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1.
Clin Neuropathol ; 42(6): 212-218, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37840526

RESUMEN

Pick's disease (PiD) is a rare form of frontal temporal lobar degeneration. The pathognomonic feature is atrophy of the frontotemporal lobes and intraneuronal deposits of 3R-τ inclusions, the Pick body. Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome with a heterogeneous spectrum of underlying pathologies. We report a case of clinically diagnosed CBS with a post-mortem diagnosis of PiD and conduct a clinicopathological review of the literature on this unusual presentation.


Asunto(s)
Degeneración Corticobasal , Enfermedad de Pick , Humanos , Enfermedad de Pick/patología , Atrofia , Proteínas tau
2.
Clin Neuropathol ; 41(5): 197-201, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35361329

RESUMEN

A stillbirth fetus with semilobar holoprosencephaly was induced at 24 weeks gestational age. While the eyes appeared unremarkable externally, there was an absence of optic nerves. At the ventral hypothalamicdiencephalic region there was an area of bilateral epithelioid cells containing melanin. Immunohistochemical characterization revealed the cells to be of neuroepithelial origin with features of retinal pigment epithelium. These findings reflect abnormalities in eye development in holoprosencephaly, especially when coupled with other structural defects in the visual system.


Asunto(s)
Holoprosencefalia , Femenino , Feto , Humanos , Melaninas , Embarazo , Retina , Mortinato
3.
Mol Cell Biochem ; 476(7): 2633-2650, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33661429

RESUMEN

Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), can be clinically heterogeneous which may be explained by the co-inheritance of multiple genetic variants that modify the clinical course. In this study we examine variants in three genes in a family with one individual presenting with ALS and lipodystrophy. Sequencing revealed a p.Gly602Ser variant in LMNA, and two additional variants, one each in SETX (g.intron10-13delCTT) and FUS (p.Gly167_Gly168del). These latter genes have been linked to ALS. All family members were genotyped and each variant, and each combination of variants detected, were functionally evaluated in vitro regarding effects on cell survival, expression patterns and cellular phenotype. Muscle biopsy retrieved from the individual with ALS showed leakage of chromatin from the nucleus, a phenotype that was recapitulated in vitro with expression of all three variants simultaneously. Individually expressed variants gave cellular phenotypes there were unremarkable. Interestingly the FUS variant appears to be protective against the effects of the SETX and the LMNA variants on cell viability and may indicate loss of interaction of FUS with SETX and/or R-loops. We conclude that these findings support genetic modifications as an explanation of the clinical heterogeneity observed in human disease.


Asunto(s)
Esclerosis Amiotrófica Lateral , ADN Helicasas , Lamina Tipo A , Lipodistrofia , Enzimas Multifuncionales , Mutación Missense , ARN Helicasas , Proteína FUS de Unión a ARN , Sustitución de Aminoácidos , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , ADN Helicasas/genética , ADN Helicasas/metabolismo , Familia , Femenino , Células HEK293 , Humanos , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Lipodistrofia/genética , Lipodistrofia/metabolismo , Lipodistrofia/patología , Masculino , Enzimas Multifuncionales/genética , Enzimas Multifuncionales/metabolismo , ARN Helicasas/genética , ARN Helicasas/metabolismo , Proteína FUS de Unión a ARN/genética , Proteína FUS de Unión a ARN/metabolismo
4.
Epilepsy Behav ; 118: 107940, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33838622

