Schwannomatose - primeiros casos relatados no Brasil / Schwannomatosis - first reported cases in Brazil

A dor neuropática pode ser decorrente de diversas causas, entre elas a schwannomatose (SCH), uma doença que acomete cerca de cinco mil brasileiros. A SCH é caracterizada por schwannomas múltiplos e intensamente dolorosos. O diagnóstico diferencial de SCH inclui especialmente as neurofibromatoses do tipo 1 e 2. Um caso típico de SCH, provavelmente o primeiro registrado no Brasil, é apresentado e discutido em detalhes e dois outros casos subsequentes são comparados quanto a determinados aspectos clínicos e radiológicos. Paciente feminina de 33 anos de idade foi admitida com queixas de dor e diminuição progressivada força no membro inferior esquerdo, havia cinco anos, associadas ao surgimento de nodulações muito dolorosas naquela região. Apresentava também duas manchas café com leite (<1 cm). A RNM detectou tumores de partes moles em região subcutânea e intracavitárias. Foram realizadas duas biópsias em regiões distintas e o exame microscópico de dois nódulos revelou células de Schwann envoltas por abundante estroma mixóide. O exame imuno-histoquímico mostrou marcação forte e difusa para proteína S-100. O exame ultraestrutural demonstrou nas áreas centrais células de Schwann, com restos membranosos intracitoplasmáticos e, focalmente, membrana basal redundante. A sintomatologia álgica, o padrão de crescimento neoplásico intraneural, com acentuado edema peritumoral, hialinização vascular e reatividade imuno-histoquímica para proteína S-100 nas células de Schwann no centro das lesões possibilitaram o diagnóstico de schwannomatose. O tratamento farmacológico para a dor foi a opção possível, obtendo-se remissão parcial da dor...

Neuropathic pain stems various sources including schwannomatosis (SCH), a disease that affects about five thousand Brazilians. SCH is characterized by multiple and intensely painful schwannomas. Differential diagnosis of SCH includes, especially, neurofibromatosis types 1 and 2. A typical case of SCH, possibly the first recorded in Brazil, is presented and discussed in detail and compared with two other subsequent cases with regards to selected clinical and radiological aspects. A 33 year-old female patient was admitted with pain and progressive loss of strength in the left lower limb for the past five years. These complaints were associated withthe appearance of very painful nodules in the same region. She also had two light brown (café-au-lait) spots (<1 cm). MRI detected soft tissue tumors in the subcutaneous and intracavitary regions. Two distinct biopsies of different regions and microscopic examination of two nodulesrevealed Schwann cells surrounded by abundant myxoid stroma. Immunohistochemical examination showed strong and diffuse markers of S-100 protein. Ultrastructural examination showed Schwann cells in the core areas with traces of intracytoplasmic membranes and foci of redundant basement membrane. The pain symptoms, the pattern of intraneural neoplastic growth with marked peritumoral edema, vascular hyalinization, and immunohistochemical reactivity for S-100 protein in Schwann cells in lesion cores suggested the diagnosis of schwannomatosis. Pharmacological pain treatment achieved partial remission of pain...

Ethidium bromide-induced demyelination in the sciatic nerve of diabetic rats / Desmielinização induzida pelo brometo de etídio no nervo ciático de ratos diabéticos

This study aims to observe the process of myelin loss and repair following the injection of the gliotoxic agent ethidium bromide (EB) in the sciatic nerve of rats previously induced to diabetes mellitus by streptozotocin. Injection of EB was also done in non-diabetic rats. The animals were euthanatized from 3 to 31 days after intraneural injection and nerve sections were collected for ultrastructural study. In non-diabetic rats, Schwann cells (CS) showed signs of intoxication 3 days after, with cytoplasmic vacuolization and rejection of their myelin sheaths. Myelin debris were removed by macrophages in the endoneurium and mast cells were abundant in the lesions. From 14 days following EB injection, supernumerary CS were seen in the expanded endoneurium as well as thin myelin sheaths indicating remyelination. Diabetic rats presented a more extensive myelin vesiculation and segmentar demyelination, with delayed activities from both macrophages and remyelinating SC. No mast cells were noted.

