Symptomatic brain involvement as the initial manifestation of neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder that predominantly affects the optic nerve and spinal cord; however, symptomatic brain involvement is not rare and is sometimes an initial manifestation in NMO. In this study, we investigated the characteristic features of patients with NMO with symptomatic brain involvement as the initial manifestation of disease (NMO_brain) compared with patients with NMO who presented initially with optic neuritis or myelitis (NMO_ON/myelitis). We retrospectively reviewed 27 consecutive Korean patients with NMO with aquaporin-4 antibodies. Patients with NMO_brain (n = 9) initially presented with intractable hiccup/nausea/vomiting and/or encephalopathy at a younger age than the patients with NMO_ON/myelitis (n = 18) (p < 0.01). During the disease course, the patients with NMO_brain continued to show more frequent symptomatic involvement of the brain than the 18 patients with NMO_ON/myelitis (p < 0.05). At the final visit, the mean age was also significantly lower in patients with NMO_brain than in patients with NMO_ON/myelitis (p < 0.01); however, the Expanded Disability Status Scale scores, used to evaluate disease progression, were not different between the two groups. Our study suggests that patients with NMO who present initially with symptomatic brain involvement may have earlier disease onset and become disabled at a younger age compared to patients with typical NMO. Additional large scale prospective studies are warranted.     

Variantes del gen ABCB1 como factores de riesgo y factores moduladores de la edad de inicio en pacientes mexicanos con enfermedad desmielinizante

IntroductionThe C1236T, G2677T/A, and C3435T variants of the ABCB1 gene alter the functioning of P-glycoprotein and the transport of endogenous and exogenous substances across the blood-brain barrier, and act as risk factors for some neurodegenerative diseases.This study aimed to determine the association between demyelinating disease and the C1236T, G2677T/A, and C3435T variants of ABCB1 and its haplotypes and combinations of genotypes.MethodsPolymerase chain reaction with restriction fragment length polymorphism analysis (PCR-RFLP) and Sanger sequencing were used to genotype 199 patients with demyelinating disease and 200 controls, all Mexicans of mixed race; frequencies of alleles, genotypes, haplotypes, and genotype combinations were compared between patients and controls. We conducted a logistic regression analysis and calculated chi-square values and 95% confidence intervals (CI); odds ratios (OR) were calculated to evaluate the association with demyelinating disease.ResultsThe TTT and CGC haplotypes were most frequent in both patients and controls. The G2677 allele was associated with demyelinating disease (OR: 1.79; 95% CI: 1.12-2.86; P = .015), as were the genotypes GG2677 (OR: 2.72; 95% CI: 1.11-6.68; P = .025) and CC3435 (OR: 1.82; 95% CI: 1.15-2.90; P = .010), the combination GG2677/CC3435 (OR: 2.02; 95% CI, 1.17-3.48; P = .010), and the CAT haplotype (OR: 0.21; 95% CI: 0.05-0.66; P = .001).TTTTTT carriers presented the earliest age of onset (23.0 ± 7.7 years, vs. 31.6 ± 10.7; P = .0001).ConclusionsThe GG2677/CC3435 genotype combination is associated with demyelinating disease in this sample, particularly among men, who may present toxic accumulation of P-glycoprotein substrates.In our study, the G2677 allele of ABCB1 may differentially modulate age of onset of demyelinating disease in men and women.     

Variations in inflammation-related genes may be associated with childhood febrile seizure susceptibility

