‘Timed up and go’ and brain atrophy: a preliminary MRI study to assess functional mobility performance in multiple sclerosis

Motor and cognitive disabilities are related to brain atrophy in multiple sclerosis (MS). ‘Timed up and go’ (TUG) has been recently tested in MS as functional mobility test, as it is able to evaluate ambulation/coordination-related tasks, as well as cognitive function related to mobility. The objective of this study is to evaluate the relationship between brain volumes and TUG performances. Inclusion criteria were a diagnosis of MS and the ability to walk at least 20 m. TUG was performed using a wearable inertial sensor. Times and velocities of TUG sub-phases were calculated by processing trunk acceleration data. Patients underwent to a brain MRI, and volumes of whole brain, white matter (WM), grey matter (GM), and cortical GM (C) were estimated with SIENAX. Sixty patients were enrolled. Mean age was 41.5 ± 11.6 years and mean EDSS 2.3 ± 1.2. Total TUG duration was correlated to lower WM (ρ = 0.358, p = 0.005) and GM (ρ = 0.309, p = 0.017) volumes. A stronger association with lower GM volume was observed for intermediate (ρ = 0.427, p = 0.001) and final turning (ρ = 0.390, p = 0.002). TUG is a useful tool in a clinical setting as it can not only evaluate patients’ disability in terms of impaired functional mobility, but also estimate pathological features, such as grey atrophy.     

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.

     

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.

     

Hemodynamic contribution of transdural collateral flow in adult patients with moyamoya disease

To evaluate the hemodynamic contributions of collateral flow in adult patients with moyamoya disease, neurological deterioration or fluctuation during admission, Suzuki grade, various collateral routes, lesion volume, cerebral blood flow (CBF), and their associations were analyzed. Thirty patients (60 cerebral hemispheres, mean age 45 ± 25 years, and 73.3 % female) who were diagnosed with moyamoya disease or syndrome were enrolled over 3 years. Moyamoya stages from each hemisphere were stratified according to the Suzuki’s criteria through six-vessel angiography into internal carotid arteries (ICAs), external carotid arteries (ECAs), and vertebral arteries (VAs). Collateral routes were categorized into the circle of Willis, leptomeningeal, and transdural. The volume of ipsilateral infarction was analyzed by magnetic resonance imaging. CBF volume was measured using color-coded duplex sonography. Suzuki’s grade was inversely correlated with flow volume of the ICAs (p < 0.001), whereas no association was found with that of the ECAs (p = 0.445) or VAs (p = 0.096). Among hemispheres with ≥ grade 3 (n = 36), patients with transdural ECA collateral flow had less neurological deterioration or fluctuation (0.0 vs. 30.8 %, p = 0.047), smaller lesion volume (2.4 ± 3.6 vs. 27.6 ± 59.3 mL, p = 0.041), lower ICA flow (88.4 ± 45.9 vs. 146.2 ± 121.7 mL/min, p = 0.022), higher ECA flow (205.7 ± 77.7 vs. 135.9 ± 52.7 mL/min, p = 0.046), and a higher ECA/ICA flow volume ratio (31.8 ± 92.8 vs. 1.7 ± 1.9, p = 0.024). Our results suggest that ICA flow volume is inversely correlated with Suzuki grade, and that transdural ECA collaterals appear to be an important detour in adult patients with advanced stage moyamoya disease, suggesting a protector against an impending ischemic attack.     

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

Objective

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

Methods

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

Results

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

Conclusion

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

     

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

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

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

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

Mood Spectrum Disorders and Perception of Pain

Evaluation of pain perception in chronic pain patients with a concomitant mood-spectrum disorder. Design: The observational retrospective study is based on patient data collected in psychosomatic consultations held at the Gift Institute for Integrative Medicine in Pisa, Italy, from 2002 to 2014. Evoked pain stimulus threshold and tolerance were evaluated using the cold pressor test. Clinical pain intensity and Sensorial, Affective, and Evaluative dimensions were assessed using the Italian Pain Questionnaire, and Anxiety and Depressive symptoms using the Hospital Anxiety Depression Scale. Mood-spectrum disorders were diagnosed via the Mini-International Neuropsychiatric Interview, and affective temperament in accordance with Akiskal and Pinto’s criteria (1999). Of a total of 627 chronic pain clinic patients, 381 were diagnosed with a concomitant mood-spectrum (MS) disorder, unipolar (US) in 61.41%. Pain threshold (t = 2.28; p < 0.05) was lower, and all clinical pain dimensions (t = 2.28; p < 0.05) increased, in MS patients compared to those without psychiatric disorders. Pain intensity (F = 3.5, p < 0.05) and cognitive pain component scores (F = 7.84; p < 0.0001) were higher in US and, to a lesser extent Bipolar Spectrum, than in subjects with other (n.112) or no psychiatric disorders (n. 134). Suicide ideation was highest in US (F = 37.20; p < 0.0001), although in BS major depressive episodes had more melancholic features (F = 46.73; P < 0.0001), and a longer history of psychiatric disorders before the pain onset than US (F = 20.31; p < 0.0001). Pain management should take into account pre-existing psychiatric disorders.     

