The effect of exercise therapy on cognitive functions in multiple sclerosis patients: A pilot study.

BACKGROUND: The positive impacts of exercise therapy on patients' cognitive problems still remain unknown. This study was a pilot intervention to examine the effects of combined exercise on the cognitive problems of patients with multiple sclerosis (MS) in Iranian MS Society over 2012 to 2013. METHODS: This quasi-experimental research was carried out in the form of a pretest/posttest study. Forty two patients with MS were selected from those visiting the rehabilitation center of Iranian MS Society, using non-probability convenience sampling. The Expanded Disability Status Scale (EDSS) of each patient was recorded before the intervention and Brief Repeatable Battery of Neuropsychological (BRB-N) test was administered before and after the intervention. The data were analyzed using the analytical tests such as Wilcoxon test. RESULTS: Of 21 participants, 17 subjects (82%, n=14) female with mean (±SD) age of 37 (±9.98) years and mean (±SD) EDSS of 2.35 (±0.90) completed all stages of the study. Changes in long-term storage and permanent long-term retrieval of information after the intervention were statistically significant (p<0.001). In addition, the change in the average of total delay after the intervention was also significant by 1.11 (p<0.001). CONCLUSION: Our study confirmed the possibility of change in the cognitive abilities of MS patients through physical interventions. This finding emphasizes the necessity of more clinical examinations and increases the hopes for new rehabilitation methods for the disorder.

Safinamide and flecainide protect axons and reduce microglial activation in models of multiple sclerosis.

Axonal degeneration is a major cause of permanent disability in the inflammatory demyelinating disease multiple sclerosis, but no therapies are known to be effective in axonal protection. Sodium channel blocking agents can provide effective protection of axons in the white matter in experimental models of multiple sclerosis, but the mechanism of action (directly on axons or indirectly via immune modulation) remains uncertain. Here we have examined the efficacy of two sodium channel blocking agents to protect white matter axons in two forms of experimental autoimmune encephalomyelitis, a common model of multiple sclerosis. Safinamide is currently in phase III development for use in Parkinson's disease based on its inhibition of monoamine oxidase B, but the drug is also a potent state-dependent inhibitor of sodium channels. Safinamide provided significant protection against neurological deficit and axonal degeneration in experimental autoimmune encephalomyelitis, even when administration was delayed until after the onset of neurological deficit. Protection of axons was associated with a significant reduction in the activation of microglia/macrophages within the central nervous system. To clarify which property of safinamide was likely to be involved in the suppression of the innate immune cells, the action of safinamide on microglia/macrophages was compared with that of the classical sodium channel blocking agent, flecainide, which has no recognized monoamine oxidase B activity, and which has previously been shown to protect the white matter in experimental autoimmune encephalomyelitis. Flecainide was also potent in suppressing microglial activation in experimental autoimmune encephalomyelitis. To distinguish whether the suppression of microglia was an indirect consequence of the reduction in axonal damage, or possibly instrumental in the axonal protection, the action of safinamide was examined in separate experiments in vitro. In cultured primary rat microglial cells activated by lipopolysaccharide, safinamide potently suppressed microglial superoxide production and enhanced the production of the anti-oxidant glutathione. The findings show that safinamide is effective in protecting axons from degeneration in experimental autoimmune encephalomyelitis, and that this effect is likely to involve a direct effect on microglia that can result in a less activated phenotype. Together, this work highlights the potential of safinamide as an effective neuroprotective agent in multiple sclerosis, and implicates microglia in the protective mechanism.

Reversible therapy-related dysplastic hematopoiesis following Beta Interferon Therapy in Multiple Sclerosis Patients: Report of 2 Cases.

BACKGROUND: Interferon beta-la and -1b have been increasingly used for the treatment of multiple sclerosis (MS). The most frequent systemic adverse effects are flu-like symptoms. Laboratory abnormalities include asymptomatic leukopenia and elevated hepatic transaminases. Myelodysplastic Syndrome (MDS) refers to a spectrum of hematological disorders which can occur in different situations. Several hematological abnormalities have been reported following interferon therapy. METHODS: We report two cases of secondary MDS after long term interferon therapy by using the laboratory data and bone marrow results. CONCLUSION: Both of our cases were reversible; although treatment with IFNß-1a and-1b is safe and well tolerated in the majority of population, we should be careful about this premalignant hematological disorder.

Liver Kupffer cells control the magnitude of the inflammatory response in the injured brain and spinal cord.

The CNS inflammatory response is regulated by hepatic chemokine synthesis, which promotes leukocytosis and facilitates leukocyte recruitment to the site of injury. To understand the role of the individual cell populations in the liver during the hepatic response to acute brain injury, we selectively depleted Kupffer cells (KC), using clodronate-filled liposomes, and assessed the inflammatory response following a microinjection of IL-1beta into the rat brain or after a compression injury in the spinal cord. We show by immunohistochemistry that KC depletion reduces neutrophil infiltration into the IL-1beta-injected brain by 70% and by 50% into the contusion-injured spinal cord. qRT-PCR analysis of hepatic chemokine mRNA expression showed that chemokine expression in the liver after brain injury is not restricted to a single cell population. In non-depleted rats, CXCL-10, IL-1beta, CCL-2, and MIP-1alpha mRNAs were increased up to sixfold more than in KC depleted rats. However, CXCL-1 and MIP-1beta were not significantly affected by KC depletion. The reduction in chemokine mRNA expression by the liver was not associated with decreased neutrophil mobilisation as might have been expected. These findings suggest that in response to CNS injury, KC mediated mechanisms are responsible for increasing neutrophil entry to the site of CNS injury, but that neutrophil mobilisation is dependent on other non-KC mediated events. However, the suppression of KC activity may prevent secondary damage after acute brain injury.