-
Head and Neck Pathology Dec 2022Paragangliomas and pheochromocytomas are rare neuroendocrine tumors, carrying a germ-line mutation in 40% patients. Sclerosis is a rare histological feature in these...
Paragangliomas and pheochromocytomas are rare neuroendocrine tumors, carrying a germ-line mutation in 40% patients. Sclerosis is a rare histological feature in these tumors. We investigated the possible correlations between histological findings, first sclerosis, immunoreactivity for vesicular catecholamine transporters (VMAT1/VMAT2) and patients' genotype in a consecutive series of 57 tumors (30 paragangliomas and 27 pheochromocytomas) from 55 patients. The M-GAPP grading system, sclerosis (0-3 scale) and VMAT1/VMAT2 (0-6 scale) immunoreactivity scores were assessed. Germ-line mutations of Succinate Dehydrogenase genes, RET proto-oncogene and Von Hippel Lindau tumor suppressor gene were searched. A germ-line mutation was found in 25/55 (45.5%) patients, mainly with paraganglioma (N = 14/30, 46,66%). Significant (score ≥ 2) tumor sclerosis was found in 9 (16.1%) tumors, i.e., 7 paragangliomas and 2 pheochromocytomas, most of them (8/9) from patients with a germ-line mutation. M-GAPP score was higher in the mutation status (in 76% of patients involving the SDHx genes, in 12% the RET gene and in the remaining 12% the VHL gene) and in tumors with sclerosis (p < 0.05). Spearman's rank correlation showed a strong correlation of germ-line mutations with M-GAPP (p < 0.0001) and sclerosis (p = 0.0027) scores; a significant correlation was also found between sclerosis and M-GAPP scores (p = 0.029). VMAT1 expression was higher in paragangliomas than in pheochromocytomas (p = 0.0006), the highest scores being more frequent in mutation-bearing patients' tumors (p < 0.01). VMAT2 was highly expressed in all but two negative tumors. Sclerosis and VMAT1 expression were higher in paragangliomas than in pheochromocytomas; tumor sclerosis, M-GAPP and VMAT1 scores were associated to germ-line mutations. Sclerosis might represent a histological marker of tumor susceptibility, prompting to genetic investigations in paragangliomas.
Topics: Humans; Vesicular Monoamine Transport Proteins; Sclerosis
PubMed: 35524772
DOI: 10.1007/s12105-022-01455-4 -
Neurology Apr 2022The identification of possible hippocampal alterations is a crucial point for the diagnosis and therapy of patients with unilateral temporal lobe epilepsy (TLE). This...
BACKGROUND AND OBJECTIVES
The identification of possible hippocampal alterations is a crucial point for the diagnosis and therapy of patients with unilateral temporal lobe epilepsy (TLE). This study aims to investigate the role of neurite orientation dispersion and density imaging (NODDI) compared to diffusion tensor imaging (DTI) in the comprehension of hippocampal microstructure in TLE.
METHODS
DTI and NODDI metrics were calculated in the hippocampi of adult patients with TLE, with and without histology-confirmed hippocampal sclerosis (HS), and in age/sex-matched healthy controls (HC). Diffusion metrics and hippocampal volumes of the pathologic side were compared within participants and between participants among the HS, non-HS, and HC groups. Diffusion metrics were also correlated with hippocampal volume and patients' clinical features. After surgery, hippocampal specimens were processed for neuropathology examinations.
