Risk of hemorrhage in patients over age 60 with arteriovenous malformations (AVMs)

Treatment selection for patients 60 years of age and older with intracranial arteriovenous malformations (AVMs), requires careful consideration of the natural history and post-treatment hemorrhagic risk. We aimed to directly compare the natural history of AVMs with post-treatment hemorrhagic risk in this population. We retrospectively reviewed our AVM database of 683 patients. Patients ⩾60 years at diagnosis were included. Treatment modality was divided into four groups: surgery ± embolization (SE), radiosurgery ± embolization (RE), embolization only (Emb), and observation (Obs). The natural history of the AVM was defined as the annual risk of hemorrhage under observation. Risk of hemorrhage after treatment was also calculated. Sixty-one patients with complete data were included. Average age was 68.4 ± 7.5 years, with 55.7% (n = 34) being male. Twenty-seven (44.3%) patients presented with intracerebral hemorrhage (ICH). At last follow-up, modified Rankin Scale was higher in patients with subsequent hemorrhages (p = 0.023). Overall, obliteration was 65.5%, with 100.0% in the SE group and 43.8% in the RE group (p <0.001). During an average follow-up period of 2.8 ± 3.2 years, six patients (9.8%) experienced hemorrhage, with two (12.5%) in the RE group, three (9.4%) in the Obs group and one (9.1%) in the SE group, corresponding to a natural history of 3.5% annual hemorrhage rate and a post-treatment hemorrhagic risk of 3.6%. This post-treatment hemorrhage risk was 2.4% in the SE group and 4.9% in the RE group. Presenting with ICH (p = 0.042) and race (p = 0.014) were associated with a higher risk of follow-up hemorrhage. Definitive treatment for AVM patients ⩾60 years should be cautiously considered. Despite higher post-treatment obliteration rates, the subsequent hemorrhagic risk may exceed that of its natural history. For AVMs with a high risk for hemorrhage, surgery reduces hemorrhagic risk and achieves the highest rate of obliteration.     

Prediction,clinical characteristics and prognosis of intracerebral hemorrhage in hepatocellular carcinoma patients with intracerebral metastasis

The clinical characteristics of intracerebral hemorrhage (ICH) in hepatocellular carcinoma (HCC) patients with intracerebral metastasis (IcM) have not been reported on extensively. We compared the clinical characteristics between patients with ICH (w-ICH, 18 patients) and without ICH (wo-ICH, 24 patients) in HCC patients with IcM. Using multivariate logistic regression, only habitual alcohol consumption is a significant predictor of ICH in HCC patients with IcM (adjusted odds ratio [OR] = 4.7, 95% CI = 1.26–17.71, p = 0.022). Patients with ICH also had lower Glasgow Coma Scale scores at the time of admission (p = 0.032) and lower incidence of infratentorial metastasis (p = 0.014). Using correlation analysis, only blood platelet count on admission was positively correlated with survival duration after the diagnosis of IcM in the wo-ICH group (p = 0.000) but not in the w-ICH group.     

Effects of plasma D-dimer levels on early mortality and long-term functional outcome after spontaneous intracerebral hemorrhage

The activation of hemostatic systems has been detected in spontaneous intracerebral hemorrhage (ICH) patients. The influence of plasma D-dimer levels on clinical outcome remains unclear. This study aimed to investigate the impact of elevated plasma D-dimer levels on early mortality and long-term functional outcome in spontaneous ICH. A total of 259 spontaneous ICH patients (<24 hours from ictus) between November 2010 and October 2011 were included. Clinical information and radiological findings were collected at admission. Spearman correlation analyses revealed that D-dimer concentrations were correlated with midline shift, hematoma volume, intraventricular hemorrhage (IVH) score and Glasgow Coma Scale score. Patients with subarachnoid extension had significantly higher D-dimer levels than those without SAH extension. Comparison of patients with IVH and those without yielded a similar result. Multivariate stepwise backward logistic analysis identified plasma D-dimer levels as an independent risk factor for 7 day mortality (adjusted odds ratio [OR] = 1.237, 95% confidence interval [CI] 1.017–1.504, p = 0.033) and 3 month poor functional outcome (modified Rankin Scale score ⩾3) (adjusted OR = 2.279, 95% CI 1.130–6.595, p = 0.026). The mechanisms by which elevated D-dimer affects the prognoses of spontaneous ICH patients remain unclear and require clarification in future studies.     

