Role of <Emphasis Type="Italic">TLR4</Emphasis> (C1196T) and <Emphasis Type="Italic">CD14</Emphasis> (C-260T) Polymorphisms in Development of Ischemic Stroke,Its Subtypes and Hemorrhagic Stroke

In the present study, we evaluated the association of TLR4 and CD14 polymorphisms, i.e. C1196T and C-260T, respectively, with ischemic stroke (n = 700), its subtypes and hemorrhagic stroke (n = 300) in a South Indian population from Telangana. The genotypes were determined using PCR–RFLP, and the strength of association between genotypes and stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. The results revealed a lack of association for TLR4 variant with ischemic stroke and hemorrhagic stroke, although a significant association was observed with the subtypes extracranial large artery (p = 0.008), other determined aetiology (p = 0.03) and undetermined aetiology (p = 0.01). Investigations on the variant of CD14 gene revealed negative association among ischemic stroke patients; however, a significant association was observed for hemorrhagic stroke following dominant and recessive genotypic model (p = 0.05, p = 0.02). Among ischemic stroke subtype, a significant association was observed with intracranial large artery, extracranial large artery, other determined aetiology and undetermined aetiology form of stroke (p < 0.01). Further, analysis of the CD14 variant between the two major stroke types revealed a significant difference in genotype distribution following the co-dominant genotypic model (p = 0.01).     

Peripheral nerve diffusion tensor imaging as a measure of disease progression in ALS

Clinical trial design in amyotrophic lateral sclerosis (ALS) remains hampered by a lack of reliable and sensitive biomarkers of disease progression. The present study evaluated peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker of axonal degeneration in ALS. Longitudinal studies were undertaken in 21 ALS patients studied at 0 and 3 months, and 19 patients at 0, 3 and 6 months, with results compared to 13 age-matched controls. Imaging metrics were correlated across a range of functional assessments including amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R), lower limb muscle strength (Medical Research Council sum score, MRCSS-LL), compound muscle action potential amplitudes and motor unit number estimation (MUNE). Fractional anisotropy was reduced at baseline in ALS patients in the tibial (p < 0.05), and peroneal nerve (p < 0.05). Fractional anisotropy and axial diffusivity declined in the tibial nerve between baselines, 3- and 6-month scans (p < 0.01). From a functional perspective, ALSFRS-R correlated with fractional anisotropy values from tibial (R = 0.75, p < 0.001) and peroneal nerves (R = 0.52, p = 0.001). Similarly, peroneal nerve MUNE values correlated with fractional anisotropy values from the tibial (R = 0.48, p = 0.002) and peroneal nerve (R = 0.39, p = 0.01). There were correlations between the change in ALSFRS-R and tibial nerve axial diffusivity (R = 0.38, p = 0.02) and the change in MRCSS-LL and peroneal nerve fractional anisotropy (R = 0.44, p = 0.009). In conclusion, this study has demonstrated that some peripheral nerve DTI metrics are sensitive to axonal degeneration in ALS. Further, that DTI metrics correlated with measures of functional disability, strength and neurophysiological measures of lower motor neuron loss.     

Clinical Value of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratio After Aneurysmal Subarachnoid Hemorrhage

Background

Inflammation and thrombosis are associated with the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are emerging as novel inflammatory markers in stroke. We aimed to identify the association of NLR and PLR with delayed cerebral ischemia (DCI) and 3-month outcome after aSAH.

Methods

Two hundred and forty-seven patients diagnosed with aSAH within 24 h of symptoms onset were enrolled. Clinical, neuroradiological, laboratory, and follow-up data were collected from electronic database. Functional outcome was assessed by modified Rankin Scale. Admission NLR, PLR, and combined NLR-PLR associated with outcomes were evaluated by logistic regression analysis, and we used receiver operating characteristic curves to detect the overall predictive accuracy of these markers.

