Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy: clinical and pathological study of four cases
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Abstract:
Neuronal ceroid-lipofuscinosis (NCL) is a recent term, proposed for acurate designation of the late-onset types of Amaurotic Family Idiocy (AFI). Histopathology shows ubiquitous intraneuronal accumulation of lipopigments, being the most important factor for characterization of the entity at present time. Biochemical changes and pathogenesis are obscure. NCL is in contrast to the infantile type of AFI (Tay-Sachs disease), in which intraneuronal accumulation of gangliosides (sphingolipids) is due to the well known deficiency of a lysosomal enzyme. The authors report on four cases of NCL, two brothers of the late infantile (Jansky-Bielschowsky) type and a brother and a sister of the juvenile (Spielmeyer-Sjögren) type. One autopsy and three cortical biopsies revealed moderate to severe distention of the neurons by lipopigment, with nerve cell loss, gliosis and cerebral atrophy. Lipopigment was also increased in liver, heart and spleen. The patients were the first in Brazilian literature in whom the storage material was identified as lipopigment by histochemical methods. A brief summary of the clinical features of NCL is presented, and relevant problems are discussed, concerning interpretation of the nature of the storage material, and significance of the disease for gerontological research.Keywords:
Neuronal ceroid lipofuscinosis
Gliosis
Histopathology
Neuropathology
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Abstract Purpose To evaluate the diagnostic accuracy of epilepsy-dedicated 3 Tesla MRI including post-processing by correlating MRI, histopathology, and postsurgical seizure outcomes. Methods 3 Tesla-MRI including a magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence for post-processing using the morphometric analysis program MAP was acquired in 116 consecutive patients with drug-resistant focal epilepsy undergoing resection surgery. The MRI, histopathology reports and postsurgical seizure outcomes were recorded from the patient’s charts. Results The MRI and histopathology were concordant in 101 and discordant in 15 patients, 3 no hippocampal sclerosis/gliosis only lesions were missed on MRI and 1 of 28 focal cortical dysplasia (FCD) type II associated with a glial scar was considered a glial scar only on MRI. In another five patients, MRI was suggestive of FCD, the histopathology was uneventful but patients were seizure-free following surgery. The MRI and histopathology were concordant in 20 of 21 glioneuronal tumors, 6 cavernomas, and 7 glial scars. Histopathology was negative in 10 patients with temporal lobe epilepsy, 4 of them had anteroinferior meningoencephaloceles. Engel class IA outcome was reached in 71% of patients. Conclusion The proposed MRI protocol is highly accurate. No hippocampal sclerosis/gliosis only lesions are typically MRI negative. Small MRI positive FCD can be histopathologically missed, most likely due to sampling errors resulting from insufficient harvesting of tissue.
