Jean-Martin Charcot: the polymath / Jean-Martin Charcot: o polímata

Abstract Jean-Martin Charcot, widely regarded as a leading founder of modern neurology, made substantial contributions to the understanding and characterization of numerous medical conditions. His initial focus was on internal medicine, later expanding to include neuropathology, general neurology, and eventually emerging fields such as neuropsychology and neuropsychiatry. Furthermore, Charcot's intellectual pursuits extended beyond medicine, encompassing research in art history, medical iconography, sociology, religious studies, and the arts, solidifying his status as a polymath.

Resumo Jean-Martin Charcot, amplamente considerado como um proeminente fundador da neurologia moderna, fez contribuições substanciais para a compreensão e a caracterização de várias condições médicas. Seu foco inicial era a medicina interna, expandindo-se posteriormente para incluir a neuropatologia, a neurologia geral e, por fim, campos emergentes como a neuropsicologia e a neuropsiquiatria. Além disso, as buscas intelectuais de Charcot foram além da medicina, abrangendo pesquisas em história da arte, iconografia médica, sociologia, estudos religiosos e artes, solidificando seu status de polímata.

Icariin ameliorates behavioral deficits and neuropa-thology in a mouse model of multiple sclerosis / 中国药理学与毒理学杂志

Multiple sclerosis(MS)is a systemic inflammatory illness of the central nervous system that involves demyelinating lesions in the myelin-rich white matter and pathology in the grey matter.Despite signifi-cant advancements in drug research for MS,the dis-ease's complex pathophysiology makes it difficult to treat the progressive forms of the disease.In this study,we identified a natural flavonoid compound icariin(ICA)as a potent effective agent for MS in ameliorating the deterioration of symptoms including the neurological defi-cit score and the body weight in a murine experimental autoimmune encephalomyelitis(EAE)model.These improvements were associated with decreased demyelin-ation in the corpus callosum and neuron loss in the hippo-campus and cortex confirmed by immunohistochemistry analysis.Meanwhile,it was observed that the activation of microglia in cerebral cortex and hippocampus were inhibited followed by the neuroinflammatory cytokines downregulation such as IL-1β,IL-6 and TNF-α after ICA treatment,which was probably attributable to the sup-pression of microglial NLRP3 inflammasome activation.Additionally,molecular docking also revealed the binding force of ICA to NLRP3 inflammasome protein complexes in vitro.Taken together,our findings have demonstrated that ICA,as pleiotropic agent,prevents EAE-induced MS by improving demyelination and neuron loss,which inter-feres with the neuroinflammation via microglial NLRP3 inflammasome activation.

Radiologic-pathologic autopsy correlation of an internal watershed infarct, a case report

ABSTRACT Internal watershed infarcts (IWIs) occur at the junction of the deep and superficial perforating arterial branches of the cerebrum. Despite documentation in the radiology literature, IWIs are rarely encountered at the time of autopsy. Here, we report the case of a 59-year-old incarcerated male who was brought to the emergency department after being found unresponsive on the floor of his jail cell. Initial examination and imaging demonstrated right-sided hemiplegia, aphasia, right facial droop, and severe stenosis of the left middle cerebral artery, respectively. Repeat imaging 4 days after admission and 26 days before death demonstrated advanced stenosis of the intracranial, communicating segment of the right internal carotid artery, a large acute infarct in the right posterior cerebral artery territory, and bilateral deep white matter ischemic changes with a right-sided "rosary-like" pattern of injury that is typical of IWIs. Postmortem gross examination showed that the right deep white matter lesion had progressed to a confluent, "cigar-shaped" subacute IWI involving the right corona radiata. This is the first well-documented case of an IWI with radiologic imaging and photographic gross pathology correlation. This case uniquely highlights a rarely encountered lesion at the time of autopsy and provides an excellent visual representation of internal watershed neuroanatomy.

Vasculitic neuropathies / 中华神经科杂志

Vasculitic neuropathies occur when inflammatory cells infiltrate the vessels of peripheral nerves. Patients with vasculitic neuropathies typically present with multiple mononeuropathies (also known as multifocal neuropathy), characterized by the acute-to-subacute onset of painful sensory and motor deficits. Vasculitic neuropathies could develop in the setting of systemic vasculitis. It also could present as a non-systemic vasculitis without other organs involvement. Peripheral nerve biopsy has an important role in the diagnosis of vasculitic neuropathies. In this review, the classification, clinical and electrophysiological manifestations, diagnosis, treatment, and prognosis of vasculitic neuropathies are summarized, with a focus on recent progresses in these areas.

