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Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (n = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (n = 14), auditory (n = 12) and visual + auditory pathways (n = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (n = 45) identified a homoplasmic variant (MT-ND6) and a heteroplasmic variant (MT-COI) in one patient each. CES (n = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (n = 27), deafness (n = 7), ataxia (n = 4), and mitochondrial phenotypes (n = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN.
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Ataxia , DNA Mitocondrial , Humanos , Masculino , Feminino , DNA Mitocondrial/genética , Adulto , Pessoa de Meia-Idade , Ataxia/genética , Adolescente , Doenças Mitocondriais/genética , Adulto Jovem , Mitocôndrias/genética , Criança , Idoso , Sequenciamento do Exoma , FenótipoRESUMO
PURPOSE: Glioblastoma (GBM) is a highly invasive tumor. Despite advances in treatment modalities, tumor recurrence is common, seen mainly in the peritumoral brain zone (PBZ). We aimed to molecularly characterize PBZ, to understand the pathobiology of tumor recurrence. METHODS/PATIENTS: We selected eight differentially regulated genes from our previous transcriptome profiling study on tumor core and PBZ. Expression of selected genes were validated in GBM (tumor core and PBZ, n = 37) and control (n = 22) samples by real time quantitative polymerase chain reaction (qPCR). Serine protease inhibitor clade A, member 3 (SERPINA3) was selected for further functional characterization in vitro by gene knockdown approach in glioma cells. Its protein expression by immunohistochemistry (IHC) was correlated with other clinically relevant GBM markers, patient prognosis and tumor recurrence. RESULTS: The mRNA expression of selected genes from the microarray data validated in tumor core and PBZ and was similar to publicly available databases. SERPINA3 knock down in vitro showed decreased tumor cell proliferation, invasion, migration, transition to mesenchymal phenotype, stemness and radioresistance. SERPINA3 protein expression was higher in PBZ compared to tumor core and also was higher in older patients, IDH wild type and recurrent tumors. Finally, its expression showed positive correlation with poor patient prognosis. CONCLUSIONS: SERPINA3 expression contributes to aggressive GBM phenotype by regulating pro-tumorigenic actions in vitro and is associated with adverse clinical outcome.
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Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Serpinas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Tolerância a Radiação/genética , Serpinas/genética , Transcriptoma , Adulto JovemRESUMO
Rosette-forming glioneuronal tumor is a rare World Health Organization grade I neoplasm, primarily involving the posterior fossa. Most cases have been reported in young adults. Although maximal surgical resection is advocated, a precise treatment modality is yet to be established. We describe an unusual presentation of rosette-forming glioneuronal tumor occurring in the optic pathway in a child. As the site of the tumor was not amenable to resection, he underwent radiotherapy and is currently well on follow-up.
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Doenças do Sistema Nervoso/patologia , Neoplasias do Nervo Óptico/patologia , Formação de Roseta/estatística & dados numéricos , Criança , Humanos , Masculino , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/radioterapia , Neoplasias do Nervo Óptico/complicações , Neoplasias do Nervo Óptico/radioterapia , Prognóstico , Radioterapia/métodosRESUMO
Stroke is a major cause of mortality and morbidity with a wide variety of etiological risk factors. Cerebral small vessel disease (SVD) is an important cause of stroke in the young with several hereditary disorders affecting these small blood vessels. Mutations in the COL4A1 gene (COL4A1) have been shown to be associated with a broad range of disorders including hemorrhagic stroke, myopathy, glaucoma and others. We report a rare case of stroke in an intellectually disabled 18-year-old girl with radiological evidence of basal ganglia microbleeds, periventricular white matter signal changes and porencephalic cyst. Ophthalmic examination revealed bilateral microcornea and Axenfeld-Rieger anomaly. At autopsy there were hemorrhagic lesions at multiple sites within the brain. Histology revealed thickened small-caliber vessels which demonstrated disruption and fragmentation of the basement membrane by collagen type IV alpha 1 immunohistochemistry and by electron microscopy. A missense COL4A1 mutation involving glycine residue was detected in the patient. The present case illustrates the clinicopathological spectrum of COL4A1-related cerebral SVD presenting as hemorrhagic stroke in the young with porencephaly, intellectual disability, and Axenfield-Rieger anomaly and thus adds to the clinical heterogeneity of this genetic disorder.