Results

Fifty-five (22.3 %) patients had unfavorable outcome and 47 (19 %) developed DCI. Both NLR and PLR were correlated with WFNS grade (ρ = 0.35[p < 0.001], ρ = 0.28[p < 0.001]) and modified Fisher grade (ρ = 0.25[p = 0.001], ρ = 0.28[p = 0.003]) and independently related to DCI (OR 2.18, 95 %CI 1.51–3.15, p = 0.016; OR 2.21, 95 %CI 1.61–3.32, p = 0.008) and functional outcome (OR 1.89, 95 %CI 1.52–3.17, p = 0.015; OR 1.77, 95 %CI 1.48–3.21, p = 0.018) at 3 months after aneurysm repair. They had comparable predictive ability in DCI occurrence (area under the curve [AUC] 0.65, 95 %CI 0.55–0.74, p = 0.002; AUC 0.68, 95 %CI 0.60–0.76, p < 0.001) and poor outcome (AUC 0.70, 95 %CI 0.63–0.77, p < 0.001; AUC 0.65, 95 %CI 0.58–0.72, p = 0.001). However, combination of the two indexes showed a better predictive value than each alone (AUC 0.73, 95 %CI 0.66–0.81, p < 0.001 for DCI; AUC 0.76, 95 %CI 0.70–0.83, p < 0.001 for poor outcome).

Conclusions

NLR and PLR as novel inflammatory biomarkers are independent predictors of DCI development and functional outcome after acute aSAH. When combined together, they may help to identify high-risk patients more powerfully.

     

<Emphasis Type="Italic">ABCC8</Emphasis> Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI

Objective

Cerebral edema (CE) in traumatic brain injury (TBI) is the consequence of multiple underlying mechanisms and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for sulfonylurea receptor-1 (Sur1) in CE is supported. However, there are no prior studies examining the effect of genetic variability in the Sur1 gene (ABCC8) on the development of CE. We hypothesize that ABCC8 single nucleotide polymorphisms (SNPs) are predictive of CE.

Methods

DNA was extracted from 385 patients. SNPs in ABCC8 were genotyped using the Human Core Exome v1.2 (Illumina). CE measurements included acute CT edema, mean and peak intracranial pressure (ICP), and need for decompressive craniotomy.

Results

Fourteen SNPs with minor allele frequency >0.2 were identified. Four SNPS rs2283261, rs3819521, rs2283258, and rs1799857 were associated with CE measures. In multiple regression models, homozygote-variant genotypes in rs2283261, rs3819521, and rs2283258 had increased odds of CT edema (OR 2.45, p = 0.007; OR 2.95, p = 0.025; OR 3.00, p = 0.013), had higher mean (β = 3.13, p = 0.000; β = 2.95, p = 0.005; β = 3.20, p = 0.008), and peak ICP (β = 8.00, p = 0.001; β = 7.64, p = 0.007; β = 6.89, p = 0.034). The homozygote wild-type genotype of rs1799857 had decreased odds of decompressive craniotomy (OR 0.47, p = 0.004).

Conclusions

This is the first report assessing the impact of ABCC8 genetic variability on CE development in TBI. Minor allele ABCC8 SNP genotypes had increased risk of CE, while major SNP alleles were protective—potentially suggesting an evolutionary advantage. These findings could guide risk stratification, treatment responders, and the development of novel targeted or gene-based therapies against CE in TBI and other neurological disorders.