RESULTS
Fifteen patients with TLE (9 with and 6 without HS) and 11 HC were included. Hippocampal analyses resulted in a significant increase in fractional anisotropy (FA) and mean diffusivity (MD; mm/s × 10) and decrease in orientation dispersion index (ODI) comparing the pathologic side of patients with HS and their relative nonpathologic side (0.203 vs 0.183, 0.825 vs 0.724, 0.366 vs 0.443, respectively), the pathologic side of patients without HS (0.203 vs 0.169, 0.825 vs 0.745, 0.366 vs 0.453, respectively), and HC (0.203 vs 0.172, 0.825 vs 0.729, 0.366 vs 0.447, respectively). Moreover, neurite density (ND) was significantly decreased comparing both hippocampi of patients with HS (0.416 vs 0.460). A significant increase in free-water isotropic volume fraction (fiso) was found in the comparison of pathologic hippocampi of patients with HS and nonpathologic hippocampi of patients with HS (0.323 vs 0.258) and HC (0.323 vs 0.226). Hippocampal volume of all patients with TLE negatively correlated with MD ( = -0.746, = 0.0145) and positively correlated with ODI ( = 0.719, = 0.0145). Fiso and ND of sclerotic hippocampi positively correlated with disease duration ( = 0.684, = 0.0424 and = 0.670, = 0.0486, respectively). Immunohistochemistry in sclerotic hippocampal specimens revealed neuronal loss in the pyramidal layer and fiber reorganization at the level of stratum lacunosum-moleculare, confirming ODI and ND metrics.
DISCUSSION
This study shows the capability of diffusion MRI metrics to detect hippocampal microstructural alterations. Among them, ODI seems to better highlight the fiber reorganization observed by neuropathology in sclerotic hippocampi.
Topics: Adult; Atrophy; Diffusion Tensor Imaging; Epilepsy, Temporal Lobe; Hippocampus; Humans; Magnetic Resonance Imaging; Neurites; Sclerosis
PubMed: 35256485
DOI: 10.1212/WNL.0000000000200140 -
Human Brain Mapping Jan 2018Shown in every neuroanatomy textbook, a key morphological feature is the bumpy ridges, which we refer to as hippocampal dentation, on the inferior aspect of the...
Shown in every neuroanatomy textbook, a key morphological feature is the bumpy ridges, which we refer to as hippocampal dentation, on the inferior aspect of the hippocampus. Like the folding of the cerebral cortex, hippocampal dentation allows for greater surface area in a confined space. However, examining numerous approaches to hippocampal segmentation and morphology analysis, virtually all published 3D renderings of the hippocampus show the inferior surface to be quite smooth or mildly irregular; we have rarely seen the characteristic bumpy structure on reconstructed 3D surfaces. The only exception is a 9.4T postmortem study (Yushkevich et al. [2009]: NeuroImage 44:385-398). An apparent question is, does this indicate that this specific morphological signature can only be captured using ultra high-resolution techniques? Or, is such information buried in the data we commonly acquire, awaiting a computation technique that can extract and render it clearly? In this study, we propose an automatic and robust super-resolution technique that captures the fine scale morphometric features of the hippocampus based on common 3T MR images. The method is validated on 9.4T ultra-high field images and then applied on 3T data sets. This method opens possibilities of future research on the hippocampus and other sub-cortical structural morphometry correlating the degree of dentation with a range of diseases including epilepsy, Alzheimer's disease, and schizophrenia. Hum Brain Mapp 39:472-490, 2018. © 2017 Wiley Periodicals, Inc.
Topics: Adult; Algorithms; Epilepsy; Female; Hippocampus; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Middle Aged; Pattern Recognition, Automated; Sclerosis; Young Adult
PubMed: 29058349
DOI: 10.1002/hbm.23856 -
The Journal of Veterinary Medical... May 2022A two-months-old, male, mixed breed cat presented with epileptic seizures. The cat was diagnosed with drug-resistant epilepsy, and died at 3-years of age. No gross...
A two-months-old, male, mixed breed cat presented with epileptic seizures. The cat was diagnosed with drug-resistant epilepsy, and died at 3-years of age. No gross lesion was found at necropsy. Histopathologically, the dentate gyrus granule cell layer of the hippocampus was irregularly arranged. Granule cells were dispersed and ectopic cells were sporadically observed in the molecular layer. The granule cells had an enlarged cytoplasm and swollen nucleus. Immunohistochemistry for NeuN and GFAP confirmed severe neuronal loss and mild gliosis in CA1. Binucleation and ischemic change were observed in the remaining pyramidal cells. This report describes a case of feline temporal lobe epilepsy and hippocampal sclerosis associated with dentate gyrus malformation.
