Clinical Symptoms and Risk Factors in Cerebral Microangiopathy Patients

Objective

Although the clinical manifestation and risk factors of cerebral microangiopathy (CM) remain unclear, the number of diagnoses is increasing. Hence, patterns of association among lesion topography and severity, clinical symptoms and demographic and disease risk factors were investigated retrospectively in a cohort of CM patients.

Methods

Patients treated at the Department of Neurology, University of Bonn for CM (n = 223; 98m, 125f; aged 77.32±9.09) from 2005 to 2010 were retrospectively enrolled. Clinical symptoms, blood chemistry, potential risk factors, demographic data and ratings of vascular pathology in the brain based on the Wahlund scale were analyzed using Pearson''s chi square test and one-way ANOVA.

Results

Progressive cognitive decline (38.1%), gait apraxia (27.8%), stroke-related symptoms and seizures (24.2%), TIA-symptoms (22%) and vertigo (17%) were frequent symptoms within the study population. Frontal lobe WMLs/lacunar infarcts led to more frequent presentation of progressive cognitive decline, seizures, gait apraxia, stroke-related symptoms, TIA, vertigo and incontinence. Parietooccipital WMLs/lacunar infarcts were related to higher frequencies of TIA, seizures and incontinence. Basal ganglia WMLs/lacunar infarcts were seen in patients with more complaints of gait apraxia, vertigo and incontinence. Age (p = .012), arterial hypertension (p<.000), obesity (p<.000) and cerebral macroangiopathy (p = .018) were positively related to cerebral lesion load. For increased glucose level, homocysteine, CRP and D-Dimers there was no association.

Conclusion

This underlines the association of CM with neurological symptoms upon admission in a topographical manner. Seizures and vertigo are symptoms of CM which may have been missed in previous studies. In addition to confirming known risk factors such as aging and arterial hypertension, obesity appears to increase the risk as well. Since the incidence of CM is increasing, future studies should focus on the importance of prevention of vascular risk factors on its pathogenesis.     

Hyperthermia in Human Ischemic and Hemorrhagic Stroke: Similar Outcome,Different Mechanisms

Hyperthermia is a predictor of poor outcome in ischemic (IS) and intracerebral hemorrhagic (ICH) stroke. Our aim was to study the plausible mechanisms involved in the poor outcome associated to hyperthermia in stroke. We conducted a case-control study including patients with IS (n = 100) and ICH (n = 100) within the first 12 hours from symptom onset. Specifically, IS and ICH patients were consecutively included into 2 subgroups, according to the highest body temperature within the first 24 hours: Tmax <37.5°C and Tmax ≥37.5°C, up to reach 50 patients per subgroup of temperature for both IS and ICH patients. Body temperature was determined at admission and every 4 hours during the first 48 hours. Main outcome variable was poor functional outcome (modified Rankin scale score >2) at 3 months. Serum levels of glutamate and active MMP-9 were measured at admission. Our results showed that Tmax ≥37.5°C within the first 24 hours was independently associated with poor outcome in both IS (OR, 12.43; 95% CI, 3.73–41.48; p<0.0001) and ICH (OR, 4.29; 95% CI, 1.32–13.91; p = 0.015) after adjusting for variables with a proven biological relevance for outcome. However, when molecular markers levels were included in the logistic regression model, we observed that glutamate (OR, 1.01; 95% CI, 1.00–1.02; p = 0.001) and infarct volume (OR, 1.06; 95% CI, 1.01–1.10; p = 0.015) were the only variables independently associated to poor outcome in IS, and active MMP-9 (OR, 1.04; 95% CI, 1.00–1.08; p = 0.002) and National Institute of Health Stroke Scale (NIHSS) at admission (OR, 1.29; 95% CI, 1.13–1.49; p<0.0001) in ICH. In conclusion, these results suggest that although the outcome associated to hyperthermia is similar in human IS and ICH, the underlying mechanisms may be different.     