O estudo visa à observação do processo de perda e reparo mielínico pós-injeção do gliotóxico brometo de etídio (BE) no nervo ciático de ratos previamente induzidos a diabetes mellitus pela estreptozotocina. Injeção de BE foi igualmente realizada em ratos não-diabéticos. Os animais foram eutanasiados dos 3 aos 31 dias pós-injeção intraneural, com colheita de amostras neurais para estudo ultra-estrutural. Nos animais não-diabéticos, as células de Schwann (CS) mostraram sinais de intoxicação a partir dos 3 dias pós-gliotóxico, com vacuolização citoplasmática e rejeição de suas bainhas de mielina. Restos mielínicos eram removidos por macrófagos no interior do endoneuro e mastócitos eram abundantes nas lesões. A partir dos 14 dias, CS supranumerárias foram encontradas no endoneuro expandido, além de finas bainhas de mielina indicativas de remielinização. Os ratos diabéticos apresentaram vesiculação mielínica e desmielinização segmentar mais extensas, bem como ausência de mastócitos e atraso na atividade macrofágica e na função remielinizante das CS.

Ultrastructural study of the effects of cyclosporine in the brainstem of Wistar rats submitted to the ethidium bromide demyelinating model / Estudo ultra-estrutural dos efeitos da ciclosporina no tronco encefálico de ratos Wistar submetidos ao modelo desmielinizante do brometo de etídio

The ethidium bromide-demyelinating model (EB) was used to study remyelination in the brainstem under the use of cyclosporine (CsA). Wistar rats were submitted to intracisternal injection of 0.1 percent EB or 0.9 percent saline solution, and others were taken as histologic controls (group I). Within those injected with EB, some have not received immunosuppressive treatment (II); some were treated by intraperitonial route with CsA (III.E - 10 mg/kg/day). Rats from group III.C were injected with saline solution and treated with CsA. The animals were perfused from 15 to 31 days post-injection collecting brainstem sections for light and transmission electron microscopy studies. After EB injection it was noted the presence of macrophages and non-degraded myelin debris, demyelinated axons, oligodendrocyte or Schwann cell remyelinated axons, groups of infiltrating pial cells, hypertrophic astrocytes and few lymphocytes. Tissue repair of EB-induced lesions in group III.E was similar to that of group II, but with the presence of a higher density of oligodendrocytes near remyelinating areas.

Empregou-se o modelo desmielinizante do brometo de etídio (BE) com o objetivo de estudar a remielinização no tronco encefálico frente ao uso de ciclosporina (CsA). Foram utilizados ratos Wistar, submetidos à injeção de BE a 0,1 por cento ou de solução salina na cisterna pontina, assim como controles histológicos (grupo I). Dos animais injetados com BE, alguns não receberam tratamento imunossupressor (II); outros foram tratados por via intraperitoneal com CsA (III.E - 10 mg/kg/dia). O grupo III.C incluiu animais injetados com salina e tratados com CsA. Os animais foram perfundidos dos 15 aos 31 dias pós-injeção, com colheita de material do tronco encefálico para estudos de microscopia de luz e eletrônica de transmissão. Após injeção de BE, foram observados macrófagos e restos de mielina não-degradada, axônios desmielinizados ou remielinizados por oligodendrócitos e por células de Schwann, grupos de células piais infiltrantes, astrócitos hipertróficos e poucos linfócitos. O processo de reparo das lesões no grupo III.E apresentou-se similar ao do grupo II, porém com maior densidade de oligodendrócitos próximos às áreas de remielinização.

Diagnóstico de leucodistrofia de Krabbe por microscopia electrónica de transmisión: informe de un paciente / Diagnosis of Krabbe's leukodystrophy by transmission electron microscopy: case report

La leucodistrofia de Krabbe es una enfermedad rara en México, por este motivo se reporta un caso de una niña de 11 años. Se describen los estudios ultraestructurales de biopsia de nervio sural. Las vainas de mielina fueron muy delgadas. El citoplasma de las células de Schwann contenía estructuras no membranosas y estructuras en forma de agujas parcialmente curvilíneas de longitud variable. Las inclusiones a menudo tenían material electrodenso o electrolúcido. Estas características representan a la leucodistrofia de Krabbe. Los estudios ultraestructurales ayudan al diagnóstico en los casos en que no se dispone de estudios genéticos o técnicas especiales de laboratorio. En la paciente descrita el diagnóstico de enfermedad de Krabbe se estableció tardíamente de acuerdo con el inicio de los síntomas. El diagnóstico de leucodistrofia de Krabbe se puede evidenciar con el estudio de microscopia electrónica de nervio sural.

