An intellectual disability syndrome with single nucleotide variants in <i>O-GlcNAc Transferase</i>

Contains fulltext : 220584.pdf (Publisher’s version ) (Open Access)Intellectual disability (ID) is a neurodevelopmental condition that affects ~1% of the world population. In total 5-10% of ID cases are due to variants in genes located on the X chromosome. Recently, variants in OGT have been shown to co-segregate with X-linked intellectual disability (XLID) in multiple families. OGT encodes O-GlcNAc transferase (OGT), an essential enzyme that catalyses O-linked glycosylation with β-N-acetylglucosamine (O-GlcNAc) on serine/threonine residues of thousands of nuclear and cytosolic proteins. In this review, we compile the work from the last few years that clearly delineates a new syndromic form of ID, which we propose to classify as a novel Congenital Disorder of Glycosylation (OGT-CDG). We discuss potential hypotheses for the underpinning molecular mechanism(s) that provide impetus for future research studies geared towards informed interventions

Magnetic resonance imaging of pilocytic astrocytomas in adults with histopathologic correlation: a report of six consecutive cases

Pilocytic astrocytoma is a WHO grade I tumor usually diagnosed in pediatric patients, and rarely encountered in the adult population. Therefore, available information about the magnetic resonance imaging characteristics of adult pilocytic astrocytoma is scarce. We report on the MRI features and corresponding histopathologic findings of six consecutive aPA cases diagnosed. The tumors were encountered in both infra- and supratentorial compartments, and their MRI characteristics were quite heterogeneous. Features included the typical solid-cystic appearance located in the cerebellum as well as the relatively unusual multifocal and/or hemorrhagic features located intra-ventricularly. The aPA MRI characteristics are remarkably variable, and might mimic those of higher grade tumors in adult patients

Optimisation of new biodegradable microcarriers tailored for tissue engineering

Bioproductio

Vertebral body stent augmentation to reconstruct the anterior column in neoplastic extreme osteolysis

Background Extensive lytic lesions of the vertebral body (VB) increase risk of fracture and instability and require stabilization of the anterior column. Vertebral augmentation is an accepted treatment option, but when osteolysis has extensively destroyed the VB cortical boundaries (a condition herein defined as € extreme osteolysis'), the risk of cement leakage and/or insufficient filling is high. Vertebral body stents (VBSs) might allow partial restoration of VB height, cement containment, and reinforcement, but their use in extreme osteolysis has not been investigated. Objective To assess retrospectively the feasibility and safety of VBS augmentation in patients with € extreme osteolysis' of the VB. Methods We retrospectively analyzed 41 treated vertebrae (from T1 to L5). VB reconstruction was assessed on postprocedure CT images and rated on a qualitative 4-point scale (poor-fair-good-excellent). Clinical and radiological follow-up was performed at 1 month and thereafter at intervals in accordance with oncological protocols. Results VBS augmentation was performed at 12 lumbar and 29 thoracic levels, with bilateral VBS in 23/41. VB reconstruction was judged satisfactory (good or excellent) in 37/41 (90%) of levels. Bilateral VBS received higher scores than unilateral (p=0.057, Pearson's X 2). We observed no periprocedural complications. Cement leaks (epidural or foraminal) occurred at 5/41 levels (12.2%) without clinical consequences. Follow-up data were available for 27/29 patients, extending beyond 6 months for 20 patients (7-28 months, mean 15.3 months). VBS implant stability was observed in 40/41 cases (97.5%). Conclusions Our results support the use of VBS as a minimally invasive, safe and effective option for reconstructing the anterior column in prominent VB osteolysis

Multimodal assessment of motor pathways and intracortical connections in functional hemispherectomy

Purpose: For selected children with medically intractable epilepsy, hemispherectomy can be an excellent treatment option and its efficacy in achieving seizure freedom or reduction in seizure frequency has been shown in several studies, but patients’ selection could not be straightforward and often it is taken on subjective basis. We described a multimodal approach to assess patient eligible for hemispherectomy and possibly predicting post-surgical outcomes. Methods: We describe pre- and post-surgical clinical features along with neuroradiological results by magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), MR-tractography (MRT), and neurophysiological study by single and paired pulses transcranial magnetic stimulation (TMS) in a child with cerebral palsy with epileptic encephalopathy, eligible for epilepsy surgery. Results: Presurgical TMS evaluation showed a lateralization of motor function on the left motor cortex for both arms, and results were confirmed by MRI studies. Interestingly, after surgery, both epilepsy and motor performances improved and TMS showed enhancement of intracortical inhibition and facilitation activity. Conclusion: Functional hemispherectomy is an effective treatment for drug-resistant epilepsy, and multimodal presurgical assessment may be a useful approach to guide surgeons in selecting patients. Moreover, pre- and post-surgical evaluation of these patients may enhance our understanding of brain plasticity phenomena