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Doenças de Pequenos Vasos Cerebrais/genética , Colágeno Tipo IV/genética , Hemorragias Intracranianas/genética , Mutação/genética , Acidente Vascular Cerebral/genética , Adolescente , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Feminino , Humanos , Hemorragias Intracranianas/diagnóstico por imagemRESUMO
INTRODUCTION: CNS embryonal tumors comprise a group of highly malignant neoplasms with a wide spectrum of histomorphological entities that includes Medulloblastoma (MB), Atypical Teratoid/Rhabdoid Tumor (AT/RT), Neuroblastoma (NB), Ganglioneuroblastoma (GNB), Embryonal Tumor with Multilayered Rosettes (ETMR), and the embryonal tumor-Not Otherwise Specified (NOS). The entity ETMR includes previously described histopathologic patterns-Embryonal Tumor with Abundant Neuropil and True Rosettes (ETANTR), Ependymoblastoma (EBL), and Medulloepithelioma (MEPL). Based on the histopathological similarities (multilayered rosettes) among ETANTR, EBL, and MEPL, as well as uniform clinical behavior and common molecular genetic characteristics, the WHO revision has created a new entity, "ETMR." Immunoreactivity of LIN28A has been identified as a sensitive tool for the diagnosis of this entity. Since there is a paucity of literature regarding immunoreactivity of LIN28A across all embryonal CNS tumors, the present study was undertaken. MATERIALS AND METHODS: During the 5-year study period (2012 to 2016), all the embryonal tumors (MB, AT/RT, other embryonal tumors-ETANTR, MEPL, PNET) that had been earlier diagnosed in the department of neuropathology (cases operated in our institute as well as received as referral) were reviewed. The archived Hematoxylin and Eosin (H&E) and the available immunohistochemistry (IHC) sections were studied. Further, for the other embryonal tumors where the paraffin blocks were available, an extended panel of IHC was performed for confirming the diagnosis of embryonal tumor and only confirmed cases were included in the study. The demographic details of the study cohort were noted. IHC for LIN28A was performed on conventional sections. RESULTS: A total of 396 cases of embryonal tumors including 302 MB, 72 AT/RT, and 22 other embryonal tumors were diagnosed during the study period. Among these, 80 MB, 35 AT/RT, 4 ETANTR, 1 MEPL, 4 NB, 2 GNB, and 1 CNS embryonal tumor-NOS (total-127) were included for the study. LIN28A immunoreactivity was absent in all MB, GNB, NB, and CNS embryonal tumors-NOS whereas all cases of ETMR (4 ETANTR, 1 MEPL) and 8/35 (23%) of AT/RT showed immunopositivity for LIN28A, which was patchy and distinct in most of the cases of ETMR. CONCLUSION: Our study reiterates that LIN28A is a sensitive IHC marker for the diagnosis of ETMR. We also show that among CNS embryonal tumors, LIN28A is not specific to ETMRs and such immunoreactivity can also be seen in a proportion of AT/RTs.