RESUMEN

OBJECTIVE: To describe morphological characteristics of the brainstem nuclei in response to chronic vagus nerve stimulation (VNS) in patients with refractory epilepsy. BACKGROUND: VNS is a treatment option for individuals with medically refractory epilepsy. While treatment with VNS may achieve up to 50% seizure reduction and is protective against sudden unexpected death in epilepsy (SUDEP), its mechanism of action is not fully understood. Long-term structural and cellular changes in response to VNS have rarely been addressed in humans. METHODS: Four autopsy cases with history of chronic epilepsy treated with VNS (VNS+) and 4 age- and sex-matched chronic epilepsy-related death cases without VNS (VNS-) were included. Detailed clinical and postmortem data were obtained. Serial horizontal sections of the brainstem were prepared and stained with hematoxylin, eosin, and luxol fast blue (HE/LFB). Three regions of interest (ROIs) were delineated, including nucleus tractus solitarius (NTS), locus coeruleus (LC), and the rostral pontine group of raphe nuclei (rRN). Immunohistochemistry studies were performed using antibodies to GFAP, NeuN, HLA-DR, and IBA-1. Immunolabeling index was analyzed. RESULTS: Three of the 4 VNS+ patients and all 4 control (VNS-) patients died of SUDEP. There was no laterality difference in the NeuN, GFAP, HLA-DR and IBA-1 expression in LC and NTS of VNS+ patients. Similarly, there was no difference in the rRN, LC, and NTS between the VNS+ and VNS- groups. CONCLUSION: This study represents the first histopathological study of the long-term effects of VNS therapy in the human brain. There was no difference observed in the neuronal cell number, degree of astrocytosis, and neuroinflammation in the main brainstem vagal afferent nuclei after prolonged VNS treatment in patients with refractory epilepsy.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Estimulación del Nervio Vago , Tronco Encefálico , Epilepsia Refractaria/terapia , Epilepsia/terapia , Humanos , Convulsiones , Resultado del Tratamiento , Nervio Vago
5.
Brain ; 140(9): 2460-2474, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-29050386

RESUMEN

See Jellinger (doi:10.1093/awx190) for a scientific commentary on this article. The enzyme monoamine oxidases (B and A subtypes, encoded by MAOB and MAOA, respectively) are drug targets in the treatment of Parkinson's disease. Inhibitors of MAOB are used clinically in Parkinson's disease for symptomatic purposes whereas the potential disease-modifying effect of monoamine oxidase inhibitors is debated. As astroglial cells express high levels of MAOB, the enzyme has been proposed as a brain imaging marker of astrogliosis, a cellular process possibly involved in Parkinson's disease pathogenesis as elevation of MAOB in astrocytes might be harmful. Since brain monoamine oxidase status in Parkinson's disease is uncertain, our objective was to measure, by quantitative immunoblotting in autopsied brain homogenates, protein levels of both monoamine oxidases in three different degenerative parkinsonian disorders: Parkinson's disease (n = 11), multiple system atrophy (n = 11), and progressive supranuclear palsy (n = 16) and in matched controls (n = 16). We hypothesized that if MAOB is 'substantially' localized to astroglial cells, MAOB levels should be generally associated with standard astroglial protein measures (e.g. glial fibrillary acidic protein). MAOB levels were increased in degenerating putamen (+83%) and substantia nigra (+10%, non-significant) in multiple system atrophy; in caudate (+26%), putamen (+27%), frontal cortex (+31%) and substantia nigra (+23%) of progressive supranuclear palsy; and in frontal cortex (+33%), but not in substantia nigra of Parkinson's disease, a region we previously reported no increase in astrocyte protein markers. Although the magnitude of MAOB increase was less than those of standard astrocytic markers, significant positive correlations were observed amongst the astrocyte proteins and MAOB. Despite suggestions that MAOA (versus MAOB) is primarily responsible for metabolism of dopamine in dopamine neurons, there was no loss of the enzyme in the parkinsonian substantia nigra; instead, increased nigral levels of a MAOA fragment and 'turnover' of the enzyme were observed in the conditions. Our findings provide support that MAOB might serve as a biochemical imaging marker, albeit not entirely specific, for astrocyte activation in human brain. The observation that MAOB protein concentration is generally increased in degenerating brain areas in multiple system atrophy (especially putamen) and in progressive supranuclear palsy, but not in the nigra in Parkinson's disease, also distinguishes astrocyte behaviour in Parkinson's disease from that in the two 'Parkinson-plus' conditions. The question remains whether suppression of either MAOB in astrocytes or MAOA in dopamine neurons might influence progression of the parkinsonian disorders.


