Fatigue and Its Associated Factors in Spinocerebellar Ataxia Type 3/Machado-Joseph Disease

Fatigue has been described in several neurodegenerative diseases, reducing quality of life. A systematic evaluation of this clinical feature is lacking in SCA3/MJD. The aim of this study was to evaluate the frequency and the factors associated with fatigue in SCA3/MJD. Patients with SCA3/MJD and matched healthy controls answered the Modified Fatigue Impact Scale (MFIS), Beck Inventory Depression (BDI) and Epworth Sleepiness Scale (ESS). Scale for the assessment and rating of ataxia (SARA) was used to determine ataxia severity. We used Mann-Whitney and Fisher exact tests to compare mean scores and proportions between groups. Linear regression analyses were employed to investigate factors associated with fatigue in SCA3/MJD. Seventy-four patients were included with a mean age and disease duration of 47.2?±?12.8 and 9.5?±?6.37 years, respectively. There were 38 men and 36 women. Mean (CAG)n was 72.2?±?3.8. Mean MFIS score was higher in patients with SCA3/MJD (41.4?±?16.2 vs 18.4?±?12.9, p?<?0.001). According to BDI scores, relevant depressive symptoms were found in 69.4 % of patients but only in 10.4 % of controls (p?<?0.001). The proportion of patients with ESS scores indicating excessive daytime somnolence was also higher than controls (37.5 vs 22.3 %, p?=?0.05). In the multiple regression analysis, both BDI and ESS scores were associated with fatigue (r?=?0.67, p?<?0.001 and p?=?0.01). Fatigue is frequent and strongly associated with depression and excessive daytime somnolence in SCA3/MJD.     

Spinocerebellar ataxia type 3/Machado-Joseph disease starting before adolescence

Onset of Machado-Joseph disease (SCA3/MJD) before adolescence has been rarely reported. This study aims to describe a cohort of SCA3/MJD with onset before 12 years of age, comparing their disease progression with the progression observed in patients with usual disease onset. We identified all cases from our cohort whose onset was before adolescence. After consent, patients were examined with clinical scales Scale for the Assessment and Rating of Ataxia (SARA) and Neurological Examination Score for Spinocerebellar Ataxia (NESSCA). Gender, age, age at onset, disease duration, CAG expanded repeats, transmitting parent, and anticipation of cases with infantile and adult onset were studied. Progression of NESSCA and SARA scores was estimated through a mixed model, and was compared with a historical group with onset after adolescence. Between 2000 and 2014, 461 symptomatic individuals from our region were diagnosed as SCA3/MJD. Onset of eight cases (2.2 %), all heterozygotes, was before adolescence: seven were females (p?=?0.054). CAG expanded repeats—75?±?3 versus 84?±?4—and anticipations—7?±?9.7 versus 14.4?±?7.2 years—were different between early childhood and adult onset groups (p?<?0.03). The median survival of early childhood onset group was 23 years of age. The annual progression of SARA—2.3 and 0.6 points/year (p?=?0.001)—and NESSCA—2.04 and 0.88 points/year (p?=?0.043)—was faster in childhood than in adult onset group. Onset of SCA3/MJD before adolescence was related to larger expanded CAG repeats in heterozygosis; females seemed to be at higher risk. Disease progression was faster than in SCA3/MJD starting after 12 years.     

Functional impairment in patients with myotonic dystrophy type 1 can be assessed by an ataxia rating scale (SARA)

Myotonic dystrophy type 1 (DM1) is not characterised by ataxia per se; however, DM1 and ataxia patients show similar disturbances in movement coordination often experiencing walking and balance difficulties, although caused by different underlying pathologies. This study aims to investigate the use of a scale previously described for the assessment and rating of ataxia (SARA) with the hypothesis that it could have utility in DM1 patients as a measure of disease severity and risk of falling. Data from 54 DM1 patients were pulled from the PHENO-DM1 natural history study for analysis. Mean SARA score in the DM1 population was 5.45 relative to the maximum score of eight. A flooring effect (score 0) was observed in mild cases within the sample. Inter-rater and test–retest reliability was high with intraclass coefficients (ICC) of 0.983 and 1.00, respectively. Internal consistency was acceptable as indicated by a Cronbach’s alpha of 0.761. Component analysis revealed two principle components. SARA correlated with: (1) all measures of muscle function tested, including quantitative muscle testing of ankle dorsiflexion (r = ?0.584*), the 6 min walk test (r = ?0.739*), 10 m walk test (r = 0.741*), and the nine hole peg test (r = 0.602*) and (2) measures of disease severity/burden, such as MIRS (r = 0.718*), MDHI (r = 0.483*), and DM1-Activ (r = ?0.749*) (*p < 0.001). The SARA score was predicted by an interaction between modal CTG repeat length and age at sampling (r = 0.678, p = 0.003). A score of eight or above predicted the use of a walking aid with a sensitivity of 100% and a specificity of 85.7%. We suggest that further research is warranted to ascertain whether SARA or components of SARA are useful outcome measures for clinical trials in DM1. As a tool, it can be used for gathering information about disease severity/burden and helping to identify patients in need of a walking aid, and can potentially be applied in both research and healthcare settings.     

