RESUMO
Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by the accumulation of misfolded transthyretin (TTR). It usually presents with an adult-onset progressive axonal peripheral neuropathy and cardiomyopathy. In the central nervous system (CNS), variant TTR is produced by the choroid plexus and accumulates in the leptomeninges. CNS symptoms have been increasingly recognized in this population, including transient focal neurological episodes and stroke, particularly in patients with the V30M mutation and longstanding disease. The prevalence, pathophysiology, and progression of CNS involvement remain to be clarified. The present work explores if there is a recognizable sequence of CNS TTR deposition in ATTRv. We studied the topographical and severity distribution of TTR deposition in 16 patients with ATTRv, aged 27-69 years and with a mean disease duration of 10.9 years (range: 3-29). Our results suggest that CNS pathological involvement in V30M ATTRv occurs early in the disease course, probably starting in pre-symptomatic phases, and follows a distinct sequence. Leptomeninges and subarachnoid meningeal vessels are affected earlier, then followed by perforating cortical vessels and subpial deposition, and finally by deposition in the subependymal and basal ganglia vessels near the ependymal lining. Brainstem and spinal cord show early and severe involvement, with amyloid subpial deposition already seen in initial stages. Despite massive superficial amyloid deposition, no parenchymal deposition outside subpial or subependymal regions was found. Additionally, vascular lesions or superficial cortical siderosis were not frequent. Future studies with more patients from different populations and TTR mutations will be important to confirm these findings. Defining stages of TTR pathology in the CNS may be useful to better understand pathogenic mechanisms leading to symptoms and to interpret neuroimaging biomarkers.
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Neuropatias Amiloides Familiares , Doenças do Sistema Nervoso , Adulto , Humanos , Pré-Albumina/genética , Pré-Albumina/metabolismo , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/patologia , Doenças do Sistema Nervoso/patologia , Mutação/genética , Encéfalo/patologiaRESUMO
INTRODUCTION: Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder starting after 40 years old, spastic paraparesis and peripheral neuropathy. It is mainly resultant from the GBE1 homozygous p.Tyr329Ser (c.986A>C) mutation, especially in Ashkenazi-Jewish patients, although some cases of compound heterozygous have been reported. A genotype-phenotype correlation is not established, but atypical phenotypes have been described mainly in non-p.Tyr329Ser pathogenic variants. CASE REPORT: We describe an atypical case in a 62-year-old Portuguese woman, presenting the typical clinical triad of APBD plus prominent autonomic dysfunction, suggested by orthostatic hypotension and thermoregulatory dysfunction; she has compound heterozygous GBE1 mutations, namely, p.Asn541Asp (c.1621A>G) and p.Arg515Gly (c.1543C>G), the last one not yet reported in literature and whose pathogenicity was suggested by bioinformatics analysis and confirmed by sural nerve biopsy that showed intra-axonal polyglucosan bodies. DISCUSSION: Besides the report of a novel GBE1 mutation, this case also expands the phenotypic spectrum of this disorder, reinforcing autonomic dysfunction as a possible and prominent manifestation of APBD, mimicking autosomal dominant leukodystrophy with autonomic disease in some way. Therefore, we questioned a possible relationship between this genotype and the phenotype marked by dysautonomia. Additionally, we review previously reported cases of APBD in non-homozygous p.Tyr329Ser patients with atypical phenotypes.