Artificial intelligence in neuropathology: Current status and future perspectives

Machine learning and artificial intelligence (AI) have become a part of our daily routine. There are very few of us who are not influenced by this technology. There are a lot of misconceptions about the scope, utility, and fallacies of AI. Digital neuropathology is an evolving area of research. The importance of digital image processing stems from the rapid gains in computer vision and image processing that have happened in the past decade thanks to advancements in deep learning (DL). The article attempts to present to the audience a simple presentation of the technology and attempts to provide a context-based understanding of the DL process for image processing. Also highlighted are current challenges and the roadblocks in adopting the technology in routine neuropathology.

Focal cortical dysplasia: Updates

Focal cortical dysplasias (FCDs) represent the third most frequent cause of drug-resistant focal epilepsy in adults (after hippocampal sclerosis and tumours) submitted to surgery, and the most common in the pediatric age group. The International League Against Epilepsy (ILAE) classification of focal cortical dysplasia is still a reference and consists of a three-tiered system: FCD type I refers to isolated abnormalities in cortical layering; FCD type II refers to cases with abnormalities in cortical architecture and dysmorphic neurons with or without balloon cells; and FCD type III refers to abnormalities in cortical layering associated with other lesions. Recent studies have demonstrated that somatic mutations occurring post-zygotically during embryonal development and leading to mosaicism, underlie most brain malformations. The molecular pathogenesis of FCD type II is associated with activation of the mTOR pathway. Pathogenic variants in this pathway are recognized in up to 63% of cases and may occur both through single activating variants in activators of the mTOR signaling pathway or double-hit inactivating variants in repressors of the signaling pathway. The newly described mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy, has been found to show recurrent pathogenic variants in SLC35A2 with mosaicism. The present review describes the lesions of FCD and discusses the molecular pathogenesis and proposal for a revised classification.

Pathology of surgically remediable epilepsy: How to evaluate

Epilepsy surgery is a well-established treatment modality in selected cases of medically refractory epilepsy. Advances in neuroimaging technology has greatly facilitated detection of lesions that are surgically amenable. Hippocampal sclerosis is the most common pathology encountered among specimens from epilepsy-related surgeries. Other common pathologies are malformations of cortical development including focal cortical dysplasia, neoplasms, vascular malformations, inflammatory conditions including Rasmussen encephalitis and glial scars. Proper handling of surgical specimens is necessary for microscopic evaluation. Accurate interpretation and classification of lesions will help define clinically relevant etiologies. In this review, neuropathological aspects of the common etiologies underlying drug-resistant epilepsies are discussed.

Congenital Rubella Syndrome as a possible cause for persistent thrombocytopenia in early infancy: The Forgotten Culprit

Abstract We present a case of a late preterm intrauterine growth-restricted neonate with isolated and persistent severe thrombocytopenia. At birth, the neonate did not have a complete clinical spectrum of congenital rubella syndrome (CRS) but later developed peculiar findings that helped clinch the diagnosis. The neonate also had interstitial pneumonia and died secondary to superimposed acute viral infection leading to acute respiratory distress syndrome. The serology was positive for IgM antibodies against the rubella virus. The constellation of clinical manifestations of congenital rubella in the presence of positive IgM antibody against rubella and consistent histopathology confirmed the diagnosis of CRS.

Central nervous system high-grade neuroepithelial tumor with BCOR alteration: a short report

Central nervous system high-grade neuroepithelial tumors with BCOR alteration are rare. Currently, there are only 24 cases reported in the literature. These tumors are characterized by a change involving the BCOR gene and have a poor prognosis. Studies are needed to improve the current therapy and outcomes of these neoplasms. This case report describes the clinical history of a patient with this disease and aims to contribute to the current knowledge about this new entity.

First occurrence of Arnold Chiari type II malformation and associated abnormalities in a Gir calf produced in vitro from Brazil - case report / [Primeira ocorrência de malformação de Arnold Chiari tipo II e anormalidades associadas em uma bezerra Gir de produção in vitro no Brasil - relato de caso]