Seizure Control of Current Shunt on Rats with Temporal Lobe Epilepsy and Neocortical Epilepsy

Purpose

To examine the effects of current shunt on rats with temporal lobe epilepsy and neocortex epilepsy.

Experimental Design

A kainic acid (KA)-induced model of temporal lobe seizure and a penicillin-induced model of neocortical partial seizure were used in this study. Rats of each model were randomly allocated into two groups: control and model groups. The model group was further divided into the KA or penicillin group, sham conduction group and conduction group. The current shunt was realized through the implantation of a customized conduction electrode. After surgery, electroencephalogram (EEG) was recorded for two hours for each rat under anesthesia. Subsequently, the rats were video monitored for 72 h to detect the occurrence of behavioral seizures upon awakening. The average number and duration of seizures on EEG and the number of behavioral seizures were measured.

Results

In KA model, the number of total EEG seizures in conduction group (9.57±2.46) was significantly less than that in sham conduction group (15.13±3.45) (p<0.01). The duration of EEG seizures in conduction group (26.13±7.81 s) was significantly shorter than that in sham conduction group (34.17±7.25 s) (p = 0.001). A significant reduction of behavioral seizures was observed in the conduction group compared with KA (p = 0.000) and sham conduction groups (p = 0.000). In penicillin model, there was a 61% reduction in total EEG seizures in conduction group compared with sham conduction group (p<0.01), and the duration of EEG seizures in conduction group (6.29±2.64 s) was significantly shorter than that in the sham conduction group (12.07±3.81 s) (p = 0.002). A significant reduction of behavioral seizures was observed in conduction group compared with penicillin (p<0.01) and sham conduction groups (p<0.01).

Conclusion

Current shunt effectively reduces the onset and severity of seizures. Current shunt therapy could be an effective alternative minimally invasive approach for temporal lobe epilepsy and neocortex epilepsy.     

Comparing Risk Factor Profiles between Intracerebral Hemorrhage and Ischemic Stroke in Chinese and White Populations: Systematic Review and Meta-Analysis

Background

Chinese populations have a higher proportion of intracerebral hemorrhage (ICH) in total strokes. However, the reasons are not fully understood.

Methods

To assess the differences in frequency of major risk factors between ICH and ischemic stroke (IS) in Chinese versus white populations of European descent, we systematically sought studies conducted since 1990 that compared frequency of risk factors between ICH and IS in Chinese or white populations. For each risk factor, in Chinese and Whites separately, we calculated study-specific and random effects pooled prevalence and odds ratios (ORs) for ICH versus IS.

Results

Six studies among 36190 Chinese, and seven among 52100 white stroke patients studied hypertension, diabetes, atrial fibrillation (AF), ischemic heart disease (IHD), hypercholesterolemia, smoking and alcohol. Pooled prevalence of AF was significantly lower in Chinese. Pooled ORs for ICH versus IS were mostly similar in Chinese and Whites. However, in Chinese–but not Whites–mean age was lower (62 versus 69 years), while hypertension and alcohol were significantly more frequent in ICH than IS (ORs 1.38, 95% CI 1.18–1.62, and 1.46, 1.12–1.91). Hypercholesterolemia and smoking were significantly less frequent in ICH in Whites, but not Chinese, while IHD, AF and diabetes were less frequent in ICH in both.

Conclusions

Different risk factor distributions in ICH and IS raise interesting possibilities about variation in mechanisms underlying the different distributions of pathological types of stroke between Chinese and Whites. Further analyses in large, prospective studies, including adjustment for potential confounders, are needed to consolidate and extend these findings.     

