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is head of the Epilepsy Center Hessen and co-coordinator of the EpimiRNA-project. SUMMARYCerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.

Although it is widely agreed that the cerebellum is necessary for learning and consolidation of new motor tasks, it is not known whether adaptation to kinematic and dynamic errors is processed by the same cerebellar areas or whether different parts play a decisive role. We investigated arm movements in a visuomotor (VM) rotation and a force field (FF) perturbation task in 14 participants with cerebellar degeneration and 14 age- and gender-matched controls. Magnetic resonance images were used to calculate the volume of cerebellar areas (medial, intermediate, and lateral zones of the anterior and posterior lobes) and to identify cerebellar structure important for the two tasks. Corroborating previous studies, cerebellar participants showed deficits in adaptation to both tasks compared with controls (P < 0.001). However, it was not possible to draw conclusions from the performance in one task on the performance in the other task because an individual participant could show severe impairment in one task and perform relatively well in the other (rho = 0.1; P = 0.73). We found that atrophy of distinct cerebellar areas correlated with impairment in different tasks. Whereas atrophy of the intermediate and lateral zone of the anterior lobe correlated with impairment in the FF task (rho = 0.72, 0.70; P = 0.003, 0.005, respectively), atrophy of the intermediate zone of the posterior lobe correlated with adaptation deficits in the VM task (rho = 0.64; P = 0.015). Our results suggest that adaptation to the different tasks is processed independently and relies on different cerebellar structures.

Studies with patients and functional magnetic resonance imaging investigations have demonstrated that the cerebellum plays an essential role in adaptation to visuomotor rotation and force field perturbation. To identify cerebellar structures involved in the two tasks, we studied 19 patients with focal lesions after cerebellar infarction. Focal lesions were manually traced on magnetic resonance images and normalized using a new spatially unbiased template of the cerebellum. In addition, we reanalyzed data from 14 patients with cerebellar degeneration using voxel-based morphometry. We found that adjacent regions with only little overlap in the anterior arm area (lobules IV to VI) are important for adaptation in both tasks. Although adaptation to the force field task lay more anteriorly (lobules IV and V), lobule VI was more important for the visuomotor task. In addition, regions in the posterolateral cerebellum (Crus I and II) contributed to both tasks. No consistent involvement of the posterior arm region (lobule VIII) was found. Independence of the two kinds of adaptation is further supported by findings that performance in one task did not correlate to performance in the other task. Our results show that the anterior arm area of the cerebellum is functionally divided into a more posterior part of lobule VI, extending into lobule V, related to visuomotor adaption, and a more anterior part including lobules IV and V, related to force field adaption. The posterolateral cerebellum may process common aspects of both tasks.

This study examined whether lesions to the cerebellum obtained in early childhood are better compensated than lesions in middle childhood or adolescence. Since cerebellar lesions might affect motor as well a cognitive performance, posture, upper limb and working memory function were assessed in 22 patients after resection of a cerebellar tumour (age at surgery 1-17 years, minimum 3 years post-surgery). Working memory was only impaired in those patients who had received chemo- or radiation therapy. Postural sway was enhanced in 64% of the patients during dynamic posturography conditions, which relied heavily on vestibular input for equilibrium control. Upper limb function was generally less impaired, but 54% of the patients revealed prolonged deceleration times in an arm pointing task, which probably does not reflect a genuine cerebellar deficit but rather the patients' adopted strategy to avoid overshooting. Age at surgery, time since surgery or lesion volume were poor predictors of motor or cognitive recovery. Brain imaging analysis revealed that lesions of all eight patients with abnormal posture who did not receive chemo- and/or radiation therapy included the fastigial and interposed nuclei (NF and NI). In patients with normal posture, NI and NF were spared. In 11 out of 12 patients with abnormal deceleration time, the region with the highest overlap included the NI and NF and dorsomedial portions of the dentate nuclei in 10 out of 12 patients. We conclude that cerebellar damage inflicted at a young age is not necessarily better compensated. The lesion site is critical for motor recovery, and lesions affecting the deep cerebellar nuclei are not fully compensated at any developmental age in humans.

Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affective-motivational aspects of the pain response.

Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.4 (n = 18) or 0.8 ng/kg of body weight (n = 16). Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task) and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System). Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1ra), salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.

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