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1.
Cell Mol Neurobiol ; 42(8): 2863-2892, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34709498

RESUMEN

Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.


Asunto(s)
Astrocitoma , Esclerosis Tuberosa , Humanos , Astrocitoma/metabolismo , Metilación de ADN/genética , Sirolimus/uso terapéutico , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/genética , Esclerosis Tuberosa/patología
2.
Neuroradiology ; 64(1): 99-107, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34611716

RESUMEN

PURPOSE: Synthetic MRI (SyMRI) enables to quantify brain tissue and morphometry. We aimed to investigate the WM and myelin alterations in patients with unilateral hippocampal sclerosis (HS) with SyMRI. METHODS: Adult patients with isolated unilateral HS and age-matched control subjects (CSs) were included in this study. The SyMRI sequence QRAPMASTER in the coronal plane perpendicular to the hippocampi was obtained from the whole brain. Automatic segmentation of the whole brain was processed by SyMRI Diagnostic software (Version 11.2). Two neuroradiologists also performed quantitative analyses independently from symmetrical 14 ROIs placed in temporal and extratemporal WM, hippocampi, and amygdalae in both hemispheres. RESULTS: Sixteen patients (F/M = 6/10, mean age = 32.5 ± 11.3 years; right/left HS: 8/8) and 10 CSs (F/M = 5/5, mean age = 30.7 ± 7 years) were included. Left HS patients had significantly lower myelin and WM volumes than CSs (p < .05). Myelin was reduced significantly in the ipsilateral temporal lobe of patients than CSs, greater in left HS (p < .05). Histopathological examination including luxol fast blue stain also revealed myelin pallor in all of 6 patients who were operated. Ipsilateral temporal pole and sub-insular WM had significantly reduced myelin than the corresponding contralateral regions in patients (p < .05). No significant difference was found in WM values. GM values were significantly lower in hippocampi in patients than CSs (p < .05). CONCLUSION: SyMRI revealed myelin reduction in the ipsilateral temporal lobe and sub-insular WM of patients with HS. Whether this finding correlates with electrophysiological features and SyMRI could serve as lateralization of temporal lobe epilepsy need to be investigated.


Asunto(s)
Epilepsia del Lóbulo Temporal , Vaina de Mielina , Adulto , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/patología , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Vaina de Mielina/patología , Esclerosis/diagnóstico por imagen , Esclerosis/patología , Adulto Joven
3.
Pituitary ; 25(3): 474-479, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35334029

RESUMEN

PURPOSE: Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas. METHODS: The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy. RESULTS: A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types. CONCLUSIONS: Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.


Asunto(s)
Hipofisitis , Neoplasias Hipofisarias , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Estudios Retrospectivos
4.
Neurocrit Care ; 36(3): 802-814, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34782991

RESUMEN

BACKGROUND: Understanding the secondary damage mechanisms of traumatic brain injury (TBI) is essential for developing new therapeutic approaches. Neuroinflammation has a pivotal role in secondary brain injury after TBI. Activation of NLRP3 inflammasome complexes results in the secretion of proinflammatory mediators and, in addition, later in the response, microglial activation and migration of the peripheral immune cells into the injured brain are observed. Therefore, these components involved in the inflammatory process are becoming a new treatment target in TBI. Dexmedetomidine (Dex) is an effective drug, widely used over the past few years in neurocritical care units and during surgical operations for sedation and analgesia, and has anti-inflammatory effects, which are shown in in vivo studies. The aim of this original research is to discuss the anti-inflammatory effects of different Dex doses over time in TBI. METHODS: Brain injury was performed by using a weight-drop model. Half an hour after the trauma, intraperitoneal saline was injected into the control groups and 40 and 200 µg/kg of Dex were given to the drug groups. Neurological evaluations were performed with the modified Neurological Severity Score before being killed. Then, the mice were killed on the first or the third day after TBI and histopathologic (hematoxylin-eosin) and immunofluorescent (Iba1, NLRP3, interleukin-1ß, and CD3) findings of the brain tissues were examined. Nonparametric data were analyzed by using the Kruskal-Wallis test for multiple comparisons, and the Mann-Whitney U-test was done for comparing two groups. The results are presented as mean ± standard error of mean. RESULTS: The results showed that low doses of Dex suppress NLRP3 and interleukin-1ß in both terms. Additionally, high doses of Dex cause a remarkable decrease in the migration and motility of microglial cells and T cells in the late phase following TBI. Interestingly, the immune cells were influenced by only high-dose Dex in the late phase of TBI and it also improves neurologic outcome in the same period. CONCLUSIONS: In the mice head trauma model, different doses of Dex attenuate neuroinflammation by suppressing distinct components of the neuroinflammatory process in a different timecourse that contributes to neurologic recovery. These results suggest that Dex may be an appropriate choice for sedation and analgesia in patients with TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Dexmedetomidina , Animales , Antiinflamatorios , Lesiones Traumáticas del Encéfalo/complicaciones , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Interleucina-1beta/uso terapéutico , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedades Neuroinflamatorias
5.
Epilepsia ; 62(6): 1416-1428, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33949696