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Biomarcadores Tumorais/análise , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Proteínas de Ligação a RNA/biossíntese , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/análise , Estudos Retrospectivos , Tumor Rabdoide/diagnóstico , Sensibilidade e Especificidade , Teratoma/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Hospital-based cancer registries (HBCRs) provide information on the magnitude and distribution of cancers in a given hospital. Hospital-based brain tumor registry (HBBTR) data on primary intracranial tumors from a tertiary care neurological center is presented. This is compared with related national and international data. MATERIALS AND METHODS: Data of patients operated for brain tumors at the National Institute of Mental Health and Neurosciences, Bangalore, India, between January 2010 and December 2014 was collected. Patients' clinical details and histopathological diagnosis were recorded. Data was analyzed and compared with that of Tata Memorial Hospital (TMH), Mumbai, and the Central Brain Tumor Registry of the United States (CBTRUS). RESULTS: A total of 4295 primary intracranial tumors in 1847 (43%) females and 2448 (57%) male patients were recorded. Pediatric and adult patients accounted for 16.2% and 83.8% of the cases, respectively. The maximum proportion of tumors was noted in the fourth decade. Among children, astrocytomas (25.1%), embryonal (20.6%), and ependymal tumors (14.8%) were the most frequently reported histology. In adults, meningiomas (23.2%), glioblastomas (15.5%), and nerve sheath tumors (12.7%) were common. Glioblastomas and all other tumors showed a male predilection whereas meningiomas presented more commonly in females. While our HBBTR followed similar trends as TMH data, marked difference was seen in the median age of some tumor subtypes when compared to CBTRUS. CONCLUSION: This HBBTR data gives a glimpse of the prevalence of varied primary intracranial tumors. Such data can be linked to other HBCRs and population-based cancer registries in India for improved research and policy-making decisions.
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Neoplasias Encefálicas/epidemiologia , Glioblastoma/epidemiologia , Meningioma/epidemiologia , Adolescente , Fatores Etários , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Feminino , Glioblastoma/cirurgia , Humanos , Índia/epidemiologia , Masculino , Meningioma/cirurgia , Prevalência , Sistema de Registros , Atenção Terciária à SaúdeRESUMO
INTRODUCTION: Microsporidial myositis is a rare opportunistic infection that has been reported in HIV-infected and HIV-uninfected immunocompromised patients. METHODS: In this study we present a retrospective analysis of 5 cases of microsporidial myositis in HIV-infected patients, including the clinical, laboratory, and histologic features, and a review of the literature. RESULTS: Five young men with HIV infection [median CD4 count of 20 cells (range 14-144)/mm(3) ] who presented with signs and symptoms suggestive of myositis underwent EMG-NCV and muscle biopsy, which revealed signs compatible with microsporidial myositis. Early and aggressive treatment led to improvement in 3 patients. Two of the 5 patients died due to a delay in diagnosis, because the spores were mistaken for Candida without confirmatory stains or a high index of suspicion. CONCLUSIONS: Myositis in HIV-infected patients with low CD4 counts should be evaluated using muscle biopsy. A high index of suspicion is required for early diagnosis of microsporidial myositis in HIV-infected patients. Early diagnosis and immediate, aggressive treatment are the keys to favorable outcomes in these patients.
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Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Microsporidiose/complicações , Polimiosite/diagnóstico , Polimiosite/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Anti-Infecciosos/uso terapêutico , Antirretrovirais/uso terapêutico , Biópsia , Contagem de Linfócito CD4 , Evolução Fatal , Infecções por HIV/patologia , Humanos , Masculino , Microsporídios/isolamento & purificação , Músculo Esquelético/microbiologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Polimiosite/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Neurocutaneous melanocytosis (NCM) is a rare, sporadic neuroectodermal dysplasia characterized by the presence of large or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. Hitherto, unreported we describe a case of NCM with optic neuropathy and spinal cord melanoma from India. A 20 year-old-lady had headache and vomiting for 3 months followed by consecutive profound painless visual impairment. Visual acuity was counting of fingers at 1 m distance in both eyes with normal fundus. There were no symptoms of spinal cord involvement. Clinical examination showed multiple small to large melanocytic nevi over the face and body. Muscle power was normal. Tendon reflexes were exaggerated. Visual evoked potential showed bilateral prolonged P100 latency (Right eye - 144 msec; Left eye - 151 msec). Brain MRI revealed leptomeningeal enhancement of brainstem, cerebellum, oculomotor and facial-abducent nerve complex without optic nerve involvement. MRI spine showed extensive dorsal thoracic cord epidural lesion extending along the entire thoracic cord segment with dorsal cord compression. Positron Emission Tomography (PET) imaging showed Fludeoxyglucose F18 (FDG) avidity along D1-D12 levels of spinal cord. Biopsy from the cord lesion was suggestive of meningeal melanoma. Here we document a rare case of late onset NCM with intracranial meningeal infiltration and asymptomatic large epidural lesion of spinal cord, expanding its phenotypic spectrum. Optic neuropathy in NCM has not been reported earlier. Periodic screening of brain and spine is recommended for early prognostication and lesion identification in NCM.