XbaI and PvuII Polymorphisms of Estrogen Receptor 1 Gene in Females with Idiopathic Scoliosis: No Association with Occurrence or Clinical Form

Introduction

XbaI single nucleotide polymorphism (SNP) (A/G rs934099) in estrogen receptor 1 gene (ESR1) was described to be associated with curve severity in Japanese idiopathic scoliosis (IS) patients and in Chinese patients with both curve severity and predisposition to IS. PvuII SNP (C/T rs2234693) of ESR1 was described to be associated with the occurrence of IS in the Chinese population; however, two replication studies did not confirm the findings. The ESR1 SNPs have never been studied in Caucasian IS patients.

Methods

Case-control study. 287 females with IS underwent clinical, radiological and genetic examinations. The patients were divided into three groups according to curve progression velocity: non-progressive IS, slowly progressive IS (progression <1° per month), and rapidly progressive IS (progression ≥1° per month). The radiological maximum Cobb angle was measured and surgery rate established. A control group consisted of 182 healthy females.

Results

All results followed Hardy-Weinberg equilibrium. In the case-control study, genotype frequency in the patients did not differ for the XbaI (AA = 33.5%, AG = 49.1%, GG = 17.4%), nor for the PvuII (TT = 26.8%, TC = 50.2%, CC = 23.0%) comparing to controls (AA = 33.5%, AG = 50.5%, GG = 15.9%) and (TT = 23.1%, TC = 51.1%, CC = 25.8%), respectively, p = 0.3685, p = 0.6046. The haplotype frequency for the patients (AT = 47.1%, GC = 39.2%, AC = 8.9%, GT = 2.8%) did not differ from the controls (AT = 44.8%, GC = 37.4%, AC = 14.0%, GT = 3.8%), p = 0.0645. No difference was found either in XbaI (p = 0.8671) or PvuII (p = 0.3601) allele distribution between the patients and the controls. In the case study, there was no significant difference in genotype frequency for the non-progressive, slowly progressive, and rapidly progressive scoliosis. No difference was found in genotype or haplotype distribution for the mean maximum Cobb angle or the surgery rate.

Conclusions

No association was found between ESR1 XbaI or ESR1 PvuII SNP and idiopathic scoliosis in Caucasian females. None of the previously reported associations could be confirmed, regarding curve severity, progression or operation rate.     

Prevalence of PTSD in Survivors of Stroke and Transient Ischemic Attack: A Meta-Analytic Review

Background and Purpose

Posttraumatic stress disorder (PTSD) is common in survivors of acute life-threatening illness, but little is known about the burden of PTSD in survivors of stroke and transient ischemic attack (TIA). This study estimated the prevalence of stroke or TIA-induced posttraumatic stress disorder (PTSD) using systematic review and meta-analysis.

Methods

Potentially relevant peer-reviewed journal articles were identified by searching the Ovid MEDLINE, PsycINFO, PILOTS Database, The Cochrane Library and Scopus from inception to January 2013; all searches were conducted on January 31, 2013. Observational cohort studies that assessed PTSD with specific reference to a stroke or TIA that occurred at least 1 month prior to the PTSD assessment were included. PTSD rates and characteristics of the study and sample were abstracted from all included studies. The coding of all articles included demographics, sample size, study country, and method and timing of PTSD assessment.

Results

Nine studies (N = 1,138) met our inclusion criteria. PTSD rates varied significantly across studies by timing of PTSD assessment (i.e., within 1 year of stroke/TIA versus greater than 1 year post-stroke/TIA; 55% of heterogeneity explained; Q ₁ = 10.30; P = .001). Using a random effects model, the estimated rate of PTSD following stroke or TIA was 23% (95% CI, 16%–33%) within 1 year of the stroke or TIA and 11% (95% CI, 8%–14%) after 1 year.

Conclusions

Although PTSD is commonly thought to be triggered by external events such as combat or sexual assault, these results suggest that 1 in 4 stroke or TIA survivors develop significant PTSD symptoms due to the stroke or TIA. Screening for PTSD in a large population-based prospective cohort study with cardiovascular outcome assessments is needed to yield definitive prevalence, and determine whether stroke or TIA-induced PTSD is a risk factor for subsequent cardiovascular events or mortality.     