This study characterized the clinical, radiological, ultrasound, and necroscopic findings of a case of Arnold-Chiari type II malformation in a Gir breed calf from Brazil. The animal was hospitalized at sixty days of age, in permanent sternal recumbency, cutaneous appendix at the 4th lumbar vertebra and kyphoscoliosis of the caudal and lumbosacral thoracic spine. Radiographic examination of the spine and skull revealed spina bifida and suspected occipital hypoplasia. Upon examination of myelography with an injection of lumbar and atlantooccipital contrast, it was possible to visualize the meningocele at the 4th lumbar vertebra region and findings at the rhombencephalon level of increased regional pressure with failure to fill the contrast in the posterior fossa, in the presence of clear demarcation of the circumvolutions of the cerebral cortex and the subarachnoid space of the cervical spinal cord. Ultrasonographic examination of the cerebellum showed an insinuation of the cerebellar worm through the foramen magnum. The animal did not show changes in complete blood count, biochemical series, and cerebrospinal fluid and was negative for Pestivirus. There was a worsening of the clinical conditions and the animal died. This malformation of unknown etiology must be studied as a differential diagnosis of the nervous system disorders.(AU)

Este estudo caracterizou os achados clínicos, radiológicos, ultrassonográficos e necroscópicos de um caso de malformação de Arnold-Chiari tipo II em uma bezerra Gir no Brasil. O animal foi hospilatizado aos 60 dias de idade, apresentando decúbito esternal permanente, apêndice cutâneo na altura da quarta vértebra lombar e cifoescoliose da coluna vertebral torácica caudal e lombossacra. Ao exame radiográfico da coluna e do crânio, foram observadas espinha bífida e suspeita de hipoplasia occipital. Ao exame de mielografia com injeção de contraste lombar e atlanto-occipital, foi possivel visualizar a meningocele na altura da quarta vértebra lombar e achados em nível rombencefálico de aumento da pressão regional com falha de preenchimento do contraste na fossa posterior, na presença de nítida demarcação das circunvoluções do córtex cerebral e do espaço subaracnoide da medula espinhal cervical. Ao exame ultrassonográfico do cerebelo, foi observada insinuação do verme cerebelar através do forame magno. O animal não apresentou alterações em hemograma completo, série bioquímica e fluido cérebro-espinhal e foi negativo para Pestivirus. Houve uma piora do quadro clínico e o animal morreu. Essa malformação de etiologia desconhecida deve ser estudada como um diagnóstico diferencial.(AU)

Spina bifida, diplomyelia and multiple malformations in a Texel lamb / Espinha bífida, diplomielia e múltiplas malformações em um cordeiro Texel

ABSTRACT: This report described the clinical and pathological aspects of open spina bifida and diplomyelia along with multiple congenital malformations in a Texel lamb. Clinically, paresis of the thoracic limbs, paralysis of the pelvic limbs and a cutaneous opening in the lumbosacral region were observed. At necropsy, there was a focally extensive disruption of the skin associated with an absence of the dorsal portions of the lumbosacral vertebrae. Additionally, diplomyelia of the lumbar segment, mild hydromyelia of thoracic segment, and moderate communicating hydrocephalus of the lateral and third ventricles were noted. Possible viral etiologies (bovine viral diarrhea virus, bluetongue virus, and Schmallemberg virus) were not detected by RT-PCR, and toxic plants were not identified. Therefore, a possible genetic cause may not be discarded.

RESUMO: Este trabalho descreve os aspectos clínicos e patológicos de um caso de espinha bífida aberta e diplomielia, além de múltiplas malformações, em um cordeiro Texel. Clinicamente, este apresentava paresia de membros torácicos, paralisia dos membros pélvicos e uma abertura cutânea na região lombossacral desde o nascimento. À necropsia, visualizou-se solução de continuidade na pele e ausência das porções dorsais das vértebras lombossacrais. Além disso, observou-se diplomielia em segmento lombar, hidromielia discreta de segmento torácico e hidrocefalia comunicante moderada de ventrículos laterais e terceiro ventrículo. Possíveis etiologias virais (vírus da diarreia viral bovina, vírus da língua azul e Schmallemberg virus) não foram detectadas através de RT-PCR, e possíveis plantas tóxicas não foram identificadas. Portanto, uma causa genética não pode ser descartada.

Japanese encephalitis virus-induced neuropathology in mouse model infected through the conjunctival route