Assuntos
Sistema da Enzima Desramificadora do Glicogênio , Doença de Depósito de Glicogênio , Doenças do Sistema Nervoso , Adulto , Feminino , Sistema da Enzima Desramificadora do Glicogênio/genética , Homozigoto , Humanos , Pessoa de Meia-Idade , MutaçãoRESUMO
ABSTRACT McArdle's disease (glycogen storage disease type V) is an energy-dependent disorder of skeletal muscle caused by a deficiency of myophosphorylase, an important enzyme of carbohydrate metabolism that converts glycogen to glucose-1-phosphate. A 46 year-old man was sent to the rheumatology outpatient department with a 3-year history of severe exercise-induced cramps and myalgias. The episodes began when he worked in France and used to practice ski and snowboard in the Alps Mountain, with exercise intolerance, muscle cramps, and myoglobinuria. The laboratory results showed elevated serum creatine kinase levels (~15,000 U/L), and the biopsy of the deltoid muscle revealed glycogen subsarcolemmal vacuoles and absence of myophosphorylase enzymatic activity. This clinical case emphasises the importance of taking into account this metabolic disorder when faced with a patient with exercise intolerance and cramps, especially after vigorous/anaerobic exercise and elevated levels of CK activity. It is fundamental to explain the aetiology of the patient symptoms in order to improve quality of life and avoid unnecessary complications.
R E S U M E N La enfermedad de McArdle (enfermedad de almacenamiento de glucógeno tipo V) es un trastorno del músculo esquelético dependiente de la energía causado por una deficiencia de miofosforilasa, una importante enzima del metabolismo de los hidratos de carbono que convierte el glucógeno en glucosa-1-fosfato. Un hombre de 46 años de edad fue enviado al departamento de reumatología para pacientes ambulatorios con un historial de 3 años de calambres y mialgias severos inducidos por el ejercicio. Los episodios comenzaron cuando trabajó en Francia y solía practicar esquí y snowboard en el macizo de los Alpes, con intolerancia al ejercicio, calambres musculares y mioglobinuria. Las pruebas de laboratorio mostraron niveles elevados de creatina quinasa sérica (~ 15.000 U/l) y la biopsia del músculo deltoides reveló vacuolas subsarcolémicas de glucógeno y ausencia de actividad enzimática de la miofosforilasa. Nuestro caso clínico enfatiza la importancia de pensar en este trastorno metabólico cuando tenemos un paciente con intolerancia al ejercicio y calambres, especialmente después de un ejercicio vigoroso/anaeróbico y niveles elevados de actividad CK. Es fundamental explicar la etiología de los síntomas del paciente para mejorar la calidad de vida y evitar complicaciones innecesarias.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Doença de Depósito de Glicogênio Tipo V , Diagnóstico , Esqui , Exercício Físico , Músculo EsqueléticoRESUMO
Familial amyloid polyneuropathy with the substitution of methionine for valine at position 30 in the TTR gene is the most common type of hereditary transthyretin amyloidosis. Although several authors have previously reported a size-dependent fibre loss, predominantly involving unmyelinated and small-diameter myelinated fibres, the mechanisms of nerve fibre loss have not been fully understood. In this study, we establish the morphometric pattern of peripheral neuropathy in patients with familial amyloid polyneuropathy and asymptomatic mutation carriers in the biopsies from our archive and correlated the pathological findings with clinical features. A total of 98 patients with familial amyloid polyneuropathy and 37 asymptomatic mutation carriers (TTR Val30Met mutation), aged between 17 and 84 years, who underwent sural nerve biopsy between 1981 and 2017 at Centro Hospitalar Universitário do Porto were studied. Thirty-one controls were included for comparison. The median age at nerve biopsy was 26.0 [interquartile range = 23.5-39.5] years for asymptomatic mutation carriers, 45.0 [35.0-60.0] years for patients with familial amyloid polyneuropathy and 44.0 [30.0-63.0] years for controls. The median duration between nerve biopsy and symptoms' onset was 7.0 [3.3-11.8] years (range: 1-27 years) in the asymptomatic carriers. Most patients were in an earlier disease stage (93% with a polyneuropathy disability scale ≤2). Patients had loss of small and myelinated fibres compared with both asymptomatic carriers and controls (P < 0.001), whereas asymptomatic carriers showed loss of small myelinated fibres when compared with controls (P < 0.05). The loss of myelinated fibres increased with disease progression (P < 0.001), and patients in more advanced clinical stage showed more frequent amyloid deposition in the nerve (P = 0.001). There was a positive correlation between large myelinated fibre density and time to symptoms' onset in the asymptomatic carriers that developed early-onset form of the disease (r = 0.52, P < 0.01). In addition, asymptomatic carriers with amyloid deposition already present in sural nerve biopsies developed symptoms earlier than those with no amyloid (P < 0.01). In conclusion, this study confirms that the loss of small fibre size is an initial event in familial amyloid polyneuropathy, already present in asymptomatic gene carriers, starting several years before the onset of symptoms. We show for the first time that large myelinated fibres' loss and amyloid deposition are pathological features that correlate independently with short period to the onset of symptoms for asymptomatic carriers that developed early-onset form of the disease. These findings are therapeutically relevant, as it would allow for a better interpretation of the role of disease-modifying agents in transthyretin familial amyloid polyneuropathy.
