Neuroinflammation and neuroprotection: an update on (future) neurotrophin-related strategies in multiple sclerosis treatment.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), characterized by inflammation, demyelination and axonal loss underlying progressive clinical disability. The chronic inflammatory tissue damage involving myelin and axons is driven by autoreactive T cells and represents a key mechanism in the immunopathogenesis of MS. Over the last few years, evidence from MS and experimental models of neuroinflammation has suggested that autoimmune responses could exert neuroprotective effects through the release of neurotrophins by autoreactive T cells. Specifically, the role of the Brain-derived neurotrophic factor (BDNF) in facilitating brain tissue repair in experimental traumatic injury has been well recognized. Support for this hypothesis comes from recent studies showing that glatiramer acetate, a currently approved treatment for MS, promotes the expansion of T cell clones crossing the blood-brain barrier and releasing BDNF in situ. A small subset of autoreactive T cells expresses the high-affinity full-length receptor for BDNF (TrkB-TK) in the periphery. In MS patients, T cells show reduced susceptibility to activation-induced apoptosis, a crucial mechanism eliminating autoreactive T clones and contributing to peripheral immunologic tolerance. These findings suggest the existence of a dual effect exerted by BDNF, which not only provides neuroprotection in the CNS but also promotes the survival of autoreactive T cells through an autocrine/paracrine loop. The aim of this review is to discuss the neuroprotective effects of currently approved immunomodulatory treatments for MS and their role in regulating neurotrophin production. We will also describe novel therapeutic strategies arising from new insights on "neuroprotective autoimmunity".

Clinical features of Sjogren's syndrome in patients with multiple sclerosis.

OBJECTIVES: To assess the frequency of clinical features of Sjogren's syndrome (SS) in patients with multiple sclerosis (MS) receiving treatment with disease-modifying drugs (DMDs) or naïve to treatment and the possible association with clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) parameters. METHODS: A multicentre cross-sectional observational study was designed, based on a structured neurologist-administered questionnaire to 440 patients. RESULTS: Twenty-eight of 230 (12%) patients receiving treatment with DMDs (DMDs(+)) and 14 of 210 (6.6%) treatment-naïve patients (DMDs(-) ) showed clinical features of SS. Four primary SS were diagnosed, two of which were DMDs(+) and two were DMDs(-) . Sicca symptoms were significantly associated with higher EDSS scores (P = 0.018), a low frequency of gadolinium-enhanced MRI-positive lesions (P = 0.018) and cerebral disturbances (P = 0.001). CONCLUSIONS: Screening for the clinical features of SS should be performed in patients with MS both receiving treatment with immunomodulatory drugs and without therapy.

Long time interval between multiple sclerosis onset and occurrence of primary Sjögren's syndrome in a woman treated with interferon-beta.

Primary Sjören's syndrome with central nervous system involvement can clinically mimic multiple sclerosis (MS). However, SS and MS may coexist. We report here a case of a 48-year-old woman affected by relapsing-remitting MS, good responder to interferon (IFN)-beta 1a, developing sicca complex after 29 years from MS onset. At the age of 48, after 5 years successful treatment with i.m. IFN-beta 1a, xerophtalmia and xerostomia with dysphagia occurred. Autoantibody screening for connective tissue diseases, including anti-ENA, was negative. Schirmer's test showed reduced lacrimal gland function and a minor salivary gland biopsy showed chronic inflammatory infiltration with fibrosis, acinar atrophy and ductal ectasia. According to clinical and pathological findings a diagnosis of SS was made. Other cases of connective tissue diseases after IFN-beta treatment have been described. However, this is, to our knowledge, the first report on the development of primary SS after long time interval from MS onset in a woman treated with IFN-beta. Although there are no evidences about a possible role of IFN-beta in triggering SS yet, a screening for clinical and laboratory signs of SS should be assessed in MS patients during IFN-beta treatment.

Closure of the "non-healing wound" corresponds with correction of weight loss using the anabolic agent oxandrolone.

We studied the relationship between restoration of weight loss and healing of the "non-healing wound." Eight consecutive patients with large "non-healing wounds" of an average of 12 months duration, despite good local wound care, were studied. All had a weight loss of 10 percent or more of body weight, mainly lean body mass. Optimizing nutrition (4 weeks) did not significantly increase weight or healing. The addition of the oral anabolic agent oxandrolone increased restoration of weight (4 lbs/week) over a 12-week period. Five wounds completely closed and three closed by 75 percent during this period. We noted a significant correlation (r = 0.67) between restoration of weight loss and closure of the previously "non-healing wound." The rate of wound healing was most prominent after 50 percent of weight loss had been restored. This finding reflects the key relationship between restoring body weight, body protein stores, and wound healing.