Defining Trends in Global Gene Expression in Arabian Horses with Cerebellar Abiotrophy

Equine cerebellar abiotrophy (CA) is a hereditary neurodegenerative disease that affects the Purkinje neurons of the cerebellum and causes ataxia in Arabian foals. Signs of CA are typically first recognized either at birth to any time up to 6 months of age. CA is inherited as an autosomal recessive trait and is associated with a single nucleotide polymorphism (SNP) on equine chromosome 2 (13074277G>A), located in the fourth exon of TOE1 and in proximity to MUTYH on the antisense strand. We hypothesize that unraveling the functional consequences of the CA SNP using RNA-seq will elucidate the molecular pathways underlying the CA phenotype. RNA-seq (100 bp PE strand-specific) was performed in cerebellar tissue from four CA-affected and five age-matched unaffected horses. Three pipelines for differential gene expression (DE) analysis were used (Tophat2/Cuffdiff2, Kallisto/EdgeR, and Kallisto/Sleuth) with 151 significant DE genes identified by all three pipelines in CA-affected horses. TOE1 (Log₂(foldchange) = 0.92, p = 0.66) and MUTYH (Log₂(foldchange) = 1.13, p = 0.66) were not differentially expressed. Among the major pathways that were differentially expressed, genes associated with calcium homeostasis and specifically expressed in Purkinje neurons, CALB1 (Log₂(foldchange) = ?1.7, p < 0.01) and CA8 (Log₂(foldchange) = ?0.97, p < 0.01), were significantly down-regulated, confirming loss of Purkinje neurons. There was also a significant up-regulation of markers for microglial phagocytosis, TYROBP (Log₂(foldchange) = 1.99, p < 0.01) and TREM2 (Log₂(foldchange) = 2.02, p < 0.01). These findings reaffirm a loss of Purkinje neurons in CA-affected horses along with a potential secondary loss of granular neurons and activation of microglial cells.     

NESSCA Validation and Responsiveness of Several Rating Scales in Spinocerebellar Ataxia Type 2

Spinocerebellar ataxia type 2 (SCA2), caused by a CAG expansion (CAGexp) at ATXN2, has a complex clinical picture. While validated ataxia scales are available, comprehensive instruments to measure all SCA2 neurological manifestations are required. This study aims to validate the Neurological Examination Score for the assessment of Spinocerebellar Ataxias (NESSCA) to be used in SCA2 and to compare its responsiveness to those obtained with other instruments. NESSCA, SARA, SCAFI, and CCFS scales were applied in symptomatic SCA2 patients. Correlations were done with age at onset, disease duration, CAGexp, and between scales. Responsiveness was estimated by comparing deltas of stable to worse patients after 12 months, according to Patient Global Impression of change, and the area under the curve (AUC) of the Receiver Operating Characteristics curve of scores range. Eighty-eight evaluations (49 patients) were obtained. NESSCA had an even distribution and correlated with disease duration (r = 0.55), SARA (r = 0.63), and CAGexp (rho = 0.32): both explained 44% of NESSCA variance. Deltas (95% CI) after 1 year in stable and worse patients were only significantly different for SARA. NESSCA, SARA, SCAFI, and CCFS AUC were 0.63, 0.81, 0.49, and 0.48, respectively. NESSCA is valid to be used in SCA2. However, the only instrument that presented good responsiveness to change in 1 year was SARA. We suggest that NESSCA can be used as a secondary outcome in future trials in SCA2 due to the burden of neurological disabilities related to disease progression.     

