Association of HLA‐DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort

Background and objective: The HLA‐DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA‐DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS. Methods: The HLA‐DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA‐DRB1 allelic frequencies were compared between OCB‐positive and OCB‐negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA‐DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB. Results: We found 206 OCB‐positive and 62 OCB‐negative patients. The HLA‐DRB1*15 allele in OCB‐positive patients had a higher frequency when compared with OCB‐negative patients (39.3% in OCB‐positive vs. 16.1% in OCB‐negative, OR = 1.38 95% CI = 1.18–1.61, P < 0.001). The other alleles did not show differences. When we compared with controls, the HLA‐DRB1*15 allele was associated with the disease only in the OCB‐positive patients group. None of the 55 genotypes found showed any association with the presence or absence of OCB. Conclusions: HLA‐DRB1*15 allele is associated with OCB‐positive patients with MS when studying a Spanish MS population.     

Assessing the value of spinal cord lesions in predicting development of multiple sclerosis in patients with clinically isolated syndromes

The purpose of this study was to determine the value of spinal cord lesions as a predictive factor for conversion in clinically isolated syndrome (CIS) patients. Patients with CIS and without immunomodulatory treatment were prospectively included. Age at onset, sex, clinical syndrome at onset, oligoclonal bands, and presence, number and location of lesions on brain and spinal MRI were analyzed. Conversion to multiple sclerosis (MS) was the primary endpoint. Cox regression was used to compare outcomes between groups. A total of 75 patients were included: 53 (71%) women, mean age at onset 32.7 years (SD ± 7.5), mean follow-up time 72.5 months (SD ± 9; range 17-104 months). There were 11 (14.6%) patients with one focal spinal cord lesion, while 13 (17%) patients had two or more spinal cord lesions at the first scan during the onset of the disease. Of the 23 patients (30.6%) who converted to clinically definite MS (CDMS), 2 had a normal spinal cord MRI, 8 patients had one spinal cord lesion, and 13 had more than one lesion on MRI (p < 0.001). In multivariable analyses, one focal spinal cord lesion was significantly associated with increased risk of conversion to MS (p = 0.01, HR 3.5, CI 95% 2.1-6.9), while the presence of two or more focal spinal cord lesions was independently associated with a higher risk of conversion to MS (p < 0.001, HR 5.9, CI 95% 3.2-10.8). CIS patients with an abnormal baseline spinal cord MRI have a higher risk for developing clinically definite MS, independent of brain lesions as well as the presence of cerebrospinal fluid oligoclonal banding (OSF-OB) .     

Social and behavioral predictors of insufficient sleep among African Americans and Caucasians

BackgroundFew studies have examined the social and behavioral predictors of insufficient sleep.ObjectiveTo assess the social and behavioral predictors of insufficient sleep in the U.S. population.MethodsData from the 2009 Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. Telephone interviews were conducted in six representative states that completed the optional sleep module. A total of 31,059 respondents were included in the present analysis. BRFSS-provided weights were applied to analyses to adjust for the use of complex design.ResultsThe mean age for the sample was 56 ± 16 years, with 63% of the sample being female; 88% identified as non-Hispanic white and 12% identified as non-Hispanic black; 42% were not married and 8% did not have a high school degree. The prevalence of insufficient sleep (<7 hours) was 37%. Multivariate-adjusted logistic regression revealed associations of four important factors with insufficient sleep, which were: working more than 40 hours per week [OR = 1.65, p < 0.001, 95% CI = 1.65–1.66], black race/ethnicity [OR = 1.37, p < 0.001, 95% CI = 1.37–1.38], history of heart disease [OR = 1.26, p < 0.001, 95% CI = 1.25–1.28], care-giving to family/friends [OR = 1.50, p < 0.001, 95% CI = 1.49–1.51], and lack of social and emotional support [OR = 1.24, p < 0.001, 95% CI = 1. 23–1.25].ConclusionSocial and behavioral predictors of health uniquely contribute to the report of insufficient sleep and should be considered when developing programs to increase awareness of the adverse effects of insufficient sleep.     

