70 research outputs found
Effects of subthalamic nucleus deep brain stimulation on emotional working memory capacity and mood in patients with Parkinson's disease
Background: In Parkinson’s disease (PD), cognitive symptoms and mood changes
may be even more distressing for the patient than motor symptoms. Objective:
Our aim was to determine the effects of bilateral subthalamic nucleus deep
brain stimulation (STN-DBS) on working memory (WM) and mood. Methods: Sixteen
patients with PD were assessed with STN-DBS switched on (DBS-ON) and with
dopaminergic treatment (Med-ON) compared to switched off (DBS-OFF) and without
dopaminergic treatment (Med-OFF). The primary outcome measures were a Visual
Analog Mood Scale (VAMS) and an emotional 2-back WM task at 12 months after
DBS in the optimal DBS-ON/Med-ON setting compared to DBS-OFF/Med-OFF. Results:
Comparison of DBS-OFF/Med-OFF to DBS-ON/Med-ON revealed a significant increase
in alertness (meanoff/off =51.59±24.54; meanon/on =72.75; P=0.016) and
contentedness (meanoff/off =38.73±24.41; meanon/on =79.01±17.66; P=0.001,
n=16), and a trend for reduction in sedation (P=0.060), which was related to
stimulation as shown in a subgroup of seven patients. The N-back task revealed
a significant increase in accuracy with DBS-ON/Med-ON compared to DBS-OFF/Med-
OFF (82.0% vs 76.0%, respectively) (P=0.044), regardless of stimulus valence.
Conclusion: In line with previous studies, we found that patients rated
themselves subjectively as more alert, content, and less sedated during short-
term DBS-ON. Accuracy in the WM task increased with the combination of DBS and
medication, possibly related to higher alertness of the patients. Our results
add to the currently mixed results described for DBS on WM and suggest that
there are no deleterious DBS effects on this specific cognitive domain
Neuropsychological Features of Patients with Spinocerebellar Ataxia (SCA) Types 1, 2, 3, and 6
A subtype-specific impairment of cognitive functions in spinocerebellar ataxia (SCA) patients is still debated. Thirty-two SCA patients (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, episodic and semantic memory, and motor coordination. Severity of ataxia was assessed with the Scale for the Assessment and Rating of Ataxia (SARA), nonataxia symptoms with the Inventory of Non-Ataxia Symptoms. Depressive symptoms were evaluated with the Beck Depression Inventory. The SARA scores of our SCA patients (range 1–19.5) indicated an overall moderate ataxia, most pronounced in SCA6 and SCA1. Mean number of nonataxia symptoms (range 0–2.2) were most distinct in SCA1 and nearly absent in SCA6. SCA1 performed poorer than controls in 33% of all cognitive test parameters, followed by SCA2, SCA3, and SCA6 patients (17%). SCA 1–3 patients presented mainly attentional and executive dysfunctions while semantic and episodic memory functions were preserved. Attentional and executive functions were partly correlated with ataxia severity and fine motor coordination. All patients exhibited mildly depressed mood. Motor and dominant hand functions were more predictive for depressed mood than cognitive measures or overall ataxia. Besides motor impairments in all patients, SCA patients with extracerebellar pathology (SCA 1–3) were characterized by poor frontal attentional and executive dysfunction while mild cognitive impairments in predominantly cerebellar SCA6 patients appeared to reflect mainly cerebellar dysfunction. Regarding the everyday relevance of symptoms, (dominant) motor hand functioning emerged as a marker for the patient’s mood
Association Between Fatigue and Motor Exertion in Patients With Multiple Sclerosis - a Prospective Study
Background: Fatigue in multiple sclerosis (MS) is conceived as a multidimensional construct.
Objectives: This study aims to describe the changes of balance and gait parameters after 6 min of walking (6 MW) as potential quantitative markers for perceptions of state fatigue and trait fatigue in MS.
Methods: A total of 19 patients with MS (17 with fatigue) and 24 healthy subjects underwent static posturography, gait analysis, and ratings of perceived exertion before and after 6 MW.
Results: 6 MW was perceived as exhaustive, but both groups featured more dynamic comfortable speed walking after 6 MW. Shorter stride length at maximum speed and increased postural sway after 6 MW indicated fatigability of balance and gait in MS group only. While most changes were related to higher levels of perceived exertion after 6 MW (state fatigue), higher fatigue ratings (trait fatigue) were only associated with less increase in arm swing at comfortable speed. Further analysis revealed different associations of trait fatigue and performance fatigability with disability and motor functions. Performance fatigability was most closely related to the Expanded Disability Status Scale, while for trait fatigue, the strongest correlations were seen with balance function and handgrip strength.