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The etiology of intracerebral hemorrhage (ICH) is frequently undetermined. We aimed to assess the impact of the neuropathological study on the etiologic diagnosis of ICH. Patients with ICH admitted to a tertiary hospital in the last 14 years were identified, and histological samples of surgically-drained ICH were retrieved. Blinded from neuropathological results, a clinical etiology was hypothesized. Pathological samples were reviewed, and immunohistochemistry study for ß-amyloid was performed in all the cases where structural abnormalities were not identified. From 2002 - 2016, 113 patients with ICH underwent surgical drainage and had specimens taken for histology. The mean age was 51.6 years (SD = 19.2). Clinical and imaging data defined a presumable etiology in 47 patients (44.2%), including 30 patients with suspected structural pathology, 11 patients under anticoagulation, and 8 patients with probable hypertensive hemorrhage, while most had an undetermined etiology. Using neuropathological analysis, a definitive diagnosis was possible in 88.5% of the patients. Arteriovenous malformations (38.1%) and cavernous hemangiomas (16.8%) represented the most common findings. In 9.7%, the blood vessels showed cerebral amyloid angiopathy (CAA). The neuropathological study established a definite etiology in an additional 44.3% of patients other than only using the clinical and imaging data.â©.
Assuntos
Angiopatia Amiloide Cerebral/etiologia , Hemorragia Cerebral/patologia , Hipertensão/patologia , Neuropatologia , Adulto , Idoso , Angiopatia Amiloide Cerebral/patologia , Hemorragia Cerebral/diagnóstico , Feminino , Hematoma/patologia , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/patologia , Neuropatologia/métodosRESUMO
Germ cell tumors of the central nervous system (CNS) are usually located along the midline. Yolk sac tumor is a rare germ cell tumor very uncommonly located outside the midline, and, in such cases, it can be mistaken with other primary tumors. We report a case of a 32-year-old male patient who presented with a right temporal lobe tumor suggestive of a high grade glioma. He was submitted to a right temporal lobectomy with complete tumor removal. The histological exam revealed a germ cell tumor (later confirmed to be a yolk sac tumor). The search for a primary tumor outside of the CNS (including a positron emission tomography scan) was negative, making this a primary temporal lobe yolk sac tumor. The patient was submitted to chemotherapy and radiotherapy, but died 7 months after the surgery.
Assuntos
Humanos , Masculino , Adulto , Lobo Temporal , Tumor do Seio Endodérmico/tratamento farmacológico , Tumor do Seio Endodérmico/radioterapia , Tumor do Seio Endodérmico/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Lobectomia Temporal Anterior/métodosRESUMO
INTRODUCTION: Carpal tunnel syndrome (CTS) is a nonspecific manifestation of hereditary ATTR amyloidosis (ATTRm). Amyloid deposition of wild-type TTR (WT-ATTR) has been found in transverse carpal ligament (TCL) in idiopathic CTS. We retrospectively studied a group of patients with ATTRm and CTS submitted to carpal tunnel release surgery (CTRS). METHODS: From the nerve conduction studies performed in our Clinical Unit dedicated to hereditary amyloidosis between July 2009 and October 2013, we selected patients who fulfilled neurophysiological criteria for CTS, had been submitted to CTRS and whose TCL was available for pathology. Clinical registries were reviewed and amyloid detection in the ligaments was performed using Congo-red staining. RESULTS: We included 16 patients: three males (18.8%), mean age = 46.1 years old, all with V30M mutation. At the time of surgery, four patients were considered asymptomatic and 12 symptomatic carriers, five of them late-onset ATTRm (onset age >50 years old). In all but one patient, the CTS preceded the polyneuropathy. Amyloid detection in the TCL was positive in 14 patients (87.5%). DISCUSSION/CONCLUSIONS: In most patients, CTS preceded or was contemporary to the polyneuropathy and amyloid detection in TCL was positive. The detection of amyloid in TCL may add specificity to CTS as an early manifestation of the disease but more studies are needed.