     

Progression of postural changes in Parkinson’s disease: quantitative assessment

Previous studies of posture in Parkinson’s disease (PD) patients focused on the pathophysiology of severe deformities, using mainly subjective estimations or goniometric measures. The aim of this study was to investigate risk factors associated with flexed posture in PD and their effects on the course of posture variations. One hundred-ninety patients with definite PD were prospectively evaluated for angles of spinal inclination in upright position, extension, and flexion using a mechanical computer-assisted, hand-held device (SpinalMouse). Patients underwent clinical examination, including background data and bone mineral density. Motor function was evaluated with the UPDRS, and back pain with the RMDQ. Physical activity data were collected by self-report. Postural measurements were repeated after 10–17 months. Angle of upright inclination correlated with age (p = 0.0004), older age at disease onset (p = 0.0085), longer disease duration (p = 0.003), higher UPDRS motor and posture score (p = 0.0005 and 0.0001), the presence of back-pain (p = 0.0097), and osteoporosis (p = 0.027). There was no correlation between upright angle of inclination and gender, disease type, or side of disease onset. Re-evaluation of posture in 124 patients at 13.77 ± 4.4 months after the initial evaluation showed significant deterioration in forward bending (p < 0.0001) and was significantly associated with disease duration (p = 0.029), worsening of the UPDRS score (p = 0.016), right-side disease onset (p = 0.032), presence of vertebral fractures (p = 0.049), and the lack of physical activity (p = 0.0327). Older age, disease severity and duration, presence of back-pain and osteoporosis are associated with postural abnormalities in PD. Physical activity might slow the worsening of postural abnormalities in PD.     

Quality of Life and Hormonal,Biochemical, and Anthropometric Profile Between Olanzapine and Risperidone Users

This cross-sectional study compared quality of life and side effects in 108 users of olanzapine or risperidone suffering schizophrenia and being attended at psychiatric ambulatory services in Rio Grande do Norte, Brazil. Economic, socio-demographic, anthropometric, biochemical, and hormonal variables were compared. The EuroQoL Five-Dimension Scale (EQ-5D) was used to evaluate quality of life, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson–Angus Scale. Data were analysed using the χ² test and Student’s t test, with a significance level of 5 %.The household incomes of approximately 80 % of patients were <2.0 minimum wages ($678). Anthropometric variables (waist circumference, hip circumference, weight, waist-to-hip ratio) and systolic and diastolic blood pressure were noted among male olanzapine users (all p < 0.05). EQ-5D scores showed that olanzapine use significantly impacted self-help ability (p < 0.001). Risperidone users had a mean quality-adjusted life year value of 1. Mean total Simpson–Angus Scale scores was 0.38 for olanzapine users and 0.11 for risperidone users (p < 0.02). Significant differences in UKU were observed for the following items: asthenia/lassitude/fatigue (higher among olanzapine users, p = 0.02), dystonia (higher among olanzapine users, p = 0.01), tremors (higher among olanzapine users, p = 0.03), gynecomastia (higher among risperidone users, p < 0.02), and ejaculatory dysfunction (higher among risperidone users, p < 0.02). Olanzapine users had impaired quality of life, which can be explained in part by adverse motor, biochemical, and hormonal effects characteristic of metabolic syndrome.     

Positive effects of fampridine on cognition,fatigue and depression in patients with multiple sclerosis over 2 years

Objective

To assess the effects of PR-fampridine on cognitive functioning, fatigue and depression in patients with multiple sclerosis (PwMS).

Methods

Thirty-two PwMS were included in this trial. Cognitive performance was assessed in an open-label and randomized double-blind, placebo-controlled study design using a comprehensive neuropsychological test battery as well as questionnaires examining depression and fatigue.

Results

We found significant improvements in cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency (p = 0.0002) during open-label treatment with PR-fampridine. These effects of performance were paralleled by patients’ perception of reduced fatigue (physical, p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical, p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during randomized, double-blind, placebo-controlled assessment in the second year. In addition, we found positive effects of PR-fampridine on depressive symptoms (p = 0.0049). We demonstrated persisting beneficial effects of PR-fampridine on fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding cognitive performance and fatigue was not limited to walking responders.

Conclusions

Our data demonstrate significant positive effects of treatment with PR-fampridine over 2 years on different cognitive domains as well as fatigue and depression in a cohort of PwMS. These findings imply that PR-fampridine should be considered as symptomatic treatment improving aspects of cognition, fatigue and depression in PwMS.

