Cognition and cognitive rehabilitation in adult and juvenile patients with multiple sclerosis

Abstract: Multiple sclerosis (MS) is accompanied by cognitive deficits in half of adult patients and in one third of children. These deficits have a serious impact on daily functioning of patients and may influence the ability to achieve educational goals and participate in professional and social life. Therefore, the focus of this thesis is on cognitive deficits, especially the core deficit regarding working memory (WM), and their treatment with cognitive rehabilitation. The present dissertation contains three original manuscripts that target these topics and further investigate A) the importance of cognitive functioning and the utility of neuropsychological testing in MS patients, B) different patterns of response to WM training regarding cognitive and brain function in adults with MS, and C) effects of WM training in juvenile patients with MS

6-year course of sleep homeostasis in a case with epilepsy-aphasia spectrum disorder

The epilepsy-aphasia spectrum consists of epilepsies with a strong activation of epileptic discharges during non-rapid-eye-movement (NREM) sleep, variable seizure burden and language problems. The homeostatic decrease of slow waves (SW) during NREM sleep (i.e. their amplitude/slope and power) has been related to brain recovery and cognitive function. Epileptic discharges during NREM-sleep were related to an impairment of the decrease of the slope of SW and to cognitive deficits. In this longitudinal case study, we aim to relate this electrophysiological marker, i.e. overnight change of slope of SW, to imaging and behavior. We report a young girl with a fluctuating course in the epilepsy-aphasia spectrum, ranging from the benign end with self-limited childhood epilepsy with centrotemporal spikes (SLECTS) to the severe end with epileptic encephalopathy with continuous spike waves during sleep (CSWS) with two phases of cognitive regression. She was documented over a period of six years including 12 PSGs, six language fMRIs and seven neuropsychological assessments. We longitudinally studied focal and total spike wave index (SWI), detected SW during NREM sleep, calculated their slopes (first and last hour of NREM sleep and overnight change). Deterioration of overnight decrease of the slope of SW was paralleled by the occurrence of the EEG picture of bilateral synchronous electrical status epilepticus during sleep (ESES) and neuropsychological deficits, and this impairment was reversible with resolution of ESES and was accompanied by cognitive improvement. A laterality switch from left to right sided language dominance occurred during recovery from the second regression phase. This might reflect a compensating process. Later, the laterality switched back to the left, possibly facilitated by a low SWI on the left hemisphere. The qualitative analysis of this case supports the view that the longitudinal course of the overnight change of the slope of SW, as an objective, quantitative EEG measure, is related to the course of cognitive function and functional language MR analysis

Cognitive rehabilitation of working memory in juvenile multiple sclerosis-effects on cognitive functioning, functional MRI and network related connectivity.

PURPOSE To assess possible effects of working memory (WM) training on cognitive functionality, functional MRI and brain connectivity in patients with juvenile MS. METHODS Cognitive status, fMRI and inter-network connectivity were assessed in 5 cases with juvenile MS aged between 12 and 18 years. Afterwards they received a computerized WM training for four weeks. Primary cognitive outcome measures were WM (visual and verbal) and alertness. Activation patterns related to WM were assessed during fMRI using an N-Back task with increasing difficulty. Inter-network connectivity analyses were focused on fronto-parietal (left and right), default-mode (dorsal and ventral) and the anterior salience network. Cognitive functioning, fMRI and inter-network connectivity were reassessed directly after the training and again nine months following training. RESULTS Response to treatment was seen in two patients. These patients showed increased performance in WM and alertness after the training. These behavioural changes were accompanied by increased WM network activation and systematic changes in inter-network connectivity. The remaining participants were non-responders to treatment. Effects on cognitive performance were maintained up to nine months after training, whereas effects observed by fMRI disappeared. CONCLUSIONS Responders revealed training effects on all applied outcome measures. Disease activity and general intelligence may be factors associated with response to treatment

Working Memory Training in Patients with Chronic Schizophrenia: A Pilot Study

Background. There is evidence that patients with schizophrenia suffer from decline in working memory performance with consequences for psychosocial outcome. Objective. To evaluate the efficacy of a computerized working memory training program (BrainStim) in patients with chronic schizophrenia. Methods. Twenty-nine inpatients with chronic schizophrenia were assigned to either the intervention group receiving working memory training ( = 15) or the control group without intervention ( = 14). Training was performed four times a week for 45 minutes during four weeks under neuropsychological supervision. At baseline and followup all participants underwent neuropsychological testing. Results. Pre-post comparisons of neuropsychological measures showed improvements in visual and verbal working memories and visual short-term memory with small and large effect sizes in the intervention group. In contrast, the control group showed decreased performance in verbal working memory and only slight changes in visual working memory and visual and verbal short-term memories after 4 weeks. Analyses of training profiles during application of BrainStim revealed increased performance over the 4-week training period. Conclusions. The applied training tool BrainStim improved working memory and short-term memory in patients with chronic schizophrenia. The present study implies that chronic schizophrenic patients can benefit from computerized cognitive remediation training of working memory in a clinical setting

Assessment of post-stroke fatigue : the fatigue scale for motor and cognitive functions

BACKGROUND/AIMS: Post-stroke fatigue (PSF) is an important but still controversial issue since knowledge on its nature is still humble. The aim of the present study was to characterize PSF beyond the subacute phase. METHODS: Thirty-one stroke patients (gender: 6 female, 25 male; age range: 35-76 years; 28 patients with ischemic stroke, 3 patients with hemorrhagic stroke; mean delay after stroke: 50.65 +/- 31.57 days) were recruited and assessed by measures of fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC], Fatigue Severity Scale, and Modified Fatigue Impact Scale), depression (Beck Depression Inventory Fast Screen), cognition (Brief Repeatable Battery of Neuropsychological Tests) and upper and lower extremity functions (Nine-Hole Peg Test and 25-foot walk). RESULTS: Depending on the different scales, PSF prevalence ranged from 16.1 to 58.1%. Depression measures correlated significantly (r(29) 0.01) with the results of all fatigue scales. Seventy-one percent of patients showed cognitive deficits in at least one cognitive domain. Cognitive fatigue measured by one subscale of the FSMC correlated most significantly with mental speed, working memory, and verbal short-term memory, while the motor subscale was associated with upper and lower extremity functions, mental speed, visual short-term memory, and working memory. A differentiation between lesion localization and fatigue severity in the motor or cognitive domain was only possible when applying the FSMC. Patients with cortical lesions scored higher on the cognitive subscale, while patients with subcortical lesions showed higher physical subscale scores. CONCLUSION: The present pilot study revealed differences between lesion localization and subdomains of fatigue after stroke by applying a new fatigue scale (FSMC). The results underline the necessity for separate assessment of motor and cognitive fatigue in stroke patients