PurposeTo investigate whether genetic variants in inflammation-related genes are associated with increased risk of childhood-onset febrile seizures.MethodTagging single nucleotide polymorphisms (SNPs) from 19 inflammation-related candidate genes were identified and genotyped on the Sequenom platform in a sample of Caucasian childhood-onset febrile seizures cases (n = 98) compared to ethnicity, age and gender matched febrile controls presenting without seizures (n = 123). Tests for allelic association were carried out using PLINK. SNPs generating empirical P-values (P < 0.05) were analysed in an expanded Caucasian control sample (n = 2692) from the 1958 Birth Cohort.ResultsSix SNPs generated empirical pointwise significance values P < 0.05 in the febrile seizures case–control analysis in the P2X7R (purinergic receptor P2X7), TLR4 (toll-like receptor 4), IL6R (interleukin 6 receptor) and PTGER3 (prostaglandin E receptor 3, subtype EP3) genes. The most significant result was for missense SNP rs208294 in P2X7R (P = 0.009); this novel association was supported in the expanded case–control analysis using the 1958 Birth Cohort (pointwise P = 0.009, OR = 0.63, familywise P = 0.039).ConclusionGenetic variants in inflammation-related genes, specifically purinergic receptor P2X7, may be involved in susceptibility to childhood-onset febrile seizures.     

“Muscle Pics”, a new body-checking behavior in muscle dysmorphia?

Background and aimsThe internalization of ideal hypermuscular body and pro-muscularity media's influence have shown their importance in muscle dysmorphia development. The aim of the current study is to have a better understanding of links between specific body checking behaviors and muscle dysmorphia in social network context.MethodsIn total, 342 students practicing weightlifting at the university gym in Bordeaux answered to a survey with sociodemographic information and body checking symptoms including taking specific selfies of muscles and muscularity “Muscle Pics” and the MDDI (Muscle Dysmorphic Disorder Inventory).ResultsMuscle dysmorphia was prevalent in 18.7% of our population (64 students). We observed that muscle dysmorphia was correlated to “Muscle Pics”, “Follow-up”, “Message”, “Selfie”, and gym mirror checking with significant results (P < 0.01). Also, « Muscle Pics » were linked to APEDs use, pro-muscularity websites, fitness model comparison and gym mirror checking (P < 0.01). For muscle dysmorphia, “Muscle Pics” have strong predictive results (OR = 5.10, P = 0.000) and (OR = 4.08, P = 0.000) for adjusted. “Follow up” (OR = 4.76, P = 0.000) and (OR = 3.83, P = 0.000) for adjusted, “Muscle Pics Selfie” (OR = 11.20, P = 0.000) and (OR = 11.55, P = 0.000) for adjusted, “Muscle Pics Message” (OR = 4.49, P = 0.001) and (OR = 5.78, P = 0.001) for adjusted.Conclusion“Muscle Pics” showed several links with muscle dysmorphia for global score “drive for size”, “functional impairment” but not for “appearance intolerance” dimension. Pro-muscularity websites, fitness model comparisons and gym mirror checking are linked to muscle dysmorphia and “Muscle Pics”. Future research on “Muscle Pics” will help to provide a better understanding of muscle dysmorphia and its link with pro-muscularity influence websites.     

Association of alpha subunit of GABAA receptor subtype gene polymorphisms with epilepsy susceptibility and drug resistance in north Indian population

GABA (γ-amino butyric acid) receptors have always been an inviting target in the etiology and treatment of epilepsy because of its role as a major inhibitory neurotransmitter in the brain. The aim of our study was to find out the possible role of single nucleotide polymorphisms (SNPs) present in GABRA1 IVS11 + 15 A > G (rs2279020) and GABRG2 588C > T (rs211037) genes in seizure susceptibility and pharmaco-resistance in northern Indian patients with epilepsy. A total of 395 epilepsy patients and 199 control subjects were enrolled for present study. The genotyping was done by PCR-RFLP methods. The GABRA1 IVS11 + 15 A > G polymorphism conferred high risk for epilepsy susceptibility at genotype ‘AG’ (P = 0.004, OR = 1.77, 95% CI = 1.20–2.63), ‘GG’ (P = 0.01, OR = 1.80, 95% CI = 1.15–2.80) and G allele level (P = 0.001, OR = 1.50, 95% CI = 1.16–1.92). Moreover this polymorphism was also associated with multiple drug resistance in patients with epilepsy for homozygous variant ‘GG’ genotype (P = 0.031, OR = 1.84, 95% CI = 1.05–3.23) and G allele (P = 0.020, OR = 1.43, 95% CI = 1.05–1.95). However GABRG2 588C > T polymorphism was not found to be associated either with epilepsy susceptibility or with drug resistance. Overall results indicate differential role of different subunits of GABA_A receptor subtypes in epilepsy susceptibility and pharmacotherapy.     