Tonic-Clonic Activity at Subarachnoid Hemorrhage Onset: Impact on Complications and Outcome

Objective

Tonic-clonic activity (TCA) at onset complicates 3% to 21% of cases of subarachnoid hemorrhage (SAH). The impact of onset TCA on in-hospital complications, including seizures, remains unclear. One study associated onset TCA with poor clinical outcome at 6 weeks after SAH, but to our knowledge no other studies have confirmed this relationship. This study aims to assess the impact of onset TCA on in-hospital complications, poor functional outcome, mortality, and epilepsy at 3 months.

Methods

Analysis of a prospective study cohort of 1479 SAH patients admitted to Columbia University Medical Center between 1996 and 2012. TCA within 6 hours of hemorrhage onset was identified based on accounts of emergency care providers or family witnesses.

Results

TCA at onset was described in 170 patients (11%). Patients with onset TCA were younger (P = 0.002), presented more often with poor clinical grade (55% vs. 26%, P<0.001) and had larger amounts of cisternal, intraventricular, and intracerebral blood than those without onset TCA (all, P<0.001). After adjusting for known confounders, onset TCA was significantly associated with in-hospital seizures (OR 3.80, 95%-CI: 2.43–5.96, P<0.001), in-hospital pneumonia (OR 1.56, 95%-CI: 1.06–2.31, p = 0.02), and delayed cerebral ischemia (OR 1.77, 95%-CI: 1.21–2.58, P = 0.003). At 3 months, however, onset TCA was not associated with poor functional outcome, mortality, and epilepsy after adjusting for age, admission clinical grade, and cisternal blood volume.

Conclusions

Onset TCA is not a rare event as it complicates 11% of cases of SAH. New and clinically relevant findings are the association of onset TCA with in-hospital seizures, pneumonia and delayed cerebral ischemia. Despite the increased risk of in-hospital complications, onset TCA is not associated with disability, mortality, and epilepsy at 3 months.     

Prevention of Anal Condyloma with Quadrivalent Human Papillomavirus Vaccination of Older Men Who Have Sex with Men

Background

The quadrivalent human papillomavirus vaccine (qHPV) is FDA-approved for use in males 9 to 26 years old to prevent anogenital condyloma. The objective of this study is to determine if qHPV is effective at preventing anal condyloma among men who have sex with men (MSM) aged 26 years and older.

Methods

This post-hoc analysis of a nonconcurrent cohort study evaluated 210 patients without history of anal condyloma and 103 patients with previously-treated anal condyloma recurrence-free for at least 12 months prior to vaccination/time zero. We determined the rate of anal condyloma development in vaccinated versus unvaccinated patients.

Results

313 patients with mean age 42 years were followed for median 981 days. During 773.6 person-years follow-up, condyloma developed in 10 (8.6%) vaccinated patients (incidence of 3.7 per 100 person-years) and 37 (18.8%) unvaccinated patients (incidence 7.3 per 100 person-years; p = 0.05). Multivariable hazards ratio showed that qHPV was associated with decreased risk of anal condyloma development (HR 0.45; 95% CI 0.22–0.92; p = 0.03). History of anal condyloma was associated with increased risk of anal condyloma development (HR 2.28; 95% CI 1.28–4.05; p = 0.005), as was infection with oncogenic HPV (HR 3.87; 95% CI 1.66–9.03; p = 0.002).

Conclusions

Among MSM 26 years of age and older with and without history of anal condyloma, qHPV reduces the risk of anal condyloma development. A randomized controlled trial is needed to confirm these findings in this age group.     

Association of Severe Thrombocytopenia and Poor Prognosis in Pregnancies with Aplastic Anemia

Purpose

We sought to estimate the risks of adverse obstetric outcomes and disease outcomes associated with severe thrombocytopenia in pregnant women with aplastic anemia (AA).