Asunto(s)
Encéfalo/enzimología , Dopamina/deficiencia , Monoaminooxidasa/metabolismo , Atrofia de Múltiples Sistemas/metabolismo , Enfermedad de Parkinson/metabolismo , Parálisis Supranuclear Progresiva/metabolismo , Adolescente , Adulto , Estudios de Casos y Controles , Núcleo Caudado/metabolismo , Femenino , Lóbulo Frontal/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Isoenzimas/metabolismo , Masculino , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/patología , Degeneración Nerviosa/patología , Enfermedad de Parkinson/patología , Fragmentos de Péptidos/metabolismo , Fosfopiruvato Hidratasa/metabolismo , Putamen/metabolismo , Sustancia Negra/metabolismo , Parálisis Supranuclear Progresiva/patología , Tubulina (Proteína)/metabolismo , Adulto Joven , alfa-Sinucleína/metabolismo
7.
Clin Neuropathol ; 37(2): 64-67, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29189199

RESUMEN

Cavernous hemangioma in the sellar region is quite rare with only a handful of cases being reported in the English literature. Its clinical manifestations and imaging characteristics can mimic those of a pituitary adenoma. We report two cases of recurrent sellar lesions, both of which were clinically suspected of being pituitary adenomas but histologically confirmed as cavernous hemangiomas. The first case is of a 67-year-old female whose initial resection was diagnosed as "venous angioma". Neuroimaging performed 27 years later demonstrated significant growth of the lesion involving the right cavernous sinus and encasing the right internal carotid artery. The patient then underwent transsphenoidal endoscopic resection of the mass. At the time of the surgery, the lesion was noted to be quite vascular. The second case is a 48-year-old female who underwent emergency resection of a pituitary mass following an apoplectic event. On follow-up 4 years later, the patient reported recurrence of galactorrhea, and MRI had demonstrated regrowth of the mass. She subsequently underwent subtotal resection of the mass. At the time of surgery, brisk bleeding was noted in the operative area. The above two cases demonstrate that cavernous hemangiomas in the sellar region can clinically and radiologically mimic pituitary adenoma and should be considered in the differential diagnosis of hemorrhagic sellar mass.
.


Asunto(s)
Adenoma/diagnóstico , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Adenoma/patología , Anciano , Diagnóstico Diferencial , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Humanos , Persona de Mediana Edad , Neoplasias Hipofisarias/patología
10.
Neuropathology ; 37(4): 321-328, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28276094

RESUMEN

The histopathological features of leucoencephalopathy caused by illicit drugs (such as opioids and cocaine) are well documented in acute cases but not in long-survival cases. There are several hypotheses about the pathogenesis of this disorder, including hypoperfusion, direct drug toxicity resulting from the neurotoxic effects of the drug itself or contaminants in the illicit drug vehicle. We reviewed the post mortem findings in five males (aged 24 to 56 years, with survival intervals ranging from 7 days to 5 months) with a history of illicit drug use and concomitant fatal white matter changes. The histological characteristics of leucoencephalopathy vary with survival period. Prominent axonal injury and axonal spheroids were observed with shorter survival and spongiform changes becoming apparent with longer survival (acute and chronic incomplete infarct pattern). Necrosis was present in all cases and its appearance changed with longer survival (acute and chronic complete infarct pattern). Significant primary demyelination was not observed. These observations suggest that the primary defect in this leucoencephalopathy is hypoxic-ischemic injury, predominantly in the white matter. Spongiform leucoencephalopathy likely represents the longer-survival incomplete infarct pattern and is observed with polydrug abuse.