RESUMEN

OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. METHODS: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. RESULTS: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. SIGNIFICANCE: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future.


Asunto(s)
Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Malformaciones del Desarrollo Cortical/patología , Adolescente , Adulto , Edad de Inicio , Diversidad de Anticuerpos , Encéfalo/patología , Niño , Preescolar , Técnica Delphi , Femenino , Genotipo , Humanos , Inmunohistoquímica , Lactante , Imagen por Resonancia Magnética , Masculino , Malformaciones del Desarrollo Cortical/cirugía , Persona de Mediana Edad , Mutación/genética , Procedimientos Neuroquirúrgicos , Variaciones Dependientes del Observador , Fenotipo , Convulsiones/etiología , Adulto Joven
6.
Ann Diagn Pathol ; 55: 151809, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34482218

RESUMEN

Poorly differentiated chordoma is a newly recognized entity in the recent World Health Organization (WHO) classification of tumors of soft tissue and bone. Slightly over 60 such cases have been documented. Herein, we present a clinicopathological profile, including radiological features, of nine cases, which occurred in five males and four females, with age varying from 1 to 29 years (median = 43), in the cervical spine (n = 2), skull base (n = 2), clivus (n = 2), thoracic spine (n = 1) lumbar spine (n = 1) and coccyx (n = 1) Average tumor size was 4.8 cm. None of the 6-referral cases was diagnosed as a poorly differentiated chordoma at the referring laboratory. Histopathologically, all cases displayed a cellular tumor comprising polygonal cells (n = 9) displaying moderate to marked nuclear pleomorphism with prominent nucleoli (n = 7), eosinophilic (n = 9) to vacuolated cytoplasm (n = 7), rhabdoid morphology (n = 4), interspersed mitotic figures (n = 5), focal necrosis (n = 6) and inflammatory cells (n = 9). A single tumor displayed areas resembling classic chordoma, transitioning into poorly differentiated areas. There were multinucleate giant cells and physaliphorous cells in two tumors, each, respectively. Immunohistochemically, tumor cells were positive for AE1/AE3 (7/7), EMA (7/7), cytokeratin (CK) MNF116 (1/1), OSCAR (1/1), brachyury (9/9, diffusely), S100P (4/7, mostly focally), and glypican 3(2/4). SMARCB1/INI1 was completely lost in all nine tumors. A single case tested by FISH showed homozygous deletion of the SMARCB1 gene. Therapeutically (n = 7), all patients were treated with surgical resection (invariably incomplete) (n = 5), followed by adjuvant radiation therapy (n = 4) and chemotherapy (n = 4). While a single patient partially responded to treatment and another patient is alive with no evidence of disease after 23 years, three patients died of disease, six, eight, and 11 months post-diagnosis, despite adjuvant treatments. A single patient presented with a metastatic lung nodule, while another developed widespread metastasis. Poorly differentiated chordomas display a spectrum of features, are associated with a lower index of suspicion for a diagnosis, and display aggressive outcomes. Critical analysis of radiological and histopathological features, including necessary immunostains (brachyury and SMARCB1/INI1), is necessary for their timely diagnosis. These tumors show loss of SMARCB1/INI1 immunostaining and homozygous deletion of INI1/SMARCB1 gene.


