Caregivers of patients with amyotrophic lateral sclerosis: investigating quality of life,caregiver burden,service engagement,and patient survival

Few studies in amyotrophic lateral sclerosis (ALS) have profiled disease-specific features of the condition in conjunction with assessment of caregivers’ burden, distress, quality of life, and investigated patient survival. Eighty-four ALS patients and their primary caregivers were enrolled. Patients completed ALS-specific measures of physical and cognitive function, while caregivers completed measures of anxiety, depression, caregiver burden, and quality of life. Patient-caregiver dyads were interviewed about their health-service utilisation. Survival data were obtained through the Irish register for ALS. Participants were dichotomised into low/high groups according to the severity of self-reported caregiver burden, based on statistically derived cut-off scores. High-burdened caregivers (n = 43) did not significantly differ from low-burdened caregivers (n = 41) with respect to disease-specific characteristics, i.e., ALSFRS-R, bulbar- or spinal-onset ALS, disease duration, or survival data. However, significant differences were reported on subjective measures of anxiety (p < 0.000), depression (p < 0.001), distress (p < 0.000), and quality of life (p < 0.000). These data demonstrate the limited impact of ALS patient-related variables, i.e., ALSFRS-R and onset, on caregiver burden in ALS, and identify the importance of the psychological composition of caregivers. This study suggests that the subjective experience of individual caregivers is an important factor influencing the severity of experienced caregiver burden.     

Longitudinal predictors of caregiver burden in amyotrophic lateral sclerosis: a population-based cohort of patient–caregiver dyads

Objective

Caregiver burden is a recognised consequence of caring for a patient with neurodegeneration. Amyotrophic lateral sclerosis (ALS) differs from other neurodegenerations by its rapid progression and impairment of motor, cognitive, and behavioural function, which contribute to caregiver burden. However, longitudinal factors that determine the extent of caregiver burden, and in particular the impact of psychological distress among caregivers, have not been fully established.

Methods

Patients with ALS (n = 85) and their primary caregivers (n = 85) completed three serial evaluations. Caregiver burden was measured using the Zarit Burden Interview (ZBI). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). The Edinburgh Cognitive-Behavioural ALS Screen (ECAS) was used to determine cognitive function in patients. The ALS Functional Rating Scale (ALSFRS-R) measured disease progression.

Results

Using the ZBI, caregivers were categorised as high or low burden. In the low burden group, anxiety scores from the HADS predicted caregiver burden (r = 0.410, F = 3.73, p = 0.033), whereas the depression sub-score from the HADS was predictive of caregiver burden in the high burden group (r = 0.501, F = 5.87, p = 0.006) for cross-sectional analyses. Longitudinally, an elevated score on the HADS at Time 1 was the largest predictor of caregiver burden across serial assessments.

Conclusion

In a patient cohort with relatively preserved cognitive function (65%), anxiety and depression at Time 1, as measured by the HADS, were the best predictors of caregiver burden at Time 3. This observation provides a mechanism by which caregiver burden can be identified by health-care professionals and a stepped care programme of intervention initiated.

     

Association between depression and survival in Chinese amyotrophic lateral sclerosis patients

To determine the prevalence of depression, to identify correlated factors for depression, and to explore the impact on the progression or survival of amyotrophic lateral sclerosis (ALS) by depression in a Chinese population. A total of 166 ALS patients were recruited. Diagnosis of depression disorders and the severity of depression were established by using the fourth diagnostic and statistical manual of mental disorders, Hamilton Depression Rating Scale-24 items (HDRS-24) and Beck Depression Inventory (BDI). Major depression was found in 15 patients (9.6 %). The multiple regression analysis showed that a lower ALS Functional Rating Scale-Revised (ALSFRS-R) score was correlated with increasing HDRS scores and BDI scores (P = 0.018 and P = 0.012). No significant difference in the median survival time between ALS patients with and without depression was revealed by Kaplan–Meier analysis (log-rank P = 0.282). Cox hazard model showed that the presence of depression in ALS was unrelated to the survival, while the severity of depression in ALS was correlated with the survival. The presence and severity of depression in ALS did not correlate with the progression of ALS. Major depression in ALS is uncommon. Depression evaluation should be given to ALS patients, especially those with lower ALSFRS-R score. The severity of depression may be associated with the survival; however, depression does not worse the progression of ALS.     

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.     

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV? and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm²; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD (p < 0.05–0.006), while HIV duration, symptomatic, and asymptomatic cognitive impairment were associated with decreased FA and increased MD (p < 0.01–0.004). Stability of HIV treatment and antiretroviral CNS penetration efficiency in addition to current and historical immune recovery were related to higher FA and lower MD (p = 0.04–p < 0.01). In conclusion, WM DTI measures are near normal except for patients with neurocognitive impairment and longer HIV disease duration.     