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Hippocampal sclerosis
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Under the auspices of the EURO-CNS Including course books and e-learning modules: - Basic neuropathology - Neurodegenerative diseases - Leukoencephalopathies - Tumors of the CNS and PNS - Developmental neuropathology - Muscle and nerve pathology - Forensic neuropathology
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OBJECTIVE: To investigate the genetics of Late-onset Alzheimer disease by reducing phenotypic heterogeneity and studying AD coincident phenotypes. BACKGROUND: To investigate the underlying genetic mechanisms of Late-onset Alzheimer Disease (LOAD), we have performed a genome-wide association study of AD neuropathology and coincident phenotypes, including a neuropathology-confirmed case-control analysis, analyses of coincident features, including neuritic plaques (NP), lewy bodies (LB), amyloid angiopathy (AA), medial temporal sclerosis (MTS), AD Braak stage, and vascular brain injury (VBI). We used this expanded neuropathology approach to limit the effects of phenotypic heterogeneity, and provide additional insights into AD subphenotypes. DESIGN/METHODS: We examined 4914 samples with neuropathology data from 11 datasets in the Alzheimer Disease Genetics Consortium genotyped with high-density chips. Statistical aassociation was performed using logistic regression for binary traits and polytomous logistic regression for ordinal traits, followed by meta-analysis. Subjects examined included 3,887 neuropathologically-confirmed LOAD cases and 1,027 neuropathologically-confirmed cognitive controls. RESULTS: Associations of APOE and BIN1 with LOAD were confirmed. Additionally, several novel LOAD associations were found, including PHF21B (P=2.0×10-8), and SMOX (P=9.0×10-7). Multiple loci were associated with the presence of neuritic plaques, including APOE (P=1.8x10-30), GALNT7 (P=6.0×10-9), ABCG1 (P=8.0×10-9), and a region near LMX1B (P=4.3×10-8). Additional loci were found to be associated with several ordinal neuropathology traits including LB, AA, MTS, VBI, and Braak. Twelve of the 21 genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample, with nine of these showing larger ORs in the clinic-pathologic sample. At the known loci there was strong positive correlation between AD dementia effect sizes and NFT/NP effect sizes, while VBI effect sizes showed a moderate negative correlation; other coincident features showed only nominal association with known loci. CONCLUSIONS: These results confirm several known AD risk loci and implicate novel loci in the etiology of LOAD neuropathology features, particularly neuritic plaque. Additionally, they suggest a role of AD risk loci in the development of VBI, but not other coincident features.
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The frequency of histopathological sampling at autopsy varies, even though inadequate sampling may limit the value of autopsy reports. This study aims to investigate the contribution of histopathology at autopsy in a major teaching hospital.A total of 532 coronial autopsy reports from Manchester Royal Infirmary were analysed retrospectively. Gross and microscopic diagnoses were compared and classified as concordant, discordant, histology needed (i.e. indeterminate or unremarkable gross findings) or autolysed. Revisions made to the cause of death following histopathology were categorised as: altered direct cause of death, altered indirect cause of death, concordant with supportive information, irrelevant or inconclusive. The study was limited to brain, heart, kidney, liver, lung and spleen. Histopathology had been requested in 141 cases (27%), which were further analysed. The greatest discordance between gross and microscopic findings was observed in the lung (11.6%). The organs most frequently requiring histopathology to provide a diagnosis were the kidney and lung, at 52.8 and 28.2%, respectively. Alterations were made to the direct cause of death in 45% of cases where histopathology was taken; it provided additional or supportive information in a further 38%. Diagnoses of primary malignancy had a sensitivity of 74% [confidence interval (CI) = 0.59-0.86] and bronchopneumonia had a sensitivity of 45% (CI = 0.29-0.62).Histopathology has a major impact on the interpretation of organ pathology and determining a cause of death at autopsy.
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Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases with a common set of symptoms including cognitive and motor decline and vision loss. Naturally occurring sheep models of CLN5 and CLN6 disease display the key clinical features of NCL, including a progressive loss of vision. We assessed retinal histology, astrogliosis, and lysosomal storage accumulation in CLN5 affected (CLN5-/-) and CLN6 affected (CLN6-/-) sheep eyes and age-matched controls at 3, 6, 12, and 18 months of age to determine the onset and progression of retinal pathology in NCL sheep. The retina of CLN5-/- sheep shows progressive atrophy of the outer retinal layers, widespread gliosis, and accumulation of lysosomal storage in retinal ganglion cells late in disease. In contrast, CLN6-/- retina shows significant atrophy of all retinal layers, progressive gliosis, and earlier accumulation of lysosomal storage. This study has highlighted the differential vulnerability of retinal layers and the time course of retinal atrophy in two distinct models of NCL disease. This data will be valuable in determining potential targets for ocular therapies and the optimal timing of these therapies for protection from retinal dysfunction and degeneration in NCL.
Neuronal ceroid lipofuscinosis
Gliosis
Batten disease
Lipofuscin
Astrogliosis
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Neuropathology
Astrocytosis
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