Asunto(s)
Encéfalo/patología , Hipoxia-Isquemia Encefálica/patología , Drogas Ilícitas/efectos adversos , Leucoencefalopatías/inducido químicamente , Leucoencefalopatías/patología , Adulto , Autopsia , Humanos , Hipoxia-Isquemia Encefálica/etiología , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/patología , Adulto Joven
11.
Neuropathology ; 36(5): 413-420, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26932424

RESUMEN

The underlying pathological process of "ischemic leukoencephalopathy" is not well studied in humans and "demyelination" is thought to represent a major component. We selected brains from autopsy cases with definite histories of recent cardiac arrest, in which the autopsy findings demonstrated gray matter ischemic changes consistent with the survival time. We excluded cases with clinical or pathological evidence of other diseases that may affect the white matter, specifically those with moderate-severe edema. The selected cases were then subjected to a review of the gross pathology (photographs) and microscopy. We used the normal white matter areas in the same brains as internal controls to exclude artefactual changes. Sixteen cases were selected. The pathological changes in acute ischemic leukoencephalopathy include: white matter pallor with separation of myelinated fibers and fine vacuoles, coarse vacuoles with or without attenuated axons, apoptotic nuclei, axonal abnormalities, focal scattered demyelinated axons and infarcts. The interpretation of these findings is controversial (i.e. ischemia, edema, artifact or combination) due to the postmortem nature of the specimens. However, these factors should not affect our interpretation of minimal demyelination in the pathological process. The major underlying pathological process in acute ischemic leukoencephalopathy is axonal degeneration, while demyelination represents only a minor component.


Asunto(s)
Enfermedades Desmielinizantes/patología , Paro Cardíaco/complicaciones , Hipoxia-Isquemia Encefálica/patología , Leucoencefalopatías/patología , Adulto , Anciano , Axones/patología , Enfermedades Desmielinizantes/etiología , Femenino , Humanos , Hipoxia-Isquemia Encefálica/etiología , Leucoencefalopatías/etiología , Masculino , Persona de Mediana Edad , Sustancia Blanca/patología
12.
Neurobiol Dis ; 82: 243-253, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26102022

RESUMEN

Although gliosis is a normal response to brain injury, reports on the extent of astrogliosis in the degenerating substantia nigra in Parkinson's disease (PD) are conflicting. It has also been recently suggested that accumulation of nigral α-synuclein in this disorder might suppress astrocyte activation which in turn could exacerbate the degenerative process. This study examined brain protein levels (intact protein, fragments, and aggregates, if any) of astroglial markers and their relationship to α-synuclein in PD and in the positive control parkinson-plus conditions multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Autopsied brain homogenates of patients with PD (n=10), MSA (n=11), PSP (n=11) and matched controls (n=10) were examined for the astroglial markers glial fibrillary acidic protein (GFAP), vimentin, and heat shock protein-27 (Hsp27) by quantitative immunoblotting. As expected, both MSA (putamen>substantia nigra>caudate>frontal cortex) and PSP (substantia nigra>caudate>putamen, frontal cortex) showed widespread but regionally specific pattern of increased immunoreactivity of the markers, in particular for the partially proteolyzed fragments (all three) and aggregates (GFAP). In contrast, immunoreactivity of the three markers was largely normal in PD in brain regions examined with the exception of trends for variably increased levels of cleaved vimentin in substantia nigra and frontal cortex. In patients with PD, GFAP levels in the substantia nigra correlated inversely with α-synuclein accumulation whereas the opposite was true for MSA. Our biochemical findings of generally normal protein levels of astroglial markers in substantia nigra of PD, and negative correlation with α-synuclein concentration, are consistent with some recent neuropathology reports of mild astroglial response and with the speculation that astrogliosis might be suppressed in this disorder by excessive α-synuclein accumulation. Should astrogliosis protect, to some extent, the degenerating substantia nigra from damage, therapeutics aimed at normalization of astrocyte reaction in PD could be helpful.