Complications and operative spine fusion construct length in Parkinson’s disease: A nationwide population-based analysis

There remains a dearth of information regarding the surgical complications following multilevel spine surgery in Parkinson’s disease (PD) patients. This retrospective cohort study was performed to address this issue on a nationwide level using the Nationwide Inpatient Sample from 2001 to 2012. More than 25 postoperative variables were analyzed to assess the impact of fusion construct length on each variable. Subsequently, the same analysis was performed on admissions without PD. 4301 PD patients with spine fusion were identified, of whom 934 (21.7%) underwent fusion of at least three levels; the remaining 3367 underwent fusion of 1–2 levels. Patients with 3+ level fusions were more likely to suffer paraplegia (P = .001; OR = 3.0; 95%CI = 1.5–6.1), hematoma/seroma (P = .009; OR = 1.9; 95%CI = 1.2–3.2), IVC filter placement (P = .018; OR = 2.1; 95%CI = 1.1–3.9), RBC transfusion (P < .001; OR = 3.2; 95%CI = 2.7–3.8), PE (P = .027; OR = 4.5; 95%CI = 1.2–16.9), postoperative shock (P = .023; OR = 7.3; 95%CI = 1.3–39.6), ARDS (P < .001; OR = 4.1; 95%CI = 2.7–6.3), VTE (P = .006; OR = 2.6; 95%CI = 1.3–5.4), acute posthemorrhagic anemia (P < .001; OR = 2.0; 95%CI = 1.7–2.4), device-related complications (P < .001; OR = 3.1; 95%CI = 2.3–4.2), and in-hospital mortality (P = .005; OR = 3.4; 95%CI = 1.5–7.4). 3+ level fusions were also more likely to have LOS > 1 week (P < .001; OR = 2.1; 95%CI = 1.8–2.5), and a nonroutine discharge (P = .005; OR = 1.9; 95%CI = 1.4–2.4). 692,173 non-PD patients with spine fusion were identified; 123,964 (17.9%) underwent 3+ level fusion. Differences between 3+ versus 1–2 level fusions were similar to those in PD patient, but unlike PD patients, postoperative infection was significant while in-hospital mortality, PE and VTE were not. Fusion of at least three levels increased morbidity, mortality, and adverse discharge disposition compared with 1–2 level fusions. Nearly 80% of all spine fusions performed in the United States are fewer than three levels. These findings are worth considering during operative decision-making in both PD and non-PD patients.     

The role of aquaporin-4 antibodies in Chinese patients with neuromyelitis optica

We determined the presence of aquaporin-4 (AQP4) antibodies by indirect immunofluorescence in human AQP4-transfected cells, and evaluated the diagnostic and prognostic relevance of AQP4 antibodies in 210 Chinese patients with neuromyelitis optica (NMO), high-risk NMO (HR-NMO), classic multiple sclerosis (MS), and other neurologic diseases. Patients were enrolled from The General Hospital of the Chinese People’s Liberation Army and followed-up for a median of 2 years. The patients with HR-NMO had optico-spinal MS (OSMS; n = 3), longitudinally extensive transverse myelitis (TM) (n = 35), recurrent optic neuritis (ON) (n = 2), ON with Sjögren’s syndrome (n = 1) and TM positive for Sjögren-A(SSA) antibody (n = 1). The sensitivity and specificity of AQP4 antibodies in NMO were 70.9% and 91%, respectively. The median AQP4 antibody titer was significantly higher in patients with NMO (1:320) than in those with HR-NMO (1:100) and MS (1:50). Relapse of ON or TM was more likely in patients with AQP4 seropositive, than AQP4 seronegative, HR-NMO. Among AQP4 seropositive patients, 66.7% (36/55) had severe ON, 75.9% (41/55) had TM, and 55.6% (30/55) had spinal cord lesions longer than three segments, and there were relapses in eight of 55 patients with ON (14.8%) and 19 of 55 patients with TM (35.2%) during the 2-year follow-up. In conclusion, our study reveals that AQP4 antibody is a sensitive and specific biomarker for discrimination of NMO, classic MS, and other neurological diseases, and is particularly useful for the diagnosis of HR-NMO. AQP4 antibody-positive patients showed higher frequencies of relapse of ON or TM compared with AQP4 antibody-negative patients.     

