The relationship between metabolic syndrome,BDNF, and vitamin D in patients with schizophrenia

The objective of this study is to investigate the relationship between anthropometric (BMI and waist circumference), metabolic (glucose, insulin, insulin resistance, HbA1c, and lipid profile), psychopathologic (Positive and Negative Syndrome Scale, PANSS) parameters with vitamin D and serum brainderived neurotrophic factor (BDNF) levels in patients with schizophrenia. The study population consisted of 54 healthy control subjects, and 64 volunteer patients, monitored in the psychiatry outpatient clinics of Antalya Education and Research Hospital. Serum glucose, HDL, LDL, triglyceride, total cholesterol levels (spectrophotometric method), HbA1c (HPLC method), insulin, and vitamin 25(OH)D (chemiluminescence method), with HOMA-IR (numerical calculation), and serum BDNF levels (sandwich ELISA, enzymelinked immunosorbent assay) were quantitatively evaluated using respective analytical methods indicated in parentheses. Twenty-seven (42.18%) of 64 schizophrenia patients were diagnosed with MetS. In schizophrenia patients diagnosed with metabolic syndrome (MetS), PANSS-negative and -positive symptom scores were significantly higher, while serum BDNF levels were significantly lower. In patients with schizophrenia, significantly negative correlations were detected between PANSS-negative and -positive symptom scores, and BDNF (p < 0.001 and p < 0.001, respectively), and also between PANSS-negative symptom score and vitamin D (p = 0.022). Lower serum BDNF levels may be related to increases in the possible development of MetS and psychotic symptoms. Decrease in vitamin D levels in schizophrenia patients may be associated with an increase in PANSS-negative symptom scores. In schizophrenia patients with MetS, psychotic symptoms may be more severe.     

Comparative Studies of Glutamine Synthetase Levels in the Brains of Patients with Schizophrenia and Mentally Healthy People

In this study the authors compared the levels of glutamine synthetase (GS) enzymatic activities, as well as the levels of immunoreactive GS and GS-like protein (GSLP) in the readily soluble protein fraction of brain samples taken during autopsies of patients with schizophrenia and subjects from a control group. Enzymatic GS activity was measured and levels of immunoreactive GS and GSLP were determined in postmortem samples of the prefrontal, anterior, and posterior cingulate cortex (Brodmann areas 10, 24, and 23, respectively) and cerebellum cortex obtained from patients with schizophrenia (n = 8) and a control group (n = 9), matched according to age and postmortem interval. GS activity was evaluated in vitro in the “transferase” reaction by the formation of γ-glutamyl hydroxamate, and the levels of immunoreactive GS and GSLP were evaluated by ECL Western blotting using monoclonal and polyclonal antibodies. No differences in GS enzymatic activity were found in all of the studied brain structures. The level of immunoreactive GS in the prefrontal cortex was significantly decreased in patients with schizophrenia compared with the controls (at p < 0.001 according to the Mann–Whitney U-test); it was unchanged in the posterior cingulate cortex and significantly elevated in the anterior cingulate cortex and cerebellum (p < 0.001 and p < 0.004, respectively), whereas the level of immunoreactive GSLP was elevated in all studied brain areas (p < 0.004, p < 0.02, p < 0.04, and p < 0.006, respectively). The alteration of GS and GSLP levels in brains of patients with schizophrenia is one of the factors that disturb glutamate metabolism in these brain structures and is an important aspect of schizophrenia pathogenesis.     

A Novel <Emphasis Type="Italic">SYNJ1</Emphasis> Mutation in a Tunisian Family with Juvenile Parkinson’s Disease Associated with Epilepsy

We investigated the effect of a set of SNPs within 5 genes identified by GWASs as possible risk genes for schizophrenia (SCZ) in two independent samples, comprising 176 SCZ patients and 326 controls of Korean origin and 83 SCZ patients and 194 controls of Italian origin. The PANSS was used to assess psychopathology severity and antipsychotic response (AR). Several clinical features were assessed at recruitment. In the Korean sample, the SP4 gene haplotype rs2282888-rs2237304-rs10272006-rs12673091 (p?=?0.02) was associated with SCZ. In the Italian sample, PPP3CC rs11780915 (genotypic: p?=?0.006; allelic: p?=?0.001) and rs2249098 (genotypic: p?=?0.0004; allelic: p?=?0.00006) were associated with SCZ, as well as the PPP3CC rs11780915-rs10108011-rs2249098 and the ZNF804A rs7603001-rs1344706 haplotypes (p?=?0.03 and p?=?0.02). Several RORA variants were associated with AR in both the samples, although only the haplotype rs1020729-rs1871858 in the Korean sample survived to the statistical correction (p?=?0.01). Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2, and SP4 genes may modulate psychotic symptoms, and (2) RORA and ZNF804A genes may influence AR. Our results partially support a role for these genes in SCZ and AR. Analyses in well phenotyped samples may help to refine the role of the genes identified by GWASs.     