     

Reorganization of sensory input at brainstem in hemifacial spasm and postparalytic facial syndrome

We hypothesized the filtering of sensory input from face and hand at brainstem may reorganize in hemifacial spasm (HFS) and postparalytic facial syndrome (PFS). Thus, we examined the prepulse inhibition of blink reflex (BR-PPI) in HFS and PFS. We included 12 healthy subjects, 13 patients with HFS, and 11 patients with PFS. Baseline BR, BR recovery at interstimulus interval (ISI) of 300 ms and BR-PPI at ISI of 100 ms were performed on the right sides of healthy subjects and on both sides of patients. Within-subject analysis showed baseline BR and BR-PPI were similar between asymptomatic and symptomatic sides of patients with HFS whereas BR recovery was higher on the symptomatic side. In the PFS group, latency of R2 during baseline BR recording was longer (p = 0.022) and R2 amplitude (p = 0.046) was reduced on the symptomatic side compared to asymptomatic side. Reduction of R2 area in BR-PPI recordings was also the lowest in HFS compared to other two groups (p = 0.000); however, it was also lower in patients with PFS compared to healthy subjects (p = 0.018). BR-PPI was decreased on both sides of patients. The mean R2 recovery was higher on both sides of patients with HFS and PFS (p = 0.007). Filtering of facial sensory input is decreased probably to monitor and to correct the sequence of facial movements in these disorders.     

ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy

The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aβ(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.     

Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex

Cognitive development in patients with tuberous sclerosis complex is highly variable. Predictors in the infant years would be valuable to counsel parents and to support development. The aim of this study was to confirm factors that have been reported to be independently correlated with cognitive development. 102 patients included in this study were treated at the ENCORE-TSC expertise center of the Erasmus Medical Center-Sophia Children’s Hospital. Data from the first 24 months of life were used, including details on epilepsy, motor development and mutation status. Outcome was defined as cognitive development (intellectual equivalent, IE) as measured using tests appropriate to the patients age and cognitive abilities (median age at testing 8.2 years, IQR 4.7–12.0). Univariable and multivariable regression analyses were used. In a univariable analysis, predictors of lower IE were: the presence of infantile spasms (β = ?18.3, p = 0.000), a larger number of antiepileptic drugs used (β = ?6.3, p = 0.000), vigabatrin not used as first drug (β = ?14.6, p = 0.020), corticosteroid treatment (β = ?33.2, p = 0.005), and a later age at which the child could walk independently (β = ?2.1, p = 0.000). An older age at seizure onset predicted higher IE (β = 1.7, p = 0.000). In a multivariable analysis, only age at seizure onset was significantly correlated to IE (β = 1.2, p = 0.005), contributing to 28% of the variation in IE. In our cohort, age at seizure onset was the only variable that independently predicted IE. Factors predicting cognitive development could aid parents and physicians in finding the appropriate support and schooling for these patients.     

The BRAIN test: a keyboard-tapping test to assess disability and clinical features of multiple sclerosis

Background

The BRadykinesia Akinesia INcordination (BRAIN) test is an online keyboard-tapping test previously validated as a sensitive tool for detecting signs of Parkinson’s disease.

Objectives

To determine whether the BRAIN test can measure disability in MS and identify the presence of pyramidal or cerebellar dysfunction.

Methods

Kinesia scores (KS, number of key taps in 30 s), akinesia times (AT, mean dwell time on each key) and incoordination scores (IS, variance of travelling time between keys) were calculated in 39 MS patients. These were correlated against the Expanded Disability Status Scale (EDSS) scores, pyramidal and cerebellar functional system scores and 9-hole peg test scores.