Asunto(s)
Astrocitos/metabolismo , Núcleo Caudado/metabolismo , Lóbulo Frontal/metabolismo , Enfermedad de Parkinson/metabolismo , Putamen/metabolismo , Anciano , Biomarcadores/metabolismo , Western Blotting , Electroforesis en Gel de Poliacrilamida , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico , Humanos , Chaperonas Moleculares , Atrofia de Múltiples Sistemas/metabolismo , Parálisis Supranuclear Progresiva/metabolismo , Vimentina/metabolismo
13.
Neurobiol Dis ; 67: 107-18, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24704312

RESUMEN

Animal data show that high doses of the stimulant drug methamphetamine can damage brain dopamine neurones; however, it is still uncertain whether methamphetamine, at any dose, is neurotoxic to human brain. Since gliosis is typically associated with brain damage and is observed in animal models of methamphetamine exposure, we measured protein levels (intact protein and fragments, if any) of markers of microgliosis (glucose transporter-5, human leukocyte antigens HLA-DRα [TAL.1B5] and HLA-DR/DQ/DPß [CR3/43]) and astrogliosis (glial fibrillary acidic protein, vimentin, and heat shock protein-27) in homogenates of autopsied brain of chronic methamphetamine users (n=20) and matched controls (n=23). Intact protein levels of all markers were, as expected, elevated (+28%-1270%, P<0.05) in putamen of patients with the neurodegenerative disorder multiple system atrophy (as a positive control) as were concentrations of fragments of glial fibrillary acidic protein, vimentin and heat shock protein-27 (+170%-4700%, P<0.005). In contrast, intact protein concentrations of the markers were normal in dopamine-rich striatum (caudate, putamen) and in the frontal cortex of the drug users. However, striatal levels of cleaved vimentin and heat shock protein-27 were increased (by 98%-211%, P<0.05), with positive correlations (r=0.41-0.60) observed between concentrations of truncated heat shock protein-27 and extent of dopamine loss (P=0.006) and levels of lipid peroxidation products 4-hydroxynonenal (P=0.046) and malondialdehyde (P=0.11). Our failure to detect increased intact protein levels of commonly used markers of microgliosis and astrogliosis could be explained by exposure to methamphetamine insufficient to cause a toxic process associated with overt gliosis; however, about half of the subjects had died of drug intoxication suggesting that "high" drug doses might have been used. Alternatively, drug tolerance to toxic effects might have occurred in the subjects, who were all chronic methamphetamine users. Nevertheless, the finding of above-normal levels of striatal vimentin and heat shock protein-27 fragments (which constituted 10-28% of the intact protein), for which changes in the latter correlated with those of several markers possibly suggestive of damage, does suggest that some astrocytic "disturbance" had occurred, which might in principle be related to methamphetamine neurotoxicity or to a neuroplastic remodeling process. Taken together, our neurochemical findings do not provide strong evidence for either marked microgliosis or astrogliosis in at least a subgroup of human recreational methamphetamine users who used the drug chronically and shortly before death. However, a logistically more difficult quantitative histopathological study is needed to confirm whether glial changes occur or do not occur in brain of human methamphetamine (and amphetamine) users.


Asunto(s)
Encéfalo/efectos de los fármacos , Estimulantes del Sistema Nervioso Central , Gliosis/inducido químicamente , Metanfetamina , Adolescente , Adulto , Encéfalo/metabolismo , Femenino , Gliosis/metabolismo , Humanos , Masculino , Adulto Joven
14.
Lancet Neurol ; 23(5): 487-499, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38631765

