Syndrome in question

Abstract Ross syndrome is a rare disease characterized by peripheral nervous system dysautonomia with selective degeneration of cholinergic fibers. It is composed by the triad of unilateral or bilateral segmental anhidrosis, deep hyporeflexia and Holmes-Adie's tonic pupil. The presence of compensatory sweating is frequent, usually the symptom that most afflicts patients. The aspects of the syndrome are put to discussion due to the case of a male patient, caucasian, 47 years old, with clinical onset of 25 years.

Bilateral Hypertrophic Olivary Degeneration in Wilson Disease

Hypertrophic olivary degeneration resulting from lesions of the dento-rubro-olivary pathway, also called Guillain-Mollaret-triangle, has been described previously in a number of cases. Reports about bilateral hypertrophic olivary degeneration of the inferior olivary nuclei are very limited, and the magnetic resonance imaging findings of hypertrophic olivary degeneration in Wilson disease have not yet been described to the best of our knowledge. Herein, we present the first report of bilateral hypertrophic olivary degeneration diagnosed by magnetic resonance imaging in a patient suffering from Wilson disease.

Síndrome disautonómico de Ross: variaciones de un tema / Disautonomic Ross syndrome: variations about one theme

El síndrome de Ross fue descrito en 1958 como una afección degenerativa del sistema nervioso autónomo definido por la tríada de anhidrosis generalizada, disminución de los reflejos tendinosos y pupila tónica. Desde su descripción inicial se han descrito cerca de cuarenta casos. Comunicamos tres pacientes con variantes de interés que incluyen la presencia de espasmos cíclicos espontáneos del esfínter de iris, el desarrollo conjunto de síndrome de Holmes-Adie en un lado y síndrome Horner posganglionar en el otro, trastornos del desarrollo piloso en el lado de la anhidrosis, alteraciones de la motilidad intestinal, lengua sin papilas gustativas y disfunción sexual.

Ross Syndrome was described in 1958 as a degenerative condition of the autonomic nervous system defined by a triad of generalized anhidrosis, reduction of tendon reflexes and tonic pupil. Since its initial description about 40 cases have been described. We communicate three cases with variants of interest involving the presence of the simultaneous development of syndrome of Holmes-Adie on one side and Horner syndrome in the other, disorders of pilous follicle development on the side of anhidrosis, spontaneous disturbances of intestinal motility, tonque without papillae and sexual dysfunction.

Potential of immunosuppressive agents in cerebral ischaemia.

Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia.

A hereditariedade mórbida: de Kraepelin aos neokraepelinianos / The morbid heredity: from Kraepelin to the Neo-Kraepelinians

Analisamos aqui as referências que Emil Kraepelin dedica à problemática da herança mórbida. Estudamos a persistência e continuidade das principais teses de Kraepelin, incluída a etiologia hereditária de patologias mentais, na Psiquiatria contemporânea que se define como neokraepeliniana. Com esse objetivo, analisamos inicialmente as articulações teóricas e conceituais que existem entre a ideia de constituição mórbida e as estratégias propostas por Kraepelin para a realização das entrevistas psiquiátricas. A seguir, consideramos o lugar reservado aos estudos dedicados à herança mórbida no contexto histórico de surgimento da psiquiatria neokraepeliniana, especificamente a partir da elaboração do DSM III.

We analyze here the problems of the morbid heredity in the different editions of the work of Emil Kraepelin Clinical Psychiatry: a Text-book for students and physicians. We study the persistence and continuity of the main thesis of Kraepelin, included the hereditary etiology of mental pathologies, in the contemporary Psychiatry that is self-defined as Neo-kraepelinian. With this goal we study, firstly, the theoretical and conceptual articulations that exist between the idea of morbid constitution and the strategies proposed by Kraepelin for the realization of the psychiatric interviews. Next, we consider the place reserved to the studies of the morbid heredity in the historical context in which the Neo-Kraepelinian Psychiatry emerged, specifically since the elaboration of the DSM III.

Sensory involvement in the SOD1-G93A mouse model of amyotrophic lateral sclerosis

A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS-like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.