Conclusions: Fatigability of performance was closely related to perceptions of exertion after 6 MW (state fatigue) and disability in MS but distinct from fatigue ratings, conceived as trait fatigue. Our study identified postural sway, arm swing during gait, and hand grip strength as unexpected potential motor indicators of fatigue ratings in MS
Neural Processes of Psychological Stress and Relaxation Predict the Future Evolution of Quality of Life in Multiple Sclerosis
Health-related quality of life (HRQoL) is an essential complementary parameter in the assessment of disease burden and treatment outcome in multiple sclerosis (MS) and can be affected by neuropsychiatric symptoms, which in turn are sensitive to psychological stress. However, until now, the impact of neurobiological stress and relaxation on HRQoL in MS has not been investigated. We thus evaluated whether the activity of neural networks triggered by mild psychological stress (elicited in an fMRI task comprising mental arithmetic with feedback) or by stress termination (i.e., relaxation) at baseline (T0) predicts HRQoL variations occurring between T0 and a follow-up visit (T1) in 28 patients using a robust regression and permutation testing. The median delay between T0 and T1 was 902 (range: 363-1,169) days. We assessed HRQoL based on the Hamburg Quality of Life Questionnaire in MS (HAQUAMS) and accounted for the impact of established HRQoL predictors and the cognitive performance of the participants. Relaxation-triggered activity of a widespread neural network predicted future variations in overall HRQoL (t = 3.68, p(family-wise error [FWE])-corrected = 0.008). Complementary analyses showed that relaxation-triggered activity of the same network at baseline was associated with variations in the HAQUAMS mood subscale on an alpha(FWE) = 0.1 level (t = 3.37, p(FWE) = 0.087). Finally, stress-induced activity of a prefronto-limbic network predicted future variations in the HAQUAMS lower limb mobility subscale (t = -3.62, p(FWE) = 0.020). Functional neural network measures of psychological stress and relaxation contain prognostic information for future HRQoL evolution in MS independent of clinical predictors
Subjective and objective assessment of physical activity in multiple sclerosis and their relation to health-related quality of life
Background Physical activity (PA) is frequently restricted in people with
multiple sclerosis (PwMS) and aiming to enhance PA is considered beneficial in
this population. We here aimed to explore two standard methods (subjective
plus objective) to assess PA reduction in PwMS and to describe the relation of
PA to health-related quality of life (hrQoL). Methods PA was objectively
measured over a 7-day period in 26 PwMS (EDSS 1.5–6.0) and 30 matched healthy
controls (HC) using SenseWear mini® armband (SWAmini) and reported as step
count, mean total and activity related energy expenditure (EE) as well as time
spent in PA of different intensities. Measures of EE were also derived from
self-assessment with IPAQ (International Physical Activity Questionnaire) long
version, which additionally yielded information on the context of PA and a
classification into subjects’ PA levels. To explore the convergence between
both types of assessment, IPAQ categories (low, moderate, high) were related
to selected PA parameters from objective assessment using ANOVA. Group
differences and associated effect sizes for all PA parameters as well as their
relation to clinical and hrQoL measures were determined. Results Both, SWAmini
and IPAQ assessment, captured differences in PA between PwMS and HC. IPAQ
categories fit well with common cut-offs for step count (p = 0.002) and mean
METs (p = 0.004) to determine PA levels with objective devices. Correlations
between specifically matched pairs of IPAQ and SWAmini parameters ranged
between r .288 and r .507. Concerning hrQoL, the lower limb mobility subscore
was related to four PA measures, while a relation with patients’ report of
general contentment was only seen for one. Conclusions Both methods of
assessment seem applicable in PwMS and able to describe reductions in daily PA
at group level. Whether they can be used to track individual effects of
interventions to enhance PA levels needs further exploration. The relation of
PA measures with hrQoL seen with lower limb mobility suggests lower limb
function not only as a major target for intervention to increase PA but also
as a possible surrogate for PA changes
Less Is More - Estimation of the Number of Strides Required to Assess Gait Variability in Spatially Confined Settings
