Vitamin B[12] deficiency and multiple sclerosis; is there any association?

Vitamin B[12] [Cobalamin] deficiency can result in some clinical and paraclinical characteristics similar to what is seen in multiple sclerosis [MS] patients. This study aimed to evaluate the controversial association between B[12] deficiency and MS. We measured serum vitamin B[12] in 60 patients with MS and 38 healthy controls. Clinical disability was evaluated according to the Extended Disability Status Scale [EDSS]. Serum B[12] concentration was measured with Radioimmunoassay Dual Isotope method. The cutoff value for low serum vitamin B[12] concentration was 75 pg/mL. Patients were in remission at the time of blood draw. There were 13 [21.6%] MS patients and 10 [26.3%] controls with low serum B[12] concentration with no significant difference between the groups; P>0.05. The mean serum vitamin B[12] concentration in MS patients [108.9 +/- 45.3 pg/mL] was not significantly different compared with controls [98.9 +/- 44.4 pg/mL]; P=0.284. Likewise, there was no correlation between the concentration of serum vitamin B[12] and disease' age of onset, duration, subtypes, or disability status. In contrast to some previous reports, our findings did not support any association between B[12] deficiency and MS

MICB gene expression on peripheral blood mononuclear cells and susceptibility to multiple sclerosis in north of Iran

Multiple sclerosis [MS] is an autoimmune multifactorial degenerative disease with detrimental affliction on central nervous system. MHC class I chain- related geneA,B [MICA and MICB] are nonclassical human leukocyte antigens that can affect on some diseases and also on transplantation. The purpose of this study was to evaluate the MICA and MICB MRNA expression in multiple sclerosis patients. In this study, we evaluated MICA and MICB MRNA expression in the peripheral blood mononuclear cells by reverse transcryptase-polymerase chain reaction [RT-PCR] in MS patients and normal controls. The results of this study showed that 32.6% of patients with progressive clinical outcome over expressed MICB genes in comparison with controls [p=0.002]. It is concluded that the high expression of MICB gene in MS patients is an important criterion of MS disease that it may be due to the interaction between MICB and its receptor on CD8+T or NK cells

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

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

Isoprenoid pathway and free radical generation and damage in neuropsychiatric disorders.

Two substances which are products of the isoprenoid pathway, can participate in lipid peroxidation. One is digoxin, which by inhibiting membrane Na(+)-K+ ATPase, causes increase in intracellular Ca2+ and depletion of intracellular Mg2+, both effects contributing to increase in lipid peroxidation. Ubiquinone, another products of the pathway is a powerful membrane antioxidant and its deficiency can also result in defective electron transport and generation of reactive oxygen species. In view of this and also in the light of some preliminary reports on alteration in lipid peroxidation in neuropsychiatric disorders, a study was undertaken on the following aspects in some of these disorders (primary generalised epilepsy, schizophrenia, multiple sclerosis, Parkinson's disease and CNS glioma)--1) concentration of digoxin, ubiquinone, activity of HMG CoA reductase and RBC membrane Na(+)-K+ ATPase 2) activity of enzymes involved in free radical scavenging 3) parameters of lipid peroxidation and 4) antioxidant status. The result obtained indicates an increase in the concentration of digoxin and activity of HMG CoA reductase, decrease in ubiquinone levels and in the activity of membrane Na(+)-K+ ATPase. There is increased lipid peroxidation as evidenced from the increase in the concentration of MDA, conjugated dienes, hydroperoxides and NO with decreased antioxidant protection as indicated by decrease in ubiquinone, vit E and reduced glutathione in schizophrenia, Parkinson's disease and CNS glioma. The activity of enzymes involved in free radical scavenging like SOD, catalase, glutathione peroxidase and glutathione reductase is decreased in the above diseases. However, there is no evidence of any increase in lipid peroxidation in epilepsy or MS. The role of increased operation of the isoprenoid pathway as evidenced by alteration in the concentration of digoxin and ubiquinone in the generation of free radicals and protection against them in these disorders is discussed.

Imunopatologia da esclerose múltipla / Immunopathology of multiple sclerosis

A esclerose múltipla (EM) é uma doença do sistema nervoso central (SNC) na qual há destruiçäo da bainha de mielina e reaçäo inflamatória local. Acredita-se que seja uma resposta auto-imune desencadeada por fatores ambientais que induzem a superexpressäo de citocinas em indivíduos geneticamente predispostos. As citocinas implicadas nas exarcebações da EM, tais como IL-1, IL-2, IL-3, INFðy, TNF-alfa e TNF-ß, induzem a expressäo de moléculas específicas na membrana das células do SNC e ativam a funçäo fagocítica das células da micróglia