1,721,028 research outputs found
Temporobasal, Transsphenoidal Meningoencephalocele Becoming Symptomatic with Spontaneous Cerebrospinal Fluid Rhinorrhea: Diagnostic Work-up and Microsurgical Strategy
No full textBackgroundWe report the rare case of an adult transsphenoidal meningoencephalocele and outline the microneurosurgical strategy. Clinical history, the findings of computerized tomography (CT) scans and magnetic resonance imaging (MRI), the microsurgical procedure, and histopathology are reported. Case ReportA 54-year-old female patient complained about cerebrospinal fluid (CSF) rhinorrhea; a transnasal biopsy of a mass in the maxillar sinus prior to diagnostic work-up was performed elsewhere. Persisting CSF leakage prompted CT and MRI, which showed brain tissue extending from the left middle cranial fossa into the left sphenoid sinus through several bony defects. The diagnosis of a transsphenoidal meningoencephalocele was made, and the lesion was targeted via a subtemporal intradural approach with resection of the herniated brain tissue and closure of the bony as well as of dural defects. The postoperative course was uneventful without recurrence of the CSF fistula. ConclusionThe transsphenoidal subtype of basal meningoencephaloceles is exceedingly rare. Nonetheless, it has to be considered as a differential diagnosis if a nasal or intrasphenoidal mass is diagnosed. Otherwise, unjustified biopsy or unsuccessful management of CSF leakage could not be avoided. The intradural subtemporal approach is effective to treat the transsphenoidal type of basal meningoencephaloceles
Defining the Prion Type of Fatal Familial Insomnia
No full textFatal familial insomnia (FFI) belongs to the genetic human transmissible spongiform encephalopathies (TSE), such as genetic Creutzfeldt-Jakob disease (CJD) or Gerstmann-Straeussler-Scheinker syndrome (GSS). Here, we analyzed the properties of the pathological prion protein in six FFI cases by Western blot analysis, a protein aggregate stability assay, and aggregate deposition characteristics visualized with the paraffin-embedded tissue blot. While in all cases the unglycosylated fragment in Western blot analysis shared the same size with sporadic CJD prion type 2, the reticular/synaptic deposition pattern of the prion aggregates resembled the ones found in sporadic CJD type 1 (CJD types according to the Parchi classification from 1999). Regarding the conformational stability against denaturation with GdnHCl, FFI prion aggregates resembled CJD type 1 more than type 2. Our results suggest that the size of the proteinase-K-resistant fragments is not a valid criterion on its own. Additional criteria supplying information about conformational differences or similarities need to be taken into account. FFI may resemble a prion type with its own conformation sharing properties partly with type 1 and type 2 prions.Fatal familial insomnia (FFI) belongs to the genetic human transmissible spongiform encephalopathies (TSE), such as genetic Creutzfeldt-Jakob disease (CJD) or Gerstmann-Straeussler-Scheinker syndrome (GSS). Here, we analyzed the properties of the pathological prion protein in six FFI cases by Western blot analysis, a protein aggregate stability assay, and aggregate deposition characteristics visualized with the paraffin-embedded tissue blot. While in all cases the unglycosylated fragment in Western blot analysis shared the same size with sporadic CJD prion type 2, the reticular/synaptic deposition pattern of the prion aggregates resembled the ones found in sporadic CJD type 1 (CJD types according to the Parchi classification from 1999). Regarding the conformational stability against denaturation with GdnHCl, FFI prion aggregates resembled CJD type 1 more than type 2. Our results suggest that the size of the proteinase-K-resistant fragments is not a valid criterion on its own. Additional criteria supplying information about conformational differences or similarities need to be taken into account. FFI may resemble a prion type with its own conformation sharing properties partly with type 1 and type 2 prions
Liquordiagnostik bei der Parkinsonkrankheit mit und ohne Demenz und der Demenz mit Lewy-Körpern
No full textWith an ageing population neurodegenerative diseases like dementia and Parkinson's disease are becoming more prevalent. To date the clinical diagnosis of neurodegenerative diseases is based on clinical criteria and clinical follow-up observations. For this reason there is a need to develop objective biological markers to establish an early and differential diagnosis in this field. Receptor imaging techniques of dopamine transporters with single photon emission tomography (SPECT) may contribute to the differential diagnosis of Parkinson syndromes or to distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). For routine diagnosis a biological marker must be cheap, easy to detect and validated in terms of sensitivity and specificity. As already established for the diagnosis of AD, the analysis of specific CSF proteins might become an important diagnostic tool for other neurodegenerative diseases. The aim of this article is to give an overview of the current findings in the field of CSF biomarkers in Parkinson's disease, Parkinson dementia and dementia with Lewy bodies