Background: Gait variability is an established marker of gait function that can be assessed using sensor-based approaches. In clinical settings, spatial constraints and patient condition impede the execution of longer distance walks for the recording of gait parameters. Turning paradigms are often used to overcome these constraints and commercial gait analysis systems algorithmically exclude turns for gait parameters calculations. We investigated the effect of turns in sensor-based assessment of gait variability. Methods: Continuous recordings from 31 patients with movement disorders (ataxia, essential tremor and Parkinson's disease) and 162 healthy elderly (HE) performing level walks including 180° turns were obtained using an inertial sensor system. Accuracy of the manufacturer's algorithm of turn-detection was verified by plotting stride time series. Strides before and after turn events were extracted and compared to respective average of all strides. Coefficient of variation (CoV) of stride length and stride time was calculated for entire set of strides, segments between turns and as cumulative values. Their variance and congruency was used to estimate the number of strides required to reliably assess the magnitude of stride variability. Results: Non-detection of turns in 5.8% of HE lead to falsely increased CoV for these individuals. Even after exclusion of these, strides before/after turns tended to be spatially shorter and temporally longer in all groups, contributing to an increase of CoV at group level and widening of confidence margins with increasing numbers of strides. This could be attenuated by a more generous turn excision as an alternative approach. Correlation analyses revealed excellent consistency for CoVs after at most 20 strides in all groups. Respective stride counts were even lower in patients using a more generous turn excision. Conclusion: Including turns to increase continuous walking distance in spatially confined settings does not necessarily improve the validity and reliability of gait variability measures. Specifically with gait pathology, perturbations of stride characteristics before/after algorithmically excised turns were observed that may increase gait variability with this paradigm. We conclude that shorter distance walks of around 15 strides suffice for reliable and valid recordings of gait variability in the groups studied here
Neurochemical Differences in Spinocerebellar Ataxia Type 14 and 1
Autosomal-dominant spinocerebellar ataxias (SCA) are neurodegenerative diseases characterized by progressive ataxia. Here, we report on neurometabolic alterations in spinocerebellar ataxia type 1 (SCA1; SCA-ATXN1) and 14 (SCA14; SCA-PRKCG) assessed by non-invasive 1H magnetic resonance spectroscopy. Three Tesla 1H magnetic resonance spectroscopy was performed in 17 SCA14, 14 SCA1 patients, and in 31 healthy volunteers. We assessed metabolites in the cerebellar vermis, right cerebellar hemisphere, pons, prefrontal, and motor cortex. Additionally, clinical characteristics were obtained for each patient to correlate them with metabolites. In SCA14, metabolic changes were restricted to the cerebellar vermis compared with widespread neurochemical alterations in SCA1. In SCA14, total N-acetylaspartate (tNAA) was reduced in the vermis by 34%. In SCA1, tNAA was reduced in the vermis (24%), cerebellar hemisphere (26%), and pons (25%). SCA14 patients showed 24% lower glutamate+glutamine (Glx) and 46% lower γ-aminobutyric acid (GABA) in the vermis, while SCA1 patients showed no alterations in Glx and GABA. SCA1 revealed a decrease of aspartate (Asp) in the vermis (62%) and an elevation in the prefrontal cortex (130%) as well as an elevation of myo-inositol (Ins) in the cerebellar hemisphere (51%) and pons (46%). No changes of Asp and Ins were detected in SCA14. Beyond, glucose (Glc) was increased in the vermis of both SCA14 (155%) and SCA1 (247%). 1H magnetic resonance spectroscopy revealed differing neurochemical profiles in SCA1 and SCA14 and confirmed metabolic changes that may be indicative for neuronal loss and dysfunctional energy metabolism. Therefore, 1H magnetic resonance spectroscopy represents a helpful tool for in-vivo tracking of disease-specific pathophysiology
Altered Coupling of Psychological Relaxation and Regional Volume of Brain Reward Areas in Multiple Sclerosis
Background:Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects. Objective:To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS). Methods:36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during a mild stress task. These markers were related to regional GM volumes, heart rate, and depressive symptoms. Results:Relaxation was differentially linked to heart rate in both groups (t= 2.20,p= 0.017), i.e., both markers were only related in HCs. Relaxation was positively linked to depressive symptoms across all participants (t= 1.99,p= 0.045) although this link differed weakly between groups (t= 1.62,p= 0.108). Primarily, the volume in medial temporal gyrus was negatively linked to relaxation in PwMS (t= -5.55, p(family-wise-error(FWE)corrected)= 0.018). A group-specific coupling of relaxation and GM volume was found in ventromedial prefrontal cortex (VMPFC) (t= -4.89, p(FWE)= 0.039). Conclusion:PwMS appear unable to integrate peripheral stress signals into their perception of relaxation. Together with the group-specific coupling of relaxation and VMPFC volume, a key area of the brain reward system for valuation of affectively relevant stimuli, this finding suggests a clinically relevant misinterpretation of stress-related affective stimuli in MS