Background & objectives: Mouse is a preferred animal model for studying pathogenesis of Japanese encephalitis virus (JEV) infections, and different routes of inoculation have been tried. Some neurotropic viruses can reach the brain following infection through ocular route. This study was undertaken to establish JEV-induced clinical disease in mouse model through conjunctival route and document the neuropathological effects. Methods: Ten two-week old Swiss albino mice were inoculated with 5 ?l Vero cell cultured virus containing 104.7 TCID50 JEV through conjunctival route. Clinical signs of mice were observed twice daily. After necropsy examination, different organs including eyes and olfactory bulbs were collected for histopathological examination, quantification of viral copy number and antigen by real-time TaqMan assay and immunohistochemistry, respectively. Results: Infected mice showed characteristic clinical signs of JE by 4 days post-infection (dpi). Histopathological lesions in brain included perivascular cuffing by mononuclear cells, focal gliosis, necrosis of neurons and neuronophagia and astrocytosis in the cerebrum, cerebellum and the brainstem. JEV viral load was highest in the brain followed by intestine, heart, liver, spleen, lung and kidney. JEV antigen was detected in the bipolar and ganglion cells of the retina and in the mitral cells and periglomerular cells of olfactory bulb and other parts of the brain. Interpretation & conclusions: JEV infection in mice through conjunctival route produced characteristic clinical signs of the disease and neuropathological lesions. Demonstration of JEV antigen in association with neuropathological lesions in the central nervous system and neuronal cells of the eye showed that conjunctival route could be an effective alternate route for virus invasion into the brain. These findings have biosafety implications for researchers, veterinary practitioners and pig farmers.

Franz Nissl (1860-1919), noted neuropsychiatrist and neuropathologist, staining the neuron, but not limiting it / Franz nissl (1860-1919), notável neuropsiquiatra e neuropatologista, tingindo o neurônio, mas não o limitando

ABSTRACT Franz Alexander Nissl carried out studies on mental and nervous disorders, as a clinician, but mainly as a pathologist, probably the most important of his time. He recognized changes in glial cells, blood elements, blood vessels and brain tissue in general, achieving this by using a special blue stain he himself developed - Nissl staining, while still a medical student. However, he did not accept the neuron theory supported by the new staining methods developed by Camillo Golgi and Santiago Ramón y Cajal. Nissl had worked with the crème de la crème of German neuropsychiatry, including Alois Alzheimer, besides Emil Kraepelin, Korbinian Brodmann and Walther Spielmeyer. He became (1904), Kraepelin's successor as Professor of Psychiatry and Director of the Psychiatric Clinic, in Heidelberg. Moreover, in 1918, the year before Nissl´s death, Kraepelin offered him a research position as head of the Histopathology Department of the newly founded "Deutsche Forschungsanstalt fur Psychiatrie" of the Max Planck Institute for Psychiatry, in Munich.

RESUMO Franz Alexander Nissl realizou estudos sobre transtornos mentais e nervosos, como clínico, mas principalmente como patologista, provavelmente o mais importante de seu tempo. Ele reconheceu mudanças nas células gliais, elementos sangüíneos, vasos sangüíneos e tecido cerebral em geral, realizando-o por meio de um corante azul especial desenvolvida por ele mesmo - coloração de Nissl, ainda como estudante de medicina. No entanto, ele não aceitou a teoria do neurônio esclarecida pelos novos métodos de coloração desenvolvidos por Camillo Golgi e Santiago Ramón y Cajal. Nissl havia trabalhado com o crème de la crème da neuropsiquiatria alemã, como Alois Alzheimer, além de Emil Kraepelin, Korbinian Brodmann e Walther Spielmeyer. Ele se tornou (1904), o sucessor de Kraepelin como professor de psiquiatria e diretor da Clínica Psiquiátrica, em Heidelberg. Além disso, em 1918, um ano antes da morte de Nissl, Kraepelin o convidou para um cargo de pesquisador, como chefe do departamento de histopatologia da recém-fundada "Deutsche Forschungsanstalt fur Psychiatrie" do Instituto Max Planck de Psiquiatria, em Munique.

Feline lymphoma in the nervous system: pathological, immunohistochemical, and etiological aspects in 16 cats / Linfoma no sistema nervoso de felinos: aspectos patológicos, imuno-histoquímicos e etiológicos em 16 gatos

The pathological, immunohistochemical (IHC), and etiological features of lymphoma involving the nervous system (NS) in cats were analyzed through a retrospective study (2004-2017) in Rio Grande do Sul State, Brazil. The NS involvement was observed in 16 (12.2%) of 125 felines with lymphoma. Young cats were mainly affected, with a median of 24 months old. Most cases were secondary central NS lymphoma, whereas in three cats, the NS involvement was primary. IHC revealed 14 (87.5%) FeLV-positive, six FIV-positive, and one FeLV/FIV-negative cats. Distribution of feline lymphoma in the NS was 8/16 in the spinal cord, 7/16 in the brain, and 1/16 in the paravertebral nerves and ganglia (neurolymphomatosis). The lymphoma pattern in the spinal cord was exclusively extradural, often focal (6/8), and located in the lumbar (3/6), sacral (1/6), thoracic (1/6), and cervical segments (1/6). Brain neuroanatomical patterns were: leptomeningeal lymphomatosis (4/7), lymphomatous choroiditis (2/7), and intradural lymphoma (1/7). The feline with primary neurolymphomatosis presented a marked thickening of paravertebral nerves and ganglia from the sacral region. B-cell lymphoma (75%) was often diagnosed, and diffuse large B-cell lymphoma (DLBCL) (11/16) was the main subtype. T-cell lymphoma (25%) was less commonly observed and was classified as peripheral T-cell lymphoma (PTCL) (3/16) and T-cell lymphoblastic lymphoma (T-LBL) (1/16).(AU)