Assuntos
Amiloide/metabolismo , Amiloidose Familiar/metabolismo , Síndrome do Túnel Carpal/metabolismo , Ligamentos/metabolismo , Adulto , Idoso , Amiloide/genética , Amiloidose Familiar/genética , Amiloidose Familiar/patologia , Amiloidose Familiar/cirurgia , Síndrome do Túnel Carpal/genética , Síndrome do Túnel Carpal/patologia , Síndrome do Túnel Carpal/cirurgia , Feminino , Humanos , Ligamentos/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Pathogenic variants in ryanodine receptor type 1 (RYR1) gene are an important cause of congenital myopathy. The clinical, histopathologic and genetic spectrum is wide. OBJECTIVE: Review a group of the patients diagnosed with ryanodinopathy in a tertiary centre from North Portugal, as an attempt to define some phenotypical patterns that may help guiding future diagnosis. METHODS: Patients were identified from the database of the reference centre for Neuromuscular Disorders in North Portugal. Their data (clinical, histological and genetic) was retrospectively accessed. RESULTS: Seventeen RYR1-related patients (including 4 familial cases) were identified. They were divided in groups according to three distinctive clinical characteristics: extraocular muscle (EOM) weakness (Nâ=â6), disproportionate axial muscle weakness (Nâ=â2) and joint laxity (Nâ=â5). The fourth phenotype includes patients with mild tetraparesis and no distinctive clinical features (Nâ=â4). Four different histopathological patterns were found: centronuclear (Nâ=â5), central core (Nâ=â4), type 1 fibres predominance (Nâ=â4) and congenital fibre type disproportion (Nâ=â1) myopathies. Each index case, except two patients, had a different RYR1 variant. Four new genetic variants were identified. All centronuclear myopathies were associated with autosomal recessive inheritance and EOM weakness. All central core myopathies were caused by pathogenic variants in hotspot 3 with autosomal dominant inheritance. Three genetic variants were reported to be associated to malignant hyperthermia susceptibility. CONCLUSIONS: Distinctive clinical features were recognized as diagnostically relevant: extraocular muscle weakness (and centronuclear pattern on muscle biopsy), severe axial weakness disproportionate to the ambulatory state and mild tetraparesis associated with (proximal) joint laxity. There was a striking genetic heterogeneity, including four new RYR1 variants.