Quality of life and social functioning of former long-stay psychiatric patients transferred into the community: a 10 year follow up study

Purpose

Deinstitutionalisation in Ireland began following the impetus of the successful transfer of psychiatric patients into the community in other countries. This study sought to evaluate the quality of life (QoL) and social functioning (SF) of former long-stay institutionalised patients with severe and enduring mental illness who had been relocated into local community settings and followed up 10 years later.

Method

One month prior to hospital closure, 87 former long-stay psychiatric patients, the majority of whom had a diagnosis of schizophrenia, were assessed on a range of QoL and SF measures. Patients were followed-up 10 years later in the community, to evaluate baseline predictors of quality of life and social functioning.

Results

Study completers (n?=?35) improved significantly on a range of QoL and SF measures over the 10 year period. Specific improvements were noted in domestic skills (t = ? 2.8, p?<?0.0008), community skills (t = ? 4.9, p?<?0.001), as well as the activity and social relations measure (t = ? 4.1, p?<?0.001). Increased social function (t = ? 6.3, p?<?0.001) and improvement on the social behaviour scale (t?=?7.6, p?<?0.001) were noted at follow-up. Linear regression analysis found that less social behaviour problems at baseline predicted QoL 10 years later (t = ? 2.6, p?<?0.02).

Conclusion

This study demonstrated that transfer into the community from an institutional environment was associated with long-term improvements in quality of life and social functioning, even in those who spent many years in the institution. Those who demonstrated the greatest improvement in QoL had less social behavioural problems at baseline assessment, providing further evidence of the success of community living for former long-stay patients.

     

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.     

Low prevalence of lipid metabolism abnormalities in <Emphasis Type="Italic">APOE</Emphasis> ε2-genotype and male patients 60 years or older with schizophrenia

Background

Schizophrenia is a serious mental disorder largely manageable with atypical antipsychotics; however, these drugs have been associated with glucose/lipid metabolism issues such as diabetes and hyperlipidaemia. Apolipoprotein E (APOE) is the most abundant apolipoprotein, and APOE genotypes have been correlated with lipid metabolism phenotypes in an age-dependent manner. Studies examining the relationship between the APOE genotype and lipid abnormalities in patients with schizophrenia have been inconclusive, but primarily focused on adult patient populations. Therefore, we explored the correlations between the APOE genotype and glucose/lipid metabolism indicators and abnormalities in hospitalized patients 60 years or older with schizophrenia with a history of long-term antipsychotics use.

Methods

We assessed APOE genotype, age, weight, height, blood glucose, triglycerides, cholesterol, high-density lipoprotein, and low-density lipoprotein in a total of 294 patients. APOE genotypes were divided into three groups: APOE ε2 (ε2/ε2 and ε2/ε3), APOE ε3 (ε3/ε3), and APOE ε4 (ε3/ε4 and ε4/ε4), and comparisons were conducted among these groups or according to ε2 carrier status.

Results

APOE ε3/ε3 was the most common genotype (68.3%) and at least one ε3 allele was present in 81.8% of patients. There were no differences in antipsychotics type or dose according to the APOE genotype, but serum cholesterol values varied near significantly (P?=?0.052) and low-density lipoprotein values varied significantly according to genotype (P?<?0.05, lowest in the APOE ε2 genotype). Men had lower cholesterol and low-density lipoprotein levels (P?<?0.05) than women. Compared to patients administered typical antipsychotics, those administered atypical antipsychotics had higher triglyceride, cholesterol, and low-density lipoprotein levels (P?<?0.05). Stepwise linear regressions showed that cholesterol and low-density lipoprotein levels were influenced by sex, the APOE ε2 genotype, and atypical antipsychotics use.

Conclusions

In the context of atypical antipsychotics use, carriers of the APOE ε2-genotype and male patients with schizophrenia 60 years or older may be less likely to develop a lipid metabolism abnormality.