Causes of death in patients with multiple sclerosis and matched referent subjects: a population‐based cohort study

Background and purpose: Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death. Methods: We conducted a population‐based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs). Results: Patients with MS had a 3.5‐fold increased mortality rate for all‐cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63–4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16–10.87) (but not in ex‐smokers) and subjects with a body mass index of <20 kg/m² (HR 6.67, 95% CI 3.50–12.73). The HR was highest for infectious/respiratory‐related deaths (HR 7.69, 95% CI 4.92–12.02) and was significantly increased for deaths related to cardiovascular diseases (2.4‐fold) and cancer (1.9‐fold), but not for accidents and suicide related deaths. Conclusion: British patients with MS have a 3.5‐fold increased mortality rate compared with the general population. Smoking and respiratory diseases are major (potentially preventable) factors related to increased mortality rate amongst patients with MS.     

The role of routine echocardiography in unselected patients with cerebrovascular ischaemic events

Background: Cardiac embolism is an important etiology of cerebrovascular ischaemic events (CIE). Echocardiography is routinely performed in patients with CIE despite guidelines recommending restriction of echocardiography to patients with clinically suspected cardioembolism. Objective: The aim of this study was to examine the therapeutic impact and prognostic role of echocardiographic findings in an unselected population suffering from CIE. Methods: Between November 2006 and November 2007, 319 patients with CIE underwent evaluation by transthoracic echocardiography (TTE) and in addition by transesophageal echocardiography (TEE) if deemed mandatory (n = 49). The combined clinical end‐point included death or recurrent CIE, occurring during a follow‐up period of 3 and 12 months, respectively. Results: After 3 months of follow‐up, the combined end‐point was noted in 30 (9%) and after 12 months in 43 (13%) patients. In multivariate analysis, atrial fibrillation (AF) (HR 2.12, 95% CI 1.38–3.25; P < 0.001) and coronary artery disease (CAD: HR 1.85, 95% CI 1.21–2.81; P = 0.004) were predictors of events occurring during short‐term follow‐up. After 1 year of follow‐up, AF (HR 1.67, 95% CI 1.19–2.32; P = 0.003) and CAD (HR 1.5, 95% CI 1.09–2.06; P = 0.01) were associated with the combined end‐point. Echocardiographic parameters assessed at study entry were not independently related to an adverse outcome. Conclusion: Whereas AF and CAD appear to increase the risk of events after suffering from CIE, echocardiographic findings were not independently associated with the combined end‐point of recurrent CIE or death.     

Infections of the central nervous system as a risk factor for mental disorders and cognitive impairment: A nationwide register-based study

BackgroundCNS infections have been suggested as risk factors for cognitive decline and mental disorders; however, large-scale studies have been lacking regarding types and agents of CNS infections.MethodsWe utilized the unique personal registration number to create a cohort of 1,709,867 individuals born 1977–2010. CNS infection was exposure and data were analysed with 1) cox regression analyses estimating hazard ratios (HR) for developing mental disorders and 2) binomial regression estimating relative risk (RR) for completion of 9th grade including average grade score in a sub-cohort born 1988–1998.ResultsCNS infection increased the risk for developing mental disorders with a HR of 1.34 (95% CI 1.27–1.42). The highest risk observed was within the first 6 months after the CNS infection with a HR of 26.98 (95% CI 21.19–34.35). Viral CNS infections (HR 1.47, 95% CI 1.35–1.61) conferred a higher risk (p < 0.001) than bacterial (HR 1.24, 95% CI 1.15–1.35). Encephalitis (HR 1.64, 95% CI 1.41–1.90) conferred a higher risk (p < 0.001) than meningitis (HR 1.26, 95% CI 1.18–1.35). The risk was highest for organic mental disorders (HR 6.50, 95% CI 5.11–8.28) and disorders of intellectual development (HR 3.56, 95% CI 2.94–4.31), with a HR of 19.19 (95% CI 7.46–49.35) for profound disorder of intellectual development (IQ < 20). Furthermore, CNS infection decreased the RR of completing 9th grade of mandatory schooling (RR 0.89, 95% CI 0.88–0.91) and lowered average grade score for completers (p < 0.001).ConclusionsCNS infections increased the risk for mental disorders and decreased the likelihood of completing 9th grade, indicating long-term consequences of CNS infections.     