Methods

In a retrospective study, we compared demographics, clinical characteristics, laboratory results, and outcomes between severe thrombocytopenia (ST) and non-severe thrombocytopenia (non-ST) groups comprising pregnant women with AA.

Results

Of 61 AA patients, 43 (70%) were diagnosed as AA before pregnancy and 18 (30%) were AA during pregnancy. The ST group exhibited lower gestational age at nadir of platelet count (26.0 versus 37.0 weeks, p<0.001) and at delivery (37.3 versus 39.1 weeks, p = 0.008), and a higher rate of bleeding gums (33.8 versus 7.7%, p = 0.015) than the non-ST group. In addition, the ST group exhibited more transfusions during pregnancy (72.7 versus 15.4%, p<0.001) and postpartum period (45.0 versus 2.7%, p<0.001), and more bone marrow transplant after delivery (25.0 versus 0.0%, p<0.001) than the non-ST group. The ST group had a higher odds ratio of composite disease complications (OR, 9.63; 95% CI, 2.82–32.9; p<0.001) and composite obstetric complications (OR, 6.78; 95% CI, 2.11–21.8; p = 0.001) than the non-ST group.

Conclusions

Severe thrombocytopenia is more associated with obstetric and disease complications than is non-severe thrombocytopenia in pregnant women with AA.     

Predictors of Seizure Outcomes in Children with Tuberous Sclerosis Complex and Intractable Epilepsy Undergoing Resective Epilepsy Surgery: An Individual Participant Data Meta-Analysis

Objective

To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery.

Data Sources

Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions.

Study Selection

We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion.

Data Extraction

One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes.

Data Synthesis

To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable.

Results

Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2–8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1–24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4–7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8–13.5, p = 0.002) were associated with a good postoperative seizure outcome.

Conclusions

Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review.     

Outcomes of Sustained-Release Formulation of Valproate and Topiramate Monotherapy in Patients with Epilepsy: A Multi-Centre,Cohort Study

Background

New-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown.

Methodology/Principal Findings

Two broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR).Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HR = 0.62, [95% CI 0.49–0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HR = 0.73, [95% CI 0.62–0.86]; p = 0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HR = 1.01, [95% CI 0.84–1.23]; p = 0.88) and time to 24-month remission (34.7% vs. 25.2%; HR = 1.11, [95% CI 0.88–1.42]; p = 0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (p = 0.70).

Conclusions

The SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.     

Traumatic Intracranial Hemorrhage Correlates with Preinjury Brain Atrophy,but Not with Antithrombotic Agent Use: A Retrospective Study

Background

The impact of antithrombotic agents (warfarin, clopidogrel, ASA) on traumatic brain injury outcomes is highly controversial. Although cerebral atrophy is speculated as a risk for acute intracranial hemorrhage, there is no objective literature evidence.

Materials and Methods

This is a retrospective, consecutive investigation of patients with signs of external head trauma and age ≥60 years. Outcomes were correlated with antithrombotic-agent status, coagulation test results, admission neurologic function, and CT-based cerebral atrophy dimensions.

Results

Of 198 consecutive patients, 36% were antithrombotic-negative and 64% antithrombotic-positive. ASA patients had higher arachidonic acid inhibition (p = 0.04) and warfarin patients had higher INR (p<0.001), compared to antithrombotic-negative patients. Antithrombotic-positive intracranial hemorrhage rate (38.9%) was similar to the antithrombotic-negative rate (31.9%; p = 0.3285). Coagulopathy was not present on the ten standard coagulation, thromboelastography, and platelet mapping tests with intracranial hemorrhage and results were similar to those without hemorrhage (p≥0.1354). Hemorrhagic-neurologic complication (intracranial hemorrhage progression, need for craniotomy, neurologic deterioration, or death) rates were similar for antithrombotic-negative (6.9%) and antithrombotic-positive (8.7%; p = 0.6574) patients. The hemorrhagic-neurologic complication rate was increased when admission major neurologic dysfunction was present (63.2% versus 2.2%; RR = 28.3; p<0.001). Age correlated inversely with brain parenchymal width (p<0.001) and positively with lateral ventricular width (p = 0.047) and cortical atrophy (p<0.001). Intracranial hemorrhage correlated with cortical atrophy (p<0.001) and ventricular width (p<0.001).