Asunto(s)
Cordoma , Proteína SMARCB1 , Adolescente , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Niño , Preescolar , Cordoma/diagnóstico , Cordoma/diagnóstico por imagen , Cordoma/genética , Cordoma/patología , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Metástasis de la Neoplasia/patología , Proteína SMARCB1/análisis , Proteína SMARCB1/genética , Eliminación de Secuencia
7.
Ophthalmic Plast Reconstr Surg ; 37(2): e59-e60, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32618827

RESUMEN

Recurrence of cavernous venous malformation is exceedingly rare. In 1995, a 16-year-old woman was referred for left axial proptosis. Her left visual acuity was 20/200, and there were choroidal folds in the OS. MRI studies showed a well-circumscribed retrobulbar intraconal mass in the left orbit. The tumor was totally removed with intact capsule through a transconjunctival orbitotomy and proved to be a cavernous venous malformation. In 2020, at the age of 41 years and 25 years after the operation, she again presented with left proptosis. Imaging results were very similar to those at first presentation. This tumor was also extirpated in its entirety via an inferior forniceal orbitotomy with the histopathologic diagnosis of a cavernous venous malformation. Her final left visual acuity remained 20/50. Women with orbital cavernous venous malformations, especially those who undergo surgical removal at a relatively young age are advised to have long-term follow up complemented with occasional imaging studies.


Asunto(s)
Exoftalmia , Hemangioma Cavernoso , Neoplasias Orbitales , Adolescente , Adulto , Femenino , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/cirugía , Humanos , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia , Órbita , Neoplasias Orbitales/diagnóstico , Neoplasias Orbitales/cirugía
8.
J Stroke Cerebrovasc Dis ; 30(9): 105997, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34303089

RESUMEN

OBJECTIVES: To identify the underlying genetic defect for a consanguineous family with an unusually high number of members affected by cerebral small vessel disease. MATERIALS AND METHODS: A total of 6 individuals, of whom 3 are severely affected, from the family were clinically and radiologically evaluated. SNP genotyping was performed in multiple members to demonstrate genome-wide runs-of-homozygosity. Coding variants in the most likely candidate gene, HTRA1 were explored by Sanger sequencing. Published HTRA1-related phenotypes were extensively reviewed to explore the effect of number of affected alleles on phenotypic expression. RESULTS: Genome-wide homozygosity mapping identified a 3.2 Mbp stretch on chromosome 10q26.3 where HTRA1 gene is located. HTRA1 sequencing revealed an evolutionarily conserved novel homozygous c.824C>T (p.Pro275Leu) mutation, affecting the serine protease domain of HtrA1. Early-onset of cognitive and motor deterioration in homozygotes are in consensus with CARASIL. However, there was a clear phenotypic variability between homozygotes which includes alopecia, a suggested hallmark of CARASIL. All heterozygotes, presenting as CADASIL type 2, had spinal disk degeneration and several neuroimaging findings, including leukoencephalopathy and microhemorrhage despite a lack of severe clinical presentation. CONCLUSION: Here, we clearly demonstrate that CARASIL and CADASIL type 2 are two clinical consequences of the same disorder with different severities thorough the evaluation of the largest collection of homozygotes and heterozygotes segregating in a family. Considering the semi-dominant inheritance of HTRA1-related phenotypes, genetic testing and clinical follow-up must be offered for all members of a family with HTRA1 mutations regardless of symptoms.


Asunto(s)
Alopecia/genética , CADASIL/genética , Infarto Cerebral/genética , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Leucoencefalopatías/genética , Mutación , Enfermedades de la Columna Vertebral/genética , Adulto , Edad de Inicio , Alopecia/diagnóstico , Alopecia/fisiopatología , CADASIL/diagnóstico , CADASIL/fisiopatología , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatología , Consanguinidad , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Herencia , Heterocigoto , Homocigoto , Humanos , Leucoencefalopatías/diagnóstico , Leucoencefalopatías/fisiopatología , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Índice de Severidad de la Enfermedad , Enfermedades de la Columna Vertebral/diagnóstico , Enfermedades de la Columna Vertebral/fisiopatología
9.
Acta Neuropathol ; 139(1): 193-209, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31563982

RESUMEN

The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.