Assuntos
Instabilidade Articular/fisiopatologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Músculos Oculomotores/fisiopatologia , Paresia/fisiopatologia , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Heterogeneidade Genética , Variação Genética , Humanos , Lactente , Instabilidade Articular/etiologia , Instabilidade Articular/genética , Instabilidade Articular/patologia , Masculino , Hipertermia Maligna/genética , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Debilidade Muscular/etiologia , Debilidade Muscular/genética , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Doenças Musculares/complicações , Doenças Musculares/genética , Doenças Musculares/patologia , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Miopatias Congênitas Estruturais/fisiopatologia , Miopatia da Parte Central/genética , Miopatia da Parte Central/patologia , Miopatia da Parte Central/fisiopatologia , Músculos Oculomotores/patologia , Paresia/etiologia , Paresia/genética , Paresia/patologia , Fenótipo , Portugal , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária , Adulto JovemRESUMO
INTRODUCTION: Mitochondrial disorders display remarkable genetic and phenotypic heterogeneity. METHODS: We performed a retrospective analysis of the clinical, histological, biochemical, and genetic features of 65 patients with molecular diagnoses of mitochondrial disorders. RESULTS: The most common genetic diagnosis was a single large-scale mitochondrial DNA (mtDNA) deletion (41.5%), and the most frequent clinical phenotype was chronic progressive external ophthalmoplegia (CPEO). It occurred in 41.5% of all patients, primarily in those with mtDNA deletions. Histological signs of mitochondrial dysfunction were found in 73.8% of patients, and respiratory chain enzyme assay (RCEA) abnormalities were detected in 51.9%. CONCLUSIONS: This study confirms the high relative frequency of single large-scale deletions among mitochondrial disorders as well as its particular association with CPEO. Muscle histology seems to be particularly useful in older patients and those with mtDNA deletions, whereas RCEA might be more helpful in young children or individuals with mtDNA depletion. Muscle Nerve 56: 868-872, 2017.
Assuntos
DNA Mitocondrial/genética , Doenças Mitocondriais , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Músculo Esquelético/patologia , Deleção de Sequência/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Oftalmoplegia Externa Progressiva Crônica/genética , Portugal , Adulto JovemRESUMO
Congenital myopathies (CMs) are a heterogeneous group of muscle diseases characterized by hypotonia, delayed motor skills and muscle weakness with onset during the first years of life. The diagnostic workup of CM is highly dependent on the interpretation of the muscle histology, where typical pathognomonic findings are suggestive of a CM but are not necessarily gene specific. Over 20 loci have been linked to these myopathies, including three exceptionally large genes (TTN, NEB and RYR1), which are a challenge for molecular diagnosis. We developed a new approach using massive parallel sequencing (MPS) technology to simultaneously analyze 20 genes linked to CMs. Assay design was based on the Ion AmpliSeq strategy and sequencing runs were performed on an Ion PGM system. A total of 12 patients were analyzed in this study. Among the 2534 variants detected, 14 pathogenic mutations were successfully identified in the DNM2, NEB, RYR1, SEPN1 and TTN genes. Most of these had not been documented and/or fully characterized, hereby contributing to expand the CM mutational spectrum. The utility of this approach was demonstrated by the identification of mutations in 70% of the patients included in this study, which is relevant for CMs especially considering its wide phenotypic and genetic heterogeneity.
Assuntos
Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Doenças Musculares/congênito , Doenças Musculares/diagnóstico , Adolescente , Adulto , Idoso , Alelos , Substituição de Aminoácidos , Biópsia , Criança , Análise Mutacional de DNA , Dinamina II/genética , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Mutação , Linhagem , Fenótipo , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Adulto JovemRESUMO
Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests by migraine with aura, cerebral ischemic events, mood disturbances and dementia. Brain MRI lesions typically precede the symptoms from 10 to 15 years and previous evidence showed all CADASIL patients above 35 years old have an abnormal MRI, supporting the clinical diagnosis. Case results We present a 37-year-old female patient with migraine without aura, a family history of CADASIL, normal brain 3-Tesla MRI and normal skin biopsy, even though a pathogenic NOTCH3 gene mutation (allele 2, exon 11, c.1672 C\gtT, p.Arg558Cys) was detected. Conclusions When CADASIL is strongly suspected, a normal brain MRI, even in the fourth decade of life, does not rule out the diagnosis and should not discourage the genetic test.
