Excessive Daytime Sleepiness Is a Common Symptom in Fabry Disease

Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by a deficient activity of the enzyme α-galactosidase A, resulting in a vasculopathic involvement of various organ systems, e.g. cerebral structures. Marked cerebral vasculopathy with subsequent white matter lesions (WML) are a frequent finding in FD patients. Recent studies discussed an association between cerebral white matter changes and sleep-related disturbances of breathing, which may lead to excessive daytime sleepiness (EDS). A 56-year-old Caucasian female FD patient with EDS was admitted to our sleep laboratory. Overnight polysomnography showed a Cheyne-Stokes respiration pattern with significant O2 desaturation. MR imaging revealed confluent WML including the brain stem, but no renal or cardiac involvement. We then evaluated the clinical data of 49 genetically proven FD patients (27 males; mean age 43 years) from our FD centre. With a frequency of 68%, EDS exceeds the prevalence of other common symptoms of FD (angiokeratomas 61%; acroparaesthesia 51%; renal involvement 29%; cardiac involvement 27%), and the prevalence of chronic fatigue (48%). EDS was independently associated with the physical component summary of the SF-36 data (corrected R2 = −0.323, p < 0.001). EDS and age explained a quarter of variance in mental component summary (corrected R2 = −0.253, p < 0.001). We conclude that EDS is a common and underdiagnosed symptom in FD patients, accompanied by a significant impact on quality of life. EDS might be caused by central breathing disorders due to an affection of brain regions associated with respiratory control in FD

Imaging short- and long-term training success in chronic aphasia

<p>Abstract</p> <p>Background</p> <p>To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language training in chronic post-stroke aphasia patients.</p> <p>Results</p> <p>Eight patients were trained daily for three hours over a period of two weeks in naming of concrete objects. Prior to, immediately after, and eight months after training, patients overtly named trained and untrained objects during event-related fMRI. On average the patients improved from zero (at baseline) to 64.4% correct naming responses immediately after training, and treatment success remained highly stable at follow-up. Regression analyses showed that the degree of short-term treatment success was predicted by increased activity (compared to the pretraining scan) bilaterally in the hippocampal formation, the right precuneus and cingulate gyrus, and bilaterally in the fusiform gyri. A different picture emerged for long-term training success, which was best predicted by activity increases in the right-sided Wernicke's homologue and to a lesser degree in perilesional temporal areas.</p> <p>Conclusion</p> <p>The results show for the first time that treatment-induced language recovery in the chronic stage after stroke is a dynamic process. Initially, brain regions involved in memory encoding, attention, and multimodal integration mediated treatment success. In contrast, long-term treatment success was predicted mainly by activity increases in the so-called 'classical' language regions. The results suggest that besides perilesional and homologue language-associated regions, functional integrity of domain-unspecific memory structures may be a prerequisite for successful (intensive) language interventions.</p

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Neuronavigation in brain tumor surgery:clinical beta-phase of the Oulu Neuronavigator System

Abstract Interactive image-guided neurosurgery for the resection of brain tumors was developed within the last 10 years at different neurosurgical centers around the world to improve the safety of the surgery and the functional outcome of the patients. Since 1987, the Oulu Neuronavigator System, consisting mainly of a mechanical arm, visualization software, an ultrasound transducer and a computer, was developed at the Neurosurgical Research Unit, University of Oulu, Finland. It was the first system to incorporate the principle of the common surgical axis for visualization, including intraoperative ultrasonography. A precommercial version of the device was jointly developed with Elekta Ab, Stockholm, Sweden, as a public project under EUREKA and introduced into a clinical beta-phase trial in 1994 as the Leksell Index System™. A total of 19 operations were performed at the Oulu University Hospital between September 1994 and September 1996 for patients harboring different kinds of intracranial tumors, especially cerebral gliomas. This thesis gives a comprehensive review of the literature from the roots of stereotaxy to the latest developments in interactive image-guided neurosurgery and discusses the advantages and disadvantages of the Leksell Index System™ with special reference to the clinical series that was performed at our institution. Future therapy strategies for the treatment of patients with cerebral gliomas, especially glioblastoma multiforme are envisioned, focusing on the further improvement of surgical interventions. The clinical trial proved that the employed neuronavigator system is versatile and safe and that there are no adverse effects, complications or surgical mortality due to the device. It enabled the surgeon to plan smaller sized and better centered skin incisions and craniotomies and to approach the target lesion with less dissection of intact brain tissue. Despite more radical removal of lesions the overall invasiveness of the operation was decreased in 63.2% of the cases, the duration of the procedure was decreased in 78.9%, and the surgeon's feeling of safety could be improved in 89.5% of the operations. Due to the use of intraoperative imaging (with ultrasound) the experience provides a unique basis for next generation neuronavigators and also for interventional MRI