Investigation of Visual System Involvement in Spinocerebellar Ataxia Type 14
Spinocerebellar ataxia type 14 (SCA-PRKCG, formerly SCA14) is a rare, slowly progressive disorder caused by conventional mutations in protein kinase Cγ (PKCγ). The disease usually manifests with ataxia, but previous reports suggested PRKCG variants in retinal pathology. To systematically investigate for the first time visual function and retinal morphology in patients with SCA-PRKCG. Seventeen patients with PRKCG variants and 17 healthy controls were prospectively recruited, of which 12 genetically confirmed SCA-PRKCG patients and 14 matched controls were analyzed. We enquired a structured history for visual symptoms. Vision-related quality of life was obtained with the National Eye Institute Visual Function Questionnaire (NEI-VFQ) including the Neuro-Ophthalmic Supplement (NOS). Participants underwent testing of visual acuity, contrast sensitivity, visual fields, and retinal morphology with optical coherence tomography (OCT). Measurements of the SCA-PRKCG group were analyzed for their association with clinical parameters (ataxia rating and disease duration). SCA-PRKCG patients rate their vision-related quality of life in NEI-VFQ significantly worse than controls. Furthermore, binocular visual acuity and contrast sensitivity were worse in SCA-PRKCG patients compared with controls. Despite this, none of the OCT measurements differed between groups. NEI-VFQ and NOS composite scores were related to ataxia severity. Additionally, we describe one patient with a genetic variant of uncertain significance in the catalytic domain of PKCγ who, unlike all confirmed SCA-PRKCG, presented with a clinically silent epitheliopathy. SCA-PRKCG patients had reduced binocular vision and vision-related quality of life. Since no structural retinal damage was found, the pathomechanism of these findings remains unclear
MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study
Introduction: Brain atrophy is a widely accepted marker of disease severity with association to clinical disability in multiple sclerosis (MS). It is unclear to which extent this association reflects common age effects on both atrophy and function. Objective: To explore how functional performance in gait, upper extremities and cognition is associated with brain atrophy in patients with Clinically Isolated Syndrome (CIS) and relapsing-remitting MS (RRMS), controlling for effects of age and sex. Methods: In 27 patients with CIS, 59 with RRMS (EDSS <= 3) and 63 healthy controls (HC), 3T MRI were analyzed for T2 lesion count (T2C), volume (T2V) and brain volumes [normalized brain volume (NBV), gray matter volume (NGMV), white matter volume (NWMV), thalamic volume (NThaIV)]. Functional performance was measured with short maximum walking speed (SMSW speed), 9-hole peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models were created for functional variables with stepwise inclusion of age, sex and MR imaging markers. Results: CIS differed from HC only in T2C and T2V. RRMS differed from HC in NBV, NGMV and NThaIV, T2C and T2V, but not in NWMV. A strong association with age was seen in HC, CIS and RRMS groups for NBV (r = -0.5 to -0.6) and NGMV (r = -0.6 to -0.8). Associations with age were seen in HC and RRMS but not CIS for NThaIV (r = -0.3; r = -0.5), T2C (r(s) = 0.3; r(s) = 0.2) and T2V (r(s) = 0.3; r(s) = 0.3). No effect of age was seen on NWMV. Correlations of functional performance with age in RRMS were seen for SMSW speed, 9HPTand SDMT (r = -0.27 to -0.46). Regression analyses yielded significant models only in the RRMS group for 9HPT, SMSW speed and EDSS. These included NBV, NGMV, NThaIV, NWMV, logT2V, age and sex as predictors. NThalV was the only MRI variable predicting a functional measure (9HPT(r)) with a higher standardized beta than age and sex (R2 = 0.36, p < 1e-04). Conclusion: Thalamic atrophy was a stronger predictor of hand function (9HPT) in RRMS, than age and sex. This underlines the clinical relevance of thalamic atrophy and the relevance of hand function as a clinical marker even in mildly disabled patients
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