Results

EDSS correlated with KS (r = ? 0.594, p < 0.001), AT (r = 0.464, p = 0.003) and IS (r = 0.423, p = 0.007). 9-HPT scores strongly correlated with KS (r = 0.926, p < 0.001). Pyramidal scores correlated with KS (r = ? 0.517, p < 0.001). Cerebellar scores correlated with KS (r = ? 0.665, p < 0.001), AT (r = 0.567, p < 0.001) and IS (r = 0.546, p = 0.007). Receiver operating characteristic curves demonstrate that KS can distinguish between the presence or absence of pyramidal and cerebellar dysfunction with area under curve 0.840 (p < 0.001) and 0.829 (p < 0.001), respectively.

Conclusions

The BRAIN test can remotely measure disability in MS. Specific scores differ according to the presence and severity of pyramidal or extrapyramidal dysfunction. It demonstrates huge potential in monitoring disease progression in clinical trials.

     

The Reciprocal Influence of Callous-Unemotional Traits,Oppositional Defiant Disorder and Parenting Practices in Preschoolers

The present study investigates reciprocal associations between positive parenting, parental monitoring, CU traits, and ODD in children assessed at age 3 and again at age 6. Data were collected from a sample of preschoolers (N = 419; 51.58 % female) through diagnostic interviews and questionnaires answered by parents and teachers. Structural equation modeling revealed a bidirectional relationship between poor monitoring and ODD, with poor monitoring at age 3 predicting ODD at age 6 (β = 0.11, p < 0.05), and ODD at age 3 predicting poor monitoring at age 6 (β = 0.10, p < 0.05). While poor monitoring at age 3 predicted CU traits at age 6 (β = 0.11, p < 0.05), CU traits at age 3 predicted positive parenting (β = 0.09, p < 0.05) and ODD (β = 0.13, p < 0.05) at age 6. Results have important implications for early targeted parenting interventions for CU traits and ODD.     

Evaluation of retinal nerve fiber layer,ganglion cell layer and macular changes in patients with migraine

The aim of this study was to investigate retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) thickness, macular changes (central subfield thickness (CST), cube average thickness (CAT), cube volume (CV) in patients with migraine using spectral-domain optical coherence tomography (OCT) and to assess if there was any correlation with white matter lesions (WML). In this prospective case–control study, RNFL, GCL thickness and macular changes of 19 migraine patients with aura (MA), 41 migraine without aura (MO) and 60 age- and gender-matched healthy subjects were measured using OCT device. OCT measurements were taken at the same time of the day to minimize the effects of diurnal variation. The average, inferior and superior quadrant RNFL thickness were significantly thinner in patients with migraine (p = 0.017, p = 0.010, p = 0.048). There was also a significant difference between patients with and without aura in the mean and superior quadrant RNFL thickness (p = 0.02, p = 0.043).While there was a significant thinning in CST and CAT in patients with migraine (p = 0.020), there were no significant difference in GCL measurements (p = 0.184). When the groups were compared to the control group, there were significant differences between MA and the control group regarding average, superior and inferior quadrant RNLF thickness (p < 0.001, p = 0.025, p < 0.001). On the other hand, there were significant differences between MO and the control group regarding average and inferior faces (p = 0.037, p = 0.04). When OCT measurements were evaluated according to the frequency of attacks, CST and GCL thickness were significantly thinner in patients who had more than four attacks a month (p = 0.024, p = 0.014). In patients with WML, only CV measurements were significantly thinner than migraine patients without WML (p = 0.014). The decreased RNFL, CST, CAT and CV of the migraine patients might be related to the vascular pathology of the disease. Because WML was not correlated with the same measurements except CV, we think that further studies are needed to evaluate the etiopathologic relationship between OCT measurements and WML in migraine patients.     