Krabbe's leukodystrophy is a rare hereditary disease in Mexico. For that reason we report the case of an 11-year-old child. Ultrastructural studies of sural nerve biopsy specimen are described. Myelin sheaths were uniformly thin for the fiber diameters. Cytoplasm of Schwann cells exhibited a moderate dilatation with non-membrane masses with partly curvilinear, needle-shaped structures of variable length. The inclusions often had electron-dense or electron-lucent halos. These inclusions ultrastructurally represented Krabbe's leukodystrophy, and this method aids in the diagnosis in cases that are not available for genetic studies or special laboratory techniques. In this patient, diagnosis of Krabbe's disease was delayed and established several years after the initial symptoms. Electron microscopic examination of a sural nerve provided evidence for a diagnosis of Krabbe's leukodystrophy.

Delayed Schwann cell and oligodendrocyte remyelination after ethidium bromide injection in the brainstem of Wistar rats submitted to streptozotocin diabetogenic treatment

Schwann cell disturbance followed by segmental demyelination in the peripheral nervous system occurs in diabetic patients. Since Schwann cell and oligodendrocyte remyelination in the central nervous system is a well-known event in the ethidium bromide (EB) demyelinating model, the aim of this investigation was to determine the behavior of both cell types after local EB injection into the brainstem of streptozotocin diabetic rats. Adult male Wistar rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 æL 0.1 percent (w/v) EB or 0.9 percent saline solution into the cisterna pontis. Ten microliters of 0.1 percent EB was also injected into non-diabetic rats. The animals were anesthetized and perfused through the heart 7 to 31 days after EB or saline injection and brainstem sections were collected and processed for light and transmission electron microscopy. The final balance of myelin repair in diabetic and non-diabetic rats at 31 days was compared using a semi-quantitative method. Diabetic rats presented delayed macrophage activity and lesser remyelination compared to non-diabetic rats. Although oligodendrocytes were the major remyelinating cells in the brainstem, Schwann cells invaded EB-induced lesions, first appearing at 11 days in non-diabetic rats and by 15 days in diabetic rats. Results indicate that short-term streptozotocin-induced diabetes hindered both oligodendrocyte and Schwann cell remyelination (mean remyelination scores of 2.57 ± 0.77 for oligodendrocytes and 0.67 ± 0.5 for Schwann cells) compared to non-diabetic rats (3.27 ± 0.85 and 1.38 ± 0.81, respectively).

relationship between Schwann cells and endoneurial macrophages after sciatic nerve crush injury

Twenty eight male albino rats aged 6-8 weeks [weighed 300g to 350g] were used in this study: Twenty animals were used for the ultrastuctural study while eight animals were used for the ferritin intravenous injection study. The animals of the ultrastuctural study were divided into two groups; the experimental group [16 rats] and the control group [4 rats]. The left sciatic nerves of the experimental rats were subjected to crush injury while the right and left sciatic nerves of the other 4 rats were used as a control.The animals of the ferritin intravenous injection study were divided into the experimental group [4 rats] and the control group [4 rats]. The left sciatic nerves of the experimental rats were subjected to crush injury. After one week, ferritin was injected intravenously through the vein of the rat tail. The control 4 rats were intravenously injected with ferritin without crush injury and used as a control group.The ultrastractural study of the crushed sciatic nerves showed that nerve fibres could be classified into three main categories. These are the regenerating, recovering and degenerating nerve fibres. The regenerating myelinated and recovering nerve fibres were surrounded by endoneurial macrophages, fibroblasts and collagen fibrils. The cytoplasm of the Schwann cells of the recovering nerve fibres contained large fat globules. They also showed increased pinocytotic vesicles in their cytoplasmic membranes and basal laminae. Macrophages sent their processes to be in close contact to the basal laminae of Schwann cells of the regenerating nerve fibres. Most of the regenerating unmyelinated nerve fibres were not surrounded by the endoneurial macrophages. Active mitosis of the Schwann cells was recorded during the first four weeks after the crush injury.Ferritin intravenous injection study showed that after crush injury, ferritin particles did not cross the cytoplasmic membrane of the Schwann cells indicating that fat cells inside them were of endogenous origin.It could be concluded that there are three types of nerve fibres after peripheral nerve crush injury. They are the regenerating, the recovering and degenerating nerve fibres. The presence of macrophages, fibroblasts and collagen bundles around the nerve fibres could be an indication to its viability. Macrophages might play a role in promoting the Schwann cells for myelin formation and possibly for active mitosis. The myelin carried by the endoneurial macrophages is probably the wasted myelin