Differences in corticospinal system activity and reaction response between karate athletes and non-athletes

The aim of this study was to verify the hypothesis that transcranial magnetic stimulation (TMS) parameters over the hand region of the motor cortex, such as resting motor threshold (rMT) and motor evoked potential (MEP) latency, predict the behavioural performance of karate athletes in the response time (RT) test. Twenty-five male karate athletes (24.9 ± 4.9 years) and 25 matched non-athletes (26.2 ± 4.5 years) were recruited. Using TMS, we investigated cortico-spinal system excitability. Compared with controls, the athletes showed faster RT (p < 0.001), lower rMT (p < 0.01), shorter MEP latency (p < 0.01), and higher MEP amplitude (p < 0.01); moreover, there was a significant positive linear correlation between RT and rMT (p < 0.001), between RT and MEP latency (p < 0.0001), and a negative correlation between RT and MEP amplitude (p < 0.001). The practice of competitive sports affects both the central and peripheral nervous system. Subjects that showed higher cortical excitability showed also higher velocity, at which the neural signal is propagated from the motor cortex to the muscle and consequently better RT. The lower rMT and the shorter MEP latency observed in athletes support the effects of training in determining specific brain organizations to meet specific sport challenges.     

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.

     

Vancomycin Pharmacokinetic Parameters in Patients with Hemorrhagic Stroke

Background

Infections are a common medical complication in hemorrhagic stroke patients, with vancomycin commonly used as empiric therapy. The purpose of this study was to evaluate the pharmacokinetic parameters of vancomycin in hemorrhagic stroke patients.

Methods

This was a retrospective study of adult patients with aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH) admitted between May 2010 and February 2015 who received vancomycin. Predicted pharmacokinetic parameters based on population data were compared with calculated pharmacokinetic parameters based on serum trough concentrations.

Results

Eighty aSAH patients and 66 ICH patients met inclusion criteria. In the aSAH group, the mean dosing regimen was 17.6 ± 4 mg/kg every 12 (8–12) h. The mean measured trough concentration was lower than the predicted trough concentration (9.9 ± 4.1 vs. 19 ± 8.7 μg/mL; p < 0.001). The mean calculated elimination rate constant was higher than the predicted value (0.135 ± 0.04 vs. 0.092 ± 0.03 h^?1; p < 0.001), and the mean calculated half-life was lower than predicted (5.7 ± 1.8 vs. 8.3 ± 2.9 h; p < 0.001). In the ICH group, the mean dosing regimen was 15.9 ± 4.3 mg/kg every 12 (8–12) h. Similarly, the mean measured trough concentration was lower than the predicted trough concentration (10.7 ± 4.6 vs. 17.5 ± 8.5 μg/mL; p < 0.001). The mean calculated elimination rate constant was higher than the predicted value (0.106 ± 0.03 vs. 0.079 ± 0.02 h^?1; p < 0.001), and the mean calculated half-life was lower than predicted (7.2 ± 2.3 vs. 9.6 ± 3.2 h; p < 0.001).

Conclusions

Patients with hemorrhagic stroke exhibited pharmacokinetic alterations favoring increased elimination of vancomycin when compared to predicted pharmacokinetic parameters based on population data. This may result in underexposure to vancomycin, leading to treatment failure and other medical complications.

     

<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.

     

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.

     

Delayed Fever and Neurological Outcome after Cardiac Arrest: A Retrospective Clinical Study

Background

The aim of this study was to evaluate the association between fever after the first days of ICU stay and neurological outcome after cardiac arrest (CA).

Methods

We retrospectively analyzed CA patients admitted to intensive care unit (ICU). Inclusion criteria: age ≥18 years, Glasgow Coma Scale score ≤8 at ICU admission and assessment of body core temperature (BCT) using bladder or intravascular probes. Exclusion criteria: ICU length of stay (LOS) <3 days and pregnancy. The primary endpoint was neurological outcome assessed with Cerebral Performance Category (CPC) scale 6 months after CA.

Results

One hundred thirty-two patients were analyzed. Fever was present in 105 (79.6 %) patients. Variables associated with unfavorable outcome were (1) older age (p < 0.0025); (2) non-shockable cardiac rhythms (p < 0.0001); (3) higher Simplified Acute Physiology Score (SAPS) II (p < 0.0001); (4) pupillary abnormalities at ICU admission (p < 0.018); and (5) elevated degree of maximal BCT (Tmax) during ICU stay (p < 0.046). After multivariate analysis, Tmax maintained a significant relationship with neurological outcome. An increase of 1 °C in Tmax during ICU stay decreased the odds ratio for a favorable outcome by a factor of 31 % (p < 0.001). Moreover, we discovered a significant interaction between the day of Tmax (t-Tmax) and Tmax (p = 0.004); the later Tmax occurs, the more deleterious effects are observed on outcome.

Conclusions

Fever is frequent after CA, and Tmax in ICU is associated with worsened neurological outcome. This association becomes stronger as the timing of Tmax extends further from the CA.

     

Health-related quality of life and suicide risk in postural tachycardia syndrome

Purpose

Postural tachycardia syndrome (POTS) is a disorder featured by orthostatic intolerance. The purpose of this study was to investigate the severity of quality of life issues in POTS patients.