     

Hypo-metabolism of the rostral anterior cingulate cortex associated with working memory impairment in 18 cases of schizophrenia

Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions. This retrospective study of 18 schizophrenia cases and 10 matched controls used proton magnetic resonance spectroscopic imaging (¹H-MRSI, TR/TE = 1800/35 ms, 0.5 cm³ spatial resolution) to test whether the Work-Mem Index of the Wechsler Adult Intelligence Scale, third edition is associated with differences in the rostral to caudal ACC ratios of N-acetylaspartate (NAA) and creatine (Cr). Higher caudal:rostral ACC Cr (but not NAA) concentrations were associated with decreased Work-Mem Index in cases (r?=?-0.6, p?=?0.02), with a similar trend in controls (r?=?-0.56, p?=?0.10), although caudal:rostral ACC Cr correlated with NAA in cases and controls (r?=?0.67 and 0.62, p?<?0.05 for both). NAA and Cr ratios did not correlate with myo-inositol, excluding gliosis as the underlying process. Subjects’ sex and age had no effects on these relationships. The findings suggest that rostral ACC energy hypo-metabolism, possibly arising from neurodevelopmental processes, is associated with working memory impairment in schizophrenia. Changes in the rostral (not the expected caudal) subregion underscore the interconnections between the ACC subregions and may offer laboratory markers for treatment trials, etiology studies, and perhaps even enhanced identification of prodromal “at risk” subjects.     

Thiol/disulphide homeostasis in schizophrenia patients with positive symptoms

Introduction: This study aims to investigate the dynamic thiol/disulphincide homeostasis in patients with schizophrenia who have positive psychotic indications.

Materials and methods: Forty-four patients (26 males, 18 females; mean age?=?34.40?±?8.98 years) accepted at the Department of Psychiatry of the Ankara Numune Training and Research Hospital and 33 healthy controls (15 males, 18 females; mean age of 30.30?±?8.48 years) were included in the study. Serum native thiol and total thiol were measured with a novel colorimetric, automated method. The disulfide levels and disulfide/native thiol ratios were also calculated from these measured parameters.

Results: Serum native thiol and the total thiol concentration were significantly lower in schizophrenia compared with the control group (p?p?Conclusion: The disulfide/native thiol ratio in patients with schizophrenia who have been using medication for the last 2 months has been found to be significantly higher than controls who have not been using medication, may be indicating that the level of native thiol does not increase in a correlation as high as the increase in disulfide levels. It demonstrates that thiol/disulfide equilibrium has shifted towards the disulfide. The excess disulfide amounts might associated with both disease itself and the using medication.     

Social networks and symptomatic and functional outcomes in schizophrenia: a systematic review and meta-analysis

Purpose

To conduct a systematic review and meta-analysis to examine the strength of associations between social network size and clinical and functional outcomes in schizophrenia.

Method

Studies were identified from a systematic search of electronic databases (EMBASE, Medline, PsycINFO, and Web of Science) from January 1970 to June 2016. Eligible studies included peer-reviewed English language articles that examined associations between a quantitative measure of network size and symptomatic and/or functional outcome in schizophrenia-spectrum diagnoses.

Results

Our search yielded 16 studies with 1,929 participants. Meta-analyses using random effects models to calculate pooled effect sizes (Hedge’s g) found that smaller social network size was moderately associated with more severe overall psychiatric symptoms (N?=?5, n?=?467, g?=???0.53, 95% confidence interval (CI)?=???0.875, ??0.184, p?=?0.003) and negative symptoms (N?=?8, n?=?577, g?=???0.75, 95% CI?=???0.997, ??0.512, p?=?0.000). Statistical heterogeneity was observed I²?=?63.04%; I²?=?35.75%,) which could not be explained by low-quality network measures or sample heterogeneity in sensitivity analyses. There was no effect for positive symptoms (N?=?7, n?=?405, g?=???0.19, 95% CI?=?0.494, 0.110, p?=?0.213) or social functioning (N?=?3, n?=?209, g?=?0.36, 95% CI?=???0.078, 0.801, p?=?0.107). Narrative synthesis suggested that larger network size was associated with improved global functioning, but findings for affective symptoms and quality of life were mixed.

Conclusion

Psychosocial interventions which support individuals to build and maintain social networks may improve outcomes in schizophrenia. The review findings are cross-sectional and thus causal direction cannot be inferred. Further research is required to examine temporal associations between network characteristics and outcomes in schizophrenia and to test theoretical models relating to explanatory or mediating mechanisms.

     

Cerebral spectroscopic and oxidative stress studies in patients with schizophrenia who have dangerously violently offended

Background

The aim of this study was to bring together all the results of in vivo studies of ethane excretion and cerebral spectroscopy in patients with schizophrenia who have dangerously seriously violently offended in order to determine the extent to which they shed light on the degree to which the membrane phospholipid hypothesis and the actions of free radicals and other reactive species are associated with cerebral pathophysiological mechanisms in this group of patients.