RESUMEN

BACKGROUND: Pick's disease is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. Pick's disease is pathologically defined by the presence in the frontal and temporal lobes of Pick bodies, composed of hyperphosphorylated, three-repeat tau protein, encoded by the MAPT gene. MAPT has two distinct haplotypes, H1 and H2; the MAPT H1 haplotype is the major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy and corticobasal degeneration), and the MAPT H2 haplotype is protective for these disorders. The primary aim of this study was to evaluate the association of MAPT H2 with Pick's disease risk, age at onset, and disease duration. METHODS: In this genetic association study, we used data from the Pick's disease International Consortium, which we established to enable collection of data from individuals with pathologically confirmed Pick's disease worldwide. For this analysis, we collected brain samples from individuals with pathologically confirmed Pick's disease from 35 sites (brainbanks and hospitals) in North America, Europe, and Australia between Jan 1, 2020, and Jan 31, 2023. Neurologically healthy controls were recruited from the Mayo Clinic (FL, USA, or MN, USA between March 1, 1998, and Sept 1, 2019). For the primary analysis, individuals were directly genotyped for the MAPT H1-H2 haplotype-defining variant rs8070723. In a secondary analysis, we genotyped and constructed the six-variant-defined (rs1467967-rs242557-rs3785883-rs2471738-rs8070723-rs7521) MAPT H1 subhaplotypes. Associations of MAPT variants and MAPT haplotypes with Pick's disease risk, age at onset, and disease duration were examined using logistic and linear regression models; odds ratios (ORs) and ß coefficients were estimated and correspond to each additional minor allele or each additional copy of the given haplotype. FINDINGS: We obtained brain samples from 338 people with pathologically confirmed Pick's disease (205 [61%] male and 133 [39%] female; 338 [100%] White) and 1312 neurologically healthy controls (611 [47%] male and 701 [53%] female; 1312 [100%] White). The MAPT H2 haplotype was associated with increased risk of Pick's disease compared with the H1 haplotype (OR 1·35 [95% CI 1·12 to 1·64], p=0·0021). MAPT H2 was not associated with age at onset (ß -0·54 [95% CI -1·94 to 0·87], p=0·45) or disease duration (ß 0·05 [-0·06 to 0·16], p=0·35). Although not significant after correcting for multiple testing, associations were observed at p less than 0·05: with risk of Pick's disease for the H1f subhaplotype (OR 0·11 [0·01 to 0·99], p=0·049); with age at onset for H1b (ß 2·66 [0·63 to 4·70], p=0·011), H1i (ß -3·66 [-6·83 to -0·48], p=0·025), and H1u (ß -5·25 [-10·42 to -0·07], p=0·048); and with disease duration for H1x (ß -0·57 [-1·07 to -0·07], p=0·026). INTERPRETATION: The Pick's disease International Consortium provides an opportunity to do large studies to enhance our understanding of the pathobiology of Pick's disease. This study shows that, in contrast to the decreased risk of four-repeat tauopathies, the MAPT H2 haplotype is associated with an increased risk of Pick's disease in people of European ancestry. This finding could inform development of isoform-related therapeutics for tauopathies. FUNDING: Wellcome Trust, Rotha Abraham Trust, Brain Research UK, the Dolby Fund, Dementia Research Institute (Medical Research Council), US National Institutes of Health, and the Mayo Clinic Foundation.


Asunto(s)
Enfermedad de Pick , Tauopatías , Femenino , Humanos , Masculino , Estudios de Asociación Genética , Haplotipos , Enfermedad de Pick/genética , Proteínas tau/genética
16.
Can J Neurol Sci ; 40(3): 361-5, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23603172