Role of serum levels of neurotensin in children with autism spectrum disorder

AimNeuroinflammation may play a role in the pathogenesis of autism in some patients. The aim of this study was to measure serum levels of neurotensin (NTS) in relation to the degree of the severity of autism.MethodsSerum NTS was measured in autistic children (n = 38; mean age 7.02 ± 2.03 years) and healthy, unrelated sex matched controls (n = 39); mean age 7.25 ± 1.64 years). The severity of autism symptoms was assessed using Childhood Autism Rating Scale (CARS) scores.ResultsThe serum level of NTS was significantly (P < 0.001) lower in autistic children (mean ± S.D. = 54.71 ± 12.4 pg/ml) than control group (mean ± S.D. = 77.58 ± 10.29 pg/ml). Children with severe autism had significantly lower serum NTS levels than patients with mild to moderate autism (P < 0.002). There was significant negative correlation between serum levels of NTS and CARS SCORES (r² = 0.79, P = 0.001).ConclusionsSerum NTS levels were elevated in some autistic children and they were significantly correlated with the severity of autism. However, this is an initial report that warrants further research to determine the pathogenic role of NTS and its possible link to neuroinflammation in autism.     

Intracerebral hemorrhage due to developmental venous anomalies

Developmental venous anomalies (DVA) and cavernous malformations (CM) are a common form of mixed vascular malformation. The relationship between DVA, CM and hemorrhage is complicated. It is important to differentiate hemorrhagic CM and hemorrhagic DVA. A retrospective review of all patients with acute spontaneous intracerebral hemorrhages (ICH) between 1 May 2008 and 1 May 2013 was performed. ICH due to DVA or CM were identified and compared for demographic features, clinical symptoms, neurological deficits, and radiological findings. A total of 1706 patients with acute spontaneous ICH were admitted to our hospital during the study period. Among these, 10 (0.59%) were caused by DVA and 42 (2.47%) were caused by CM. No significant differences were found in age (p = 0.252) or sex ratio (p = 1.000) between the two groups. Compared with CM-induced ICH, DVA-induced ICH were characterized by cerebellar predominance (p = 0.000) and less severe neurological deficits (p = 0.008). Infratentorial hemorrhagic DVA are characterized by cerebellar predominance and benign clinical course. Infratentorial hemorrhagic CM are mainly located in the brainstem. DVA should be given suspected rather than CM when considering the etiology of a cerebellar hemorrhage, especially in young adults.     

MMP-9 levels in elderly patients with cognitive dysfunction after carotid surgery

Approximately 25% of elderly patients scheduled for carotid endarterectomy (CEA) develop post-operative cognitive dysfunction (CD). We tested the hypothesis that the plasma levels of matrix metalloproteinase 9 (MMP-9) are predictive of moderate to severe CD after CEA. A total of 73 patients were prospectively enrolled in this Institutional Review Board–approved study. Plasma samples were obtained at baseline and day 1 post-surgery. We measured the plasma concentrations of both MMP-9 and its inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1). We estimated the MMP-9 activity by calculating the MMP-9:TIMP-1 ratio. The cognitive performance day 1 post-surgery was quantified with z-scores, using a control group who were undergoing spinal surgery. The criteria used to define CD was performance of ?1.5 standard deviations worse than the control group; approximately 19% of eligible patients developed CD. Compared to patients without CD, this group had both higher total (81.66 ± 12.25 ng/mL versus [vs.] 43.18 ± 4.44 ng/mL, p = 0.005) and activity (0.88 ± 0.24 ng/mL vs. 0.54 ± 0.06 ng/mL, p = 0.003) MMP-9 levels at baseline. All of the results were adjusted for age, diabetes and neurovascular symptoms.     