Relationship Between Alcohol Use,Spirituality, and Coping

Authors investigated a relationship between the frequency of alcohol consumption, spirituality, and coping with everyday life events in a cross-sectional, community-based sample of 320 adults in Ukraine, the country with one of the highest alcohol consumption levels in the world. Face-to-face interviews with participants took place in rural and urban locations across Eastern, Southern, and Central Ukraine. Results of the ordinary least-squares regression suggest that a higher frequency of alcohol consumption was related with the lower use of positive reappraisal (β = ?.27, p < .001), higher use of escape-avoidance (β = .23, p < .01) and confrontive (β = .15, p < .05) coping strategies, lower spirituality (β = ?.20, p < .001), and younger age (β = ?.11, p < .05). On the whole, current findings suggest that specific coping behaviors, younger age, and lower spirituality are involved in higher frequency of alcohol consumption among Ukrainian adults.     

Sympathetic cardiovascular and sudomotor functions are frequently affected in early multiple sclerosis

Objective

The aim of this study was to determine the prevalence of autonomic dysfunction using the composite autonomic scoring scale (CASS) and heart rate variability (HRV) in patients with clinically isolated syndrome (CIS) and to correlate autonomic dysfunction with other measures of MS disease activity.

Methods

CASS, HRV and plasma catecholamines during supine and tilted phase were performed in 104 CIS patients. MRI findings were analyzed for total number of lesions and the presence of brainstem and cervical spinal cord lesions.

Results

Autonomic dysfunction (CASS >1) was present in 59.8 % of patients, parasympathetic dysfunction in 5 %, sympathetic in 42.6 % and sudomotor in 32.7 % of patients. Patients with autonomic dysfunction on CASS had lower level of norepinephrine in the supine position compared to patients without autonomic dysfunction (1.06 ± 0.53 vs. 1.37 ± 0.86, p = 0.048). The CASS score showed positive correlation with s-HF (r = 0.226, p = 0.031), s-SDNN (r = 0.221, p = 0.035), t-HF (r = 0.225, p = 0.032), and t-HFnu (r = 0.216, p = 0.04), and a negative correlation with t-LF/HF (r = ?0.218, p = 0.038). More patients with MRI brainstem lesions had a positive adrenergic index (p = 0.038). Patients with MRI brainstem lesions also had a lower t-SDNN (26.2 ± 14.2 vs. 32 ± 13.3, p = 0.036) and a lower t-LF (median 415.0 vs. 575.5, p = 0.018) compared to patients without these lesions. Patients with adrenergic index ≥1 had a significantly higher standing heart rate compared to patients with an adrenergic index of 0 (96 ± 13.5 vs. 90 ± 12, p = 0.032).

Conclusion

Autonomic (primarily sympathetic) dysfunction is present in a large proportion of early MS patients and it seems to be related to brainstem involvement.

     

Insular multiple sclerosis lesions are associated with erectile dysfunction

Erectile function (EF) is frequently compromised in men with multiple sclerosis (MS). Functional neuroimaging in healthy men identified a network of brain areas, such as the insula, visual and somatosensory association areas, cingulate gyrus, prefrontal cortex, as well as subcortical regions, contributing to EF. This study intended to determine associations between EF deterioration during MS and cerebral MS-associated lesion sites. In 31 men with MS (mean age 38.2 ± 11.2 years), we evaluated MS-related EF deterioration by comparing scores of the 5-item International Index of Erectile Function-5 questionnaire (IIEF5) at the time of study and retrospectively, 3 months prior to MS diagnosis, by calculating score differences as DeltaIIEF5 (DeltaIIEF5 score < 0 indicated EF deterioration). To assess the impact of confounding factors of EF, patient age, disease duration, disease severity, depressiveness, bladder and bowel symptoms, and total cerebral MS lesion volume were correlated with DeltaIIEF5 scores (Spearman rank correlation) and compared between patients with and without EF deterioration (t tests or Mann–Whitney U test). MS lesions were assessed on T2-weighted magnetic resonance imaging (MRI; 1.5 or 3 T). We determined the lesion overlap (prevalence of identical lesion sites among patients), subtracted lesion overlaps in patients without EF deterioration from overlaps in patients with EF deterioration, and compared DeltaIIEF5 scores voxel-wise between patients with and without lesions in a given voxel (t test; significance: p < 0.05). In 14 patients (45.2%), DeltaIIEF5 scores indicated EF deterioration. DeltaIIEF5 scores were not associated with age (ρ = 0.06; p = 0.74), disease duration (ρ = 0.26; p = 0.15), disease severity (ρ = ? 0.19; p = 0.31), depressiveness (ρ = 0.07; p = 0.72), bladder symptoms (ρ = ? 0.11; p = 0.57), bowel symptoms (ρ = 0.17; p = 0.37), and total lesion volume (ρ = ? 0.13; p = 0.47). The voxel-wise analysis showed associations between EF deterioration and MS lesions primarily in the bilateral, and predominantly left juxtacortical insular region. In conclusion, MS lesions particularly in the left insular region, which is activated with sexual arousal, contribute to erectile dysfunction.     