Os aspectos patológicos, imuno-histoquímicos (IHQ) e etiológicos do linfoma envolvendo o sistema nervoso de felinos foram analisados através de um estudo retrospectivo (período de 2004-2017) no Estado do Rio Grande do Sul, Brasil. O envolvimento do sistema nervoso foi observado em 16 (12,2%) dos 125 felinos com linfoma desse estudo e afetou principalmente, jovens com idade mediana de 24 meses. A grande maioria dos casos o linfoma era secundário no sistema nervoso central e somente em três gatos o linfoma foi primário do sistema nervoso. Na IHQ, 14 (87,5%) casos foram positivos para FeLV, seis (37,5%) para FIV, e um foi negativo para ambos. A distribuição do linfoma no sistema nervoso foi em 8/16 felinos na medula espinhal, 7/16 no encéfalo e em 1/16 em nervos e gânglios paravertebrais (neurolinfomatose). Na medula espinhal, o padrão do linfoma foi exclusivamente extradural e frequentemente focal (6/8), localizadas nos segmentos lombares (3/6), sacrais (1/6), torácicos (1/6) e cervicais (1/6). No encéfalo, os padrões neuroanatômicos observados foram: linfomatose leptomeningeal (4/7), coroidite linfomatosa (2/7), linfoma intradural (1/7). No felino diagnosticado com neurolinfomatose primária, foi observado acentuado espessamento dos nervos e gânglios paravertebrais da região sacral. Os linfomas de células de células B (75%) foram os mais frequentes e o principal tipo foi o linfoma difuso de grandes células B (11/16). Os linfomas de células T (25%), menos observados, foram classificados como linfomas de células T periférico inespecífico (3/16) e linfoma linfoblástico T (1/16).(AU)

Neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state, Brazil / Enfermidades neurológicas em bovinos causadas por plantas e micotoxinas no estado de Santa Catarina

This study described the epidemiological and clinical-pathological aspects of 25 outbreaks of neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state. Six of them were due to Sida carpinifolia poisoning, five to Solanum fastigiatum, five to Phalaris angusta, three to Claviceps paspali, three to Claviceps purpurea, and three outbreaks were of unknown etiology. The clinical signs observed in the affected cattle were mild to severe and characterized by generalized muscle tremors, incoordination, hypermetria, wide-based stance, intentional head tremors, dull staring eyes, and frequent ear twitching, with convulsions in some cases. At necropsy, lesions were observed only for P. angusta poisoning, characterized by gray-greenish discoloration in thalamus and midbrain. Microscopically, rarefaction and/or disappearance of Purkinje neurons with substitution by Bergmann cells were observed for S. carpinifolia and S. fastigiatum poisoning. For P. angusta poisoning, thin granular brown-yellowish pigment was observed in the cytoplasm of some neurons. Gross and microscopic findings were not observed in three outbreaks of tremorgenic disease of unknown etiology. Experiments conducted with leaves, flowers and seeds of Ipomoea indivisa and Ipomoea triloba, as well as with maize and soybean residues contaminated with Ipomoea spp. did not reproduced clinical signs.(AU)

Descrevem-se os aspectos epidemiológicos e clinico-patológicos de 25 surtos de enfermidade neurológica em bovinos no estado de Santa Catarina causadas por plantas e micotoxinas. Destes, seis corresponderam a intoxicação por Sida carpinifolia, cinco por Solanum fastigiatum, cinco por Phalaris angusta, três por Claviceps paspali, três por Claviceps purpurea e três surtos de etiologia não definida. Os sinais clínicos observados nos bovinos afetados eram de intensidade leve a acentuada e caracterizados por tremores musculares generalizados, incoordenação, hipermetria, aumento da base de sustentação, balanço contínuo de cabeça, olhar atento e movimentos frequentes de orelhas, e em alguns surtos convulsões. Por meio de necropsia foram observadas alterações somente na intoxicação por P. angusta as quais caracterizaram por coloração cinza-esverdeada no tálamo e mesencéfalo. Na histologia, rarefação e/ou desaparecimento de neurônios de Purkinje com substituição por células de Bergmann foram observadas na intoxicação por S. carpinifolia e S. fastigiatum. Na intoxicação por P. angusta foi observado no citoplasma de alguns neurônios do tronco encefálico com pigmentação finamente granular marrom-amarelada. Nos três surtos de enfermidade tremorgênica com etiologia não definida não foram observadas lesões macroscópicas e microscópicas. Experimentos com folhas, flores e sementes de Ipomoea indivisa e Ipomoea triloba e resíduos de milho e soja contaminados com sementes destas duas plantas não produziram alterações clínicas.(AU)