Asunto(s)
Neoplasias Encefálicas/genética , Glioma/genética , Proteínas Proto-Oncogénicas c-myb/genética , Proteínas Proto-Oncogénicas/genética , Transactivadores/genética , Adulto , Neoplasias Encefálicas/patología , Niño , Preescolar , Variaciones en el Número de Copia de ADN , Metilación de ADN , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Fusión de Oncogenes , Adulto Joven
10.
Epilepsia ; 61(3): 421-432, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32080846

RESUMEN

OBJECTIVE: The microscopic review of hematoxylin-eosin-stained images of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex remains challenging. Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. We trained a convolutional neural network (CNN) to classify both entities and visualize the results. Additionally, we propose a new Web-based deep learning application as proof of concept of how deep learning could enter the pathologic routine. METHODS: A digital processing pipeline was developed for a series of 56 cases of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex to obtain 4000 regions of interest and 200 000 subsamples with different zoom and rotation angles to train a neural network. Guided gradient-weighted class activation maps (Guided Grad-CAMs) were generated to visualize morphological features used by the CNN to distinguish both entities. RESULTS: Our best-performing network achieved 91% accuracy and 0.88 area under the receiver operating characteristic curve at the tile level for an unseen test set. Novel histopathologic patterns were found through the visualized Guided Grad-CAMs. These patterns were assembled into a classification score to augment decision-making in routine histopathology workup. This score was successfully validated by 11 expert neuropathologists and 12 nonexperts, boosting nonexperts to expert level performance. SIGNIFICANCE: Our newly developed Web application combines the visualization of whole slide images with the possibility of deep learning-aided classification between focal cortical dysplasia IIb and tuberous sclerosis complex. This approach will help to introduce deep learning applications and visualization for the histopathologic diagnosis of rare and difficult-to-classify brain lesions.


Asunto(s)
Corteza Cerebral/patología , Aprendizaje Profundo , Epilepsia/patología , Malformaciones del Desarrollo Cortical de Grupo I/patología , Neuronas/patología , Esclerosis Tuberosa/patología , Algoritmos , Área Bajo la Curva , Diagnóstico por Computador , Epilepsia/diagnóstico , Humanos , Internet , Malformaciones del Desarrollo Cortical de Grupo I/diagnóstico , Redes Neurales de la Computación , Neuropatología , Prueba de Estudio Conceptual , Curva ROC , Reproducibilidad de los Resultados , Esclerosis Tuberosa/diagnóstico
11.
Horm Metab Res ; 52(4): 220-227, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32268423

RESUMEN

Primary hypophysitis (PH) is a rare autoimmune inflammatory disease of the pituitary gland. The aim of the study was to evaluate clinical characteristics, disease management, and outcomes of cases with PH. Medical records of PH patients admitted to Hacettepe University Hospital between 1999 and 2017 were analyzed retrospectively. Paraffin-embedded pathology blocks were obtained for both re-examination and IgG4 immunostaining. Twenty PH patients (15 females, 5 males) were evaluated. Mean age at diagnosis was 41.5±13.4 years. Some form of hormonal disorder was present in 63.2% of cases, hypogonadism (66.6%) being the most common. Panhypopituitarism was present in 36.8%. All patients had pituitary gland enlargement on magnetic resonance imaging; stalk thickening and loss of neurohypophyseal bright spot were present in 17.6 and 23.5%, respectively. Lymphocytic hypophysitis was the most common histopathological subtype (50%). Among pathology specimens available for IgG and IgG4 immunostaining (n=10), none fulfilled the criteria for IgG4-related hypophysitis. Four patients were given glucocorticoid treatment in diverse protocols; as initial therapy in 3. Sixteen cases underwent surgery, 7 of whom due to neuro-ophthalmologic involvement. Only 1 patient was observed without any intervention. Reduction of pituitary enlargement was seen in all surgical and glucocorticoid treated cases. None of the surgical patients showed hormonal improvement while one case in glucocorticoid group improved. PH should be considered in the differential diagnosis of sellar masses causing hormonal deficiencies. MRI findings are usually helpful, but not yet sufficient for definitive diagnosis of PH. Treatment usually improves symptoms and reduces sellar masses while hormonal recovery is less common.