Further evidence for genetic association of CACNA1C and schizophrenia: New risk loci in a Han Chinese population and a meta-analysis

CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case–control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P = 0.0108, OR = 1.16, 95% CI: 1.03–1.29) and rs1024582 (P = 0.0062, OR = 1.18, 95% CI: 1.05–1.33), and identified a novel risk locus, rs2007044 (P = 0.0053, OR = 1.08, 95% CI: 1.02–1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR = 1.14, 95% CI: 1.07–1.22, P = 0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (χ²[1] = 0.07, P = 0.795), and the difference in pooled ORs between ancestries was not significant (Z = 0.25, P = 0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.     

Facteurs individuels et contextuels participant à l’apparition de comportements violents en cours d’hospitalisations psychiatriques

BackgroundThe prevention of Physical Violent Behavior (VB) toward others during psychiatric hospitalization is a major concern of clinicians. These VBs can have a deleterious impact on the victims, inpatients or caregivers, as well as on the therapeutic milieu. Such violence can also have negative consequences for the assailant patients, such as repeatedly being hospitalized under restraint, stigmatization, and difficulties reintegrating into the community.ObjectivesThis study explored individual (age, gender, marital status, living status, diagnostic) and institutional (type of admission, length of stay, number of previous hospitalizations) risk factors, and how their interactions could increase the risk of VB during psychiatric hospitalizations.MethodThe study was carried out over a period of four years in the psychiatry department of the Lausanne University Hospital, on the 15 wards (219 beds) specialized in acute psychiatric care for adults. All the patients admitted to one of these wards during this period (n = 4518), aged between 18 and 65 years, were included in the study. The sample was divided in two groups: non-violent patients (NVPs) and violent patients (VPs). VBs, defined as physical aggressions against another person, were assessed by the Staff Observation Aggression Scale – Revised (SOAS – R). Only physical assaults, associated or not with other types of violence, involving hospitalized patients were analyzed. Personal and institutional factors were extracted from the hospital database. Chi² independence tests were used to assess differences between groups. Logistic regression models were used to identify the links between each factor and the VB. Classification and regression trees were used to study the hierarchical effect of factors, and combinations of factors, on VBs.ResultsDuring the study period, 414 VBs were reported involving 199 patients (4.40 % of all patients). VPs were significantly younger, male, more likely to be unmarried and living in sheltered housing before hospitalization. In this group, the proportion of patients with diagnoses of schizophrenia, and/or schizophrenia with comorbid substance abuse and cognitive impairment, were higher compared to NVPs. VPs were more frequently admitted involuntarily, had a longer average length of stay and a greater number of previous hospitalizations. The logistic regression model performed on individual factors have shown a significant link between age (OR = 0.99; CI: 0.97–1.00; P-value = 0.024), living in sheltered housing before admission (OR = 2.46; CI: 1.61–3.75; P-value < 0.000), schizophrenic disorders (OR = 2.18; CI: 1.35–3.57; P-value = 0.001), schizophrenic disorders with substance abuse comorbidity (OR = 2.00; CI: 1.16–3.37; P-value = 0.016), cognitive impairment (OR = 3.41; CI: 1,21–8.25; P-value = 0.010), and VBs. The logistic regression model on institutional factors have shown a significant link between involuntary hospitalization (OR = 4.38; CI: 3.20–6.08; P-value < 0.000), length of previous stay (OR = 1.01; CI: 1.00–1.01; P-value < 0.000), number of previous hospitalizations (OR = 1.06; CI: 1.00–1.12; P-value = 0.031), and VBs. The logistic regression model on individual and institutional factors have shown a significant link between age (OR = 0.99; CI: 0.97–1.00; P-value = 0.008), living in sheltered housing before admission (OR = 2.46: CI: 1.61–3.75; P-value = 0.034), cognitive impairment (OR = 3.41; CI: 1.21–8.25; P-value = 0.074), involuntary hospitalization (OR = 3.46; CI: 2.48–4.87; P-value < 0.000), length of previous stay (OR = 1.01; CI: 1.00–1.01; P-value < 0.000), and VBs. The classification and regression trees have shown that the relationship between long length of stay and repeated hospitalizations mainly potentiate the risk of violence.ConclusionThe results of this study have shown the existence of a small group of vulnerable patients who accumulate constrained hospital stays during which violence occurs. Exploring the clinical profiles and institutional pathways of patients could help to better identify these patients and promote a more appropriate mode of support, such as intensive clinical case management. This model could facilitate the development of a clinical network and the links between the structures and partners caring for a patient. This would create a continuous support, avoiding or limiting the lack of continuity of care and care disruption.     