Clinical and pathological aspects of bovine lymphoma affecting the spinal cord / Aspectos clínicos e patológicos de linfoma bovino afetando a medula espinhal

Clinical and pathological features of bovine lymphoma involving the spinal cord were evaluated through a retrospective study of the necropsy database from 2005 to 2017. Thirty-four cases of bovine lymphoma were found, 24 of which had central nervous system involvement restricted to the spinal cord. All cattle were Holstein cows 2.5-12 years-old (median age, six years-old). The clinical course was 7-21 days, and the main neurological sign was pelvic limb paresis (81.8%). The lymphoma often affected the spinal cord in a multifocal manner. Lumbar segments were the mostly affected sites (23/24), followed by the sacral segments and cauda equina (20/24), cervical (5/24) and thoracic (5/24) segments. Tumors were in the epidural space, peripheral to the pachymeninges (extradural) and between layers of adipose tissue. In addition, two cases had progressive hemorrhagic myelomalacia. Further organs affected included the lymph nodes (100%), abomasum (79.2%), heart (75%) and kidneys (45.8%). Microscopically, all lymphomas had a diffuse pattern, with no meningeal or medullar infiltration. According to the REAL/WHO classification, all these neoplasms were mature B-cell lymphomas. Diffuse large B-cell lymphoma (DLBCL) was observed in 95.8% (23/24) of the cases. The following subtypes were observed in the DLBCL group in descending order: immunoblastic (60.9%, 14/23), centroblastic (26.1%, 6/23), anaplastic (8.7%, 2/23) and T-cell rich (4.3%, 1/23).(AU)

Os aspectos clínicos e patológicos do linfoma bovino afetando a medula espinhal foram avaliados através de um estudo retrospectivo dos protocolos de necropsia durante o período de 2005-2017. De um total de 34 bovinos com linfoma, 24 apresentaram afecção do sistema nervoso central (SNC) restrito a medula espinhal. Todos os bovinos afetados eram fêmeas, da raça Holandesa, com 2,5 a 12 anos de idade (idade mediana de seis anos). Clinicamente, os casos tiveram uma evolução de sete a 21 dias, com a principal alteração neurológica caracterizada por paresia de membros pélvicos, a qual foi observada em 81,8% dos casos. O linfoma afetou frequentemente a medula espinhal de maneira multifocal. Os segmentos lombares foram os mais envolvidos (23/24), seguidos pelos sacrais e cauda equina (20/24), cervicais (5/24) e torácicos (5/24). Os tumores estavam localizados no espaço epidural, periférica à paquimeninge (extradural) e associada ao tecido adiposo. Em dois casos foi também observada mielomalacia hemorrágica progressiva. Os órgãos acometidos com maior frequência, concomitantemente ao espaço epidural, foram os linfonodos (100%), abomaso (79,2%), coração (75%) e rins (45,8%). Microscopicamente, todos os linfomas exibiam um padrão difuso, sem infiltração em meninges e medula espinhal (extradural). De acordo com a classificação da REAL/WHO, todos esses neoplasmas foram incluídos como linfomas de células B maduras. O linfoma difuso de grandes células B (LDGCB) foi observado em 95,8% (23/24) dos casos. Os subtipos classificados dentro do grupo dos LDGCB's foram em ordem decrescente: imunoblástico (60,9%; 14/23), centroblástico (26,1%; 6/23), anaplásico (8,7%; 2/23), e rico em células T (4,3%; 1/23).(AU)

Clinico-pathological investigations of a distinct variant of focal cortical dysplasia characterized by neuronal loss of layer four / 中华神经科杂志