RESUMEN

BACKGROUND: The current methods to predict recurrence and aggressive behaviour of meningiomas rely mainly on histological grading, histological subtype, proliferative index, as well as brain invasion. In many instances, histological grade alone fails to predict recurrence in the grade I and grade II meningiomas. Deletions of 1p and 14q have previously been reported to correlate with poor prognosis in terms of either recurrence or higher histological grades. The Her2neu (ErbB2) amplification has been shown to be a useful predictor of aggressive behaviour in breast and ovarian tumours, but its significance in meningioma is so far uncertain. METHOD: In order to determine the cytogenetic differences between 22 recurrent and 25 non-recurrent meningiomas of all grades, we used fluorescent in situ hybridization (FISH) DNA probes for 1p36, 14q11.2 and 17q11.2-12 (Her2neu) on formalin fixed paraffin embedded (FFPE) tissue from the Brain Tumour Tissue Bank (BTTB), London Health Science Center (LHSC). RESULTS: We showed a positive association for meningioma recurrence correlated with 1p36 deletion plus or minus 14q 11.2 deletions in all grades of meningiomas. The Her2neu amplification was strongly associated with 1p/14q co-deletion in cases of recurrent meningiomas, especially the higher grade tumours. CONCLUSION: These cytogenetic markers can be applied in addition to histological grading for predicting the risk of recurrence and biological behaviour.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 14/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Recurrencia Local de Neoplasia/genética , Receptor ErbB-2/genética , Cromosomas Humanos Par 1/genética , Citogenética , Femenino , Estudios de Asociación Genética , Humanos , Hibridación Fluorescente in Situ , Estudios Longitudinales , Masculino
17.
Cogn Behav Neurol ; 26(3): 146-54, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24077574

RESUMEN

OBJECTIVE: To specify the presenting symptoms and clinical course of patients with frontotemporal dementia (FTD) and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. BACKGROUND: The 2011 discovery of the C9ORF72 repeat expansion causing familial FTD and amyotrophic lateral sclerosis has permitted retrospective evaluation of potential defining clinical characteristics that may distinguish carriers of the C9ORF72 mutation from other patients with FTD. Prior reports identified a subset of patients with FTD who had an unusually high prevalence of psychosis, although their specific symptoms had not yet been fully described. METHODS: From a cohort of 62 patients with FTD, we conducted a retrospective chart review of 7 patients who had C9ORF72 mutations on genetic testing, and 1 untested sibling of a C9ORF72 carrier. RESULTS: Detailed histories revealed a higher prevalence of psychosis, including visual and auditory hallucinations and delusions, in the 8 C9ORF72 carriers than in our patients with sporadic FTD. CONCLUSIONS: This cohort confirms and adds clinical details to the reports of a high prevalence of psychotic phenomena in patients who have C9ORF72 mutations as well as FTD or amyotrophic lateral sclerosis.


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Demencia Frontotemporal/genética , Alucinaciones/genética , Mutación , Proteínas/genética , Trastornos Psicóticos/genética , Adulto , Anciano , Esclerosis Amiotrófica Lateral/epidemiología , Ganglios Basales/patología , Proteína C9orf72 , Corteza Cerebral/patología , Estudios de Cohortes , Comorbilidad , Expansión de las Repeticiones de ADN , Resultado Fatal , Femenino , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/epidemiología , Demencia Frontotemporal/patología , Alucinaciones/epidemiología , Heterocigoto , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Trastornos Psicóticos/epidemiología , Estudios Retrospectivos , Sustancia Negra/patología
18.
Clin Neuropathol ; 32(6): 461-70, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24131748