Inflammatorische Form der zerebralen Amyloid-Angiopathie: Ein Fall mit subakuter, reversibler Leukenzephalopathie
No full textTypes and Strains: Their Essential Role in Understanding Protein Aggregation in Neurodegenerative Diseases
No full textProtein misfolding and aggregation is a key event in diseases like Alzheimer's disease (AD) or Parkinson's disease (PD) and is associated with neurodegeneration. Factors that initiate protein misfolding and the role of protein aggregation in the pathophysiology of disease pose major challenges to the neuroscientific community. Interestingly, although the accumulation of the same misfolded protein, e.g., alpha-synuclein is detectable in all idiopathic PD patients, the disease spectrum covers a variety of different clinical presentations and disease courses. In a more recent attempt this clinical variance is being explained in analogy to prion diseases by different protein aggregate conformations. In prion diseases a relationship between protein aggregate conformation properties and the clinical disease course was shown by relating different prion types to a dementia and an ataxic disease course in Creutzfeldt-Jakob patients. This principle is currently transferred to AD, PD and other neurodegenerative diseases with protein aggregation. However, differences in protein aggregate conformation are frequently addressed as disease strains. The term "strain" also derives from prion research and evolved by adopting the virus terminology at a time when transmissible spongiform encephalopathies (TSEs; later called prion diseases) were assumed to be caused by a virus. The problem is that in virus taxonomy the term "type" refers to properties of the disease agent itself and the term "strain" refers to host associated factors that interact with the disease agent and may moderately modify the clinical disease presentation. Strain factors can be discovered only after transmission and passaging of the agent in a host of a different species. The incorrect use of the terminology confuses disease agent and host factors and hampers the understanding of the pathophysiology of protein aggregate-associated neurodegenerative diseases. In this review article the discoveries are reviewed that explain how the terms "type" and "strain" emerged for unconventional disease agents. This may help to avoid confusion in the terminology of protein aggregation diseases and to reflect correctly the impact of protein aggregate conformation as well as host factor contribution on different clinical variations of AD, PD and other neurodegenerative diseases
beta-amyloid is a substrate of autophagy in sporadic inclusion body myositis
No full textObjective: Sporadic Inclusion Body Myositis (sIBM) is the most common acquired muscle disease in patients above 50 years of age. Apart from inflammation in the skeletal muscle, overexpression of amyloid precursor protein (APP) and intracellular accumulation of its proteolytic fragment fi-amyloid play a central role in the pathogenesis of sIBM. In neurodegenerative disorders, similar aggregations of aberrant proteins have recently been shown to be susceptible to autophagic degradation. Therefore, we analyzed macroautophagy of APP in human muscle cell lines and sIBM muscle biopsies. Methods: Colocalization of APP with the essential autophagy protein Atg8/LC3, which associates with preautophagosomal and autophagosomal membranes via lipidation, was analyzed in the CCL-136 muscle cell line and muscle biopsies by immunofluorescence. While APP was visualized with specific antibodies in the muscle cell line and in tissue sections. Atg8/LC3 localization was analyzed after GFP-Atg8/LC3 transfection or with an Atg8/LC3 specific antiserum, respectively. Results: We demonstrate here that Atg8/LC3 colocalizes with APP in cultured human muscle cells. In addition, APP/beta-amyloid-containing autophagosomes can be observed at increased frequency in muscle fibers of sIBM muscle biopsies, but not in non-myopathic muscle or non-vacuolated myopathic controls. APP/beta-amyloid and Ata8/LC3 double-positive compartments were almost exclusively observed in degenerating muscle fibers of the type II (fast-twitching) and were in part associated with overexpression of major histocompatibility complex (MHC) class I and II on myofibers and invasion by CD4(+) and CD8(+) cells. Interpretation: These findings indicate that APP/beta-amyloid is targeted for lysosomal degradation via macroautophagy and suggest that the autophagy pathway should be explored for its potential therapeutic merit in sIBM
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