Methods

Online surveys for health related quality of life, sleep quality, fatigue, pain, and suicidal ideation were completed by 624 POTS patients and 139 controls.

Results

People with POTS have significantly more days of poor physical health (p < 0.001), fewer days with good energy (p < 0.001), and significantly more days with activity limitations (p < 0.001) than controls. Pain severity was significantly higher for those with POTS (p < 0.001) while feelings of control over life was lower than controls (p < 0.001). Sleep quality and daytime fatigue were also significantly worse for those with POTS than controls (p < 0.001). Finally, those with POTS have a significantly higher risk of suicide compared with controls (p < 0.001).

Interpretation

The myriad of symptoms from which many POTS patients suffer is associated with a decreased quality of life. Nearly half of our sample with POTS was at high risk for suicide. More work needs to be done to determine the underlying issues surrounding suicide in POTS so that an appropriate treatment regimen can be developed.

     

The Diagnosis and Natural History of Multiple System Atrophy,Cerebellar Type

The objective of this study was to identify key features differentiating multiple system atrophy cerebellar type (MSA-C) from idiopathic late-onset cerebellar ataxia (ILOCA). We reviewed records of patients seen in the Massachusetts General Hospital Ataxia Unit between 1992 and 2013 with consensus criteria diagnoses of MSA-C or ILOCA. Twelve patients had definite MSA-C, 53 had possible/probable MSA-C, and 12 had ILOCA. Autonomic features, specifically urinary urgency, frequency, and incontinence with erectile dysfunction in males, differentiated MSA-C from ILOCA throughout the disease course (p?=?0.005). Orthostatic hypotension developed later and differentiated MSA-C from ILOCA (p?<?0.01). REM sleep behavior disorder (RBD) occurred early in possible/probable MSA-C (p?<?0.01). Late MSA-C included pathologic laughing and crying (PLC, p?<?0.01), bradykinesia (p?=?0.01), and corticospinal findings (p?=?0.01). MRI distinguished MSA-C from ILOCA by atrophy of the brainstem (p?<?0.01) and middle cerebellar peduncles (MCP, p?=?0.02). MSA-C progressed faster than ILOCA: by 6 years, MSA-C walker dependency was 100 % and ILOCA 33 %. MSA-C survival was 8.4?±?2.5 years. Mean length of ILOCA illness to date is 15.9?±?6.4 years. A sporadic onset, insidiously developing cerebellar syndrome in midlife, with autonomic features of otherwise unexplained bladder dysfunction with or without erectile dysfunction in males, and atrophy of the cerebellum, brainstem, and MCP points strongly to MSA-C. RBD and postural hypotension confirm the diagnosis. Extrapyramidal findings, corticospinal tract signs, and PLC are helpful but not necessary for diagnosis. Clarity in early MSA-C diagnosis can prevent unnecessary investigations and facilitate therapeutic trials.     

The initial glycemic variability is associated with early neurological deterioration in diabetic patients with acute ischemic stroke

The association between glycemic variability and early neurological deterioration (END) in acute ischemic stroke remains unclear. This study attempted to explore whether initial glycemic variability increases END in diabetic patients with acute ischemic stroke. We enrolled type 2 diabetic patients undergoing acute ischemic stroke from November 2015 to November 2016. A total of 336 patients within 72 h from stroke onset were included. The serum glucose levels were checked four times per day during the initial 3 hospital days. The standard deviation of blood glucose (SDBG) values and the mean amplitude of glycemic excursions (MAGE) were calculated for glycemic variability. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥?2 points between hospital days 0 and 5. The frequencies of END and HbA1c were significantly different in subjects grouped according to tertiles of MAGE (9.09, 12.07 and 50.00%, p?<?0.001 for END; 7.36?±?1.91, 7.83?±?1.93 and 8.56?±?1.79, p?<?0.001 for HbA1c). Compared to patients without END, patients with END had significantly higher HbA1c levels (8.30?±?1.92 vs 7.80?±?1.93, p?=?0.043), increased SDBG (3.42?±?1.14 vs 2.60?±?0.96, p?<?0.001), and increased MAGE (6.46?±?2.09 vs 4.59?±?1.91, p?<?0.001). In a multivariable logistic regression, stroke etiology (OR 0.675; 95% CI 0.485–0.940, p?=?0.020), baseline NIHSS (OR 1.086; 95% CI 1.004–1.175, p?=?0.040), and MAGE (OR 1.479; 95% CI 1.162–1.882, p?=?0.001) were significantly associated with END. Initial glycemic variability is associated with END in diabetic patients with acute ischemic stroke.     