Objective To investigate the clinical pathologic features of a distinct variant of focal cortical dysplasia (FCD) characterized by neuronal loss of layer four.Methods Between 2005 and 2017,approximately 3 000 surgeries were performed for the treatment of intractable epilepsy at Xuanwu Hospital,Capital Medical University and Yuquan Hospital,Tsinghua University.Retrospective analysis of clinic-pathological data of patients with epilepsy surgery was made and histological manifestations of neuronal loss of cortical layer four were included in this study.Results In this cohort,25 patients (22 males and three females) were identified with early onset pharmaco-resistant epilepsy and regionally circumscribed neuronal loss of cortical layer four in surgical specimens from the occipital lobe.Histologically,except for neuronal loss in cortical layer four in all cases,glial scar lesions were found in some patients.Thus the histology of those cases can be subdivided into two groups:group A (13 cases):neuronal loss of cortical layer four without glial scar lesions;and group B (12 cases):neuronal loss of cortical layer four with glial scar lesions.Due to the prominent horizontal disorganization of cortical layering and lack of any other microscopically visible principle lesion,group A should be classified hitherto as FCD International League Against Epilepsy (ILAE) type Ⅰ b,however,group B with scar lesions and cortical dysplasia around the main leision,should be classified as FCD ILAE type Ⅲd.This retrospective analysis of clinical histories revealed a perinatal distress in 20 patients (80％),suggesting an acquired pathomechanism.Magnetic resonance imaging revealed abnormal signals in the occipital lobe in all patients,and signal changes suggestive of encephalomalacia were found in 18 patients.Surgical treatment achieved favorable seizure control (Engel class Ⅰ and Ⅱ) in 18 patients (75％ among 24 available follow up).Comparion of the two groups with age at epilepsy onset (group A:5.00±2.76,group B:5.01±3.78),the proportion of perinatal distress (group A:11/13,group B:9/12) and the follow-up results (favorable seizure control of the two groups was 9/13,9/11 respectively) showed that there was no statistically significant difference between the two groups.Conculsion Neuronal loss of cortical layer four in the occipital lobe should be classified as a distinct variant of FCD ILAE type Ⅲd.

The remarkable pioneering contribution of Gaspar Vianna to the study of the neuropathology of Chagas disease / A notável contribuição pioneira de Gaspar Vianna para o estudo da neuropatologia da doença de Chagas

ABSTRACT Gaspar Vianna is considered one of the great names in Medicine and Science in Brazil. Yet, little prominence has been given to his studies in Neuropathology. He was the first to describe, in 1911, the histopathology and pathogenesis of chagasic encephalitis in the acute phase of Chagas disease, as well as the intracellular life cycle of Trypanosoma cruzi. Over 100 years have elapsed and Gaspar Vianna's pioneering study remains an example of a meticulous and still up-to-date description of central nervous system involvement in the acute phase of Chagas disease.

RESUMO Gaspar Vianna é considerado um dos grandes nomes da Medicina e da Ciência no Brasil. Contudo, pouco destaque tem sido dado aos seus estudos em Neuropatologia. Ele foi o primeiro a descrever a histopatologia e a patogênese da encefalite chagásica na fase aguda da doença de Chagas, bem como o ciclo evolutivo intracelular do Trypanosoma cruzi, em 1911. Passados mais de 100 anos, o estudo pioneiro de Gaspar Vianna permanece como exemplo de descrição minuciosa e ainda atual do envolvimento do sistema nervoso central na fase aguda da doença de Chagas.

Gross and histopathological pitfalls found in the examination of 3338 cattle brains submitted to the BSE surveillance program in Brazil / Ciladas macroscópicas e histopatológicas encontradas no exame de 3338 encéfalos de bovinos submetidos ao programa de vigilância da EEB no Brasil