Increased peripheral blood CD5+ B cells predict earlier conversion to MS in high-risk clinically isolated syndromes

Clinically isolated syndrome patients (CIS) with oligoclonal IgG bands (OCGB) are at high risk for clinically definite multiple sclerosis (MS). However, the outcome for individual patients is unpredictable and the search for reliable blood markers predicting early conversion to multiple sclerosis (MS) has clinical relevance. CD5+ B cells (CD5+Bc) are involved in some autoimmune diseases. This study investigated whether high blood CD5+Bc percentage can predict CIS conversion to MS. Fifty-five consecutive CIS showing OCGB were prospectively studied. Every patient underwent a brain MRI study and a flow cytometry analysis of CD5+Bc percentage. Conversion to MS was studied during follow-up. The CD5+Bc percentage was assessed in 40 controls and a cut-off value of 3.5% (mean+2 SD) was calculated. A blood CD5+Bc percentage above this value predicted earlier conversion to MS in the whole group (hazard ratio [HR]: 3.40; 95% confidence interval [CI]: 1.69-6.68; p=0.0005) and in CIS patients fulfilling three or more Barkhof-Tintoré criteria plus OCGB, who showed higher risk for MS (HR: 3.79; 95% CI: 1.86-15.32; p=0.0018). Multivariate analysis also showed a predictive value for high blood CD5+Bc count (HR: 4.3; 95% CI: 1.9-9.5; p<0.0001). It was concluded that high percentages of CD5+Bc independently associate with increased risk of early conversion to MS in CIS patients with OCGB and Barkhof-Tintoré criteria.     

Adherence to antidepressant medications is associated with reduced premature mortality in patients with cancer: A nationwide cohort study

Background: Depression and anxiety are common in cancer and antidepressants (AD) are efficacious treatment. The relationship between AD adherence and mortality in cancer is unclear. This study aimed to evaluate the association between adherence to AD and all‐cause mortality in a population‐based cohort of patients with cancer. Materials and Methods: We conducted a 4‐year historical prospective cohort study including 42,075 patients with cancer who purchased AD at least once during the study period. Adherence to AD was modeled as nonadherence (<20%), poor (20–50%), moderate (50–80%), and good (>80%) adherence. We conducted multivariable survival analyses adjusted for demographic and clinical variables that may affect mortality. Results: During 1,051,489 person‐years at risk follow‐up, the adjusted hazard ratios (HR) for mortality were 0.89 (95% confidence interval [CI]: 0.83–0.95), 0.77 (95% CI: 0.66–0.72), and 0.80 (95% CI: 0.76–0.85) for the poor, moderate, and good adherence groups, respectively, compared to the nonadherent group. Analysis of the entire sample and a subgroup with depression, for cancer subtypes, revealed similar patterns for breast, colon, lung, and prostate cancers, but not for melanoma patients. Multivariate predictors of premature mortality included male gender (HR 1.48 [95% CI: 1.42–1.55]), current/past smoking status (HR 1.1, [95% CI: 1.04–1.15]; P < .0001), low socioeconomic status (HR 1.1, [95% CI: 1.03–1.17]; P < .0001) and more physical comorbidities. Conclusions: The present study is the first to demonstrate that higher adherence to AD is associated with a decrease of all‐cause mortality in a large nationwide cohort of cancer patients. Our data add to the pressing need to encourage adherence to AD among cancer patients.     

