References for this review were identified from searches of Pubmed (from 1966 to 2005) and the Cochrane Library (2005, Issue 2) with the search terms

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Background: Pregnancy has a well-documented effect on relapses in multiple sclerosis (MS), whereas little is known about the impact of pregnancy and childbirth on the risk of secondary progression. Objective: To investigate the association of parity and secondary progression in women with MS. Methods: The association of the number of births and secondary progression was studied in a hospital-based cohort of 277 women with MS. Data were analysed in a multivariable logistic regression model, with adjustment for possible confounders. Results: Parity was not independently associated with secondary progression, while the factors disease duration (OR per year increase: 1.05, 95% CI 1.03 to 1.09) and use of immunomodulatory treatments (OR 0.23, 95% CI 0.08 to 0.65) were independently associated with secondary progression. Conclusion: We found no evidence that parity influences the risk of secondary progression in MS. Further population-based studies on the association of pregnancy and childbirth on the long-term prognosis of MS are needed.Multiple sclerosis (MS) affects women about twice as often as men. Since MS often begins in early adulthood, the course of the disease overlaps the childbearing years in many women with MS. A number of studies have been concerned with the impact of pregnancy on MS relapses, but little research has been done on the influence of pregnancies on the onset of secondary progression.The pathophysiological mechanisms underlying relapses are focal inflammatory lesions in the central nervous system (CNS). The main pathophysiological mechanism of secondary progression appears to be an ill-understood diffuse neurodegeneration throughout the CNS termed ''axonal degeneration.'' Axonal degeneration may begin early in the disease but becomes apparent as secondary progression when enough axons have degenerated to exhaust the functional reserve capacity of the CNS. Previous studies have shown that relapses occur less frequently during pregnancy, especially during the third trimester, and that there is a rebound effect with an increase in relapse frequency after delivery. 3 These findings have been associated with the rise and fall of oestrogen and progesterone levels over the course of pregnancy and argue for a suppressive effect of these steroid hormones on the inflammatory component of MS. One exploratory crossover trial found evidence for an effect of oral oestriol treatment on the number of enhancing MRI lesions in a group of 12 women with MS. 4 Information about the effect of pregnancy on the development of secondary progression is scarce. We found only one small study suggesting a significantly decreased risk of a progressive course in women who became pregnant after MS onset.5

Number: ISRCTN65586975.

The selective serotonin reuptake inhibitor (SSRI) fluoxetine, which is registered for a variety of psychiatric disorders, has been found to stimulate the cAMP-responsive element binding protein (CREB), increase the production of brain-derived neurotrophic factor (BNDF) and the neurotrophic peptide S100beta, enhance glycogenolysis in astrocytes, block voltage-gated calcium and sodium channels, and decrease the conductance of mitochondrial voltage-dependent anion channels (VDACs). These mechanisms of actions suggest that fluoxetine may also have potential for the treatment of a number of neurological disorders. We performed a Pubmed search to review what is known about possible therapeutic effects of fluoxetine in animal models and patients with neurological disorders. Beneficial effects of fluoxetine have been noted in animal models of stroke, multiple sclerosis, and epilepsy. Fluoxetine was reported to improve neurological manifestations in patients with Alzheimer's disease, stroke, Huntington's disease, multiple sclerosis, traumatic brain injury, and epilepsy. Clinical studies so far were small and often poorly designed. Results were inconclusive and contradictory. However, the available preclinical data justify further clinical trials to determine the therapeutic potential of fluoxetine in neurological disorders.

Oxidative stress occurs in progressive as well as benign MS. The finding that cells withstand oxidative stress, due to upregulated cellular antioxidant defence mechanisms, suggests that reactive oxygen species (ROS) formation in MS is not necessarily deleterious.

Compared with controls, MS patients performed less well on DTs as demonstrated by a reduction in both cognitive and motor performances. This performance decrease was stronger under fatiguing conditions and was related to the sense of fatigue of MS patients. These data illustrate problems that MS patients may encounter in daily life because of their fatigue.