Tumor de células granulares de esôfago: estudo de oito casos diagnosticados por análise endoscópica, histopatológica e imunohistoquímica / Granular cell tumor of the esophagus: a study of eight cases diagnosed by endoscopis, histopathological and immunohistochemical analysis

Os autores realizam estudo de oito casos de tumor de células granulares do esôfago. Os pacientes apresentavam idades variáveis de 25 a 49 anos, sendo dois homens e seis mulheres. Todos apresentavam sintomas dispépticos sendo submetidos a endoscopia digestiva alta. O diagnóstico de tumor de células granulares foi estabelecido por estudo anátomo-patológico e a imunohistoquímica mostrou-se positiva em todos os casos para proteina S100, enolase neurônio específica e neurofilamentos, sendo negativa para mioglobina, corroborando a origem destes tumores nas células de Schwann.

Utilización de cultivos de células de Schwann para el estudio de la infección in vitro con Mycobacterium leprae / Use of Schwann cell cultures in the study of Mycobacterium leprae in vitro infection

Mycobacterium leprae es un patógeno intracelular con marcada afinidad por células de Schwann (CS) y macrófagos del sistema reticuloendotelial, que causa una neuropatía periférica en el hombre. Es un microorganismo no cultivable en medios convencionales y numerosos intentos por cultivarlo han sido infructuosos. Los modelos animales utilizados, han sido los de elección, entre estos el del cojinete plantar del ratón que es la prueba oro utilizada en el diagnóstico y el estudio de la patogenesis de la enfermedad, la viabilidad y la resistencia a antibióticos por parte del M. leprae. Conociendo que todos los tipos de lepra (LL,LT, etc.) cursan con una lepra de tipo neural, consideramos que un modelo in vitro de CS de ratón permitiría una gran aproximación al estudio de la interacción del M. leprae y su célula blanco específica en la infección, la cual se puede obtener en cultivo, conservando propiedades morfológicas y funcionales tales como es su capacidad de asociación con neuritas. Aunque las CS comprenden el 90 por ciento de la población inicial en cultivos de ganglios de raíz dorsal (DRG), su número declina debido a la rápida rata mitótica de los fibroblastos en presencia de suero fetal bovino. Sin embargo el tratamiento de los cultivos con agentes activadores del AMP cíclico inhiben el crecimiento de fibroblastos sin causar toxicidad a la CS, permitiendo su proliferación y enriquecimiento. Utilizando un tratamiento con agentes activadores del AMPc se obtuvieron cultivos enriquecidos en células de Schwann, lo cual fue corroborado por recuentos basados en sus características morfológicas y su inmunoreactividad al anticuerpo dirigido contra la proteína S-100, una proteína reguladora de la concentración de calcio intracelular, asociada a filamentos intermedios, presente en la célula de Schwann y ausente en los fibroblastos. Obtuvimos cultivos con un 88 por ciento de células de Schwann los cuales han sido usados en los ensayos de infección. Para la infección de células de Schwann por el Mycobacterium leprae, se utilizó la técnica recomendada por la O.M.S. de obtención y cuantificación de los bacilos a partir de lepromas obtenidos de pacientes con lepra lepromatosa no tratados. Cultivos enriquecidos en células de Schwann se incubaron con este M. leprae y se realizaron estudios morfológicos por microscopía óptica, usando la coloración de Zielh Neelsen caliente cuantificando el número de bacilos por célula y el porcentaje de células infectadas, estudios de...