Topics: Animals; Cat Diseases; Cats; Dentate Gyrus; Epilepsy, Temporal Lobe; Gliosis; Hippocampus; Male; Neurodegenerative Diseases; Sclerosis
PubMed: 35342145
DOI: 10.1292/jvms.22-0006 -
Brain : a Journal of Neurology May 2011Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the...
Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P<0.015) and also 5.5-6.5 years before death (P<0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer's disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing.
Topics: Aged, 80 and over; Aging; Alzheimer Disease; Cohort Studies; DNA-Binding Proteins; Female; Hippocampus; Humans; Male; Mental Status Schedule; Neuropsychological Tests; Sclerosis
PubMed: 21596774
DOI: 10.1093/brain/awr053 -
JAMA Dermatology Jul 2019Cutaneous chronic graft-vs-host disease (cGVHD) is common after allogeneic hematopoietic stem cell transplant and is often associated with poor patient outcomes. A... (Observational Study)
Observational Study
IMPORTANCE
Cutaneous chronic graft-vs-host disease (cGVHD) is common after allogeneic hematopoietic stem cell transplant and is often associated with poor patient outcomes. A reliable and practical method for assessing disease severity and response to therapy among these patients is urgently needed.
OBJECTIVE
To evaluate the interrater agreement and reliability of skin-specific and range of motion (ROM) variables of the 2014 National Institutes of Health (NIH) response criteria for cGVHD and a skin sclerosis grading scale (SSG).
DESIGN, SETTING, AND PARTICIPANTS
In this observational study performed at a single tertiary academic center, 6 academic blood and marrow transplant specialists and 4 medical dermatologists examined 8 patients with diagnosed cutaneous cGVHD on July 10, 2015. The patient cohort was enriched for patients with sclerotic features. Each patient was evaluated by using the skin-specific and ROM criteria of the 2014 NIH response criteria for cGVHD and an SSG ranging from 0 to 3. Each patient was also asked to complete quality-of-life scoring instruments. Interrater agreement and reliability were estimated by calculating the Krippendorff α and Cohen κ statistics. Data were analyzed from September 29, 2015, through November 22, 2018.
MAIN OUTCOMES AND MEASURES
Estimation of interrater agreement by interclass coefficient (Krippendorff α and Cohen κ statistics) for the skin-specific and ROM components of the 2014 NIH Response Criteria for Chronic GVHD and for the SSG.
RESULTS
The median age of the patients evaluated was 54 years (range, 46-58 years). Patients were predominantly male (6 [75%]). Six of the 8 patients had a predominantly sclerotic cutaneous phenotype. Interrater agreement among our experts was acceptable for NIH skin feature score (0.68; 95% CI, 0.30-0.86) and good for NIH ROM scoring (0.80; 95% CI, 0.68-0.86). Dermatologists had acceptable agreement for NIH skin GVHD score (0.69; 95% CI, 0.25-0.82) and skin feature score (0.78; 95% CI, 0.17-0.98), good agreement in ROM grading (0.85; 95% CI, 0.69-0.90), and near perfect agreement in identifying sclerosis (0.82; 95% CI, 0.27-0.97).
CONCLUSIONS AND RELEVANCE
Although dermatologists had acceptable agreement in NIH skin GVHD score and skin features score, near perfect agreement in identifying cutaneous sclerosis, better agreement in grading severity of cutaneous cGVHD, especially in the intermediate grades, appears to be needed.