Motor cortex plasticity predicts recovery in acute stroke

Repetitive transcranial magnetic stimulation of the brain given as intermittent theta burst stimulation (iTBS) can induce long-term potentiation (LTP)-like changes in the stimulated hemisphere and long-term depression (LTD)-like changes in the opposite hemisphere. We evaluated whether LTP-and LTD-like changes produced by iTBS in acute stroke correlate with outcome at 6 months. We evaluated the excitability of affected hemisphere (AH) and unaffected hemisphere (UH) by measuring motor threshold and motor-evoked potential (MEP) amplitude under baseline conditions and after iTBS of AH in 17 patients with acute ischemic stroke. Baseline amplitude of MEPs elicited from AH was significantly smaller than that of MEPs elicited from UH, and baseline motor threshold was higher for the AH. Higher baseline MEP values in UH correlated with poor prognosis. iTBS produced a significant increase in MEP amplitude for AH that was significantly correlated with recovery. A nonsignificant decrease in MEP amplitude was observed for the UH. When the decrease in the amplitude of UH MEPs was added to the regression model, the correlation was even higher. Functional recovery is directly correlated with LTP-like changes in AH and LTD-like changes in UH and inversely correlated with the baseline excitability of UH. © The Author 2009. Published by Oxford University Press. All rights reserved

Dedicated 3D-T2-STIR-ZOOMit imaging improves demyelinating lesion detection in the anterior visual pathways of patients with multiple sclerosis

Background and Purpose: Demyelinating lesions in the anterior visual pathways represent an underestimated marker of disease dissemination in patients with MS. We prospectively investigated whether a dedicated high-resolution MR imaging technique, the 3D-T2-STIR-ZOOMit, improves demyelinating lesion detection compared with the current clinical standard sequence, the 2DT2-STIR. Materials and Methods: 3T MR imaging of the anterior visual pathways (optic nerves, chiasm, and tracts) was performed using 3D-T2-STIR-ZOOMit and 2D-T2-STIR, in patients with MS and healthy controls. Two experienced neuroradiologists assessed, independently, demyelinating lesions using both sequences separately. 3D-T2-STIR-ZOOMit scan-rescan reproducibility was tested in 12 patients. The Cohen k was used for interrater agreement, and the intraclass correlation coefficient for reproducibility. Betweensequence detection differences and the effects of location and previous acute optic neuritis were assessed using a binomial mixed-effects model. Results: Forty-eight patients with MS with (n = 19) or without (n = 29) past optic neuritis and 19 healthy controls were evaluated. Readers' agreement was strong (3D-T2-STIR-ZOOMit: 0.85; 2D-T2-STIR: 0.90). The 3D-T2-STIR-ZOOMit scan-rescan intraclass correlation coefficient was 0.97 (95% CI, 0.96-0.98; P&lt;.001), indicating excellent reproducibility. Overall, 3D-T2-STIR-ZOOMit detected more than twice the demyelinating lesions (n=89) than 2D-T2-STIR (n=43) (OR = 2.7; 95% CI, 1.7-4.1; P&lt;.001). In the intracranial anterior visual pathway segments, 33 of the 36 demyelinating lesions (91.7%) detected by 3D-T2-STIR-ZOOMit were not disclosed by 2D-T2-STIR. 3D-T2-STIR-ZOOMit increased detection of demyelinating lesion probability by 1.8-fold in patients with past optic neuritis (OR = 1.8; 95% CI, 1.2-3.1; P=.01) and 5.9-fold in patients without past optic neuritis (OR = 5.9; 95% CI, 2.5-13.8; P&lt;.001). No false-positive demyelinating lesions were detected in healthy controls. Conclusions: Dedicated 3D-T2-STIR-ZOOMit images improved substantially the detection of MS disease dissemination in the anterior visual pathways, particularly in the intracranial segments and in patients without past optic neuritis