Asunto(s)
Hipofisitis , Adulto , Estudios de Cohortes , Femenino , Humanos , Hipofisitis/diagnóstico , Hipofisitis/epidemiología , Hipofisitis/etiología , Hipofisitis/terapia , Hipopituitarismo/diagnóstico , Hipopituitarismo/epidemiología , Hipopituitarismo/etiología , Hipopituitarismo/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Turquía/epidemiología , Adulto Joven
12.
Epilepsy Behav ; 112: 107380, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32882628

RESUMEN

INTRODUCTION: The distribution of hippocampal sclerosis (HS) subtypes, according to the classification of the International League Against Epilepsy (ILAE), has been reported mainly in adult patients. We aimed to review the pathological findings in children who had anterior temporal lobectomy accompanied with amygdalohippocampectomy, in view of the current classification, and evaluate postsurgical outcome with respect to HS subtypes in childhood. METHODS: Seventy children who underwent temporal resections for treatment of medically refractory epilepsy, with a minimum follow-up of 2 years, were included; the surgical hippocampus specimens were re-evaluated under the HS ILAE classification. RESULTS: Neuropathological evaluations revealed HS type 1 in 38 patients (54.3%), HS type 2 in 2 (2.8%), HS type 3 in 21 patients (30%), and no HS in 9 patients (12.9%). Of 70 patients, 23 (32.9%) had dual pathology, and the most common pattern was HS type 3 with low-grade epilepsy-associated brain tumors (LEAT). The distribution of HS types with respect to age revealed that HS type 3 and no HS subgroups had significantly more patients younger than 12 years, compared with those of HS type 1 (90.5%, 77.8% vs 47.4%, respectively). History of febrile seizures was higher in HS type 1. Prolonged/recurrent febrile seizures were most common in patients 12 years and older, whereas LEAT was the most common etiology in patients under 12 years of age (p < 0.001). Patients with HS type 1 had longer duration of epilepsy and an older age at the time of surgery compared with patients with HS type 3 and no HS (p: 0.031, p: 0.007). At final visit, 74.3% of the patients were seizure-free. Seizure outcome showed no significant difference between pathological subtypes. CONCLUSIONS: Our study presents the distribution of HS ILAE subtypes in an exclusively pediatric series along with long-term seizure outcome. The study reveals that the leading pathological HS subgroup in children is HS type 1, similar with adult series. Hippocampal sclerosis type 2 is significantly less in children compared with adults; however, HS type 3 emerges as the second most predominant group because of dual pathology, particularly LEAT. Further studies are required regarding clinicopathological features of isolated HS in pediatric cohort. Seizure-free outcome was favorable and similar in all HS types in children. The proportion of HS types may be better defined in pediatric patients with temporal resections, as the current HS ILAE classification becomes more widely used, and may help reveal the surgical and cognitive outcome with respect to HS types.


Asunto(s)
Epilepsia del Lóbulo Temporal , Adulto , Anciano , Lobectomía Temporal Anterior , Niño , Consenso , Epilepsia del Lóbulo Temporal/etiología , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/cirugía , Hipocampo/patología , Humanos , Estudios Retrospectivos , Esclerosis/patología , Resultado del Tratamiento
13.
Gynecol Endocrinol ; 36(2): 109-116, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31389277

RESUMEN

Pituitary apoplexy (PA) during pregnancy is a rare acute clinical situation which could have life-threatening consequences. Here we reported a case of 26-year-old nulliparous woman presenting with PA at the second trimester of her pregnancy. We also have reviewed reported cases of PA during pregnancy and conducted a detailed discussion on presenting symptoms, underlying pituitary pathology, management of apoplexy during pregnancy and outcomes.


