Spinal Cord Damage in Spinocerebellar Ataxia Type 1

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder caused by a CAG repeat expansion, characterized by progressive cerebellar ataxia and pyramidal signs. Non-motor and extracerebellar symptoms may occur. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are no data about cord damage in the disease and its clinical relevance. To evaluate in vivo spinal cord damage in SCA1, a group of 31 patients with SCA1 and 31 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images to estimate the cervical spinal cord area (CA) and eccentricity (CE) at three C2/C3 levels based on a semi-automatic image segmentation protocol. The scale for assessment and rating of ataxia (SARA) was used to quantify disease severity. The groups were significantly different regarding CA (47.26 ± 7.4 vs. 68.8 ± 5.7 mm2, p < 0.001) and CE values (0.803 ± 0.044 vs. 0.774 ± 0.043, p < 0.05). Furthermore, in the patient group, CA presented significant correlation with SARA scores (R = ?0.633, p < 0.001) and CAGn expansion (R = ?0.658, p < 0.001). CE was not associated with SARA scores (p = 0.431). In the multiple variable regression, CA was strongly associated with disease duration (coefficient ?0.360, p < 0.05) and CAGn expansion (coefficient ?1.124, p < 0.001). SCA1 is characterized by cervical cord atrophy and anteroposterior flattening. Morphometric analyses of the spinal cord MRI might be a useful biomarker in the disease.     

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.     

Early elevated levels of soluble triggering receptor expressed on myeloid cells-1 in subarachnoid hemorrhage patients

Early brain injury (EBI) contributes to poor prognosis of subarachnoid hemorrhage (SAH). This study aimed to clarify whether triggering receptor expressed on myeloid cells-1 (TREM-1) was implicated in the inflammatory mechanisms of EBI. The cerebrospinal fluid (CSF) levels of soluble TREM-1 (sTREM-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) as well as plasma levels of white blood cells (WBC) count and C-reactive protein in 17 SAH patients at early stage (within the EBI period) and 9 volunteers were observed. Also World Federation of Neurosurgical Societies (WFNS) scale of SAH patients was calculated on admission. Compared to controls, increased CSF levels of sTREM-1 (t = 5.66, P < 0.001), TNF-α (t = 5.41, P < 0.001) and IL-6 (t = 2.98, P = 0.007) as well as elevated plasma WBC counts (t = 7.61, P < 0.001) and C-reactive protein levels (t = 3.91, P = 0.001) were found in SAH patients. Considering the increased WBC counts in SAH group, covariate analysis was also performed when comparing patients’ sTREM-1 levels with respect to controls and no obvious difference was found (F = 0.982, P = 0.332). For SAH group, early CSF concentrations of sTREM-1 were correlated with those of both TNF-α (r = 0.582, P = 0.014) and IL-6 (r = 0.593, P = 0.012). Also the CSF sTREM-1 levels were positively correlated with WBC counts (r = 0.629, P = 0.007) and C-reactive protein levels (r = 0.804, P < 0.001) as well as WFNS scale (r = 0.835, P < 0.001). This study showed an early increased sTREM-1 CSF level in SAH patients, which correlated with inflammation intensity post-SAH and clinical severity, indicating that TREM-1 may participate in the inflammatory mechanisms of EBI.     

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.

     

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.

     

