Autism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour. Mutations in synaptic proteins such as neuroligins, neurexins, GKAPs/SAPAPs and ProSAPs/Shanks were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo- and heteromeric protein complexes at excitatory synapses and organize the complex protein machinery of the postsynaptic density in a laminar fashion. Here we demonstrate that genetic deletion of ProSAP1/Shank2 results in an early, brain-region-specific upregulation of ionotropic glutamate receptors at the synapse and increased levels of ProSAP2/Shank3. Moreover, ProSAP1/Shank2(-/-) mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced N-methyl-d-aspartate receptor-mediated excitatory currents at the physiological level. Mutants are extremely hyperactive and display profound autistic-like behavioural alterations including repetitive grooming as well as abnormalities in vocal and social behaviours. By comparing the data on ProSAP1/Shank2(-/-) mutants with ProSAP2/Shank3αβ(-/-) mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype.
Navigated TMS correlates well with DCS as a gold standard despite factors that are supposed to contribute to the inaccuracy of nTMS. Moreover, surgeons have found nTMS to be an additional and helpful modality during the resection of tumors affecting eloquent motor areas, as well as during preoperative planning.
This work increases the level of evidence for preoperative motor mapping by nTMS for rolandic lesions in a group comparison study. We therefore strongly advocate nTMS to become increasingly used for these lesions. However, a randomized trial on the comparison with the gold standard of intraoperative mapping seems mandatory.
Continuous MEP monitoring provides reliable monitoring of the motor system, influences the course of operation in some cases, and has to be regarded as the standard for IOM of the motor system. In our series, we found no false-negative MEP results.
Conventional DTI-FT showed significant differences between the two modalities, most likely because of the more specific definition of the seed region when DTI-FT is based on NBS. Moreover, NBS-aided DTI fiber tracking is user-independent and, therefore, a method for further standardization of DTI fiber tracking.
One- and two-level ACDF with stand-alone empty PEEK cages achieved very high fusion rates and a low rate of follow-up operations. The rate of good clinical outcome is highly satisfactory. Younger age was the single most influential factor associated with better clinical outcome.
Object
The aim of surgical glioma treatment is the complete resection of tumor tissue while preserving neurological function. Surgery-related neurological deficits arise from direct damage to the cortical or subcortical structures or from ischemia. The authors aimed to assess the incidence of resection-related ischemia of newly diagnosed or recurrent supratentorial gliomas and the sensitivity of intraoperative neuromonitoring (IOM) of motor evoked potentials (MEPs) for detecting such ischemic events and their influence on neurological motor function.
Methods
Between January 2009 and December 2010, 70 patients with tumors in motor-eloquent brain areas underwent intraoperative MEP monitoring during glioma resection and were examined by early postoperative MRI including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping. Postoperative areas of restricted diffusion were assessed by investigators blinded to the course of intraoperative MEPs and the neurological course.
Results
Among the 70 enrolled patients, a MEP amplitude decline below 50% of the baseline level was observed in 21 patients (30%). Sixteen of these patients (76%) had ischemic lesions identified on postoperative MRI scans. Forty-nine patients (70%) showed no decline in MEP amplitude, and only 16 (33%) of these patients harbored ischemic lesions. Moreover, 9 (69%) of 13 patients with a permanent loss of MEP amplitude showed postoperative ischemic lesions. Factors that promoted the occurrence of postoperative infarction were previous radiotherapy and location of the tumor close to the central arteries.
Conclusions
Alterations in the MEP amplitude during tumor resection and postoperative ischemic lesions are associated with postoperative impairment of motor function. Rather than cortical or subcortical structural damage of eloquent brain tissue alone, peri- or postoperative ischemic lesions play a crucial role in the development of surgery-related motor deficits.
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