Acute behavioral crises in psychiatric inpatients with autism spectrum disorder (ASD): Recognition of concomitant medical or non-ASD psychiatric conditions predicts enhanced improvement

During adolescence, some individuals with autism spectrum disorder (ASD) engage in severe challenging behaviors, such as aggression, self-injury, disruption, agitation and tantrums. We aimed to assess risk factors associated with very acute behavioral crises in adolescents with ASD admitted to a dedicated neurobehavioral unit. We included retrospectively in 2008 and 2009 29 adolescents and young adults with ASD hospitalized for severe challenging behaviors and proposed a guideline (Perisse et al., 2010) that we applied prospectively for 29 patients recruited for the same indications between 2010 and 2012. In total, 58 patients were admitted (n = 70 hospitalizations, mean age = 15.66 (±4.07) years, 76% male). We systematically collected data describing socio-demographic characteristics, clinical variables (severity, presence of language, cognitive level), comorbid organic conditions, etiologic diagnosis of the episode, and treatments. We explored predictors of Global Assessment Functioning Scale (GAFS) score and duration of hospitalization at discharge. All but 2 patients exhibited severe autistic symptoms and intellectual disability (ID), and two-thirds had no functional verbal language. During the inpatient stay (mean = 84.3 (±94.9) days), patients doubled on average their GAFS scores (mean = 17.66 (±9.05) at admission vs. mean = 31.4 (±9.48) at discharge). Most common etiologies for acute behavioral crises were organic causes [n = 20 (28%), including epilepsy: n = 10 (14%) and painful medical conditions: n = 10 (14%)], environmental causes [n = 17 (25%) including lack of treatment: n = 11 (16%) and adjustment disorder: n = 6 (9%)], and non-ASD psychiatric condition [n = 33 (48%) including catatonia: n = 5 (7%), major depressive episode: n = 6 (9%), bipolar disorder: n = 4 (6%), schizophrenia: n = 6 (9%), other/unknown diagnosis: n = 12 (17%)]. We found no influence of age, gender, socio-economic status, migration, level of ID, or history of seizure on improvement of GAFS score at discharge. Severity of autism at admission was the only negative predictor (p < .001). Painful medical conditions (p = .04), non-ASD psychiatric diagnoses (p = .001), prior usage of specialized ASD care programs (p = .004), functional language (p = .007), as well as a higher number of challenging behaviors upon admission (p = .001) were associated with higher GAFS scores at discharge. Clinical severity at admission, based on the number of challenging behaviors (r = .35, p = .003) and GAFS score (r = −.32, p = .008) was correlated with a longer inpatient stay. Longer hospitalization was however correlated (r = .27, p = .03) with higher GAFS score at discharge even after adjustment for confounding factors. Challenging behaviors among adolescents with ASD may stem from diverse risk factors, including environmental problems, comorbid acute psychiatric conditions, or somatic illness such as epilepsy or acute pain. The management of these behavioral challenges requires a unified, multidisciplinary approach.     

Diagnostic accuracy of flair in detection of acute subarachnoid hemorrhage in patients presenting with severe headache

BackgroundFluid attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences are previously described for the evaluation of acute subarachnoid hemorrhage (SAH) and demonstrated good sensitivity. This study was designed to find the diagnostic accuracy of FLAIR in detection of acute SAH in patients presenting with severe headache considering the fact that controversy has been observed in previous studies.ObjectiveTo determine diagnostic accuracy of FLAIR in detection of acute subarachnoid hemorrhage in patients presenting with severe headache using lumber puncture as gold standard.MethodologyA total of 245 patients fulfilling selection criteria were enrolled in the study through the emergency department of Combined Military Hospital, Lahore. MRI was performed by Philips Intera Achieva 1.5 T super conducting MR unit (Philips Medical Systems, the Netherlands), with the use of a head coil. FLAIR examination was performed at 6700/150 (TR/TE) with an inversion time (TI) of 2200 ms, a field of view 230 mm, matrix 189 × 256, scan time of 3 min 50s and section thickness 5 mm in axial plane. Following MRI, patients underwent lumbar puncture for cerebrospinal fluid (CSF) examination after 8–12 h from the onset of event. MRI and CSF analysis results were then compared.ResultsOut of 245 cases, 49.39% (n = 121) were between 20–55 years of age while 50.61% (n = 124) were between 56–70 years of age, mean ± sd was calculated as 52.13 ± 10.45 years, 53.88% (n = 132) were male while 46.12% (n = 113) were females, frequency of acute subarachnoid hemorrhage in patients presenting with severe headache was recorded as 5.71%(n = 14), diagnostic accuracy of FLAIR in detection of acute subarachnoid hemorrhage in patients presenting with severe headache taking lumbar puncture as gold standard as 78.57% sensitivity, 96.53% specificity, 57.89% positive predictive value, 98.67% negative predictive value and accuracy rate was calculated as 95.29%.ConclusionDiagnostic accuracy of FLAIR in detection of acute subarachnoid hemorrhage in patients presenting with severe headache taking lumbar puncture as gold standard is higher and reliable.     

