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.

Case-Based fMRI Analysis after Cognitive Rehabilitation in MS: A Novel Approach.

BACKGROUND: Cognitive decline in multiple sclerosis (MS) negatively impacts patients' everyday functioning and quality of life. Since symptomatic pharmacological treatment is not yet available alternative treatment strategies such as cognitive rehabilitation are of particular interest. OBJECTIVES: To analyse the ways in which MS patients respond to cognitive training, by combining behavioral and fMRI data in a case-based triangulation approach. METHODS: Ten relapsing-remitting (RR) MS patients aged between 39 and 58 years and between 1 and 8 years post MS diagnosis were included. EDSS ranged from 1 to 3.5. Participants had normal to high intelligence levels. Six patients were assigned to the training group (TG) and four to the control group (CG) without intervention. The TG received a 4-week computerized working memory (WM) training, consisting of 16 training sessions of 45 min duration each. Before and after the training a neuropsychological examination and fMRI investigation by using an N-back task of different complexity was applied. RESULTS: Patients in the TG responded differently to cognitive training. Four participants did not meet the triangulation criteria for being treatment responders. The two responders showed two distinct changes regarding activation patterns after training: (I) decreased brain activation associated with increased processing speed and (II) increased brain activation associated with higher processing speed and WM performance. CONCLUSION: The occurrence of different and opposed response patterns after the same training indicates a risk in applying classical group statistics. Different and especially opposed patterns within the same sample may distort results of classical statistical comparisons. Thus, underlying processes may not be discovered and lead to misinterpretation of results.

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.

Default mode network alterations during language task performance in children with benign epilepsy with centrotemporal spikes (BECTS).

Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic epileptic disorder in children. Besides reported cognitive deficits, functional alterations mostly in the reorganization of language areas have also been described. In several publications, it has been reported that activation of the default mode network (DMN) can be reduced or altered in different neuropsychiatric and neurological disorders in adults. Whether this also holds true for children with epilepsy has so far not been clarified. To determine the functional activation of the DMN in children with BECTS, 20 patients and 16 healthy controls were examined using functional magnetic resonance imaging (fMRI), while a sentence generation task and a reading task were applied in a block design manner. To study the default mode network and the functional alterations between groups, an independent component analysis (ICA) was computed and further analyzed using SPM5. Compared with controls, children with BECTS showed not only significantly less activation of the DMN during the rest condition but also less deactivation during cognitive effort. This was most apparent in the precuneus, a key region of the DMN, while subjects were generating sentences. From these findings, we hypothesize that children with BECTS show a functional deficit that is reflected by alterations in the DMN.

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 (N = 15) or the control group without intervention (N = 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.

Utility of neuropsychological testing for guiding treatment decisions in paediatric multiple sclerosis.

In the past years, there has been growing awareness about childhood onset multiple sclerosis (MS) and the relevance of psychosocial aspects such as cognitive disturbances, fatigue and depression in this population. We describe a case of a 16-year-old patient with relapsing-remitting multiple sclerosis (RRMS) who presented at our clinic with severe fatigue symptoms and who underwent repeated neuropsychological examinations. A sudden significant slowing indicated a new relapse while neurological examination did not. This case highlights the high sensitivity and clinical relevance of neuropsychological testing in patients with juvenile MS even in the context of treatment decisions.

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) ≥ 0.46; p < 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.