Ultrastructural changes in the pre- and post-synaptic elements of the neuromus cular junction of the adult albino rat following nerve crush lesion

Using electron microscopy, the morphological changes in the presynaptic and postsynaptic elements [nerve terminal, terminal Schwann cells and the post-synaptic folds] of the neuromuscular junction of the rat, induced by nerve crush lesion, have been investigated. Adult albino rats were used in this study. The sciatic nerve was crushed, and denervated gastrocnemius muscles were dissected at different intervals following the crush lesion. The results were given

An ultrastructural study of Schwann cells in peripheral nerves of leprosy patients.

An ultrastructural study of peripheral nerves in leprosy patients was carried out of ascertain the changes in Schwann cells containing myelinated and nonmyelinated axons. Axonal multiplication was noticed in nonmyelinated axons in specimens from both tuberculoid and lepromatous leprosy. The Schwann cells in tuberculoid nerves were devoid of M. leprae in contrast to those in lepromatous nerves in which large number of bacilli were seen. These observations suggest that the Schwann cells containing nonmyelinated axons may be affected more frequently in either type of leprosy.

Fine structure of sensore nerve endings and SEM study of the palatine mucosa of rats

Se estudió la estructura fina de las terminaciones sensoriales nerviosas, a través de microscopÍa electrónica de barrido de la superficie celular y del tejido conectivo epitelial. La superficie epitelial de la mucosa palatina de la rata mostró una superficie de células planas y algunas elevaciones de la mucosa. La superficie de la célula está caracterizada por la presencia de numerosos micropliegues. Especímenes tratados con HCL-colagenasa revelaron que la interfase del tejido conectivo-epitelial presentaba varios surcos, circulares y alargados. Las pequeñas proyecciones citoplasmáticas son claramente visibles. Las terminaciones nerviosas libres bajo el epitelio se encuentran en el pequeño tejido conectivo papilar y están circundados por una delgada lámina de células de Schwann. El axoplasma mostró numerosas mitocondrias, neurofilamentos cuerpos multicorpustulares y pequeñas protusiones citoplasmáticas

Peripheral nerve sheath tumours: an ultrastructural study of 30 cases.

This report deals with the ultrastructural observations of 30 peripheral nerve sheath tumours [PNST], which include 25 schwannomas of acoustic nerve, one schwannoma of cauda equina, one neurofibroma from a case of Von Recklinghausen's disease, one pigmented neurofibroma of spinal nerve root and a malignant schwannoma of frontal region. Interdigitating slender cytoplasmic processes covered with a continuous layer of basal lamina constitute the single most important ultrastructural attribute of Schwann cells. Myelin formation was encountered in the cell processes of four out of 25 acoustic schwannomas. In four cases Microtubular arrays identical to that in an axon were seen in Schwann cells. These two observations require further support by additional cases of PNST studies by electron microscopy. The neurofibroma consisted only of Schwann cells and no ultrastructurally identifiable perineurial cells or fibroblasts were detected. The cells in the pigmented neurofibroma revealed submicroscopic features of both Schwann cell and melanocyte, indicating their common ancestry. A unique case of malignant schwannoma arising from frontal meninges is illustrated and it is emphasized that electron microscopy is mandatory for a correct histogenetic diagnosis of malignant tumours which occur at unexpected anatomical sites.

Ultrastructure of sciatic nerve of armadillo infected with Mycobacterium leprae.

Ultrastructural observation of sciatic nerves from eight Armadillos were made. Six animals had intravenous inoculation of M. leprae, one had of foot pad, while one had natural leprosy. The available nerves were biopsied at various time sequence ranging from five weeks to twenty four months. Semithin sections did not reveal any neuropathy. Ultrastructurally perineurium was thick and endoneurial collagen was increased. Initially demyelination of non-myelinated fibres was seen in all nerves irrespective of mode of infection. This was followed by demyelination of small myelinated fibres. Active remyelination was predominantly after 17 months. Schwann cell activity was increased and various stages of division were seen. Bacilli were extracellular, intraxonal, in endothelium and in perineurium. Significant observations were on blood vessels. These observations are discussed.