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Charcot-Marie-Tooth disease 4H(CMT4H) is an autosomal recessive demyelinating form of CMT caused by FGD4/FRABIN mutations. CMT4H is characterized by early onset and slowly progressing motor and sensory deficits in the distal extremities, along with foot deformities. We describe a patient with CMT4H who presented with rapidly progressing flaccid quadriparesis during the postpartum period, which improved significantly with steroid therapy. Magnetic resonance imaging and ultrasonography demonstrated considerable nerve thickening with increased cross-sectional area in the peripheral nerves. A nerve biopsy revealed significant demyelination and myelin outfolding. This is the first report of an Indian patient with a novel homozygous nonsense c.1672C>T (p.Arg558Ter) mutation in the FGD4 gene, expanding the mutational and phenotypic spectrum of this disease.
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Doença de Charcot-Marie-Tooth , Feminino , Humanos , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Proteínas dos Microfilamentos/genética , Linhagem , Mutação , Fenótipo , Fatores de Troca do Nucleotídeo Guanina/genéticaAssuntos
Eosinófilos/patologia , Neurocisticercose/fisiopatologia , Medula Espinal/patologia , Tuberculose Meníngea/diagnóstico , Algoritmos , Feminino , Seguimentos , Humanos , Hipertensão Intracraniana/complicações , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neurocisticercose/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Tomógrafos Computadorizados , Tuberculose Meníngea/complicaçõesRESUMO
Mucopolysaccharidosis IIID (MPS IIID/Sanfilippo syndrome D, OMIM # 252940) is an autosomal recessive lysosomal storage disorder (LSD) and the rarest form of the mucopolysaccharidosis (MPS) III subtypes. It is caused by sequence variations in the gene encoding lysosomal enzyme N-acetyl glucosamine-6-sulphatase (GNS). Deficiency of GNS impairs catabolism of glycosaminoglycans causing accumulation of heparan sulphate within lysosomes of various tissues, which is visualized as membranous cytoplasmic bodies (MCBs) on electron microscopy. The recognition of this ultrastructural feature in a muscle biopsy instigated genetic evaluation for LSD in our case resulting in the detection of a novel pathogenic GNS gene variant. The patient also exhibited intellectual disability since childhood, reduced vision due to pigmentary retinopathy, and behavioral abnormalities without other systemic features of MPS. In this study, we report a patient of Indian origin with MPS IIID based on a novel pathogenic variant c.1078 G>T (p.G360C) in the GNS and the presence of MCBs in muscle biopsy, characterized by several novel findings including the occurrence of pigmentary retinopathy, which extends the clinical spectrum of MPS IIID.