<Emphasis Type="Italic">DAT1</Emphasis> and <Emphasis Type="Italic">DRD4</Emphasis> genes involved in key dimensions of adult ADHD

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder often persisting in adulthood. Genetic studies of ADHD mainly focused on the Dopamine Transporter (DAT1) and the Dopamine Receptor 4 (DRD4) genes. Nevertheless, polymorphisms of these genes explain only a small fraction of the assigned risk, suggesting that intermediate dimensions and environmental factors should also be considered. We investigated in 77 adult ADHD subjects compared to 474 controls, how polymorphisms within the genes coding for DAT1 (40-bp VNTR in 3′UTR), the Dopamine Receptor 2 (DRD2) (rs1799732) and DRD4 (48-bp VNTR in exon 3), may modulate the expression of the disorder. By genotyping DAT1, we detected a new 9.5R allele showing a deletion of 40 bp and also an insertion of 19 bp compared to the 10R allele. This novel allele was found to be significantly protective for ADHD (p < 0.0001). Another significant difference was found in the distribution of DRD4 48-bp VNTR 6R allele when comparing patients and controls (p = 0.0007). In addition significant results were also found for DAT1 9.5R allele, which was associated with impulsiveness (p = 1.98 × 10^?4) and trait anger scores (p = 7.66 × 10^?4). Moreover, impulsiveness scores were partly modulated by an interaction between the DRD4 48-bp VNTR 6R allele and childhood maltreatment (p = 0.01), however, this result did not resist correction for multiple comparisons. Altogether, our results show the putative involvement of DAT1 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder.     

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.     

Multiple sclerosis and environmental risk factors: a case-control study in Iran

Studies have shown an increase in the incidence of MS in Iran. The aim of our study was to evaluate the relationship between environmental exposure and MS in Iran. This case-control study was conducted on 660 MS patients and 421 controls. Many environmental factors are compared between the two groups. Our findings demonstrated that prematurity ([OR = 4.99 (95% CI 1.34–18.68), P = 0.017]), history of measles and mumps ([OR = 1.60 (95% CI 1.05–2.45), P = 0.029; OR = 1.85 (95% CI 1.22–2.78), P = 0.003, respectively]), breast feeding [OR = 2.90 (95% CI 1.49–5.65), P = 0.002], head trauma in childhood ([OR = 8.21 (95% CI 1.56–43.06), P = 0.013]), vaccination in adulthood ([OR = 4.57 (95% CI 1.14–18.41), P = 0.032, respectively]), migraine ([OR = 3.50 (95% CI 1.61–7.59), P = 0.002]), family history of MS, IBD, migraine, and collagen vascular diseases ([OR = 2.73 (95% CI 1.56–4.78), P < 0.001], [OR = 3.14 (95% CI 1.460–6.78), P = 0.004; OR = 3.18 (95% CI 1.83–5.53), P < 0.001; OR = 1.81 (95% CI 1.03–3.20), P = 0.040, respectively]), stressful events ([OR = 32.57 (95% CI 17.21–61.64), P < 0.001]), and microwave exposure ([OR = 3.55 (95% CI 2.24–5.63), P ≤0.001]) were more in the MS group. Sun exposure ([OR = 0.09 (95% CI 0.02–0.38), P = 0.001]), dairy and calcium consumption ([OR = 0.44 (95% CI 0.27–0.71), P = 0.001]), diabetes mellitus ([OR = 0.11 (95% CI 0.01–00.99), P = 0.049], and complete vaccination during childhood appeared to decreased MS risk. Our results investigated many risk factors and protective factors in Iran.     

<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.

     

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.     

