The genetics and neuropathology of frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of disorders characterized by disturbances of behavior and personality and different types of language impairment with or without concomitant features of motor neuron disease or parkinsonism. FTLD is characterized by atrophy of the frontal and anterior temporal brain lobes. Detailed neuropathological studies have elicited proteinopathies defined by inclusions of hyperphosphorylated microtubule-associated protein tau, TAR DNA-binding protein TDP-43, fused-in-sarcoma or yet unidentified proteins in affected brain regions. Rather than the type of proteinopathy, the site of neurodegeneration correlates relatively well with the clinical presentation of FTLD. Molecular genetic studies identified five disease genes, of which the gene encoding the tau protein (MAPT), the growth factor precursor gene granulin (GRN), and C9orf72 with unknown function are most frequently mutated. Rare mutations were also identified in the genes encoding valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B). These genes are good markers to distinguish underlying neuropathological phenotypes. Due to the complex landscape of FTLD diseases, combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis. Although major progress has been made in FTLD research in recent years, further studies are needed to completely map out and correlate the clinical, pathological and genetic entities, and to understand the underlying disease mechanisms. In this review, we summarize the current state of the rapidly progressing field of genetic, neuropathological and clinical research of this intriguing condition

"Silent witness" in Boekhoute. Archeologen en menselijke beenderen. Gerechtelijk-geneeskundig rapport.

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Pre- to postoperative longitudinal follow-up of phoneme perception in glioma patients : evidence from the Mismatch Negativity and P300

Background and AimsGlioma growth in eloquent language areas induces adaptive activation changes in the language network. The present study aimed to (1) investigate the pre- to postoperative evolution of neural phoneme perception processes in glioma patients and (2) assess if event-related potentials (ERPs) reflecting phoneme perception can provide added value to the diagnostic approach in individuals undergoing awake surgery.Methods and ProceduresIn five persons undergoing an awake craniotomy for the resection of a glioma, pre- and postoperative behavioural language assessment (Aachen Aphasia Test, Comprehensive Aphasia Test and Boston Naming Test) and electrophysiological investigation of phoneme perception was performed. For the latter, ERPs were obtained through the administration of an inattentive (Mismatch Negativity; MMN) and attentive (P300) oddball paradigm containing a phonemic articulation place contrast during EEG recording.Outcomes and ResultsAberrant phoneme categorization processing was evidenced in all five participants preoperatively based on the MMN and P300 amplitude and latency. Moreover, mild behavioural impairments were found in four participants at this time. Postoperatively, three out of five participants reached behavioural ceiling effects, while four individuals displayed normalization of electrophysiological measures.ConclusionsWhile neural processing of phoneme contrasts was preoperatively affected by glioma-induced disturbances, a high potential for postsurgical plasticity was shown. As four participants presented with a high grade glioma, tumour grade might partially account for this pattern. Addition of electrophysiological tests to the language assessment could provide benefits in both the pre- and postoperative clinical diagnostic approach in glioma patients. These preliminary results need validation in a larger sample