Topics: Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Observer Variation; Quality of Life; Reproducibility of Results; Sclerosis; Severity of Illness Index; Skin Diseases
PubMed: 30994873
DOI: 10.1001/jamadermatol.2018.5459 -
Epilepsia May 2009Familial mesial temporal lobe epilepsy (FMTLE) was first described as a benign syndrome with prominent psychic and autonomic seizures and no association with hippocampal... (Review)
Review
Familial mesial temporal lobe epilepsy (FMTLE) was first described as a benign syndrome with prominent psychic and autonomic seizures and no association with hippocampal sclerosis (HS) or febrile seizures (FS). Better definition of the syndrome allowed identification of more heterogeneous phenotypes with mild to severe epileptic disorders, and a variable association with HS and FS. The genetics of these conditions is largely unknown and the hope for the future is that the identification of FMTLE genes will lead to more appropriate approaches for the diagnosis and treatment of TLE.
Topics: Epilepsy, Temporal Lobe; Gene Expression; Hippocampus; Humans; Phenotype; Sclerosis; Seizures, Febrile
PubMed: 19469849
DOI: 10.1111/j.1528-1167.2009.02123.x -
The Turkish Journal of Gastroenterology... Aug 2023
Topics: Humans; Iridoids; Tomography, X-Ray Computed; Sclerosis
PubMed: 37434401
DOI: 10.5152/tjg.2023.23208 -
Experimental and Clinical... May 2022Encapsulated peritoneal sclerosis is a rare complication of long-term peritoneal dialysis that has a high rate of morbidity and mortality. We present an 18-year-old...
Encapsulated peritoneal sclerosis is a rare complication of long-term peritoneal dialysis that has a high rate of morbidity and mortality. We present an 18-year-old female patient who was first diagnosed with renal failure at 8 years of age and who had 7 years of peritoneal dialysis and then hemodialysis before kidney transplant from a deceased donor. Before transplant, the patient developed encapsulated peritoneal sclerosis and was treated with tamoxifen and steroids. Three years after transplant, the patient presented with complaints of vomiting, abdominal pain, and abdominal distension and was again diagnosed with encapsulated peritoneal sclerosis. The patient required excretory paracentesis, pulse steroid treatment for 3 days, and treatment with methylprednisone and tamoxifen, which resulted in regression of signs and symptoms. Factors such as long-term peritoneal dialysis, a history of bacterial peritonitis, and use of high-concentration dialysate may cause encapsulated peritoneal sclerosis, but symptoms can recur after transplant, as shown in our patient. Thus, it is important to recognize that encapsulated peritoneal sclerosis may cause graft loss due to the various complications that it can cause.
Topics: Adolescent; Female; Humans; Kidney Transplantation; Peritoneal Dialysis; Peritoneal Fibrosis; Peritonitis; Sclerosis; Tamoxifen; Treatment Outcome
PubMed: 35570613
DOI: 10.6002/ect.PediatricSymp2022.O35 -
AJNR. American Journal of Neuroradiology Apr 2020NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant... (Comparative Study)
Comparative Study
BACKGROUND AND PURPOSE
NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis.
MATERIALS AND METHODS
We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology ( = 61) or not having hippocampal sclerosis on pathology ( = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem.
RESULTS
NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; = .99) but a lower sensitivity (69.0% versus 93.0%, < .001). The positive predictive value of NeuroQuant analysis was comparable with visual MR imaging analysis (84.0% versus 89.1%), whereas the negative predictive value was not comparable (79.8% versus 95.0%).
CONCLUSIONS
Visual MR imaging analysis by a neuroradiologist with expertise in epilepsy had a higher sensitivity than did NeuroQuant analysis, likely due to the inability of NeuroQuant to evaluate changes in hippocampal T2 signal or architecture. Given that there was no significant difference in specificity between NeuroQuant analysis and visual MR imaging analysis, NeuroQuant can be a valuable tool when the results are positive, particularly in centers that lack neuroradiologists with expertise in epilepsy, to help identify and refer candidates for temporal lobe epilepsy resection. In contrast, a negative test could justify a case referral for further evaluation to ensure that false-negatives are detected.
Topics: Adult; Bayes Theorem; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Radiologists; Sclerosis; Sensitivity and Specificity; Software
PubMed: 32217554
DOI: 10.3174/ajnr.A6454