Methods

The patients investigated were inpatients from a medium secure unit with a DSM-IV-TR diagnosis of schizophrenia. There was no history of alcohol dependency or any other comorbid psychoactive substance misuse disorder. Expert psychiatric opinion, accepted in court, was that all these patients had violently offended directly as a result of schizophrenia prior to admission. These offences consisted of homicide, attempted murder or wounding with intent to cause grievous bodily harm. Excreted ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). 31-phosphorus magnetic resonance spectroscopy data were obtained at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm³ voxel).

Results

Compared with age- and sex-matched controls, in the patient group the mean alveolar ethane level was higher (p < 0.0005), the mean cerebral beta-nucleotide triphosphate was lower (p < 0.04) and the mean gamma-nucleotide triphosphate was higher (p < 0.04). There was no significant difference between the two groups in respect of phosphomonoesters, phosphodiesters or broad resonances.

Conclusion

Our results are not necessarily inconsistent with the membrane phospholipid hypothesis, given that the patients studied suffered predominantly from positive symptoms of schizophrenia. The results suggest that there is increased cerebral mitochondrial oxidative phosphorylation in patients with schizophrenia who have dangerously and seriously violently offended, with an associated increase in oxygen flux and subsequent electron 'leakage' from the electron transport chain leading to the formation of superoxide radicals and other reactive oxygen species. In turn, these reactive species might cause increased lipid peroxidation in neuroglial membranes, thereby accounting for the observation of increased ethane excretion.

     

Blood brain barrier impairment is associated with cerebrospinal fluid markers of neuronal damage in HIV-positive patients

Blood brain barrier impairment occurs early in the course of infection by HIV and it may persist in a subset of patients despite effective antiretroviral treatment. We tested the hypothesis that HIV-positive patients with dysfunctional blood brain barrier may have altered biomarkers of neuronal damage. In adult HIV-positive highly active antiretroviral treatment (HAART)-treated patients (without central nervous system infections and undergoing lumbar punctures for clinical reasons) cerebrospinal fluid albumin to serum ratios (CSAR), total tau, phosphorylated tau, 1–42 beta amyloid, and neopterin were measured. In 101 adult patients, cerebrospinal fluid-to-serum albumin ratios were 4.8 (3.7–6.1) with 12 patients (11.9 %) presenting age-defined impaired blood brain barrier. A significant correlation was observed between CSAR and total tau (p?=?0.005), phosphorylated tau (p?=?0.008), and 1–42 beta amyloid (p?=?0.040). Patients with impaired blood brain barrier showed significantly higher total tau (201.6 vs. 87.3 pg/mL, p?=?0.010), phosphorylated tau (35.3 vs. 32.1 ng/mL, p?=?0.035), and 1–42 beta amyloid (1134 vs. 830 pg/mL, p?=?0.045). Despite effective antiretroviral treatment, blood brain barrier impairment persists in some HIV-positive patients: it is associated with markers of neuronal damage and it was not associated with CSF neopterin concentrations.     

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.

     

Bone mineral density in pediatric patients with meningomyelocele

Purpose

The aim of this study was to determine the bone mineral density (BMD) and the factors leading to reduction in BMD in children diagnosed with meningomyelocele.

Methods

A total of 31 patients with meningomyelocele (mean (SD) age, 8.5 (3.9) years; 51.6 % were females) and 22 healthy children were included. BMD of femoral neck and spinal L1–L4 levels and markers for bone metabolism were recorded.

Results

BMD of femoral neck (p?=?0.001) and spinal L1–L4 (p?=?0.01), serum calcium (p?=?0.031), and urinary deoxypyridinoline (p?=?0.015) levels were significantly lower in patients than in controls. Mobilization was significantly reduced in lumbar (p?=?0.001) and thoracic (p?=?0.002) level meningomyelocele compared to controls, while a significant positive correlation was noted between BMD of spinal L1–L4 and mobility (r?=?0.58, p?=?0.015).

Conclusions

Our findings suggest a decrease in BMD in meningomyelocele patients being associated with osteoporosis rather than nutritional and hormonal factors and the negative impact of higher levels of lesion on the mobility.

     

The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: a Case-Control and Genotype-Phenotype Study

Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, p_a = 0.02; Taq, p_g = 0.02, p_a = 0.02; BsmI, p_g = 0.02, p_a = 0.04; ApaI, p_g = 0.008, p_a = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: p_g = 0.01, p_a = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT p_corr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.     