Assuntos
Encéfalo/diagnóstico por imagem , CADASIL/diagnóstico por imagem , CADASIL/genética , Imageamento por Ressonância Magnética/métodos , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca com Aura/genética , Receptor Notch3/genética , Adulto , Diagnóstico Diferencial , Reações Falso-Negativas , Feminino , Marcadores Genéticos/genética , Testes Genéticos/métodos , Humanos , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Muscular dystrophies (MDs) are a group of hereditary muscle disorders that include two particularly heterogeneous subgroups: limb-girdle MD and congenital MD, linked to 52 different genes (seven common to both subgroups). Massive parallel sequencing technology may avoid the usual stepwise gene-by-gene analysis. We report the whole-exome sequencing (WES) analysis of a patient with childhood-onset progressive MD, also presenting mental retardation and dilated cardiomyopathy. Conventional sequencing had excluded eight candidate genes. WES of the trio (patient and parents) was performed using the ion proton sequencing system. Data analysis resorted to filtering steps using the GEMINI software revealed a novel silent variant in the choline kinase beta (CHKB) gene. Inspection of sequence alignments ultimately identified the causal variant (CHKB:c.1031+3G>C). This splice site mutation was confirmed using Sanger sequencing and its effect was further evaluated with gene expression analysis. On reassessment of the muscle biopsy, typical abnormal mitochondrial oxidative changes were observed. Mutations in CHKB have been shown to cause phosphatidylcholine deficiency in myofibers, causing a rare form of CMD (only 21 patients reported). Notwithstanding interpretative difficulties that need to be overcome before the integration of WES in the diagnostic workflow, this work corroborates its utility in solving cases from highly heterogeneous groups of diseases, in which conventional diagnostic approaches fail to provide a definitive diagnosis.
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Colina Quinase/genética , Distrofias Musculares/genética , Adulto , Sequência de Bases , Colina Quinase/metabolismo , Análise Mutacional de DNA , Exoma , Feminino , Expressão Gênica , Estudos de Associação Genética , Humanos , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Sítios de Splice de RNARESUMO
BACKGROUND: Mutations in ryanodine receptor 1 gene (RYR1) are frequent causes of myopathies. They classically present with central core disease; however, clinical variability and histopathologic overlap are being increasingly recognized. PATIENTS: Patient 1 is a 15-year-old girl with mild proximal, four-limb weakness from age 5, presenting with a progressive scoliosis starting at age 10. Patient 2 is an 18-year-old girl with progressively worsening muscle hypotrophy and mild proximal, four-limb weakness. She developed a rapidly progressive scoliosis from age 11 and needed surgical treatment at age 14 years. Patient 3 is an 11-year-old boy with moderate proximal limb weakness and progressive neck flexor weakness, first noticed at age 2. Muscle biopsies revealed type 1 fiber predominance (Patients 1 and 2) or abnormal type 1 fiber uniformity (Patient 3). Different RYR1 variants were identified in all patients. In Patients 1 and 3, these changes were validated as being pathogenic. CONCLUSIONS: These patients illustrate early-onset, progressive myopathies with predominant axial involvement. Histopathologic findings were abnormal but not specific for a diagnosis, particularly central core myopathy. Genetic testing helped broaden the range of phenotypes included in the RYR1-related myopathies. Our patients reinforce the need to recognize the broad histopathologic variability of RYR1-related myopathies and sometimes lack of pathognomonic findings that may reduce the diagnostic threshold of this disease. We suggest that the predominance of type 1 fibers and involvement of axial muscles may be an important element to consider the RYR1 gene as candidate.
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Doenças Musculares/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Adolescente , Criança , Feminino , Humanos , Masculino , Doenças Musculares/patologia , Doenças Musculares/fisiopatologia , FenótipoRESUMO
Glioblastoma is a malignant infiltrative glial tumor occurring most often over 50 years of age, with diverse clinical presentations. We describe a case of temporal lobe glioblastoma with a rare presentation as an acute ischemic stroke, discussing the imaging and histopathological findings, and reviewing the literature. A 77-year-old woman had sudden onset of left hemiparesis and hemihypoesthesia. The neuroradiological studies revealed an acute ischemic lesion in the right lenticulostriate arteries territory and a right anterior temporal lobe tumor, enhancing heterogeneously after contrast with enhancement of the right middle cerebral artery wall. Histopathological analysis of the resected temporal lesion revealed a glioblastoma multiforme with tumoral infiltration of the vascular wall. Glioblastoma should be considered in the etiology of acute ischemic stroke, where neuroimaging plays an important diagnostic role, enabling a more immediate therapeutic approach, with a consequent impact on survival.