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

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

Exercise Addiction and Psychophysiological Health in Korean Collegiate Students

This study was carried out with collegiate students who took part in an exercise program for 1 year. An exercise addiction (EA) questionnaire was used to classify EA and non-EA (NEA) groups. Exercise dependence (ED), compulsive exercise (CE), and obligatory exercise (OE) questionnaires were used to validate the EA results. A total of 38 male and 37 female college students were selected as the subjects for this study to investigate the effects of EA on psychophysiological health. The psychophysiological health variables were composed of depression, stress, body composition, and muscular joint health. This study showed that EA was significantly associated with ED (r = 0.746; P = 0.001), CE (r = 0.644; P = 0.001), and OE (r = 0.731; P = 0.001), respectively. Although there were no significant differences between EA groups and NEA groups for both males and females on depression (Z = ? 0.813; P = 0.416 and Z = ? 0.148; P = 0.882, respectively), physical stress (Z = ? 0.777; P = 0.437 and Z = ?0.074; P = 0.941, respectively), and emotional stress (Z = ? 1.035; P = 0.300 and Z = ? 0.573; P = 0.567, respectively), the elbow and knee joint functions of EA males were significantly higher compared with those of NEA males. However, the variables of body composition in EA females were not significantly different from those of NEA females. Being addicted to exercise for 1 year resulted in negative effects on the psychological health in both genders, while it had a negative effect on physical health for women only.     

Psychometric properties of the Italian version of the multifactorial memory questionnaire for adults and the elderly

Reliable and valid metamemory measures are needed to assess subjective memory complaints that can be distinct from objective memory performance. The Multifactorial Memory Questionnaire (MMQ) evaluates dimensions of subjective memory functioning such as frequency of memory problems (Ability), affect related to memory abilities (Contentment), and strategy use in everyday life (Strategy). To examine the psychometric properties of the Italian version of the MMQ, six hundred Italian healthy individuals (aged 25–91 years) completed MMQ, a questionnaire assessing metacognition (Cognitive Failures Questionnaire, CFQ) and two batteries assessing cognitive global status (Montreal Cognitive Assessment, MoCA; Mini Mental State Examination, MMSE). MMQ was easy to administer, acceptable, and had good test–retest reliability (r for the total MMQ score 0.95), and internal consistency (Cronbach’s α for the total MMQ score = 0.83). An exploratory factor analysis provided a four-factor solution: “Ability” (α = 0.99), “Contentment” (α = 0.91), “External Strategies” (α = 0.85) and “Internal Strategies” (α = 0.78) factors. MMQ total score and MMQ-Ability factor score showed good convergent validity when compared to CFQ score (r _rho ≥ 0.51), whereas MMQ total score and the four MMQ factors showed good divergent validity when compared to MoCA and MMSE score (r _rho ≤ 0.27). Demographic variables significantly influenced MMQ total score and most subscale scores. From the derived linear equations, we computed correction factors for raw scores and percentile distribution of adjusted scores. The Italian version of MMQ is reliable and valid to assess dimensions of metamemory in adult and elderly subjects.     

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

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

A wearable proprioceptive stabilizer for rehabilitation of limb and gait ataxia in hereditary cerebellar ataxias: a pilot open-labeled study

The aim of this pilot study is to test the feasibility and effectiveness of a wearable proprioceptive stabilizer that emits focal mechanical vibrations in patients affected by hereditary cerebellar ataxias. Eleven adult patients with a confirmed genetic diagnosis of autosomal dominant spinocerebellar ataxia or Friedreich’s ataxia were asked to wear an active device for 3 weeks. Assessments were performed at baseline, after the device use (T1), and 3 weeks after (T2). SARA, 9-HPT, PATA, 6MWT, and spatial and temporal gait parameters, measured with a BTS-G-Walk inertial sensor, were used as study endpoints. As expected, no adverse effects were reported. Statistically significant improvements in SARA, 9HPT dominant hand, PATA test, 6MWT, cadence, length cycle, support right/cycle, support left/cycle, flight right/cycle, flight left/cycle, double support right/cycle, double support left/cycle, single support right/cycle, and single support left/cycle were observed between T0 and T1. All parameters improved at T1 did not show statistically significant differences a T2, with the exception of length of cycle. This small open-labeled study shows preliminary evidence that focal mechanical vibration exerted by a wearable proprioceptive stabilizer might improve limb and gait ataxia in patients affected by hereditary cerebellar ataxias.     

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.