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Mucopolissacaridose III , Retinose Pigmentar , Humanos , Criança , Mucopolissacaridose III/genética , Mucopolissacaridose III/diagnóstico , Mucopolissacaridose III/patologia , Glicosaminoglicanos/metabolismo , Genômica , Reconhecimento PsicológicoRESUMO
Background: SH3TC2 variations lead to demyelinating recessive Charcot-Marie-Tooth (CMT) disease, which is commonly associated with early-onset scoliosis and cranial neuropathy. Data from Indian ethnicity is limited. Objective: We aim to report the characteristics of patients with SH3TC2-associated neuropathy from an Indian cohort. Patients and Methods: Data of five unrelated subjects with SH3TC2 variations were analyzed. Results: Clinical features included female predominance (n = 4), early-onset neuropathy (n = 2), pes cavus and hammer toes (n = 4), kyphoscoliosis (n = 1), impaired vision and hearing (n = 1), facial muscle weakness (n = 1), impaired kinaesthetic sense (n = 3), tremor (n = 2), and ataxia (n = 1). Four patients had the "CMT" phenotype, while one patient had Roussy-Levy syndrome. All had demyelinating electrophysiology with conduction velocities being "very slow" in one, "slow" in one, "mildly slow" in two, and "intermediate" in one patient. Brain stem auditory evoked potentials were universally abnormal though only one patient had symptomatic deafness. Seven variants were identified in SH3TC2 [homozygous = 3 (c.1412del, c.69del, c.3152G>A), heterozygous = 4 (c.1105C>T, c.3511C>T, c.2028G>C, c.254A>T)]. Except for c.3511C>T variant, the rest were novel. Three patients had additional variations in genes having pathobiological relevance in other CMTs or amyotrophic lateral sclerosis. Conclusion: We provide data on a cohort of patients of Indian origin with SH3TC2 variations and highlight differences from other cohorts. Though the majority were not symptomatic for hearing impairment, evoked potentials disclosed abnormalities in all. Further studies are required to establish the functional consequences of novel variants and their interacting molecular partners identified in the present study to strengthen their association with the phenotype.
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Doença de Charcot-Marie-Tooth , Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Feminino , Masculino , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Fenótipo , Doença de Charcot-Marie-Tooth/genética , Fenômenos EletrofisiológicosRESUMO
Background and Objectives: Charcot-Marie-Tooth (CMT) disease is the commonest inherited neuromuscular disorder and has heterogeneous manifestations. Data regarding genetic basis of CMT from India is limited. This study aims to report the variations by using high throughput sequencing in Indian CMT cohort. Methods: Fifty-five probands (M:F 29:26) with suspected inherited neuropathy underwent genetic testing (whole exome: 31, clinical exome: 17 and targeted panel: 7). Their clinical and genetic data were analysed. Results: Age at onset ranged from infancy to 54 years. Clinical features included early-onset neuropathy (n=23), skeletal deformities (n=45), impaired vision (n=8), impaired hearing (n=6), facial palsy (n=8), thickened nerves (n=4), impaired cognition (n=5), seizures (n=5), pyramidal signs (n=7), ataxia (n=8) and vocal cord palsy, slow tongue movements and psychosis in one patient each. Twenty-eight patients had demyelinating electrophysiology. Abnormal visual and auditory evoked potentials were noted in 60.60% and 37.5% respectively. Sixty two variants were identified in 37 genes including variants of uncertain significance (n=34) and novel variants (n=45). Eleven patients had additional variations in genes implicated in CMTs/ other neurological disorders. Ten patients did not have variations in neuropathy associated genes, but had variations in genes implicated in other neurological disorders. In seven patients, no variations were detected. Conclusion: In this single centre cohort study from India, genetic diagnosis could be established in 87% of patients with inherited neuropathy. The identified spectrum of genetic variations adds to the pool of existing data and provides a platform for validation studies in cell culture or animal model systems.
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OBJECTIVES: We aimed to evaluate the expression pattern of chitinase 3-like 2 (CHI3L2) in the tumor core and peritumoral brain zone (PBZ) of newly diagnosed glioblastoma (GBM) in recurrent tumors and its association with patient prognosis. METHODS: The study was conducted on three sample sets derived from different patient cohorts. Messenger RNA (mRNA) expression of CHI3L2 in the tumor core and PBZ (n = 34) compared with control (n = 20) tissues was studied by quantitative polymerase chain reaction in sample set 1. Sample set 2 included 19 paired, primary-recurrent GBM tissues. Sample set 3 comprised 82 GBM tissues of patients with treatment and follow-up information. Immunohistochemistry (IHC) was performed on all three sample sets. RESULTS: mRNA expression of CHI3L2 was significantly higher in the tumor core and PBZ compared with control (P < .0001). By IHC, CHI3L2 showed strong cytoplasmic staining in tumor cells. Recurrent tumors had a higher expression of CHI3L2 compared with primary tumors (P = .007). Survival analysis showed CHI3L2 expression was associated with shorter overall survival (P = .034) and progression-free survival (P = .010), which was in line with The Cancer Genome Atlas cohort (P = .043). CONCLUSIONS: High expression of CHI3L2 in the tumor core and PBZ, as well as its association with tumor recurrence and poor patient prognosis, suggests it might be contributing to tumor spread and recurrence.