Patient and Clinician Assessments of Symptomatology Changes on Older Adults Following a Psycho-educational Program for Depression and Anxiety

Important attention has been given to the assessment of patients’ perspectives on treatment, especially as outcomes have been typically evaluated by clinicians. This study examined the association between patient and clinician ratings on perceived improvement and symptomatology changes for an older adult population participating in an ongoing psycho-educational program. Pre-post measures including depression (GDS), anxiety (BAI) and general well-being (GWBS) were collected in a sample of 34 older adults (age = 71.32 ± 6.46 years). Post-testing data included perceived improvement rated by patients, and clinician assessment of depressive symptoms (CS-GDS). Results indicate significant correlations between pre-post changes of the GDS and patients’ PIQ (r = ?0.37, n = 31, p < 0.05), but not on symptomatic changes of the BAI (r = 0.012, n = 32, p > 0.05) or the GWBS (r = 0.12, n = 31, p > 0.05). Relationships between patients’ PIQ and post-ratings on GDS (r = -0.74, n = 33, p < 0.05) and CS-GDS (r = -0.48, n = 32, p < 0.05) are also significant. Results imply that pre-post improvement in depressive symptoms is associated with a patient’s perceived improvement and that clinician and patient ratings on depression symptoms post-treatment were both inversely correlated to patients’ perceived improvement. Findings suggest that the PIQ is a good indicator to assess symptomatic change by patients and clinicians although they are possibly placing attention on different aspects of treatment outcome, as indicated by differences on sub-scales of the PIQ. Clinicians possibly place a strong focus on assessments of depression symptomatology. Future studies may integrate simultaneous assessments of instruments exploring aspects other than depression, especially those examining representations of illness in older adults.     

Neutrophil to lymphocyte ratio may be a helpful marker to evaluate disease activity in NMOSD

Neutrophil to lymphocyte ratio (NLR) was introduced to assess the activity in autoimmune diseases. Neuromyelitis optica spectrum disorder (NMOSD) has been defined as a chronic inflammatory disease with a course of relapse-remission. Therefore, the relationship between NLR and NMOSD was assessed in this article. Data of NMOSD patients was extracted. NLR is calculated as the absolute count of neutrophil divided by the absolute count of lymphocytes. Correlations between NLR and characteristics of NMOSD patients were evaluated. Effect of treatments on NLR was also analyzed. Increased level of NLR was observed in patients with NMOSD compared healthy individuals (p < 0.001); moreover, patients who were experiencing acute attack had a higher level of NLR compared with those who in remission (p < 0.001). NLR was correlated with RDW (r = 0.288, p = 0.021), ΔEDSS (r = 0.301, p = 0.016). NLR may be a helpful marker to assess the disease activity of NMOSD. Meanwhile, NLR may reflect the aggravated degree of neurological disability.     

Perihematomal Edema Expansion Rates and Patient Outcomes in Deep and Lobar Intracerebral Hemorrhage

Background

Perihematomal edema (PHE) expansion rate may predict functional outcome following spontaneous intracerebral hemorrhage (ICH). We hypothesized that the effect of PHE expansion rate on outcome is greater for deep versus lobar ICH.