Long-term far-transfer effects of working memory training in children with ADHD: a randomized controlled trial

ADHD affects working memory (WM) and other executive functions (EFs) and thereby negatively impacts school performance, clinical symptoms and functional impairment. The main aim of this study was to analyse the efficacy of computerized WM training (CWMT) on EF rating scales. A secondary objective was to assess its efficacy on performance-based measures of EF (PBMEF), learning, clinical symptoms and functional impairment. 66 children with combined-type ADHD between 7 and 12 years of age from the Child and Adolescent Psychiatric Unit (Spain) were included in this randomized, double-blind, placebo-controlled, parallel-group clinical trial. The participants were randomized (1:1) to an experimental group (EG) (CWMT) (n = 36) or a control group (CG) (placebo training). Assessments were conducted at baseline (T0), 1–2 weeks (T1), and 6 months post-intervention (T2) with the administration of EF rating scales, PBMEF, measures of academic achievement, and questionnaires regarding clinical symptoms and functional impairment. Participants, parents, teachers and professionals who performed the cognitive assessments were blinded. Adjusted multiple linear regression analysis showed significant improvements in EF scales-parent version, from T1 to T2, on the metacognition index [p = 0.03, d′ = ?0.78 (95 % CI ?1.28 to ?0.27)] and on WM (also significant at T2–T0) and plan/organize subscales. Significant improvements were also noted in EF scales-teacher version, from T0 to T1 and T2, on the metacognitive index [p = 0.05, d′ = ?0.37 (95 % CI ?0.86 to 0.12) T1–T0, p = 0.02, d’ = ?0.81 (95 % CI ?1.31 to ?0.30) T2–T0] and on the initiate, WM, monitor and shift subscales. There were also significant improvements in PBMEF, ADHD symptoms, and functional impairment. CWMT had a significant impact on ADHD deficits by achieving long-term far-transfer effects.     

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.     

Do cognition and other non-motor symptoms decline similarly among patients with Parkinson’s disease motor subtypes? Findings from a 5-year prospective study

Among patients with Parkinson’s disease (PD), a wide range of motor and non-motor symptoms (NMS) are evident. PD is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) motor subtypes. We evaluated the effect of disease duration and aimed to characterize whether there are differences in the deterioration of cognitive function and other NMS between the PIGD and TD subtypes. Sixty-three subjects were re-evaluated at the follow-up visit about 5 years after baseline examination. Cognitive function and other NMS were assessed. At follow-up, the PIGD and TD groups were similar with respect to medications, comorbidities and disease-related symptoms. There was a significant time effect for all measures, indicating deterioration and worsening in both groups. However, cognitive scores, particularly those related to executive function, became significantly worse in the PIGD with a more moderate decrease in the TD group. For example, the computerized global cognitive score declined in the PIGD group from 94.21 ± 11.88 to 83.91 ± 13.76, p < 0.001. This decline was significantly larger (p = 0.03) than the decrease observed in the TD group (96.56 ± 10.29 to 92.21 ± 14.20, p = 0.047). A significant group × time interaction effect was found for the change in global cognitive score (p = 0.047), the executive function index (p = 0.002) and accuracy on a motor-cognitive catch game (p = 0.008). In contrast, several NMS including depression, health-related quality of life and fear of falling deteriorated in parallel in both subtypes, with no interaction effect. The present findings highlight the difference in the natural history of the disease between the two PD “motor” subtypes. While the PIGD group demonstrated a significant cognitive decline, especially in executive functions, a more favorable course was observed in the TD subtype. This behavior was not seen in regards to the other NMS.     

Quality of life predictors in patients with chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic disease which can lead to many functional impairments, and like most other chronic disorders it might significantly affect quality of life (QoL). Information about QoL in patients with CIDP from developing countries is still lacking. We, therefore, sought to complete these data mosaic by investigating QoL in patients with CIDP from Serbia and surrounding countries. Our study comprised 106 patients diagnosed with CIDP. QoL was investigated using the Serbian version of the SF-36 questionnaire. The Medical Research Council 0–5 point scale, INCAT motor and sensory scores, Krupp’s Fatigue Severity Scale, and Beck Depression Inventory were also used. Factors that significantly correlated with SF-36 total score in univariate analysis were included in the multiple linear regression analysis. Physical domains of the SF-36 were more affected than mental, and the overall score was 56.6 ± 25.4. Significant predictors of worse SF-36 score in our patients with CIDP were severe fatigue (β = ? 0.331, p < 0.01), higher INCAT motor score (β = ? 0.301, p < 0.01), depression (β = ? 0.281, p < 0.01), being unemployed/retired (β = ? 0.188, p < 0.05), and shorter duration of CIDP (β = + 0.133, p < 0.01). QoL was reduced in CIDP patients, especially in physical domains. Patients with presence of fatigue and depression, with more severe motor disability, unemployed/retired ones, and those with shorter duration of the disease need special attention of clinicians since they could be at higher risk to have worse QoL.     

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).