Conclusions

Intracranial hemorrhage is not associated with antithrombotic agent use. Intracranial hemorrhage patients have no demonstrable coagulopathy. The association of preinjury brain atrophy with acute intracranial hemorrhage is a novel finding. Contrary to antithrombotic agent status, admission neurologic abnormality is a predictor of adverse post-admission outcomes. Study findings indicate that effective hemostasis is maintained with antithrombotic therapy.     

Multidisciplinary Team-Based Approach for Comprehensive Preoperative Pulmonary Rehabilitation Including Intensive Nutritional Support for Lung Cancer Patients

Background

To decrease the risk of postoperative complication, improving general and pulmonary conditioning preoperatively should be considered essential for patients scheduled to undergo lung surgery.

Objective

The aim of this study is to develop a short-term beneficial program of preoperative pulmonary rehabilitation for lung cancer patients.

Methods

From June 2009, comprehensive preoperative pulmonary rehabilitation (CHPR) including intensive nutritional support was performed prospectively using a multidisciplinary team-based approach. Postoperative complication rate and the transitions of pulmonary function in CHPR were compared with historical data of conventional preoperative pulmonary rehabilitation (CVPR) conducted since June 2006. The study population was limited to patients who underwent standard lobectomy.

Results

Postoperative complication rate in the CVPR (n = 29) and CHPR (n = 21) were 48.3% and 28.6% (p = 0.2428), respectively. Those in patients with Charlson Comorbidity Index scores ≥2 were 68.8% (n = 16) and 27.3% (n = 11), respectively (p = 0.0341) and those in patients with preoperative risk score in Estimation of Physiologic Ability and Surgical Stress scores >0.3 were 57.9% (n = 19) and 21.4% (n = 14), respectively (p = 0.0362). Vital capacities of pre- and post intervention before surgery in the CHPR group were 2.63±0.65 L and 2.75±0.63 L (p = 0.0043), respectively; however, their transition in the CVPR group was not statistically significant (p = 0.6815). Forced expiratory volumes in one second of pre- and post intervention before surgery in the CHPR group were 1.73±0.46 L and 1.87±0.46 L (p = 0.0012), respectively; however, their transition in the CVPR group was not statistically significant (p = 0.6424).

Conclusions

CHPR appeared to be a beneficial and effective short-term preoperative rehabilitation protocol, especially in patients with poor preoperative conditions.     

The Incidence and Relative Risk of Stroke among Patients with Bipolar Disorder: A Seven-Year Follow-Up Study

Objective

This study aimed to estimate the incidence and relative risk of stroke and post-stroke all-cause mortality among patients with bipolar disorder.

Methods

This study identified a study population from the National Health Insurance Research Database (NHIRD) between 1999 and 2003 that included 16,821 patients with bipolar disorder and 67,284 age- and sex-matched control participants without bipolar disorder. The participants who had experienced a stroke between 1999 and 2003 were excluded and were randomly selected from the NHIRD. The incidence of stroke (ICD-9-CM code 430–438) and patient survival after stroke were calculated for both groups using data from the NIHRD between 2004 and 2010. A Cox proportional-hazards model was used to compare the seven-year stroke-free survival rate and all-cause mortality rate across the two cohorts after adjusting for confounding risk factors.