Increased risk of snoring and adenotonsillectomy in children referred for tympanostomy tube insertion

ObjectiveEustachian tube dysfunction and sleep-disordered breathing (SDB) share common pathophysiologic mechanisms. Our objective was to investigate whether children referred for isolated TTI (tympanostomy tube insertion) are at increased risk for snoring and upper airway procedures.MethodsTelephone interviews to parents of children who underwent isolated TTI and to age- and gender-matched controls were conducted.ResultsFour hundred fifty-seven children were included in the study; 352 had isolated TTI (study group) and 105 children were controls. Twenty-two percent of children in the study group were reported to snore compared with 7.6% in the controls (p = 0.001). Eighteen percent of children in the study group were reported to have undergone adenotonsillectomy compared with 4.8% in the controls (p = 0.0005). Future SDB, i.e., either snoring or adenotonsillectomy following TTI, was found in 34% of children in the study group compared with 11% in the controls (p = 0.0004). Children who underwent isolated TTI were at increased risk for future snoring (OR = 3.4, CI: 1.6–7.2) and future adenotonsillectomy (OR = 4.4, CI: 1.7–11.2).ConclusionsChildren who undergo isolated TTI are at increased risk for snoring and for adenotonsillectomy. We suggest that these children be followed for symptoms of SDB on a scheduled basis to allow for early diagnosis and intervention.     

Anticeramide antibody and butyrylcholinesterase in peripheral neuropathies

Ceramide is a glycosphingolipid, a component of nerve and non neuronal cell membrane and plays a role in maintaining the integrity of neuronal tissue. Butyrylcholinesterase (BChE) is a multifunctional enzyme, its involvement in neurodegenerative diseases has been well established. Anticeramide antibody (Ab-Cer) and enzyme BChE have been implicated in peripheral neuropathies. The present study investigates whether there is an association between Ab-Cer and BChE activities and peripheral neuropathies. Patients included: human immunodeficiency virus associated peripheral neuropathy (HIV-PN, n = 39), paucibacillary leprosy (PB-L, n = 36), multibacillary leprosy (MB-L, n = 52), diabetic neuropathy (DN, n = 22), demyelinating sensory motor polyneuropathy (DSMN, n = 13) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 10). Plasma Ab-Cer was measured by indirect enzyme linked immune assay (ELISA) and BChE activity in plasma was measured by colorimetric method. Ab-Cer levels were significantly elevated in MB-L and DN as compared to healthy subjects (HS). BChE levels were significantly higher in MB-L and DN as well as in HIV and HIV-PN. There is no significant difference in either Ab-Cer or BChE levels in DSMN and CIDP. Elevated plasma Ab-Cer and BChE levels may be considered significant in the pathogenesis of neuropathies. The variation in concurrent involvement of both the molecules in the neuropathies of the study, suggest their unique involvement in neurodegenerative pathways.     