Serum uric acid level in patients with relapsing-remitting multiple sclerosis

Uric acid (UA) is a hydrophilic antioxidant product associated with multiple sclerosis (MS). We conducted a randomized case-control study to evaluate the serum level of UA in different phases of MS in comparison with levels in a healthy control population. Serum UA was checked in 130 patients with relapsing-remitting MS (85 patients in remitting and 45 patients in relapsing phase) and 50 age-matched controls using a quantitative enzyme-linked immunosorbent assay (ELISA). The mean concentrations of UA in serum was 6.41(±3.18) mg/dL in patients with remitting MS, 4.76(±1.66) mg/dL in patients with relapsing MS and 6.33(±2.94) mg/dL in controls. There was a significant difference between mean UA concentration in relapsing MS and remitting MS (p < 0.001), and between patients with relapsing MS and controls (p = 0.002); however, the difference between levels for patients in the remitting phase of MS and the control group was not significant (p = 0.87). It seems probable that UA has a role in the prevention of disease activity in MS.     

Assessment of both serum S-100B protein and neuropeptide-Y levels in childhood breath-holding spells

ObjectiveBreath-holding spells are common paroxysmal events in children. Although the spells have a benign prognosis in the long term, they may be complicated by loss of consciousness, tonic–clonic movements, and occasionally seizures. Hence, this study aimed to measure the levels of serum S-100B proteins and neuropeptide-Y in the blood of children who experience breath-holding spells.MethodsThe study groups consisted of 45 patients (13 females, 32 males) with breath-holding spells and a control group of 32 healthy individuals (12 females, 20 males). The serum S-100B levels were measured using commercially available ELISA kits. The neuropeptide-Y levels in the serum were measured with RayBio® Human/Mouse/Rat Neuropeptide Y ELISA kits.ResultsThe mean serum S-100B protein level of the breath-holding spells group was 56.38 ± 13.26 pg/mL, and of the control group, 48.53 ± 16.77 pg/mL. The mean neuropeptide-Y level was 62.29 ± 13.89 pg/mL in the breath-holding spells group and 58.24 ± 12.30 pg/mL in the control group. There were significant differences between the groups with respect to serum S-100B protein levels (p = 0.025), while there was no statistically significant difference in neuropeptide-Y levels between the breath-holding spells group and the control group (p = 0.192).ConclusionsThe findings of this study suggest that frequent and lengthy breath-holding may lead to the development of neuronal metabolic dysfunction or neuronal damage which is most likely related to hypoxia. In light of these findings, future studies should be conducted using biochemical and radiological imaging techniques to support these results.     

Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy

ObjectiveHigher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr).MethodsPlasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12 months of effective antiretroviral therapy (ART). Results were compared with CD4⁺ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin.ResultsBefore ART, phe/tyr was mean ± S.D.: 0.99 ± 0.57 μmol/μmol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs = 0.434, and rs = 0.392; both p < 0.001) and less strongly with HIV-RNA levels (rs = 0.173) and CD4⁺ counts (rs = ?0.182, both p < 0.05). After ART, phe/tyr dropped to 0.72 ± 0.16 (=?27%; U = 5.21, p = 0.01) which was due to an average decline of ?14% of phe concentrations from 73.1 ± 34.0 μmol/L at baseline to 62.9 ± 17.8 μmol/L after ART (U = 2.51, p = 0.01) and a concomitant increase of tyr concentrations (+13%, U = 2.46, p = 0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART.ConclusionsIncreased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients.     

Clinical and neuroradiological predictors of mortality in patients with primary pontine hemorrhage