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Neoplasias Encefálicas , Quitinases , Glioblastoma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Quitinases/genética , Glioblastoma/diagnóstico , Glioblastoma/genética , Humanos , Recidiva Local de Neoplasia/metabolismo , Prognóstico , RNA MensageiroRESUMO
Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological and auditory manifestations usually precede the involvement of other sites. Patients may manifest with "complete" or "incomplete" syndrome. We report two patients who presented with acute headache and impaired vision. Fundus examination revealed optic disc hyperemia and exudative retinal detachment which provided a clue for the diagnosis at the bedside. Fundus fluorescein angiogram (FFA) revealed abnormal dye leakage, whereas B scan showed choroid thickening. Cerebrospinal fluid (CSF) pleocytosis contrasted with unremarkable brain magnetic resonance imaging and lack of meningeal signs. Melanophagocytosis was evidenced by melanin-laden macrophages in CSF and skin biopsy. This finding is specific for VKH syndrome and helps to clinch the diagnosis even when the complete syndrome is not present cross-sectionally. VKH syndrome should be suspected in patients with aseptic meningitis if tests for common infectious and immune-mediated diseases are negative.
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BACKGROUND: Perls Prussian blue stain (PPB) for hemosiderin, a marker of vascular injury is often employed as an adjunct in the diagnosis of vasculitic neuropathies. However, inflammation/vascular injury is also seen in leprosy, immune mediated, paraproteinemic, diabetic neuropathies, etc. The frequency of detection of hemosiderin in these neuropathies and its utility in diagnosis of vasculitis has not been explored. OBJECTIVE: We evaluated 208 peripheral nerve biopsies for hemosiderin deposits by PPB stain in vasculitis (78) and compared with inflammatory/immune neuropathies [leprous neuritis-32, chronic inflammatory demyelinating polyneuropathy (CIDP)-15, paraproteinemic neuropathies (POEMS)-12, diabetic neuropathy-37] and nonimmune neuropathies [Charcot-Marie-Tooth (CMT) disease-15, vitamin B12 deficiency-7, and ischemic neuropathy in aged-12)]. RESULTS: Hemosiderin deposits were most frequent in vasculitis (48.72%) [59.2% in systemic; 43.1% in nonsystemic vasculitides] and enhanced the sensitivity of diagnosis in "probable" vasculitis (34.48%) that lacked transmural inflammation. Hemosiderin was also detected in infectious/immune-mediated neuropathies (leprous neuritis-56%, POEMS-33.3%, diabetes-18.9%) but absent in CMT, B12 deficiency, and ischemic neuropathy. Hemosiderin deposits involved epineurium in vasculitis, compared to endoneurial/perineurial location in leprosy and perineurial in POEMS and diabetic neuropathy. The sensitivity of detection was high in vasculitic neuropathy (49.35%) compared to other inflammatory neuropathies (22.3%) (P < 0.05) with high specificity (77.69% [positive predictive value (PPV)-56.71%; negative predictive value (NPV)-71.6%]. The specificity increased to 89% if leprous neuropathy was excluded, with PPV-77.5% while NPV dropped to 68.5%. CONCLUSION: These findings suggest that PPB stain for detection of hemosiderin is a useful adjunct in diagnosis of vasculitic neuropathy with high specificity but low sensitivity.