Methods

Subjects (n = 115) were retrospectively identified from a prospective ICH cohort enrolled from 2000 to 2013. Inclusion criteria were age ≥ 18 years, spontaneous supratentorial ICH, and known onset time. Exclusion criteria were primary intraventricular hemorrhage (IVH), trauma, subsequent surgery, or warfarin-related ICH. ICH and PHE volumes were measured from CT scans and used to calculate expansion rates. Logistic regression assessed the association between PHE expansion rates and 90-day mortality or poor functional outcome (modified Rankin Scale > 2). Odds ratios are per 0.04 mL/h.

Results

PHE expansion rate from baseline to 24 h (PHE24) was associated with mortality for deep (p = 0.03, OR 1.13[1.02–1.26]) and lobar ICH (p = 0.02, OR 1.03[1.00–1.06]) in unadjusted regression and in models adjusted for age (deep p = 0.02, OR 1.15[1.02–1.28]; lobar p = 0.03, OR 1.03[1.00–1.06]), Glasgow Coma Scale (deep p = 0.03, OR 1.13[1.01–1.27]; lobar p = 0.02, OR 1.03[1.01–1.06]), or time to baseline CT (deep p = 0.046, OR 1.12[1.00–1.25]; lobar p = 0.047, OR 1.03[1.00–1.06]). PHE expansion rate from baseline to 72 h (PHE72) was associated with mRS > 2 for deep ICH in models that were unadjusted (p = 0.02, OR 4.04[1.25–13.04]) or adjusted for ICH volume (p = 0.02, OR 4.3[1.25–14.98]), age (p = 0.03, OR 5.4[1.21–24.11]), GCS (p = 0.02, OR 4.19[1.2–14.55]), or time to first CT (p = 0.03, OR 4.02[1.19–13.56]).

Conclusions

PHE72 was associated with poor functional outcomes after deep ICH, whereas PHE24 was associated with mortality for deep and lobar ICH.

     

Increased cell-free mitochondrial DNA is a marker of ongoing inflammation and better neurocognitive function in virologically suppressed HIV-infected individuals

Cell-free mitochondrial DNA (mtDNA) is a highly immunogenic molecule that is associated with several inflammatory conditions and with neurocognitive impairment during untreated HIV infection. Here, we investigate how cell-free mtDNA in cerebrospinal fluid (CSF) is associated with inflammation, neuronal damage, and neurocognitive functioning in the context of long-term suppressive antiretroviral therapy (ART). We quantified the levels of cell-free mtDNA in the CSF from 41 HIV-infected individuals with completely suppressed HIV RNA levels in blood plasma (<50 copies/mL) by droplet digital PCR. We measured soluble CD14, soluble CD163, interferon γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), neopterin, and neurofilament light chain (NFL) by immunoassays in CSF supernatant or blood plasma. Higher levels of mtDNA in CSF were associated with higher levels of MCP-1 (r = 0.56, p < 0.01) in CSF and TNF-α (r = 0.43, p < 0.01) and IL-8 (r = 0.44, p < 0.01) in blood plasma. Subjects with a previous diagnosis of AIDS showed significantly higher levels of mtDNA (p < 0.01) than subjects without AIDS. The associations between mtDNA and MCP-1 in CSF and TNF-α in blood remained significant after adjusting for previous diagnosis of AIDS (p < 0.01). Additionally, higher levels of mtDNA were associated with a lower CD4 nadir (r = ?0.41, p < 0.01) and lower current CD4% (r = ?0.34, p = 0.03). Paradoxically, higher levels of mtDNA in CSF were significantly associated with better neurocognitive performance (r = 0.43, p = 0.02) and with less neuronal damage (i.e. lower NFL). Higher cell-free mtDNA is associated with inflammation during treated HIV infection, but the impact on neurocognitive functioning and neuronal damage remains unclear and may differ in the setting of suppressive ART.