Background and purposePrimary pontine hemorrhage (PPH) accounts aproximately for about 5–10% of intracranial hemorrhages, and PPHs are known to have a much less uniform prognosis. We aimed to evaluate the clinical and radiological predictors affecting the mortality in 32 patients with PPH.Material and methodsWe retrospectively evaluated the data of 32 patients with PPH admitted to our clinic between 1994 and 2004. We divided the patients into two groups: (1) patients who survived (14 patients), and (2) patients who died (18 patients). The two groups were compared for age, gender, diabetes mellitus, hypertension, initial clinical status, initial GCS, pupillary abnormalities, ophthalmoparesis, volume and localisation of hemorrhage, intraventricular and extrapontine extension, necessity of mechanical ventilation and hydrocephalus. The hematoma volumes were measured with the formulation described by Broderick.ResultsEighteen patients (56%) died and 14 patients (44%) survived. The patients who died (61.3 ± 8.8) were older than the survivors (56.4 ± 11.0), but the difference was not statistically significant. The mean GCS was 4.4 ± 0.2, the mean hematoma volume was 9.9 ± 3.3 ml for patients who died and the mean GCS was 10.1 ± 3.3, the mean hematoma volume was 3.3 ± 1.2 ml for survivors (p < 0.001). Coma on admission (p = 0.001), extrapontine extension (p = 0.001), intraventricular extension (p = 0.019), necessity of mechanical ventilation (p = 0.007), hydrocephalus (p = 0.024), massive and bilateral tegmental localisation (p = 0.006) were found statistically significant predictors for mortality with univariate comparison, and coma on admission (p = 0.038) was the only significant predictor with multivariate regression analysis.ConclusionIn patients with PPH, it is important to know the prognostic factors for mortality for planning the treatment protocol, and coma and bad clinical status on admission was found the only significant prognostic predictor for mortality with multivariate regression analysis.     

The rs9509 polymorphism of MMP-9 is associated with risk of hemorrhage in brain arteriovenous malformations

We examined whether single nucleotide polymorphisms (SNP) of the matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 4 (TIMP-4) genes are associated with risk of intracranial hemorrhage (ICH) among patients with brain arteriovenous malformation (BAVM). For 311 Chinese patients with BAVM, we performed genotyping analysis for 11 selected SNP of MMP-9 and TIMP-4 using the MassARRAY genotyping system (Sequenom, San Diego, CA, USA). Associations between each genotype and risk of hemorrhage were evaluated using logistic regression analysis. Multivariate logistic regression analysis revealed that MMP-9_rs9509 was significantly associated with ICH among patients with BAVM with adjustments for BAVM size, venous drainage type, age and sex (adjusted odds ratio [OR] = 0.19; 95% confidence interval [CI] = 0.05–0.66; p = 0.009 for CC compared with TT genotype). However, the association was not significant (p = 0.072) after Bonferroni correction and was not significant (p = 0.064) in the univariate model. The TIMP-4_rs3755724 polymorphism did not have a statistically significant effect in the multivariate model (adjusted OR = 0.57; 95% CI = 0.32–1.01; p = 0.055 for CT compared with TT genotype). The global score test did not reveal any statistically significant differences in haplotype frequency distributions for these two genes. Our findings suggest that the MMP-9_rs9509 polymorphism may be associated with ICH in patients with BAVM.     

An unbiased,staged, multicentre,validation strategy for Alzheimer's disease CSF tau levels

Newly proposed diagnostic criteria for Alzheimer's disease include cerebrospinal fluid (CSF) tau levels as one core supportive criterion. The published high sensitivity and specificity figures for CSF tau levels in Alzheimer's disease are offset by the large range of proposed cutoff values (9.6 pg/mL to 1140 pg/mL). This study aimed to provide guidance on how to establish, validate and audit CSF tau cutoff values using an unbiased, two-stage multicentre strategy. Both receiver operator characteristics (ROC) optimised and population-based cutoff values were calculated on a pilot dataset (n = 99), validated in a large dataset (n = 560) and then compared to the literature. The data suggest using an ROC optimised cutoff level of 323 ± 51.7 pg/mL allowing for the published inter-laboratory coefficient of variation of 16%. This cutoff level was confirmed in a prospective audit (n = 100). As demand for CSF tau levels will increase globally, the accuracy of local CSF hTau cutoff levels can be compared against this benchmark.     

Stigmatizing attitudes and social perception towards mental illness among Moroccan medical students

