA, a phenotype considerably milder than previously reported. Surprisingly, despite the molecular role currently proposed for BRAT1 in ATM regulation, this disorder is unlikely to result from defective ATM kinase or mitochondrial dysfunction.

Impact of body mass index on high blood pressure among obese children in the western region of Saudi Arabia.

OBJECTIVES: To evaluate the impact of body mass index (BMI) on high blood pressure among obese children and adolescents in western region, Saudi Arabia.  Methods: Cross-sectional data were obtained from 306 (female: 140, male: 166) child, between August 2016 and March 2017. A questioner was filled by health professionals at ambulatory pediatric clinic followed by waist-hip circumference, height, weight, and blood pressure measurement. Diastolic blood pressure (DBP) and systolic blood pressure (SBP) were adjusted to gender, height, and age. World Health Organization growth standards were used to calculate BMI z-scores. Results: The mean age of subjects was 10.1 years. Body mass index increased SBP by 1.722 mmHg (p=0.001), and DBP by 0.901 mmHg (p=0.006) in boys, and 0.969 mmHg (p=0.036), and DBP by 0.704 mmHg (p=0.045) in girls. Waist hip ratio showed significant difference p=0.041, (p=0.0001) between male and female. Of the baseline characteristics, age greater than 11 years showed significant difference. Symptomatic manifestation of high blood pressure, family history of hypertension, level of activity, income level and post-secondary education in parents, did not show any significant results. Conclusion: Elevated BMI is associated with significantly increased diastolic and systolic blood pressure in obese children, especially in children older than 11 years.

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Bone Characteristics of Two Novel Mutations.

BACKGROUND AND OBJECTIVES: Plastin 3 (PLS3) mutations are associated with an X-linked osteoporosis. Here we describe two new families with novel mutations, including one with a whole gene PLS3 deletion, and review the literature on 9 previously reported cases. RESULTS: Hemizygous male carriers presented with multiple peripheral bone fractures, low bone mineral density (BMD), and vertebral compression fractures. Heterozygous female carriers did not have a history of fragility fractures, although 1 individual presented with low BMD. Apart from greyish-tinged sclera, no other extraskeletal features of osteogenesis imperfecta were identified. Histomorphometry from a transiliac bone biopsy in one of our index patients demonstrated significantly low trabecular bone volume with increased bone turnover. Bisphosphonate treatment was associated with a reduction in the fracture rate and increased bone density. CONCLUSION: Hemizygous mutations in PLS3 may cause a monogenic form of X-linked osteoporosis presenting in childhood with a nonspecific phenotype. No characteristic ocular, dental, or joint abnormalities are defined. When genetic testing is undertaken to investigate for primary causes of bone fragility, we suggest PLS3 be included in order not to miss this diagnosis.