Inmunohistoquímica de los cambios degenerativos del sistema nervioso central en paraparesias esp sticas asociadas al virus linfotrópico humanoTtipol(HTLV-l) / Immunohistochemistry of degenerative changes in the central nervous system in spastic paraparesis associated to human T lymphotropic virus type I (HTLV-I)

Background: Human T lymphotropic virus type I is associated with tropical spastic paraparesis, that is a chronic and progressive disease which damages specially the cortiespinal tracts. The pathogenesis of this degenerative process remains unknown. Aim: To identify histopathological aspects that could suggest a pathogenic hypothesis we studied immunohistochemical features in spinal cords obtained from patients that died due to progressive spastic paraparesis. Patients and Methods: Five males and five females, who died between 1990 and 2000, with a mean age of 52 years and mean disease duration of 8.6, were studied. All had a complete clinical and virological diagnosis. Samples were obtained from the frontal motor cortex and spinal cord (cervical, dorsal and lumbar segments), were fixed in formol (10 percent), included in paraffin, and stained with Haematoxylin and Luxol-fast-blue. Immunohistochemical study was made with anti-neurofilament antibodies 1:100 (M0762, DAKO), anti-APP 1:20 (Rabbit Pre Amyloid protein 51-2700 ZYMED), anti-tau 1:100 (A0024DAKO) and anti-ubiquitine 1:50 (NCL UBIQm Novocastra). Results: All cases had demyelinization and axonal loss in the cortico-spinal tracts; distal and segmental demyelinization of Goll tract; axonal thickening, amyloid precursor protein deposits in the white matter; tau protein aggregation in the spinal cord oligodendrocytes; axonal ubiquitination of sensitive and motor tracts, and subcortical white matter. Neurona! injury was absent. Conclusions: The systematic damage of motor and sensitive tracts of the spinal-cord and the absence of neurona! damage, defines a degenerative process limited to axons. This central axonopathie could be caused by a disturbance of axoplasmic transport.

Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo

A degree of brain inflammation is required for repair of damaged tissue, but excessive inflammation causes neuronal cell death. Here, we observe that IL-10 is expressed in LPS-injected rat cerebral cortex, contributing to neuronal survival. Cells immunopositive for IL-10 were detected as early as 8 h post-injection and persisted for up to 3 d, in parallel with the expression of IL-1beta, TNF-alpha, and iNOS. Double immunofluorescence staining showed that IL-10 expression was localized mainly in activated microglia. Next, we examined the neuroprotective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action caused a significant loss of neurons both 3 d and 7 d after LPS injection. Further, the induction of mRNA species encoding IL-1beta, TNF-alpha, and iNOS, reactive oxygen species (ROS) production, and NADPH oxidase activation, increased after co-injection of LPS and IL-10NA, compared to the levels seen after injection of LPS alone. Taken together, these results clearly suggest that LPS-induced endogenous expression of IL-10 in microglia contributes to neuronal survival by inhibiting brain inflammation.

Compromiso neuronal en esclerosis multiple / Neuronal injury in multiple sclerosis

La esclerosis múltiple (EM) ha sido considerada clásicamente como una enfermedad desmielinzante. Si bien el compromiso neurodegenerativo fue previamente descripto, sólo recientemente ha sido enfatizado. Por estudiosos recientes se ha identificado la degeneración axonal como el mayor determinante de discapacidad neurológica irreversible en pacientes con EM. El daño axonal se inicia tempranamente y permanece silente durante años, la discapacidad neurológica se desarrolla cuando se alcanza cierto umbral de pérdida axonal y los mecanismos de compensación se agotan. Se han propuesto tres hipótesis para explicar el daño axonal: 1) El daño es causado por un proceso inflamatorio, 2) Existe una excesiva acumulación de Ca2+ intra-axonal, 3) Los axones desmienlinizados evolucionan a un proceso degenerativo producto de la falta de soporte trófico provisto por la mielina o células formadoras de mielina. Si bien la EM fue tradicionalmente considerada como una enfermedad de la sustancia blanca, el proceso de desmielinización tambiém ocurre en la corteza cerebral

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment

Mielopatía por déficit de vitamina B12: caracterización clínica de 11 casos / Subacute combined degeneration of the spinal cord caused by vitamin B12 deficiency: report of 11 cases