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Isquemia Encefálica/etiologia , Neoplasias Encefálicas/complicações , Glioblastoma/complicações , Acidente Vascular Cerebral/etiologia , Idoso , Isquemia Encefálica/patologia , Neoplasias Encefálicas/patologia , Angiografia Cerebral , Feminino , Glioblastoma/patologia , Humanos , Hipestesia/etiologia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Paresia/etiologia , Acidente Vascular Cerebral/patologia , Tomografia Computadorizada por Raios XRESUMO
Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoproliferative disorder characterized by massive intravascular growth of lymphoma cells with a predilection for the central nervous system (CNS). Diagnosis is generally delayed by variable clinical presentation and nonspecific laboratory findings. Brain biopsy is the gold standard diagnostic test. Prognosis is poor with a high mortality rate. We report a case of "in vivo" diagnosis of IVLBCL presenting with rapidly progressive encephalopathy secondary to multiple cerebral infarcts. This case highlights IVLBCL as a possible cause of unexplained multifocal and recurrent strokes. Earlier diagnosis and consequent earlier treatment may be associated with better prognosis.
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Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Infarto Cerebral/diagnóstico , Linfoma de Células B/diagnóstico , Linfoma de Células B/terapia , Neoplasias do Sistema Nervoso Central/complicações , Infarto Cerebral/complicações , Infarto Cerebral/terapia , Feminino , Humanos , Linfoma de Células B/complicações , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Gliomatosis cerebri is a specific entity defined as a diffuse neoplastic glial cell infiltration of the brain, preserving the architecture of the normal surrounding tissues, involving more than 2 cerebral lobes. Clinical symptoms or radiologic features are nonspecific, and patients are often misdiagnosed with other neurologic diseases. REVIEW SUMMARY: Here, we report the diagnostic workup of 2 patients with gliomatosis cerebri, discussing the clinical, radiologic, and pathologic findings. Case 1: a 64-year-old woman who presented with an intracranial hypertension syndrome and had symmetrical white matter T2-weighted and fluid-attenuated inversion recovery hyperintensities pattern on magnetic resonance imaging; and case 2: a 54-year-old man with the diagnosis of multiple sclerosis for 8 years who presented with de novo cognitive impairment and focal deficits. CONCLUSIONS: This report highlights the difficulty of this differential diagnosis and the need of considering it also in the presence of a symmetrical pattern of white matter involvement. Cerebral biopsy remains crucial for the correct diagnosis and treatment approach.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Neuroepiteliomatosas/diagnóstico , Encéfalo/patologia , Transtornos Cognitivos/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/complicaçõesRESUMO
Acute hemorrhagic leukoencephalitis (AHLE) is a rare and fulminant demyelinating disease considered to be the most severe form of acute disseminated encephalomyelitis (ADEM). A 70-year-old man was admitted to our emergency department (ED) after 1 week of unspecific abdominal symptoms and moderate fever in the first 3 days. Within the ED he developed a rapid onset coma and flaccid tetraparesis. Cerebrospinal fluid (CSF) analysis showed mild polymorphonuclear pleocytosis and magnetic resonance imaging (MRI) revealed supratentorial focal white matter lesions and diffuse involvement of the medulla and spinal cord. A presumptive diagnosis of ADEM was made and the patient was treated with corticosteroids followed by intravenous immunoglobulin. His neurological state did not improve and the MRI on day 8 after admission showed an increased number of lesions, mainly in the brainstem, with hemorrhagic foci. The patient died the following day and pathological features confirmed the diagnosis of AHLE. This is a unique presentation of a rare disease with detailed MRI characteristics and pathological confirmation. Although this condition is usually fatal, early recognition and aggressive therapeutic management can facilitate survival.