Results

A total of 472 (2.81%) patients with bipolar disorder and 1,443 (2.14%) controls had strokes over seven years. Patients with bipolar disorder were 1.24 times more likely to have a stroke (95% CI = 1.12–1.38; p<0.0001) after adjusting for demographic characteristics and comorbid medical conditions. In addition, 513 (26.8%) patients who had a stroke died during the follow-up period. The all-cause mortality hazard ratio for patients with bipolar disorder was 1.28 (95% CI = 1.06–1.55; p = 0.012) after adjusting for patient, physician and hospital variables.

Conclusions

The likelihood of developing a stroke was greater among patients with bipolar disorder than controls, and the all-cause mortality rate was higher among patients with bipolar disorder than controls during a seven-year follow-up period.     

Cognitive and Surgical Outcome in Mesial Temporal Lobe Epilepsy Associated with Hippocampal Sclerosis Plus Neurocysticercosis: A Cohort Study

Background

Where neurocysticercosis (NCC) is endemic, chronic calcified neurocysticercosis (cNCC) can be observed in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). Considering that both disorders cause recurrent seizures or cognitive impairment, we evaluated if temporal lobectomy is cognitively safe and effective for seizure control in MTLE-HS plus cNCC.

Methods

Retrospective cohort study of neuropsychological profile and surgical outcome of 324 MTLE-HS patients submitted to temporal lobectomy, comparing the results according to the presence or absence of cNCC.

Findings

cNCC occurred in 126 (38.9%) of our MTLE-HS patients, a frequency higher than expected, more frequently in women than in men (O.R. = 1.66; 95% C.I. = 1.05–2.61; p = 0.03). Left-side (but not right side) surgery caused impairment in selected neuropsychological tests, but this impairment was not accentuated by the presence of cNCC. Ninety-four (74.6%) patients with MTLE-HS plus cNCC and 153 patients (77.3%) with MTLE-HS alone were Engel class I after surgery (O.R. = 1.16; 95% C.I. = 0.69–1.95; p = 0.58). However, the chances of Engel class IA were significantly lower in MTLE-HS plus cNCC than in patients with MTLE-HS alone (31.7% versus 48.5%; O.R. = 2.02; 95% C.I. = 1.27–3.23; p = 0.003). Patients with MTLE-HS plus cNCC showed higher rates of Engel class ID (15.1% versus 6.6%; O.R. = 2.50; 95% C.I. = 1.20–5.32; p = 0.012).

Interpretation

cNCC can be highly prevalent among MTLE-HS patients living in areas where neurocysticercosis is endemic, suggesting a cause-effect relationship between the two diseases. cNCC does not add further risk for cognitive decline after surgery in MTLE-HS patients. The rates of Engel class I outcome were very similar for the two groups; however, MTLE-HS plus cNCC patients achieved Engel IA status less frequently, and Engel ID status more frequently. Temporal lobectomy can be safely performed in most patients with MTLE-HS plus cNCC without affecting cognitive outcome. Long-term surgical seizure control in MTLE-HS plus cNCC is still satisfactory, as long as selected patients remain under medication.     

Prevalence of SCN1A-Related Dravet Syndrome among Children Reported with Seizures following Vaccination: A Population-Based Ten-Year Cohort Study

Objectives

To determine the prevalence of Dravet syndrome, an epileptic encephalopathy caused by SCN1A-mutations, often with seizure onset after vaccination, among infants reported with seizures following vaccination. To determine differences in characteristics of reported seizures after vaccination in children with and without SCN1A-related Dravet syndrome.

Methods

Data were reviewed of 1,269 children with seizures following immunization in the first two years of life, reported to the safety surveillance system of the Dutch national immunization program between 1 January 1997 and 31 December 2006. Selective, prospective follow-up was performed of children with clinical characteristics compatible with a diagnosis of Dravet syndrome.