Background: Subacute combined degeneration is a clinical manifestation of vitamin B12 deficiency, that we observe with unusual frequency. Aim: To report a series of eleven patients with subacute combined degeneration. Patients and methods: Retrospective analysis of 11 patients hospitalized in a public hospital in Santiago, between March 2001 and February 2003. All had a myelopathy of more than three weeks of evolution with serum vitamin B12 levels of less than 200 pg/ml. Results: A risk factor was identified in 10 cases and the most common was an age over 60 years old. The main presenting symptom was the presence of paresthesias. On admission, sphincter dysfunction, posterior column and pyramidal syndromes coexisted in nine patients. A level of sensitive deficit was detected in six. Ten patients had macrocytosis and eight were anemic. Serum vitamin B12 was measured in ten and in nine, it was below 200 pg/ml. The mean lapse between onset of symptoms and treatment was eight months. All received intramuscular vitamin B12 in doses on 1,000 to 10,000 IU/day. Sphincter dysfunction and propioception were the first symptoms to improve. Conclusions: Subacute combined degeneration must be suspected in patients older than 60 years with a subacute myelopathic syndrome and low serum vitamin B12 levels.

O sistema glutamatérgico e desordens neuropsiquiátricas: aspectos funcionais e fisiopatológicos / The glutamatergic system and neuropsychiatric disorders: functional and pathophysiological aspects

O sistema glutamatérgico tem sido objeto de numerosos estudos recentes devido à crescente importância que lhe é atribuída em função da plasticidade neural e da excitotoxicidade, os principais pontos enfocados nessa revisão. A plasticidade neural (sináptica) tem como base neurofisiológica a potenciação dos variados receptores glutamatérgicos ionotrópicos e metabotrópicos, centralizados pelo receptor NMDA. As complexas modificações de longa duração subjacentes a essa atividade têm como substrato a mudança do número de receptores AMPA e NMDA na zona ativa das sinapses envolvidas (mecanismos de deslocamento, exocitose e endocitose) e a sinalização para o núcleo da célula (transcrição gênica com síntese de proteínas e enzimas). Essas modificações plásticas encontram-se subjacentes aos mecanismos de aprendizagem e memória. A participação do sistema em condições patológicas também é de alta relevância, já que glutamato em excesso apresenta ação tóxica ('excitotoxicidade') e junto com os receptores super-estimulados que permitem um aumento da entrada de cálcio para a célula, leva a modificações agudas (modelo hipóxico-isquêmico) ou crônicas (modelo neurodegenerativo - doença de Alzheimer e a 'hipótese glutamatérgica'), capazes de causar disfunção, lesão e morte neuronal. Esses conhecimento a respeito do sistema glutamatérgico são fundamentais para a compreensão de funções e disfunções ligadas à processos cognitivos e degenerativos, assim como para utilizá-los objetivando intervenções terapêuticas

Cambios neurofisiológicos en el adulto mayor: sensibilidad y reflejos / Neurophysiologic changes in the major: sensibility and reflex

Se tomaron 200 casos de ambos sexos mayores de 65 años, excluyéndose los pacientes: diabeticos, con enfermedad cerebrovascular, neuropatía periférica, en coma o con cualquier psicopatía. Se exploraron las siguientes variables: sensibilidad térmica, discriminatoria, sentido de posición segmentaria, estereognosia y vibratoria y los reflejos osteomusculotendinosos bicipital, tricipital, estilorradial cubitopronador, abdominales, mediopubiano, patelar y aquiliano. Los resultados fueron los siguientes: no hubo alteración en la exploración de la sensibilidad térmica y el sentido de las posiciones segmentarias. Se encontró diferencias estadísticamente significativas en las modalidades sensoriales de la discriminatoria, estereognosia, afectándose el grupo de 75 años y más. La sensibilidad vibratoria se encontró disminuida en miembros inferiores en forma significativa para ambos grupos de edad. Los reflejos osteomusculotendinosos más alterados fueron el patelar y aquiliano para ambos grupos de edad (21 y 44 respectivamente). Se concluye que en la muestra estudiada la prevalencia de anormalidad encontrada fué menor que la demostrada por otros investigadores y que las alteraciones encontradas en los adultos mayores no se pueden atribuir solo al proceso de envejecimiento.