     

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   

Cerebral Ventricular Dimensions After Decompressive Craniectomy: A Comparison Between Bedside Sonographic Duplex Technique and Cranial Computed Tomography

Background

The objective of this study was to assess and compare ventricle diameters in patients after decompressive craniectomy by using cranial computed tomography (CCT) versus sonographic duplex technique (SDT).

Methods

A total of 102 consecutive patients after decompressive craniectomy following brain infarct, bleeding and trauma were examined by CCT and SDT. SDT was performed within 24 h after repeated postinterventional control CCT and the correlation between both methods was assessed via measurement of dimensions of all four ventricles. In addition, midline shifts and overall cerebral anatomy was evaluated.

Results

A high correlation was found between CCT and SDT in measuring the diameters of all four ventricles (right lateral r = 0.978, p < 0.001; left lateral r = 0.975, p < 0.001; third r = 0.987, p < 0.001 and fourth ventricle r = 0.954, p < 0.001). Deviations of midline structure was observed in SDT as well as in CCT (r = 0.992, p < 0.001).

Conclusion

SDT in patients after decompressive craniectomy may represent an additional bedside tool to assess the dimensions of the ventricular system, anatomical structures, e.g., subdural hygromas, hematomas, midline shifts, gyri and sulci. The measurement of the dimensions of all four ventricles by using SDT delivers accurate values and may be considered as an alternative to CCT or a trigger for CCT prior to further treatment.

     

Correlation between physical activity,aerobic fitness and body fat against autonomic function profile in children

Aim

To evaluate correlations between physical activity, VO_2PEAK and body fat versus autonomic function in children.

Methods

Children (n = 98) between 10 and 12 years underwent a maximal exercise test (VO_2PEAK) and dual-energy X-ray absorptiometry measured body fat. General physical activity, moderate to vigorous physical activity and vigorous physical activity were assessed by accelerometers. Deep breath test with E/I-ratio calculation and a head-up tilt test were performed. The sum of z-scores represented an index score for autonomic function profile and included E/I-ratio plus difference in blood pressure and heart rate between supine and tilted position. Correlation analyses were performed between physical activity parameters, body fat and VO_2PEAK versus autonomic function profile.

Results

No significant correlations were found between autonomic function profile and physical activity or body fat (p > 0.05). VO_2PEAK was correlated with autonomic function profile in boys (r = 0.30, p < 0.05), but not in girls (r = 0.04, NS). One girl and eight boys terminated head-up tilt test prematurely due to intolerance. Minutes of vigorous physical activity per day was lower in these boys compared with those (n = 48) who completed the head-up tilt test (5.1 ± 3.3 vs. 10.4 ± 6.6, p < 0.05).

Conclusion

Physical activity or body fat was not associated with autonomic function profile. VO_2PEAK correlated to autonomic function profile in boys.

     

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.     

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.     

Diabetic polyneuropathy,deep white matter lesions,and carotid atherosclerosis: is there any association?

The morphologic and functional damages of diabetes mellitus (DM) on microcirculation can play a role in the pathogenesis of both polyneuropathy and cerebral white matter lesions. The aim of this study is to investigate the relation between polyneuropathy and cerebral deep white matter lesions (DWMLs) and carotid atherosclerosis in patients with type 2 DM. Sixty-six patients with type 2 DM without any disorder that may cause polyneuropathy, and vascular risk factors except for DM and hyperlipidemia were included in the study. DWMLs and carotid atherosclerosis were investigated in patients with and without polyneuropathy. Forty patients (60.6%) had diabetic sensorimotor polyneuropathy. DWMLs were more frequent in patients with polyneuropathy compared to patients without polyneuropathy (p = 0.003). Logistic regression analysis confirmed association between polyneuropathy and DWMLs after adjusted for age (p = 0.013), duration of DM (p = 0.007), and both age and duration of DM (p = 0.016). No statistically significant difference was found between patients with and without polyneuropathy for carotid atherosclerosis. Among patients with polyneuropathy, those having DWMLs had higher mean age (p = 0.003) and longer symptom duration (p = 0.020) compared to patients without DWMLs. No association was found between DWMLs and carotid atherosclerosis. Polyneuropathy and cerebral DWMLs in type 2 DM patients may share common pathogenesis; presence and duration of polyneuropathy symptoms may predict ischemic white matter damage independent of carotid atherosclerosis.     