Impact of insurance status and race on receipt of treatment for acoustic neuroma: A national cancer database analysis

Acoustic neuroma (AN) management involves surgery, radiation, or observation. Previous studies have demonstrated that patient race and insurance status impact in-hospital morbidity/mortality following surgery; however the nationwide impact of these demographics on the receipt of each treatment modality has not been examined. The National Cancer Data Base (NCDB) from 2004 to 2013 identified AN patients. Multivariate analysis adjusted for several variables within each treatment modality, including patient age, race, sex, income, primary payer for care, tumor size, and medical comorbidities. Patients who were African-American (OR = 0.7; 95%CI = 0.5–0.9; p = 0.01), elderly (minimum age 65) (OR = 0.4; 95%CI = 0.4–0.6; p < 0.0001), on Medicare (OR = 0.6; 95% CI = 0.4–0.7; p = 0.0005), or treated at a community hospital (OR = 0.4; 95%CI = 0.2–0.7; p = 0.007) were less likely to receive surgery. Patients on Medicaid (OR = 1.2; 95%CI = 0.8–1.8; p = 0.04) or treated at an integrated network (OR = 1.2; 95%CI = 0.9–1.6; p = 0.0004) were more likely to receive surgery. Patients who were elderly (OR = 2.2; 95%CI = 1.7–2.9; p < 0.0001) or treated in a comprehensive cancer center (OR = 1.5; 95%CI = 1.3–1.9; p = 0.02) were more likely and Medicaid patients (OR = 0.8; 95%CI = 0.5–1.2; p = 0.04) were less likely to receive radiation. Patients who were elderly (OR = 2.2; 95%CI = 1.7–2.7; p < 0.0001), African-American (OR = 1.5; 95%CI = 1.1–2.0; p = 0.01), on Medicare (OR = 1.8; 95%CI = 1.4–2.3; p = 0.0003), or treated in a community hospital (OR = 3.0; 95%CI = 1.6–5.6; p = 0.0007) were more likely to receive observation. Patients on Medicaid (OR = 0.8; 95%CI = 0.5–1.2; p = 0.04) or treated in an integrated network (OR = 0.8; 95%CI = 0.6–1.0; p = 0.0001) were less likely to receive observation. African-American race, elderly age, and community hospital treatment triaged towards observation/away from surgery; age also triaged towards radiation. Conversely, integrated networks triaged towards surgery/away from observation; comprehensive cancer centers triaged towards radiation. Medicaid insurance triaged towards surgery/away from radiation/observation; this may be detrimental since lack of private insurance is a known risk factor for increased in-hospital postoperative morbidity.     

Serotonin genes and gene–gene interactions in borderline personality disorder in a matched case-control study

Lines of evidence suggest serotonin genes are susceptibility candidates in borderline personality disorder (BPD). However, few molecular genetic studies on BPD have been reported, especially an overall lack of study on epistatic interactions. We genotyped 27 polymorphisms in 7 serotonin genes in 113 Caucasian BPD patients and matched (sex, age and ethnicity) controls. Program UNPHASED was used to perform association analyses for genotypes, alleles and haplotypes with a permutation test of 10,000 simulations. The Multifactor Dimensionality Reduction analysis was used to examine gene–gene interactions in serotonin system, including three other genes (5-HTT, 5-HT2A and MAOA) that we previously reported. Genotype and allele analyses showed that BPD significantly associated with 5-HT2C and TPH2. BPD patients had high frequencies of the 5-HT2C rs6318G allele (p = 0.021) and G/G genotype (OR = 2.25); and TPH2 rs2171363T allele (p = 0.001) and T containing genotypes (OR = 3.40). The 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3A and TPH1 showed no significant association with BPD for genotype, allele and haplotype analyses. We also detected significant interactions between 5-HT2C and TPH2 (p = 0.001), and among 5-HT2C, 5-HTT, MAOA and TPH2 (p = 0.001) in BPD. Patients with 5-HT2C rs6318G/G genotype had a high frequency of TPH2 rs2171363C/T genotype compared with controls. Our study indicates ““that serotonin genes and their interactions may play a role in the susceptibility to borderline personality disorder.     