Asunto(s)
Apoplejia Hipofisaria/diagnóstico por imagen , Neoplasias Hipofisarias/diagnóstico por imagen , Complicaciones Neoplásicas del Embarazo/diagnóstico por imagen , Prolactinoma/diagnóstico por imagen , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Apoplejia Hipofisaria/etiología , Neoplasias Hipofisarias/complicaciones , Embarazo , Segundo Trimestre del Embarazo , Prolactinoma/complicaciones
14.
Int J Neurosci ; 129(11): 1139-1144, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31234674

RESUMEN

Aim: The aim of the present study is to investigate the neuroprotective effects of l-Arginine (l-arg) in the seven-day-old rat hypoxia-ischemia model. Materials and methods: L-Arginine (n = 10) or saline (n = 8) was administered intraperitoneally to seven-day-old rats before hypoxia-ischemia. In addition, 18 seven-day-old rats were given l-Arginine (n = 10) or saline (n = 8) after hypoxic-ischemic insult. Neuronal apoptosis was investigated by terminal dUDP-biotin nick end-labeling (TUNEL) following three days of recovery. The ratios of right side numerical density to the sum of right and left sides' numerical densities (right apoptosis index) were calculated for every brain region in rats receiving l-arginine and they were compared with the vehicle groups. Results: Right side apoptosis indexes of the hippocampus (mean ± SD; 35.0 ± 16.1) and striatum (41.9 ± 16.0) were significantly decreased in the l-Arginine post-treatment groups when compared to vehicles (61.0 ± 17.0 and 62.4 ± 27.0 respectively) (p < 0.05). There was no significant difference in the right apoptosis indexes of the cortex between l-Arginine post-treated group and the vehicle group. There were also no significant differences between the right side apoptosis indexes of the l-Arginine pretreatment groups and those of the vehicle group in any of the three regions (p > 0.05). Conclusions: It is concluded that neuronal apoptosis due to hypoxic-ischemic injury may likely to be reduced by post-treatment of l-Arginine in the neonatal rat model and l-Arginine provides a new possibility for neuroprotective strategies based on NO production.


Asunto(s)
Apoptosis/efectos de los fármacos , Arginina/farmacología , Cuerpo Estriado , Hipocampo , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/patología , Fármacos Neuroprotectores/farmacología , Animales , Animales Recién Nacidos , Arginina/administración & dosificación , Cuerpo Estriado/citología , Cuerpo Estriado/efectos de los fármacos , Modelos Animales de Enfermedad , Hipocampo/citología , Hipocampo/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Fármacos Neuroprotectores/administración & dosificación , Ratas , Ratas Wistar
15.
Clin Immunol ; 191: 21-26, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29307770

RESUMEN

Pattern recognition receptors (PRRs), receptors of the innate immune system, are important in interaction with pathogens. Caspase Recruitment Domain-containing protein 9 (CARD9), a member of PRRs, is an intracellular adaptor protein important in fungal defense. CARD9 deficiency causes a rare primary immunodeficiency (PID) characterized by superficial and deep fungal infections. We report a 17year-old female with a homozygous nonsense mutation in CARD9, who presented with severe cerebral fungal infection of the central nervous system. She was also found to have an heterozygous NLRP12 mutation, which may have had add-on effect on the severity of the infection.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD/genética , Infecciones Fúngicas del Sistema Nervioso Central/etiología , Codón sin Sentido , Micosis/etiología , Adolescente , Proteínas Adaptadoras de Señalización CARD/deficiencia , Infecciones Fúngicas del Sistema Nervioso Central/genética , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Micosis/genética
16.
Neuropediatrics ; 49(1): 63-67, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28938499

RESUMEN

Herpes simplex encephalitis (HSE) has been increasingly reported after neurosurgical procedures, mostly after tumor resections in patients with a prior history of HSE. Early detection and appropriate treatment are essential to prevent high mortality of the disease; however, there are diagnostic difficulties due to nonspecific prodromal symptoms. In addition, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been reported after HSE as an immunological relapse. Here, we report a case of postherpetic anti-NMDAR encephalitis following right hemispherotomy for intractable startle-induced seizures, to emphasize the importance of early diagnosis and appropriate treatment. To our knowledge, this is the first reported case of anti-NMDAR encephalitis after postoperative HSE, and the third reported case of hemispherotomy as a curative treatment for startle epilepsy.