Concomitant irritable bowel syndrome is associated with failure of step‐down on‐demand proton pump inhibitor treatment in patients with gastro‐esophageal reflux disease

Background The predictors for treatment failure of on‐demand proton pump inhibitor (PPI) therapy in gastro‐esophageal reflux disease (GERD) patients are unclear. We studied the efficacy and predictors for treatment failure of step‐down on‐demand PPI therapy in patients with non‐erosive reflux disease (NERD) and those with low grade erosive esophagitis. Methods Consecutive symptomatic GERD patients who had positive esophageal pH studies and complete symptom resolution with initial treatment of esomeprazole were given step‐down on‐demand esomeprazole for 26 weeks. Patients with esophagitis of Los Angeles (LA) grade C or above and recent use of PPI were excluded. Treatment failure was defined as an inadequate relief of reflux symptoms using global symptom assessment. Potential predictors of treatment failure were determined using multivariate analysis. Key Results One hundred and sixty three NERD and 102 esophagitis patients were studied. The 26‐week probability of treatment failure was 36.2% (95% CI: 23.9–46.5%) in NERD group and 20.1% (95% CI: 10.9–28.3%) in esophagitis group, respectively (P = 0.021). Irritable bowel syndrome (adjusted HR: 2.1, 95% CI: 1.5–3.8, P = 0.01), in addition to daily reflux symptom (adjusted hazard ratio: 2.7, 95% CI: 1.9–4.2, P = 0.001) and concomitant dyspepsia (adjusted hazard ratio: 1.7, 95% CI: 1.1–2.8, P = 0.04), were independent predictors for treatment failure. Conclusions & Inferences Compared to patients with esophagitis, NERD patients have higher failure rate of on‐demand PPI therapy. Concomitant irritable bowel syndrome, in addition to daily reflux symptom and dyspepsia, is associated with the failure of on‐demand PPI in these patients.     

High‐Sensitivity C‐Reactive Protein is a Strong Risk Factor for Death after Acute Ischemic Stroke among Chinese

Background and purpose: Elevated plasma C‐reactive protein (CRP) has been suggested as a risk factor for ischemic stroke (IS) and coronary ischemic disease. Evidence has shown that high‐sensitivity CRP (hs‐CRP) is related to a worsening prognosis after IS, but hs‐CRP was rare in a large‐sample study in a Chinese population. We investigated the associations between hs‐CRP and outcome of Chinese patients after acute IS. Methods: Seven hundred and forty‐one consecutive acute IS patients (74.9% male, mean age 60.9 years), with baseline characteristics and hs‐CRP measured within 24 h after hospitalization, were admitted in this study. We also prospectively followed up for clinical outcome and death 3 months after disease onset. hs‐CRP was divided into two categories: hs‐CRP >3 mg/L and hs‐CRP ≤3 mg/L. Survival analysis using multivariable Cox regression was performed to analyze the association between hs‐CRP and stroke outcomes after adjusting for potential confounding factors. Results: Compared with low hs‐CRP, patients with high hs‐CRP (>3 mg/L) had a significantly higher rate of all‐cause death (0.71% vs. 10.00%; P < 0.001) at 3 months after stroke onset. High hs‐CRP was an independent risk factor for all‐cause death (HR, 6.48; 95% CI, 1.41 to 29.8; P= 0.016), as well as history of atrial fibrillation (HR, 5.24; 95% CI, 1.83 to 15.0; P= 0.002), no statin therapy during hospitalization (HR, 4.56; 95% CI, 2.18 to 9.55; P < 0.001), high homocysteine (>15.1 mmol/L) (HR, 2.66; 95% CI, 1.26 to 5.60; P= 0.01); fasting glucose (>6.1 mmol/L) (HR, 9.14; 95% CI, 3.34 to 25.0; P < 0.001), NIHSS at admission (HR, 2.35; 95% CI, 1.35 to 4.09; P= 0.003) and history of coronary heart disease (CHD) (HR, 2.34; 95% CI, 1.06 to 5.17; P= 0.035). Kaplan–Meier survival curves showed a higher risk of death for patients with hs‐CRP >3 mg/L (P= 0.016). Conclusion: Elevated plasma hs‐CRP independently predicted risk of all‐cause death within 3 months after acute IS in Chinese patients.     

Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology

Aim Biomarkers such as autoantibodies, neopterin, and oligoclonal bands (OCBs) are increasingly used for the diagnosis of treatable inflammatory central nervous system (CNS) disorders. We investigated the correlation between the results of OCB testing and clinical diagnoses in a large contemporary cohort of children with a broad range of neurological conditions. Method Cerebrospinal fluid (CSF) and serum from 200 children (94 females, 106 males; age range 2mo–15y 10mo, mean age 6y 9mo, SD ±4.9) who underwent CSF investigation for their neurological condition were tested for OCBs using isoelectric focusing. Results The patients were divided into those with inflammatory (n=58) and non‐inflammatory (n=142) CNS disorders. Intrathecal OCBs (OCBs restricted to the CSF) were found in 11 out of 58 (19%) of those with inflammatory CNS disorders compared with none of the 142 patients with non‐inflammatory CNS disorders (p<0.001). Diseases associated with intrathecal OCB were multiple sclerosis, Rasmussen encephalitis, N‐methyl‐d ‐aspartate receptor (NMDAR) encephalitis, voltage‐gated potassium channel (VGKC) encephalopathy, herpes (HSV) encephalitis, ‘other’ encephalitides, acute cerebellar ataxia, and aseptic meningitis. Mirrored OCBs (identical OCBs in the serum and CSF) were less specific but were still found in 14 out of 58 (24%) children with inflammatory CNS disorders compared with only 6 out of 142 (4%) children with non‐inflammatory CNS disorders (p<0.001). Diseases associated with mirrored OCBs included acute disseminated encephalomyelitis (ADEM), VGKC encephalopathy, West syndrome, NMDAR encephalitis, ‘other’ encephalitides, polio‐like illness, Rasmussen encephalitis, cerebral vasculitis, metachromatic leukodystrophy, and bacterial meningitis. Intrathecal OCBs and mirrored OCBs had a positive predictive value for inflammatory CNS disease of 1 (95% confidence interval [CI] 0.68–1) and 0.7 (95% CI 0.46–0.87) respectively. Conclusion Intrathecal OCBs were restricted to patients with inflammatory CNS disorders. They are a useful, but non‐specific, biomarker of CNS inflammation of multiple causes. Mirrored OCBs are less specific, but still support a possible inflammatory CNS disorder. The presence of either intrathecal or mirrored OCBs should raise suspicion of an inflammatory CNS disorder.     

The impact on socio‐emotional development and quality of life of language impairment in 8‐year‐old children

Aim To estimate the impact of different types of language disorders on socio‐emotional development and health‐related quality of life (HRQOL) in 8‐year‐old children. Method In a prospective cohort including 13 427 newborns, of 10 911 eligible children (66 excluded because of intellectual disability or foreign language, 2448 lost to follow‐up due to house moves, refusal, death or other reasons) written consent was obtained from the parents of 6051 then 8‐year‐old children (55%). Questionnaires, completed by the parents of 4745 children (2323 males, 2412 females) and the teachers of 4771 children (2360 males, 2411 females), included validated measures to define type of language disorder and to assess socio‐emotional development and HRQOL. Results In 377 (8.2%) children, speech/language disorders were identified. Children with receptive language disorders had more unfavourable scores for extraversion (9.7, 99% CI 9.3–10.1, p=0.006), school attitude (7.8, 99% CI 7.4–8.2; p<0.001), agreeableness (9.1, 99% CI 8.6–9.6, p<0.001; normal ranges 7–13), and quality of life (49.6, 99% CI 48.8–51.0, p<0.001; normal range 40–60), as compared to children without these disorders. Pragmatic disorders and suspected autism were associated with the most unfavourable scores, for school attitude 8.1 (99% CI 6.9–9.3, p<0.001) and 7.5 (99% CI 6.1–8.9, p=0.002), and for quality of life 42.9 (99% CI 40.3–45.5, p<0.001) and 36.2 (99% CI 30.0–42.4, p<0.001). Interpretation Language impairment at school age has a large impact on children’s behaviour and daily life.     