CSF concentrations of adipsin and adiponectin in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is described as a neurodegenerative disorder. However, neuroinflammation and chemokine expression are prominent pathological finding at sites of injury. Adipsin and adiponectin are molecules that are implicated in the pathogenesis of neurodegenerative and neuroimmune disorders. Adipsin and adiponectin concentrations were determined in the CSF of ALS patients and controls and the relationship of these chemokines with clinical severity and disease duration in ALS was determined. Seventy-seven ALS patients (mean age 49.5 ± 10.4 years) (mean body mass index 23.5 ± 4.5) were included. Twenty patients had bulbar, 53 spinal, and four bulbospinal onset ALS. Median adipsin CSF level was 12,650.94 pg/ml in ALS patients and 3290.98 pg/ml in controls (p < 0.001). Median adiponectin CSF level was 4608 pg/ml in ALS patients and 3453 pg/ml in controls (p = 0.1). No differences were observed in disease duration, progression rate or disease severity. There was a significant positive correlation between adipsin and adiponectin concentrations (r = 0.379, p = 0.01). No correlation with age, body mass index or ALFRS-R score was found. Adipsin was significantly elevated in CSF, suggesting that this chemokine might have a role in ALS pathogenesis. Adiponectin showed a trend towards higher concentrations, but failed to reach statistical significance. Due to the clinical heterogeneity in our cohort, these chemokines do not appear to be associated with disease duration or severity.     

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.

     

Relevance of neuroimaging for neurocognitive and behavioral outcome after pediatric traumatic brain injury

This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8–14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mild^RF+, n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mild^RF+ TBI (35%; p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029, ds ≥ ?0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mild^RF+ TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging.     

Fractional anisotropy in the supplementary motor area correlates with disease duration and severity of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is progressive and fatal neurodegenerative disorder with upper and lower motor neuron signs. There are no biomarkers to track disease progression. To address this issue, we investigated regions in which fractional anisotropy (FA) values derived from diffusion weighted images correlated with both disease severity and duration in ALS patients. Fourteen patients with ALS were enrolled in this study. Voxel-based analysis revealed volume of interests (VOIs) showing significant correlation. Finally, Spearman rank correlation coefficient was assessed between FA value in each VOI and disease severity or duration. In the VOI of left supplementary motor area (SMA), FA value significantly correlated with disease severity and duration both (disease severity, rho = 0.59, p = 0.025; disease duration, rho = ?0.69, p = 0.006). The present finding suggested the possibility that the abnormality in motor-related region including SMA could be a candidate for a biomarker to track disease progression.     

White matter integrity in polydrug users in relation to attachment and personality: a controlled diffusion tensor imaging study

The relationship between substance use disorders (SUD. In this study we compared two groups of PUD inpatients (abstinent: n = 18, in maintenance treatment: n = 15) to healthy controls (n = 16) with respect to neural connectivity in white matter, and their relation to behavioral parameters of personality factors/organization and attachment styles. Diffusion Tensor Imaging was used to investigate white matter structure. Compared with healthy controls, the PUD patients showed reduced fractional anisotropy (FA) and increased radial diffusivity (RD) mainly in the superior fasciculus longitudinalis and the superior corona radiata. These findings suggest diminished neural connectivity as a result of myelin pathology in PUD patients. In line with our assumptions, we observed FA in the biggest cluster as negatively correlated with anxious attachment (r = 0.36, p < 0.05), personality dysfunctioning (r = ?0.41; p < 0.01) as well positively correlated with personality factors Openness (r = 0.34; p < 0.05) and Agreeableness (r = 0.28; p < 0.05). Correspondingly these findings were inversely mirrored by RD. Further research employing enhanced samples and addressing longitudinally neuronal plastic effects of 相似文献   

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.     

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).     

<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.

     

Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of <Emphasis Type="SmallCaps">l</Emphasis>-Serine

β-N-Methylamino-l-alanine (BMAA) has been linked to Guam ALS/PDC and shown to produce neurodegeneration in vitro and in vivo (Drosophila, mice, rats, primates). BMAA misincorporation into neuroproteins produces protein misfolding and is inhibited by l-serine. Case-control studies in Northern New England indicate that living near to water-bodies with cyanobacterial blooms increases the risk of developing amyotrophic lateral sclerosis (ALS). The distribution of addresses of ALS cases in New Hampshire, Vermont, and Florida was compared to that of controls. Areas of statistically significantly increased numbers of ALS cases were examined for sources of environmental toxins. A phase I trial of oral l-serine was performed in 20 ALS patients (0.5 to 15 g twice daily). Safety and tolerability were assessed by comparing the rate of deterioration with 430 matched placebo controls. The distribution of residential addresses of ALS cases in New England and Florida revealed many areas where the age- and gender-adjusted frequency of ALS was greater than expected (P < 0.01). GIS studies of these “hot spots” in relation to sources of environmental pollutants, like cyanobacterial blooms, Superfund and Brownfield sites, and landfills, are ongoing. In the phase I trial of l-serine, two patients withdrew from because of gastrointestinal side effects. Three patients died during the study, which was about the expected number. The ALSFRS-R in the l-serine-treated patients showed a dose-related decrease in the rate of progression (34% reduction in slope, P = 0.044). The non-random distribution of addresses of ALS patients suggests that residential exposure to environmental pollutants may play an important role in the etiology of ALS. l-Serine in doses up to 15 g twice daily appears to be safe in patients with ALS. Exploratory studies of efficacy suggested that l-serine might slow disease progression. A phase II trial is planned.     

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.

     

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 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.     

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.     

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.