ObjectivesThis study aimed to explore medical students’ attitudes, social perception, and knowledge towards mental illness and identify the associated factors.MethodsA cross-sectional study was conducted in the Medical Faculty of Fez. A representative sample of 420 Moroccan students from the first to the seventh years was selected randomly during the academic year (2018/2019). They completed the Mental Illness Clinicians Attitudes scale (MICA) and a self-questionnaire exploring sociodemographic data, the university course, social perception and knowledge towards mental illness, and the potential consideration of psychiatry as a career.ResultsThe average age of participants was 21.73 years (SD ± 2.60), and 72.4% (n = 304) of respondents were female (M/F gender ratio = 0.39). The participants held stigmatizing attitudes and negative social perceptions towards mental illness, as indicated by the high score of the MICA scale (mean = 57.24; SD ± 9.95). Females (p = 0.02) and married students (p = 0.02) showed significantly more tolerant attitudes. The attitudes of students (p = 0.37) who completed the psychiatry clerkship were slightly more favorable (p = 0.15). There was no significant difference in attitudes according to the level of study (p = 0.06). Students with a lower socioeconomic level tended to be less stigmatizing (p = 0.08). The assessment of knowledge about mental illness among students objectified major gaps. A total of 17.9% (n = 75) considered psychiatry as a career.ConclusionThe attitudes of medical students in this study were stigmatizing, and this should without delay motivate Moroccan research, educational and health authorities to investigate further scientific research in this area to address these attitudes and remedies.     

MMP-2 concentrations in stroke according to etiology: Adjusting for enzyme degradation in stored deep-frozen serum and other methodological pitfalls

Matrix metalloproteinases (MMP) have a prominent role in the pathophysiology of stroke. We investigated potential differences in MMP-2 concentrations with respect to acute stroke etiology. For another MMP family member, MMP-9, significant degradation over time has been found even when stored at ?80 °C, so we measured temporal degradation of MMP-2 and adjusted for this and other factors potentially affecting our results. For 264 patients with acute stroke at baseline and a control cohort of 120 subjects, MMP-2 concentrations were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. For each stroke patient, stroke etiology was categorized as cardioembolic, large vessel or small vessel ischemic stroke, or primary hemorrhage. Stroke patients had significantly lower MMP-2 concentrations than controls (mean ± standard deviation: 175.6 ± 65.6 ng/mL versus 212.0 ± 54.8 ng/mL, p < 0.001). However, sample degradation (average sample storage time: 240.0 ± 113.7 days) was considerable, amounting to approximately 15% per year. The full extent of differences in MMP-2 concentrations between stroke of different subtypes only became evident when results were adjusted for enzyme degradation during storage and other methodological pitfalls. Before adjustment, the only significant difference between etiologies was that the cardioembolic stroke group had a significantly higher concentration of MMP-2 than the hemorrhage group. After adjustment for time to analysis and ELISA plate clustering, patients with cardioembolic stroke had significantly higher MMP-2 concentrations in comparison to all other stroke subtypes.     

Impact of sleeping position on central sleep apnea/Cheyne–Stokes respiration in patients with heart failure

BackgroundThe present study determines the influence of sleeping position on central sleep apnea (CSA) in patients with heart failure (HF).MethodsThe apnea/hypopnea index (AHI) during different body positions while asleep was examined by cardiorespiratory polygraphy in 71 patients with HF (ejection fraction <45%).ResultsTwenty-five of the patients having predominantly CSA (central apnea index ?10/h) with a lower obstructive apnea index (<5/h) were assigned to groups with positional (lateral to supine ratio of AHI <50%, n = 12) or non-positional (ratio ?50%, n = 13) CSA. In the non-positional group the BNP level was higher, the ejection fraction was lower and the trans-tricuspid pressure gradient was higher than in the positional group. Multiple regression analysis revealed more advanced age (p = 0.006), log₁₀ BNP (p = 0.017) and lung-to-finger circulation time (p = 0.020) as independent factors of the degree of positional CSA. Intensive treatment for HF changed CSA from non-positional to positional in all eight patients tested. Single night of positional therapy reduced CSA (p < 0.05) and BNP level (p = 0.07) in seven positional patients.ConclusionAs cardiac dysfunction progresses, severity of CSA also increases and positional CSA becomes position-independent. Positional therapy could decrease CSA, thereby having a valuable effect on HF.     

Alzheimer-associated urine neuronal thread protein level increases with age in a healthy Chinese population