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.     

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.

     

Deciphering the causes of sporadic late-onset cerebellar ataxias: a prospective study with implications for diagnostic work

The management of sporadic late-onset cerebellar ataxias represents a very heterogeneous group of patients and remains a challenge for neurologist in clinical practice. We aimed at describing the different causes of sporadic late-onset cerebellar ataxias that were diagnosed following standardized, exhaustive investigations and the population characteristics according to the aetiologies as well as at evaluating the relevance of these investigations. All patients consecutively referred to our centre due to sporadic, progressive cerebellar ataxia occurring after 40 years of age were included in the prospective, observational study. 80 patients were included over a 2 year period. A diagnosis was established for 52 patients (65%) corresponding to 18 distinct causes, the most frequent being cerebellar variant of multiple system atrophy (n = 29). The second most frequent cause was inherited diseases (including spinocerebellar ataxias, late-onset Friedreich’s disease, SLC20A2 mutations, FXTAS, MELAS, and other mitochondrial diseases) (n = 9), followed by immune-mediated or other acquired causes. The group of patient without diagnosis showed a slower worsening of ataxia (p < 0.05) than patients with multiple system atrophy. Patients with later age at onset experienced faster progression of ataxia (p = 0.001) and more frequently parkinsonism (p < 0.05) than patients with earlier onset. Brain MRI, DaT scan, genetic analysis and to some extent muscle biopsy, thoracic-abdominal-pelvic tomodensitometry, and cerebrospinal fluid analysis were the most relevant investigations to explore sporadic late-onset cerebellar ataxia. Sporadic late-onset cerebellar ataxias should be exhaustively investigated to identify the underlying causes that are numerous, including inherited causes, but dominated by multiple system atrophy.     

Increased pro-inflammatory cytokine gene expression in peripheral blood mononuclear cells of patients with polyneuropathies

Background

Distinct cytokine expression patterns have been reported in biomaterial of patients with polyneuropathies (PNP). We investigated gene expression profiles of pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMC) of patients with neuropathies of different etiologies.

Methods

We prospectively studied 97 patients with neuropathies and compared data between diagnostic subgroups and healthy controls. Gene expression of a panel of pro- and anti-inflammatory cytokines was analyzed (interleukin-1 [IL-1], IL-2, IL-6, IL-8, tumor necrosis factor alpha [TNF], IL-4, and IL-10) in PBMC samples. Furthermore, protein levels of IL-6, IL-8, and TNF were measured in supernatant of PBMC stimulated with lipopolysaccharide (LPS).

Results

PNP were associated with higher PBMC gene expression of IL-1 (p < 0.05), IL-2 (p < 0.05), IL-8 (p < 0.001), and TNF (p < 0.01) compared to healthy controls. Inflammatory neuropathies were associated with higher gene expression of IL-8 (p < 0.001) and TNF (p < 0.05) and lower gene expression of IL-10 (p < 0.05) compared to healthy controls. More pro-inflammatory cytokines were elevated in painful neuropathy (IL-1, IL-2 [p < 0.05], IL-8 [p < 0.001] and TNF [p < 0.05]) than in painless neuropathy (IL-8 [p < 0.01] and TNF [p < 0.01]) compared to healthy controls, while IL-10 expression was higher in treatment naïve patients with painless neuropathy compared to patients with painful neuropathy (p < 0.05). Disease duration positively correlated with IL-6 gene expression (p < 0.01). Supernatant protein levels of IL-6, IL-8, and TNF did not differ between groups.

Conclusion

Systemic gene expression of pro-inflammatory cytokines is increased in patients with neuropathies and may be influenced by the presence of neuropathic pain.

     

Connection Between Experiences of Bullying and Risky Behaviors in Middle and High School Students

The goal of the current study was to investigate the association of experiences of bullying with 17 individual risk behaviors in a large, non-clinical sample of middle and high school students. Data were analyzed from the 2013 Georgia Student Health Survey II, administered to 6th–12th grade students in all public schools in Georgia (n = 513,909). Bullied students reported higher levels of engagement in every risk behavior investigated, with the largest connections related to safety-related absenteeism (OR 25.4, p < 0.001 and OR 17.0, p < 0.001 for high/middle school students, respectively) and bringing a weapon to school (OR 10.9, p < 0.001 and OR 6.81, p < 0.001 for high/middle school students, respectively). Overall, the current findings reveal alarming relationships between bullying and risk-taking behaviors that suggest bullying is associated with a large portion of substance use, self-harm, and weapons seen in middle and high school students. These behaviors place bullied children at risk of long-term physical and psychological consequences, as well as potential legal complications.     

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.