Asunto(s)
Epilepsia/etiología , Hemisferectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Adolescente , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico por imagen , Encefalitis Antirreceptor N-Metil-D-Aspartato/cirugía , Epilepsia/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética
17.
Childs Nerv Syst ; 34(5): 877-882, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29455242

RESUMEN

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common autosomal dominantly inherited disorder that affects both the skin and the nervous system. NF1 occurs due to the mutations in the NF1 gene. Neurofibromas are the most common Schwann cell-based tumors in NF1 patients, which are mainly categorized into dermal and plexiform neurofibromas. Studies on different tumor types demonstrate that CXCR4 expression increases in tumor tissues and is linked to metastasis and cancer progression. PURPOSE: In the present study, we aimed to analyze the gene expression of CXCR4, and its ligand CXCL12, in human neurofibromas. METHODS: Eight NF1 patients aged between 5 and 37 (2 males, 6 females) were selected. The patient group comprised 1 plexiform neurofibroma, 1 pheochromocytoma, and 6 dermal neurofibromas. Following pathological examination and diagnosis, tumors were co-stained with antibodies against Schwann cell marker S100 and target molecule CXCR4. CXCR4 expression in Schwann cell-based tumors was detected at the protein level. RNA isolated from the same tumors was used for RT-PCR-based studies to measure the quantitative expression of CXCR4 and CXCL12. RESULTS: CXCR4 gene expression increased 3- to 120-fold and CXCL12 gene expression increased 33- to 512-fold in all human Schwann cell-based tumors. CONCLUSION: In order to validate the role of CXCR4 and its relationship with CXCL12 in NF1, future studies should be performed with additional tumors and different tumor types.


Asunto(s)
Quimiocina CXCL12/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Neurofibroma/patología , Neurofibromatosis 1/patología , Receptores CXCR4/metabolismo , Células de Schwann/metabolismo , Adolescente , Adulto , Quimiocina CXCL12/genética , Niño , Preescolar , Femenino , Humanos , Masculino , Neurofibroma/complicaciones , Neurofibroma/metabolismo , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/metabolismo , Receptores CXCR4/genética , Proteínas S100/metabolismo , Adulto Joven
18.
Int J Neurosci ; 128(5): 421-428, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-28988523

RESUMEN

PURPOSE: There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types. METHODS: 22 patients who had undergone epilepsy surgery due to mesial TLE-HS were included. The sera of patients are tested for neuronal antibodies to N-methyl-D-aspartate receptors (NMDAR), leucine-rich, glioma inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid B receptor (GABABR) and glutamic acid decarboxylase (GAD). Pathological and immunohistochemical investigations including neuronal nuclei (NeuN), NMDAR, GAD, glial fibrillary acidic protein (GFAP), CD8+-CD3+ lymphocytes and immunoglobulin G (IgG) were done. Patients were grouped according to type of HS. Clinical features and immunohistochemical changes were defined in these groups. RESULTS: Available sera of 15 patients did not have any neuronal antibodies. Thirteen of 22 patients had HS type 1, three had HS type 2 and two had HS type 3. According to immunohistochemical investigations CD3+ and CD8+ T cell infiltration was more prominent in the hippocampus of patients with classical HS (International League Against Epilepsy (ILAE) Type 1 HS) and there was a significant negative correlation between epilepsy duration and numbers of CD3+-CD8+ lymphocytes in temporal lobe parenchyma. CONCLUSION: The role of T cell-mediated immunopathology and immunopathological difference in a variety of drug resistant TLE-H2S patients was suggested. These findings can be helpful in understanding the epileptogenicity of HS.