Correlation between muscle electrophysiology and strength after fibular nerve injury

Muscle strength measurement is important when evaluating the degree of impairment in patients with nerve injury. However, accurate and objective evaluation may be difficult in patients with severe pain or those who intentionally try to avoid full exertion. We investigated the usefulness of the affected-to-unaffected side electrophysiological parameter ratios as a measure of objective ankle dorsiflexion (ADF) strength in patients with unilateral fibular nerve injury (FNI). ADF strength was measured in patients with FNI via handheld dynamometer and manual muscle test (MMT). Fibular nerve compound muscle action potential (CMAP) amplitude and latency and ADF strength of the affected side were presented as ratios to the corresponding measurements of the unaffected side. We analysed the correlation of the CMAP ratio with the ADF strength ratio using a dynamometer and compared the CMAP ratios according to MMT grade. Fifty-two patients with FNI were enrolled. The mean CMAP latency ratio did not differ between MMT groups (p = 0.573). The CMAP amplitude ratio proportionally increased with the quantified ADF strength ratio via dynamometer increase (ρ = 0.790; p < 0.001), but the CMAP latency ratio and the quantified ADF strength ratio did not significantly correlate (ρ = 0.052; p = 0.713). The average CMAP amplitude ratio significantly differed between MMT groups (p < 0.001), and post hoc tests showed significant differences in all paired comparisons except of Fair and Good grades (p = 0.064). Electrophysiological parameter ratio, such as the affected-to-unaffected side CMAP amplitude ratio, might be sensitive parameters for ADF power estimation after FNI.     

Primary lateral sclerosis and the amyotrophic lateral sclerosis–frontotemporal dementia spectrum

Aim

To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum of diseases.

Methods

Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n?=?27) and ALS–FTD (n?=?12). Clinical features, Addenbrooke’s Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS).

Results

Global cognition was impaired in PLS (mean total ACE score 82.5?±?13.6), similar to ALS–FTD (mean total ACE score 76.3?±?7.7, p?>?0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5?±?6.2) compared ALS–FTD (50.1?±?7.2, p?<?0.001) and ALS (62.3?±?12.6, p?=?0.046). Average short-interval intracortical inhibition (SICI) was similar in all three patient groups. The mean survival time was longest in PLS (217.4?±?22.4 months) and shortest in ALS–FTD (38.5?±?4.5 months, p?=?0.002). Bulbar onset disease (β?=???0.45, p?=?0.007) and RMT (β?=?0.54, p?=?0.001) were independent predictors of global cognition while motor scores (β?=?0.47, p?=?0.036) and SICI (β?=?0.58, p?=?0.006) were significantly associated with ALSFRS.

Conclusion

The cognitive profile in PLS resembles ALS–FTD, without prominent behavioural disturbances. A higher RMT in PLS than ALS and ALS–FTD is consistent with differential cortical motor neuronal abnormalities and more severe involvement of corticospinal axons while SICI, indicative of inhibitory interneuronal dysfunction was comparable with ALS and ALS–FTD. Overall, while these findings support the notion that PLS lies on the ALS–FTD spectrum, the mechanisms underlying slow disease progression are likely to be distinct in PLS.

     

Obstructive sleep apnea and cerebral white matter change: a systematic review and meta-analysis

Obstructive sleep apnea (OSA) can cause sleep fragmentation and intermittent hypoxemia, which are linked to oxidative stress. White matter changes (WMCs) representing cerebrovascular burden and are at risk factor for oxidative ischemic injury. The current study explores the mutual relationships between OSA and WMCs. We performed a systematic review of electronic databases for clinical studies investigating OSA and WMCs. Random-effects models were used for pooled estimates calculation. A total of 22 studies were included in the meta-analysis. The results revealed a significantly higher prevalence rate of WMCs [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.52–2.80, p?<?0.001] and significantly higher severity of WMCs (Hedges’ g?=?0.23, 95% CI 0.06–0.40, p?=?0.009) in the patients with OSA than in controls. Furthermore, the results revealed a significantly higher apnea–hypopnea index (Hedges’ g?=?0.54, 95% CI 0.31–0.78, p?<?0.001) and significantly higher prevalence rate of moderate-to-severe OSA (OR 2.86, 95% CI 1.44–5.66, p?=?0.003) in the patients with WMCs than in controls, however there was no significant difference in the prevalence rate of mild OSA between the patients with WMCs and controls (OR 0.71, 95% CI 0.20–2.54, p?=?0.603). OSA was associated with a higher prevalence and more severe WMCs, and the patients with WMCs had an increased association with moderate-to-severe OSA. Future large-scale randomized controlled trials with a longitudinal design are essential to further evaluate treatment in patients with OSA.     

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.     

Impaired white matter connectivity between regions containing mirror neurons,and relationship to negative symptoms and social cognition,in patients with first-episode schizophrenia

In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.