Alzheimer-associated neuronal thread protein (AD7c-NTP) has been found to be a biomarker for Alzheimer’s disease (AD) with elevated levels in the cerebrospinal fluid and urine from AD patients in the early stage of the disease. Whether the urine level of AD7c-NTP in healthy people is age-related is still unclear. We aimed to measure the level of urine AD7c-NTP in a healthy Chinese population of different ages. Urine samples of 294 subjects were collected from the Department of Health Examination Center at Xuanwu Hospital of Capital Medical University, China. The samples were divided into five groups by age: Group 1 (20–29 years), Group 2 (30–39 years), Group 3 (40–49 years), Group 4 (50–59 years) and Group 5 (⩾60 years). The Mini Mental State Examination and Montreal Cognitive Assessment were carried out. The level of AD7c-NTP in the urine specimen was detected by enzyme-linked immunosorbent assay. The urine AD7c-NTP levels in Group 1, 2, 3, 4 and 5 were 0.3012 ± 0.2373, 0.3702 ± 0.2422, 0.3914 ± 0.2442, 0.4844 ± 0.2908 and 0.5880 ± 0.2638 ng/ml (mean ± standard error of the mean), respectively. The urine AD7c-NTP levels among the five groups differed significantly (F = 6.181, p = 0.00). Females had a higher urine AD7c-NTP content than males, and the urine AD7c-NTP level increased with age (r = 0.28, p = 0.00). To our knowledge this study is the first to show that urine AD7c-NTP level increases with age in a healthy Chinese population without cognitive dysfunction. This study suggests that different cut-off values aimed at different age groups should be established for diagnosing cognitive impairments in clinical practice.     

Seizures and antiepileptic drugs in patients with spontaneous intracerebral hemorrhages

PurposePatients with intracerebral hemorrhage (ICH) are often initiated on antiepileptic drugs without a clear indication. We compared the percentage of patients with spontaneous ICH who had seizures at onset or during hospitalization, and examined empiric use of antiepileptic drugs (AEDs) in these patients in 2 cohorts 10 years apart.MethodsUsing a clinical data registry at a tertiary care adult hospital, we retrospectively selected admissions for spontaneous ICH between 1/1/99–12/31/00 (Cohort A, n = 30) and 1/1/09–12/31/10 (Cohort B, n = 108). Clinical, neurophysiological and radiological data were collected in both cohorts.ResultsIn Cohorts A and B respectively, AEDs were started in 53.3% and 50.0%, and continued on discharge in 50.0% and 20.4% of patients; 86.6% and 59.1% of patients discharged on AEDs did not have a clinical/electrographic seizure or epileptiform EEG findings. Seizures occurred in 6.6% and 13.0% in Cohorts A and B respectively. The presence of a seizure at presentation (p = 0.01) and during hospitalization (p = 0.02) were predictors for continuing AED on discharge.ConclusionIn both cohorts, a significant number of patients were discharged on AEDs without a clear indication, though there is a change in practice between the two cohorts.     

Inflammatory molecules in Frontotemporal Dementia: Cerebrospinal fluid signature of progranulin mutation carriers

Mutations in progranulin gene (GRN) are one of the major causes of autosomal dominant Frontotemporal Lobar Degeneration (FTLD). Progranulin displays anti-inflammatory properties and is likely a ligand of Tumor Necrosis Factor (TNF) receptor 2, expressed on microglia. A few cytokines and chemokines are altered in cerebrospinal fluid (CSF) from patients with sporadic FTLD, whereas no information is available in familial cases. We evaluated, through BioPlex, levels of 27 inflammatory molecules, including cytokines, chemokines, and related receptors, in CSF and matched serum, from FTLD patients carrying GRN mutations as compared with sporadic FTLD with no GRN mutations and controls. Mean ± SD Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly increased in CSF from sporadic FTLD patients as compared with controls (334.27 ± 151.5 versus 159.7 ± 49 pg/ml; P ⩽ 0.05). In GRN mutation carriers versus controls, CSF levels of MCP-1 were unchanged, whereas Interferon-γ-inducible protein-10 (IP-10) levels were increased (809.17 ± 240.0 versus 436.61 ± 202.5 pg/ml; P = 0.012). In the same group, TNFα and Interleukin (IL)-15 levels were decreased (3.18 ± 1.41 versus 35.68 ± 30.5 pg/ml; P = 0.013 and 9.34 ± 5.54 versus 19.15 ± 10.03 pg/ml; P = 0.023, respectively). Conversely, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) levels were decreased in patients, with or without mutations, as compared with controls (4.63 ± 3.30 and 2.58 ± 20 versus 87.57 ± 70 pg/ml, respectively; P < 0.05). Moreover, IP-10, IL-15 and RANTES CSF levels were not influenced by age, whereas MCP-1 levels increased with age (ρ = 0.48; P = 0.007). In conclusion, inflammatory de-regulation was observed in both sporadic FTLD and GRN carriers compared to controls, with a specific inflammatory profile for the latter group.