Asunto(s)
Epilepsia del Lóbulo Temporal/sangre , Epilepsia del Lóbulo Temporal/inmunología , Hipocampo/patología , Inmunoglobulina G/sangre , Linfocitos/metabolismo , Adolescente , Adulto , Antígenos CD/inmunología , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Glutamato Descarboxilasa/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Proteínas del Tejido Nervioso/inmunología , Receptores de Superficie Celular/inmunología , Estudios Retrospectivos , Esclerosis/clasificación , Esclerosis/etiología , Esclerosis/patología , Estadística como Asunto , Lóbulo Temporal/metabolismo , Lóbulo Temporal/patología , Adulto Joven
19.
Clin Neuropathol ; 36(5): 227-232, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28502320

RESUMEN

Atypical teratoid rhabdoid tumor (AT/RT) is a rare and aggressive tumor usually occurring at younger ages. Pleomorphic xanthoastrocytomas (PXA) on the other hand are quiescent tumors with benign behavior. AT/RTs arising in the setting of PXA are exceptional. We present the case of a 23-year-old female patient, the fourth in the literature, speculated as having AT/RT arising within a PXA, as demonstrated by the presence of INI1 mutation. The patient presented with a short history of headache, which increased over time, and emerging seizures. She had a contrast-enhancing mass in the left temporal area demonstrated by MRI. Pathological examination demonstrated a dimorphic tumor containing a spindle-pleomorphic component reminiscent of PXA and a rhabdoid component with INI1 loss showing features of AT/RT. Both components shared the same BRAF mutation, supporting their common origin, and hence the case was speculated as an AT/RT arising in the setting of a PXA by secondary genetic change of inactivation of INI1. She had a poor outcome despite surgery and died 8 months after her diagnosis.
.


Asunto(s)
Astrocitoma/patología , Neoplasias Encefálicas/patología , Neoplasias Primarias Múltiples/patología , Tumor Rabdoide/patología , Teratoma/patología , Astrocitoma/genética , Neoplasias Encefálicas/genética , Resultado Fatal , Femenino , Humanos , Mutación , Neoplasias Primarias Múltiples/genética , Proteínas Proto-Oncogénicas B-raf/genética , Tumor Rabdoide/genética , Teratoma/genética , Adulto Joven
20.
Acta Neurochir (Wien) ; 158(5): 933-42, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26970763

RESUMEN

BACKGROUND: We report herein a retrospective analysis of the results of 142 consecutive prolactinoma cases operated upon using an endoscopic endonasal trans-sphenoidal approach over a period of 6 years. METHODS: Medical records of 142 cases were analysed with respect to indications for surgery, duration of hospital stay, early remission rates, failures and recurrence rates during a median follow-up of 36 months. RESULTS: On the basis of magnetic resonance imaging (MRI) data, 19 patients (13.4 %) had microadenoma, 113 (79.6 %) had macroadenoma, and the remaining 10 (7.0 %) had giant adenomas. Cavernous sinus invasion was identified in 25 patients by MRI and confirmed during surgery. Atypical adenoma was diagnosed in 16 patients. Sparsely granulated prolactin adenoma was identified in 99 patients (69.7 %). Our results demonstrate that male sex and higher preoperative prolactin levels are independent factors predicting persistent disease. The post-surgical complications are as follows: 2.8 % patients had meningitis, 2.1 % patients had postoperative cerebrospinal fluid leak and 2.1 % patients had panhypopituitarism. At the end of follow-up, 74.6 % patients went into remission. During follow-up period, five patients who had initial remission developed recurrence. CONCLUSIONS: Our series together with literature data suggest that an endoscopic endonasal trans-sphenoidal approach in the treatment of proloctinomas has a favourable rate of remission. According to the findings of this study, endoscopic endonasal trans-sphenoidal surgery might be an appropriate therapy choice for patients with prolactinoma who could not have been managed with recommended therapeutic modalities.


Asunto(s)
Pérdida de Líquido Cefalorraquídeo/etiología , Endoscopía/efectos adversos , Hipopituitarismo/etiología , Meningitis/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Neoplasias Hipofisarias/cirugía , Prolactinoma/cirugía , Adulto , Anciano , Endoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Resultado del Tratamiento
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