Results

In 21.9% (n = 279) of children, a diagnosis of Dravet syndrome could not be excluded based on available clinical data (median age at follow-up 16 months). Additional follow-up data were obtained in 83.9% (n = 234) of these children (median age 8.5 years).15 (1.2% of 1,269; 95%CI:0.6 to 1.8%) children were diagnosed with SCN1A-related Dravet syndrome. Of all reported seizures following vaccinations in the first year of life, 2.5% (95%CI:1.3 to 3.6%) were due to SCN1A-related Dravet syndrome, as were 5.9% of reported seizures (95%CI:3.1 to 8.7%) after 2^nd or 3^rd DTP-IPV-Hib vaccination.Seizures in children with SCN1A-related Dravet syndrome occurred more often with a body temperature below 38.5°C (57.9% vs. 32.6%, p = 0.020) and reoccurred more often after following vaccinations (26.7% vs. 4.0%, p = 0.003), than in children without a diagnosis of SCN1A-related Dravet Syndrome.

Conclusions

Although Dravet syndrome is a rare genetic epilepsy syndrome, 2.5% of reported seizures following vaccinations in the first year of life in our cohort occurred in children with this disorder. Knowledge on the specific characteristics of vaccination-related seizures in this syndrome might promote early diagnosis and indirectly, public faith in vaccination safety.     

Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)

Background

Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis.

Methods

Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA). We evaluated associations with clinicopathological parameters and prognosis.

Results

There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04) and overall survival (OS) (69.6% versus 44.3%, p  = 0.05). Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards significance for OS.

Conclusions

The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis.     

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

Background

Immunosuppressive therapy is usually administered following renal transplantation to protect the graft from rejection. However, this often causes complications such as infections to occur. Single nucleotide polymorphisms (SNPs) within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown.

Methods

In this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012.

Results

The frequency of the rs4553808 GG genotype was significantly higher in recipients with viral infection (14.89%) than in those without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant difference (p = 0.001) in patients with the rs4553808 GG genotype from those with the AA+AG genotypes was found in the viral cohort using the log-rank test. A significant association was found between the rs4553808 genotype and onset of viral infection in transplant recipients (p = 0.001). The frequencies of the CGTAG and CGCAG haplotypes were significantly higher in the viral infection group (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149 and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was found. Multivariate analyses revealed that one risk factor, the use of antibody induction therapy (p = 0.007), was associated with bacterial infection, and two risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p = 0.001), were associated with viral infection.

Conclusions

The rs4553808 GG genotype may be a risk factor for viral infection in kidney transplantation. The CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development of viral infection in Chinese kidney transplant recipients.     

Diagnostic Yield of Universal Urine Toxicology Screening in an Unselected Cohort of Stroke Patients

Background

Illicit drug use increases the risk of cerebrovascular events by a variety of mechanisms. A recent report suggested that universal urine toxicology (UTox) screening of patients with stroke may be warranted. We aimed to evaluate the diagnostic yield of urine drug screening among unselected patients admitted with acute stroke or transient ischemic attack (TIA).

Methods

Using a single-center prospective study design, we evaluated consecutive patients with acute ischemic stroke, TIA, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) over one year. Urine samples were collected within 48 hours of admission and analyzed for common classes of abused drugs. Prevalence of positive UTox screening was determined. We evaluated whether baseline demographics and clinical factors were associated with UTox results.

Results

Of 483 eligible patients (acute ischemic stroke 66.4%; TIA 18.8%; ICH 7.7%; SAH 7.0%), 414 (85.7%) completed UTox screening. The mean (standard deviation) age was 65.1 (15.6) years, 52.7% were male, and 64.3% were Caucasian. Twenty-two (4.6%) patients had positive screening—cannabinoids were detected in 13 cases (3.1%), cocaine in 5 cases (1.2%), amphetamines in 1 case, and phencyclidine in 1 case. The highest yield (14.1%) was observed in patients < 60 years old with history of tobacco use while it was < 5% in the remaining subgroups (p<0.01).

Conclusions

Consistent with current guidelines, a selective approach to UTox screening should be pursued in acute stroke evaluation. The highest diagnostic yield is likely to be for cannabinoids and cocaine testing in younger patients with a history of concurrent tobacco use.