A randomised,placebo-controlled 52-week trial of continued quetiapine treatment in recently depressed patients with bipolar I and bipolar II disorder

Objectives. To examine the longer-term efficacy of quetiapine monotherapy in bipolar depression in a preplanned pooling of data from the EMBOLDEN I and II studies. Methods. Patients (N = 584) with bipolar I or II disorder (most recent episode: depressed) who achieved remission after 8 weeks of treatment with quetiapine (300 or 600 mg/day) were randomised to the same quetiapine dose or placebo for 26–52 weeks or until mood event recurrence. Results. The risk for recurrence of a mood event was significantly lower with quetiapine than placebo (HR 0.51 (95% CI: 0.38–0.69); P < 0.001). Quetiapine was associated with a lower risk for recurrence of depressive events (HR 0.43 (95% CI: 0.30–0.62); P < 0.001) but recurrence of manic/hypomanic events was not significantly reduced (HR 0.75 (95% CI: 0.45–1.24; P = 0.263). There was a lower risk of recurrence of mood events in bipolar I (HR 0.58 (95% CI: 0.41–0.82), P = 0.002) and bipolar II patients (HR 0.33 (95% CI: 0.18–0.60), P < 0.001). Discontinuation rates due to adverse events were 4.3, 4.0 and 1.7% for quetiapine 300 mg/day, 600 mg/day and placebo, respectively. Safety data, including changes in lipid and glucose parameters, were consistent with the recognized profile of quetiapine. Conclusions. The efficacy of quetiapine monotherapy in bipolar depression is maintained during continued treatment for 26–52 weeks. Quetiapine was generally well tolerated.     

Gender differences in bipolar disorder type I and II

Objective: We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in‐ and out‐patients. Method: In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in‐ and out‐patients, 160 patients (85.1%) could be followed up for 18 months with a life chart. Results: After adjusting for confounders, no marked differences in illness‐related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12–16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16–0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22–3.27). Conclusion: Men and women with type I and II BD have fairly similar illness‐related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium‐term follow‐up, females appear to have a higher hazard of recurrence than males.     

Predictors and course of medically intractable epilepsy in young children presenting before 36 months of age: A retrospective, population-based study

Purpose: To determine the prevalence and identify predictors of medical intractability in children presenting with epilepsy before 36 months of age, and to assess the effect of medical intractability on long‐term mortality and intellectual function. Methods: Children with newly diagnosed epilepsy before 36 months between 1980 and 2009 while resident in Olmsted County, MN, were identified. Medical records were reviewed to collect epilepsy‐specific variables and long‐term outcome data. Medically intractable epilepsy was defined as either (1) seizure frequency greater than every 6 months at final follow‐up and failure of two or more antiepileptic drugs for lack of efficacy, or (2) having undergone epilepsy surgery after failure to respond to two or more antiepileptic drugs. Key Findings: One hundred twenty‐seven children with new‐onset epilepsy were identified and followed for a median of 78 months. Medically intractable seizures occurred in 35%, and significant predictors on multivariate analysis were age ≤12 months at diagnosis (odds ratio [OR] 6.76, 95% confidence interval [CI] 2.00, 22.84, p = 0.002), developmental delay at initial diagnosis of epilepsy (OR 20.03, 95% CI 3.49, 114.83, p = 0.0008), neuroimaging abnormality (OR 6.48, 95% CI 1.96, 21.40, p = 0.002), and focal slowing on initial EEG (OR 5.33, 95% CI 1.14, 24.88, p = 0.03). Medical intractability occurred early in the course in most children, being seen in 61% by 1 year, and 93% by 5 years after initial diagnosis. Mortality was higher (20% vs. 0%, p < 0.001) and intellectual outcome poorer (p < 0.001) if epilepsy was medically intractable. Significance: One third of children presenting with epilepsy before 36 months will be medically intractable, and significant predictors are identified. Medically intractable epilepsy is associated with increased mortality risk and significant intellectual disability.     