Correlation between indexes of autonomic maneuvers and heart rate variability in hemodialysis patients

Purpose

The autonomic maneuvers are simple methods to evaluate autonomic balance, but the association between autonomic maneuvers and heart rate variability (HRV) in hemodialysis patients remains unknown. This study aimed to evaluate the correlation between HRV and respiratory sinus arrhythmia (RSA) and Valsalva maneuver (VM) indexes in hemodialysis patients and to compare two methods for RSA indexes acquisitions.

Methods

Forty-eight volunteers on hemodialysis (66.7 % men) were evaluated by VM, RSA, and 24 h Holter monitoring. At the VM, the Valsalva index (VI) was the variable considered. In the RSA, the ratio and difference between the RR intervals of inspiratory and expiratory phase (E:I and E–I, respectively) were considered by traditional form (average of respiratory cycles) and independent respiratory cycles (E:Iindep and E–Iindep). The HRV indexes evaluated were standard deviation of all normal RR intervals (SDNN), standard deviation of sequential 5-min RR interval means (SDANN), root mean square of the successive differences (rMSSD) and percentage of adjacent RR intervals with difference of duration greater than 50 ms (pNN50).

Results

The SDNN, SDANN showed significant correlation with all classic indexes of RSA (E:I: r = 0.62, 0.55, respectively, E–I: r = 0.64, 0.57, respectively), E:Iindep (r = 0.59, 0.54, respectively), E–Iindep (r = 0.47, 0.43, respectively) and VI (r = 0.42, 0.34, respectively). Significant correlation of rMSSD with E:I (r = 0.37), E–I (r = 0.41) and E:Iindep (r = 0.34) was also observed. There was no association of any variable with pNN50. Have been show high values for all variables of independent cycles method (p < 0.05).

Conclusion

The autonomic maneuvers, especially RSA, are useful methods to evaluate cardiac autonomic function in hemodialysis patients. The acquisition of the RSA index by independent cycles should not be used in this population.

     

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.

     

Elevated serum IL-11, TNF α, and VEGF expressions contribute to the pathophysiology of hypertensive intracerebral hemorrhage (HICH)

To study the changes in serum interleukin-11 (IL-11), tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) expressions following hypertensive intracerebral hemorrhage (HICH), and explore their associations with disease severity and prognosis. Serum IL-11, TNF-α, and VEGF levels after 1, 3, 7, and 14 days after HICH were assayed using enzyme-linked immunosorbent assay (ELISA), and neurological deficit score (NDS) were recorded at admission and discharge for 99 HICH cases. Then 45 healthy controls were included and assayed for serum IL-11, TNF-α, and VEGF levels. Serum IL-11, TNF-α, and VEGF levels were higher in HICH patients than healthy controls (all P < 0.05). TNF-α was higher at the 3rd day following disease onset than other time points (all P < 0.05), while IL-11 and VEGF peaked at the 7th day and dropped below baseline values at the 14th day (all P < 0.05). Serum IL-11 was positively correlated with TNF-α (r = 0.70, P < 0.05) and VEGF (r = 0.72, P < 0.05). Serum TNF-α was positively correlated with VEGF (r = 0.46, P < 0.05). Serum IL-11, TNF-α, and VEGF were associated with disease severity in HICH patients. Patients with more severe disease tended to have higher NDS at admission, and higher IL-11, TNF-α, and VEGF during treatment were associated with higher NDS at discharge. Serum IL-11, TNF-α, and VEGF may involve in the pathophysiology of HICH, thus IL-11, TNF-α, and VEGF may be prognostic factors for post HICH neurologic damage.