RESUMEN

AIMS: Pathologists are under increasing pressure to accurately subclassify sarcomas, yet neuropathologists have limited collective experience with rare sarcoma types such as synovial sarcoma. We reviewed 9 synovial sarcomas affecting peripheral nerve diagnosed by neuropathologists and explored the morphologic and immunohistochemical differences between these and MPNST. Our goal was to make practical recommendations for neuropathologists regarding which spindle cell tumors affecting nerve should be sent for SYT-SSX testing. METHODS: Clinical records and genetics were reviewed retrospectively and central pathology review of 9 synovial sarcomas and 6 MPNST included immunohistochemistry for SOX10, S100, BAF47, CK (lmw, pan, CK7, CK19), EMA, CD34, bcl2, CD99, and neurofilament. RESULTS: Common synovial sarcoma sites were brachial plexus, spinal and femoral nerve, none were "intra-neural", all had the SYTSSX1 translocation, and 6/9 were monophasic with myxoid stroma and distinct collagen. Half of the monophasic synovial sarcomas expressed CK7, CK19 or panCK in a "rare positive cells pattern", 8/9 (89%) expressed EMA, and all were SOX10 immunonegative with reduced but variable BAF47 expression. CONCLUSIONS: We recommend that upon encountering a cellular spindle cell tumor affecting nerve neuropathologists consider the following: 1) SYT-SSX testing should be performed on any case with morphology suspicious for monophasic synovial sarcoma including wiry or thick bands of collagen and relatively monomorphous nuclei; 2) neuropathologists should employ a screening immunohistochemical panel including one of CK7, panCK or CK19, plus EMA, S100 and SOX10, and 3) SYT-SSX testing should be performed on any spindle cell tumor with CK and/or EMA immunopositivity if SOX10 immunostaining is negative or only labels entrapped nerve elements.


Asunto(s)
Neoplasias del Sistema Nervioso Periférico/diagnóstico , Sarcoma Sinovial/diagnóstico , Adulto , Anciano , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Periférico/clasificación , Guías de Práctica Clínica como Asunto , Sarcoma Sinovial/clasificación
19.
Am J Forensic Med Pathol ; 34(2): 98-102, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23629390

RESUMEN

Extensive nontraumatic subarachnoid hemorrhage is an important cause of unexpected death in young adults. Segmental arterial mediolysis (SAM) represents an uncommon pathologic finding in the intracranial blood vessels associated with this type of hemorrhage. Segmental arterial mediolysis is a pathologic entity with putative vasospastic etiology, which recently has been reported to be associated with Ehlers-Danlos syndrome type 4. We describe 2 additional cases of ruptured intracranial vertebral artery with features of SAM that resulted in fatal subarachnoid hemorrhage. We also review the literature on vessels with features of SAM that are either intracranial or affecting the internal carotid artery with major direct effects (ie, stroke or transient ischemic attack) on the central nervous system.


Asunto(s)
Aneurisma Intracraneal/patología , Enfermedades Arteriales Intracraneales/patología , Hemorragia Subaracnoidea/patología , Túnica Media/patología , Disección de la Arteria Vertebral/patología , Disección Aórtica/patología , Aneurisma Roto/patología , Fibrosis , Patologia Forense , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Subaracnoidea/etiología , Vacuolas
20.
J Neuropathol Exp Neurol ; 82(4): 296-301, 2023 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-36718578

RESUMEN

The COVID-19 pandemic has had a significant impact on medical services. Many countries postponed nonemergent procedures to preserve hospital resources for the unprecedented situation. Surgical backlogs caused by the COVID-19 pandemic have been evaluated by different groups. However, the impact of this pandemic on pathology and specifically neuropathology (NP) services has received limited attention. In this study, we reviewed all NP reports of the London Health Sciences Centre from January 2018 (2 years before the pandemic declaration) until the end of the year 2021. Demographic information and pathology details were collected. For tumors, site, histopathology types, and WHO grading were analyzed. In nontumoral specimens, pathological diagnoses were compared in pre- and postpandemic time. The total number of NP samples reached its lowest in April 2020, corresponding to the first Ontario provincial lockdown, and fluctuated throughout the studied period. Among the different types of NP surgical specimens, muscle and epilepsy-related specimens showed a more significant reduction, compared to neoplastic specimens. In 2020, the proportion of tumor specimens from patients older than 40 years of age increased. Similarly, the proportion of high-grade glioma and brain metastasis diagnoses also increased. Lastly, we observed a marked increase in biopsies for temporal arteritis and other inflammatory lesions.


Asunto(s)
COVID-19 , Humanos , Canadá/epidemiología , Control de Enfermedades Transmisibles , Pandemias , Biopsia
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