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Hemossiderina , Vasculite , Idoso , Biópsia , Ferrocianetos , Humanos , Nervos Periféricos , Vasculite/diagnósticoRESUMO
Infections of the central nervous system (CNS) presenting as space-occupying lesions are not uncommon, particularly in developing countries. Most often, infective organisms gain entry into the CNS through the hematogenous route, seed the parenchyma, and cause tissue destruction. Subsequently, some form mass lesions in a manner similar to neoplastic growths. The commonality in pathogenesis and pathology between infective agents and neoplastic cells underlies the similarities in their presentations. Although neoplasms are the common considerations in the presence of enhancing lesions with perilesional edema and mass effect on neuroimaging, nonneoplastic conditions-in particular, infectious lesions--can have similar imaging characteristics. The widening spectrum of opportunistic and newly recognized pathogens has added to the difficulties. Biopsy diagnosis is mandatory for neoplasms, both for confirmation of diagnosis as well as grading, but most infectious lesions are managed conservatively if the diagnosis is established by noninvasive means. This review discusses some of the common infectious lesions that mimic CNS neoplasms, with emphasis on pyogenic, tuberculous, and fungal lesions as well as parasitic and viral infections that present as intracranial space-occupying lesions. The data of infective lesions that mimicked intracranial neoplasms, from our institute, over the last 5 years, are also presented. Awareness of the pathogenetic basis of tissue injury and host response, resulting in the spectrum of clinical and imaging patterns as well as a high index of clinical suspicion, are essential for accurate diagnosis, to ensure appropriate management.
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Neoplasias Encefálicas/diagnóstico , Infecções do Sistema Nervoso Central/diagnóstico , Adolescente , Adulto , Idoso , Infecções do Sistema Nervoso Central/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Atypical teratoid rhabdoid tumor (AT/RT) is a highly malignant embryonal CNS tumor, generally unresponsive to any form of therapy, uniformly fatal within 1 year. We report 15 cases of AT/RT diagnosed at our center over a period of 5 years (2003-08). Tumors were located in different sites of the neuraxis, posterior fossa being the most common (n = 10) followed by cerebral lobes (n = 3). There was one each at the supra sellar and cervical spinal regions, respectively. Radiologically most of the tumors were heterodense and enhancing heterogeneously. The tumors exhibited diverse histological profile that included rhabdoid and PNET areas in all cases, mesenchymal and epithelial areas in 73.3% and 53.3% cases, respectively. Necrosis was evident in all cases and one showed calcification. Tumor cells displayed a polyphenotypic immunoprofile. All cases were consistently positive for vimentin and epithelial membrane antigen and were negative for desmin. Variable positivity was seen for other markers. The number of cases positive for these were: CK (53%), SMA (60%), synaptophysin (66%), NFP (33.3%) and GFAP (85%). CK staining was prominent in epithelial areas, while PNET cells labeled prominently with synaptophysin. There was lack of INI1 expression in all cases. Follow-up was available in 46.6% of cases which revealed a uniform poor prognosis.
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Neoplasias do Sistema Nervoso Central/química , Neoplasias do Sistema Nervoso Central/patologia , Tumor Rabdoide/química , Tumor Rabdoide/patologia , Teratoma/química , Teratoma/patologia , Neoplasias do Sistema Nervoso Central/imunologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Índia , Lactente , Masculino , Necrose , Estudos Retrospectivos , Tumor Rabdoide/imunologia , Teratoma/imunologiaRESUMO
BACKGROUND: Rathke's cleft cyst is a rare benign sellar lesion. The exact preoperative diagnosis of this lesion by clinical and radiological features is difficult. Hence it is often misdiagnosed as craniopharyngioma. AIM: To identify the radiological pointers for pre operative diagnosis of Rathke's cleft cyst. MATERIALS AND METHODS: This study presents the details of nine patients who were operated in our institution between 1998 and 2008. Radiological and histopathological variations were studied. RESULTS: The possibility of Rathke's cleft cyst was considered pre operatively in one patient only. On reviewing the images, characteristic imaging findings were observed in a few cases. CONCLUSION: As minimally invasive trans-sphenoidal approach is sufficient for treating these lesions, pre operative diagnosis is important.