Identificación de factores de riesgo genéticos asociados a la enfermedad vascular cerebral de tipo isquémico en jóvenes mexicanos

IntroductionNumerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis.MethodsWe performed a case-control study of consecutive ischaemic stroke survivors aged ≤  45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke.Results204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P = .03), tobacco use (P = .02), and the polymorphisms Glu298Asp (genotype: P = .001, allele frequency: P = .001) and C677T (genotype: P = .01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P = .03) and T (P = .01) alleles, hypertension (P = .03), tobacco use (P = .01) and family history of stroke (P = .04) were identified as independent risk factors.ConclusionsThe polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.     

MTHFR C677T polymorphism and migraine risk: A meta-analysis

Many molecular epidemiological studies were carried out in recent years to assess the association between the MTHFR C677T polymorphism and migraine risk in diverse populations. However, the results remain controversial rather than conclusive. The objective of this study was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis. We performed a meta-analysis of published case–control studies concerning the association of the C677T MTHFR polymorphism and migraine. Pooled ORs were established using both random and fixed effects models. This meta-analysis on 17 studies with 8903 cases and 27,637 controls showed that the allele 677T was associated with a significantly increased risk of total migraine in Asians (TT vs. CT + CC: OR = 1.62, 95% CI: 1.13–2.32, P_H = 0.573, I² = 0.0%; T vs. C: OR = 1.18, 95% CI: 1.00–1.40, P_H = 0.147, I² = 44.1%). Similar results were also presented in Asian populations with MA (TT vs. CC: OR = 1.62, 95% CI: 1.11–3.75; TT vs. CT + CC: OR = 2.00, 95% CI: 1.01–3.95; T vs. C: OR = 1.31, 95% CI: 1.02–1.69) without significant heterogeneity. We conclude that the C677T MTHFR polymorphism, responsible for a reduction of the MTHFR activity in folate metabolism, may act as a genetic susceptibility factor for migraine, MA in particular among the subjects of Asian descent.     

General anesthesia or conscious sedation for endovascular therapy of basilar artery occlusions: ETIS registry results

Background and purposeAcute basilar artery occlusions (BAO) are associated with poor outcome despite modern endovascular treatment (EVT). The best anesthetic management during EVT is not known and may affect the procedure and clinical outcome. We compared the efficacy and safety of general anesthesia (GA) and conscious sedation/local anesthesia (CS/LA) in a large cohort of stroke patients with BAO treated with EVT in current clinical practice.MethodsData from the ongoing prospective multicenter Endovascular Treatment In Ischemic Stroke Registry of consecutive acute BAO patients who had EVT indication from January 1st, 2015, to December 31st, 2021, were retrospectively analyzed. Two groups were compared: patients treated with CS/LA versus GA (both types of anesthesia being performed in the angiosuite). Good outcome was defined as modified Rankin Scale (mRS) score 0–3 at 90 days.ResultsAmong the 524 included patients, 266 had GA and 246 had CS/LA (67 LA). Fifty-three patients finally did not undergo EVT: 15 patients (5.9%) in the GA group and 38 patients (16.1%) in the CS/LA group (P < 0.001). After matching, two groups of 129 patients each were retained for primary analysis. The two groups were well balanced in terms of baseline characteristics. After adjustment, CS/LA compared to GA was not associated with good outcome (OR = 0.90 [95%CI 0.46–1.77] P = 0.769) or mortality (OR = 0.75 [0.37–1.49] P = 0.420) or modified thrombolysis in cerebral infarction score 2b-3 (OR = 0.43 [0.16–1.16] P = 0.098). On mixed ordinal logistic regression, the modality of anesthesia was not associated with any significant change in the overall distribution of the 90-day mRS (adjusted OR = 1.08 [0.62–1.88] P = 0.767).ConclusionsSafety, outcome and quality of EVT under either CS/LA or GA for stroke due to acute BAO appear similar. Further randomized trials are warranted.     