Long‐term employment of adults with childhood‐onset epilepsy: A prospective population‐based study

Purpose: Our aim was to determine the long‐term employment and predictive factors in adults with childhood‐onset epilepsy living in the community. Methods: A population‐based incidence cohort of 144 children prospectively followed since their first unprovoked seizure before the age of 16 years up to a mean age of 48. Results: At a mean age of 23 years (range 18–35 years) 85 (71%) of 119 patients living in the community were employed. Predictive of employment at a mean age of 23 were normal intelligence [odds ratio (OR) 14.5, 95% confidence interval (CI) 4.5–46.8, p < 0.01], vocational education (OR 15.2, 95% CI 2.9–79.9, p < 0.01), and age at onset of epilepsy older than 6 years (OR 4.9, 95% CI 1.3–19.2, p = 0.02). At the mean age of 48 years (range 43–59 years), 45 (59%) of 76 patients living in the community were employed, as were 63 (78%) of 81 controls (patients vs. controls, p = 0.01). In 40 (53%) of 76 surviving patients employed between age 23 and 48, four factors were found to predict employment: normal intelligence (OR 15.8; 95% CI 2.4–102.4, p < 0.01), having offspring (OR 6.1; 1.5–25.0, p = 0.01), uninterrupted 5‐year terminal remission (5YTR) from age 23 to age 48 (OR 4.8; 1.1–19.9, p = 0.03), and no history of status epilepticus (OR 12.8; 1.8–90.9, p = 0.01). Conclusions: Normal intelligence, onset of epilepsy at age older than 6, and good vocational education appear to predict employment in early adulthood. Normal intelligence, having offspring, uninterrupted remission, and no history of status epilepticus appear to predict lasting employment into middle age.     

Alcohol consumption in the elderly and risk of dementia related death - a Norwegian prospective study with a 17-year follow-up

Purpose: The aim of this study was to determine the association between alcohol intake and risk of dementia related death, taking into account relevant confounding and mediating factors. Materials and Methods: Data was obtained from a Norwegian prospective study with a 17-year follow-up. The study population comprised 25,635 participants aged between 60 and 80 years at the time of examination from the Cohort of Norway (CONOR). Cox regression was used to investigate the association between alcohol use and dementia related death. Results: Nearly half (12,139) of the study population died during follow-up, of which 1,224 had a diagnosis of dementia on their death certificate. The risk of dementia related death was significantly higher among abstainers than among individuals that drank alcohol once per month (HR = 1.33, 95% CI = 1.14–1.56, p < 0.001, in a fully adjusted model). Respondents with missing information regarding alcohol consumption (representing 5% of the study population) had the highest risk of dementia related death (HR = 1.60, 95% CI = 1.28–2.00, p < 0.001) and also significantly higher mortality rates due to alcohol-related causes (HR = 1.41, 95% CI = 1.03–1.93, p = 0.031) and other causes (HR = 1.32, 95% CI = 1.21–1.43, p < 0.001), all compared to those drinking alcohol no more than once per month. Conclusion: These findings suggest that the risk of dementia related death is significantly higher among elderly abstainers than among those who drink alcohol, after adjusting for relevant confounders. However, care should be taken in interpretation of data due to missing information on drinking frequency, as this missing-group might have a large share of the heavy drinkers in the study cohort.     

Seizure worsening and its predictors after epilepsy surgery

Purpose: This study aims to investigate seizure worsening and its predictors after epilepsy surgery. Methods: A retrospective chart review of patients who underwent unilobar epilepsy surgery between 1990 and 2007 and had recurrence of at least one seizure was performed. Seizure worsening was defined as an increase in total average monthly seizure frequency, average monthly generalized tonic–clonic seizures (GTCS), new‐onset GTCS, or new‐onset status epilepticus. The occurrence of sudden unexpected death in epilepsy (SUDEP) was captured. Multivariate logistic regression analysis was used to identify predictors of worsening. Key Findings: A total of 276 patients with postoperative seizure recurrence were identified. Monthly average seizure frequency worsening occurred in 9.8%, GTC worsening in 8.0%, new‐onset GTCs in 1.4%, new‐onset status epilepticus in 2.2%, and death from SUDEP in 1.4%. A higher risk of worsening was seen with extratemporal resections as compared to temporal lobe surgeries (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.21–7.95; p = 0.018), and in patients with low preoperative seizure frequency <30 seizures/month (OR 14.82, 95% CI 2.81–275.41; p = 0.0003). Predictors of increased GTCs included an incomplete resection (OR 3.98, 95% CI 1.39–12.59; p = 0.010) and multiple recorded ictal patterns (OR 5.91, 95% CI 1.20–26.96; p = 0.030). Multiple seizure semiologies correlated with worsening after temporal lobe resections. Significance: The most vulnerable patients for seizure worsening following epilepsy surgery include those with extratemporal resections, incomplete resections, and multiple recorded ictal patterns.     