This study stems from the findings during the gross and histopathological exam of 3,338 cattle brains as part of the bovine spongiform encephalopathy (BSE) active surveillance program of the Brazilian Ministry of Agriculture, Livestock, and Supply from 2001 to 2005. The work was carried out in the Veterinary Pathology Laboratory of the Federal University of Santa Maria which at the time (2001-2007) was the national reference laboratory for the diagnosis of BSE and other transmissible spongiform encephalopathies. Both gross and histopathological aspects are described. Several gross aspects were annotated: anatomic normal structures not commonly recognized (non-lesions), lesions of no clinical significance, postmortem changes and artifacts; all these can amount to important pitfalls that distract the pathologist during the routine gross examination of the central nervous system (CNS). Accordingly, equivalent pitfalls were described in the histological examination. Non-lesions observed were the pineal body, embryo remnants such as the external germinal layer of the cerebellum, subependymal plates, and clusters of neuroblasts in the basal ganglia; or circumventricular structures such as area postrema, subcomisural organ, and melanosis in the leptomeninges and vessel walls. Lesions with little or no clinical importance included age-related changes as lipofuscin, hemosiderin, mineralization and hyalinization of vessel walls within the brain and meninges. Corpora amylacea and corpora arenacea were detected respectively in astrocyte processes and the pineal body. Cytoplasmic neuronal vacuolization was observed in the red nucleus and habenular nucleus. Sarcocystis sp. without a correspondent inflammatory reaction was rarely observed. Included within findings with no clinical manifestation were axonal spheroids and perivascular mononuclear cuffings. Changes in the CNS due to killing, sampling and fixation methods can obscure or distract from the more critical lesions. The ones related to the process of killing included hemorrhages caused in cattle destroyed by a captive bolt. Artifacts related to sampling and handling of CNS tissue consisted of inclusion of bone sand in the neural tissue from sawing the calvarium; dark neurons produced by excessive handling of the brain, and micro-organisms that contaminated the tissues during sampling or histological processing. Postmortem autolytic or putrefactive changes observed included vacuolar changes in the myelin sheath, clear halos surrounding neurons and oligodendrocytes, clusters of putrefaction bacilli within vessels or dispersed throughout the brain tissue associated or not to clear halos. One interesting, and somewhat frequent, postmortem autolytic change found in the bovine brain was the partial dissolution of the granule cell layer (GCL) of the cerebellum, also referred to as conglutination of the GCL or as the French denomination "état glace". Due to the shortage of comprehensive publications in the subject, this review is intended to address the main pitfalls that can be observed in the brain of cattle hoping to help other pathologists avoiding misinterpret them.(AU)

Os resultados deste estudo foram obtidos pelo exame macroscópico e histopatológico de 3.338 cérebros de bovinos examinados durante o programa de vigilância ativa da encefalopatia espongiforme bovina (BSE) do Ministério da Agricultura, Pecuária e Abastecimento (MAPA), de 2001 a 2005. O trabalho foi realizado no Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM) que, de 2001 a 2007, foi o laboratório nacional de referência para o diagnóstico da BSE e de outras encefalopatias espongiformes transmissíveis. Macroscopicamente, foram descritas estruturas anatômicas normais (não-lesões), mas que são, com frequência, interpretadas como lesões; lesões sem significado clínico; alterações pós-mortais e artefatos. Esses achados podem confundir e desviar a atenção do patologista durante o exame de rotina do sistema nervoso central (SNC). Da mesma forma, estruturas equivalentes foram descritas no exame histológico. As não-lesões observadas foram corpo pineal, remanescentes embrionários, como a camada germinativa externa do cerebelo, placas subependimárias e aglomerados de neuroblastos nos gânglios da base; ou estruturas circunventriculares, como área de postrema, órgão subcomissural e melanose em leptomeninges e paredes dos vasos. Lesões com pouca ou nenhuma importância relacionadas ao envelhecimento incluíram lipofuscina, hemossiderina, mineralização, hialinização das paredes dos vasos do encéfalo e das meninges. Corpora amylacea foram detectados em processos astrocíticos e corpora arenacea, no corpo pineal. Adicionalmente, foi observada vacuolização no citoplasma de neurônios do núcleo vermelho e do núcleo habenular. Sarcocystis sp. sem reação inflamatória correspondente foi raramente observado. Incluídos nos achados sem manifestação clínica estavam esferóides axonais e manguitos mononucleares perivasculares. Alterações no SNC causadas pelo método de abate, amostragem e fixação podem simular ou obscurecer lesões mais importantes. Aquelas relacionadas ao método de abate incluíram hemorragias causadas em bovinos dessensibilizados pelo dardo cativo ou por punção por faca da medula na articulação atlanto-occipital. Artefatos relacionados à amostragem e manuseio de tecido do SNC consistiram na inclusão de pó de osso no tecido neural em consequência do uso de serra para abrir a caixa craniana; neurônios escuros produzidos pelo manuseio excessivo do cérebro e micro-organismos que contaminaram os tecidos durante a amostragem ou processamento histológico. Alterações autolíticas pós-mortais ou de putrefação incluíram vacuolizações na bainha de mielina, halos claros em torno dos neurônios e oligodendrócitos, aglomerados de bacilos de putrefação dentro dos vasos ou dispersos em todo o tecido cerebral, relacionados ou não a halos claros. Uma alteração autolítica pós-mortal intrigante e relativamente frequente encontrada foi a dissolução parcial da camada de células granulares (CCG) do cerebelo, também referida como conglutinação da CCG ou "état glacé". Devido à escassez de publicações abrangentes neste assunto, esta revisão pretende abordar as principais ciladas que possam aparecer no cérebro de bovinos, na esperança de ajudar outros patologistas a evitar interpretá-las erroneamente.(AU)