Dysmetabolic features of the overweight patients receiving antipsychotic drugs: A comparison with normal weight and obese subjects

BackgroundExtensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI = 25–29.9) without metabolic syndrome or diabetes has not been thoroughly investigated.ObjectiveTo assess the metabolic health of overweight patients receiving antipsychotic drugs.MethodsWe compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes.ResultsCompared with the normal weight subjects (n = 286), overweight patients (n = 212) had higher fasting insulin resistance as assessed with the homeostatic model (P = 0.023), insulin secretion during the oral glucose tolerance test (P = 0.0037), triglycerides (P = 0.0004) and low-density lipoprotein cholesterol (P = 0.0089), and lower levels of high-density lipoprotein cholesterol (P = 0.0014). The obese (n = 50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P = 0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups.ConclusionsOverweight (BMI = 25–29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.     

CSF neurofilament light chain is elevated in OMS (decreasing with immunotherapy) and other pediatric neuroinflammatory disorders

Using a panel of seven brain cell-specific biomarkers in cerebrospinal fluid (CSF), pediatric opsoclonus–myoclonus syndrome (OMS) (n = 234) was compared to pediatric non-inflammatory neurological controls (n = 84) and other inflammatory neurological disorders (OIND) (n = 44). Only CSF NFL was elevated in untreated OMS versus controls (+ 83%). It was 87% higher in OIND than in OMS. On combination treatment with front-loaded ACTH, IVIg, rituximab, median CSF NFL decreased by 60% to control levels. These biochemical data suggest neuronal/axonal injury in some children with OMS without indicators of astrogliosis, and reduction on sufficient immunotherapy.     

Rs3761389 polymorphism in autoimmune regulator (AIRE) gene is associated with susceptibility of myasthenia gravis in Chinese patients

Polymorphism in autoimmune regulator (AIRE) gene is associated with various autoimmune disorders. Abnormal AIRE expression is associated with the development of myasthenia gravis (MG). We investigated the association of polymorphism in AIRE gene and the clinical features and severity of MG. The frequencies of alleles and genotypes were compared between 480 MG patients and 487 healthy controls, as well as among subgroups of MG patients. The frequencies of rs3761389 G allele in MG group (OR = 1.213, CI 95% 1.014–1.451, p = 0.035) and in mild (Oosterhuis score 0–2) subgroup (OR = 1.393, CI 95% 1.110–1.751, p = 0.004) were significantly higher than those in the control group. There were significant differences in the frequencies of rs3761389 genotypes (OR = 1.20, CI 95% 1.00–1.43, p = 0.046, log-additive model) and mild subgroup (OR = 1.32, CI 95% 1.03–1.69, p = 0.0058, log-additive model) compared with the control group. A Logistic regression analysis did not identify rs3761389 genotype as an independent risk factor to predict the severity of MG. This study provides the necessary preliminary data on the association with rs3761389 in AIRE gene with the susceptibility of MG, but not with the severity of MG.     

Serum uric acid levels and their correlation with clinical and cerebrospinal fluid parameters in patients with neuromyelitis optica

Although uric acid (UA) concentration has been considered a surrogate marker for monitoring the progression of multiple sclerosis (MS), less is known about the relationship between UA and the progression of neuromyelitis optica (NMO). We therefore investigated the correlations between serum UA concentrations and the clinical and cerebrospinal fluid (CSF) parameters in patients with NMO. Factors assessed in patients with NMO included gender, disease duration, disease disability, CSF white blood cell (WBC) counts, oligoclonal bands (OB), 24 hour immunoglobulin (Ig)G index, and myelin basic protein (MBP) concentration. Mean serum UA concentrations were compared in patients with NMO and in a control group of patients with cerebral infarction (CI). We found that mean serum UA concentrations were significantly lower in patients with NMO compared to those with CI (206.81 compared to 274.00 μmol/L, p = 0.00). Serum UA concentration was correlated directly with NMO duration (p = 0.013) and was inversely correlated with the Expanded Disability Status Scale score (p = 0.021). Patients with NMO with lower serum UA concentrations tended to be positive for OB, to have higher CSF protein and MBP concentrations, and to have higher WBC counts and 24 hour IgG index, but no correlation was statistically significant. UA may be a useful surrogate marker for monitoring NMO activity.