Association of elevated neutrophil-to-lymphocyte ratio with increased intracranial aneurysm stability scores and aneurysm growth

Background and purposeInflammation involves in the progression of intracranial aneurysms (IAs). However, whether the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory marker links to IAs stability is unidentified. This study was performed to assess the association of the NLR with IAs stability.MethodsWe retrospectively reviewed the medical records of patients diagnosed with unruptured IAs from January 2014 to June 2018. According to the quartiles of the NLR, patients with unruptured IAs were categorized into four groups. We evaluated the association between the NLR and IAs stability scores and IAs growth. Multiple logistic regression models were used in the analysis.ResultsA significant dose-response association was found between the NLR with IAs stability scores and IAs growth. After adjustment for potential confounders, an elevated NLR (fourth quartile) was associated with increased PHASES score (>5) (adjusted odds ratio [OR], 2.007; 95% confidence interval [CI], 1.361–2.960; p<0.001 [p for trend <0.001]), increased ELAPSS score (>15) (adjusted OR, 1.581; 95% CI, 1.074–2.328; p=0.020 [p for trend =0.001]), increased JAPAN 3-year rupture risk score (>5) (adjusted OR, 1.512; 95% CI, 1.033–2.215; p=0.034 [p for trend <0.001]), and IAs growth (adjusted OR, 16.759; 95% CI, 3.022–92.928; p=0.001 [p for trend <0.001]).ConclusionAn elevated NLR was associated with increased IAs stability scores and IAs growth. The association between NLR and IAs stability need further investigate.     

Cox regression model of prognostic factors for delayed neuropsychiatric sequelae in patients with acute carbon monoxide poisoning: A prospective observational study

ObjectiveA major challenge for physicians is to identify patients with acute carbon monoxide (CO) poisoning who are likely to develop delayed neuropsychiatric sequelae (DNS). DNS is defined as neuropsychological sequelae that develops after 2–40 days of lucid interval after CO intoxication. Currently, there is no consensus on factors that predict the prognosis of CO poisoning. Thus, the purpose of this study was to identify factors predicting the development of DNS using a Cox regression model.MethodsThis prospective observational study included 310 CO-poisoned patients admitted to an emergency department in South Korea from July 2017 to February 2020. Demographic, clinical, and laboratory data were analyzed. Kaplan–Meier curves were constructed to estimate the cumulative incidence of DNS. A multivariate Cox regression model was used to identify the main predictors of the development of DNS.ResultsThe incidence of DNS was 18.8 %, and the median onset time was 23.7 days (interquartile range, 14–30 days). The Kaplan–Meier survival curve showed that a serum creatine kinase (CK) level > 175.5 U/L and initial Glasgow Coma Scale (GCS) score ≤ 9 were associated with a higher cumulative incidence of DNS (log-rank test; p < 0.01 and p = 0.02, respectively). Cox regression analysis showed that a serum CK level > 175.5 U/L (hazard ratio [HR]: 2.862, 95 % confidence interval [CI]: 1.491–5.496; p < 0.01) and an initial GCS ≤ 9 (HR: 2.081, 95 % CI: 1.048–4.131; p = 0.04) were significant prognostic factors.ConclusionIn acute CO poisoning, an initial GCS score ≤ 9 and serum CK level > 175.5 U/L are significant predictors of DNS development.