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New insights into the complex immunopathogenesis of multiple sclerosis have led to a proliferation of promising new therapeutic strategies. While the current armamentarium of immunomodulatory medications has demonstrated beneficial effects on the disease, more effective and tolerable therapies are needed. Several novel therapeutic strategies under investigation include oral therapies, monoclonal antibodies, symptomatic treatments, insights into neuroprotection and repair as well as combination regimens. New therapies may prove more efficacious and tolerable than the available arsenal of treatments; however, decisions regarding first-line therapies will expectedly become more complicated, with greater influence if risk-to-benefit ratios in light of premature safety data. Biomarker profiles may help elucidate disease subtypes as well as therapeutic response in an effort to individualize treatment choice. This review will highlight recent promising therapeutic strategies under investigation in the field of MS.

NK cells are multicompetent lymphocytes of the innate immune system with a central role in host defense and immune regulation. Studies in experimental animal models of multiple sclerosis (MS) provided evidence for both pathologic and protective effects of NK cells. Humans harbor two functionally distinct NK-cell subsets exerting either predominantly cytotoxic (CD56(dim)CD16(+)) or immunoregulatory (CD56(bright)CD16(-)) functions. We analyzed these two subsets and their functions in the peripheral blood of untreated patients with relapsing-remitting MS compared with healthy blood donors. While ex vivo frequencies of CD56(bright)CD16(-) and CD56(dim)CD16(+) NK cells were similar in patients and controls, we found that cytokine-driven in vitro accumulation and IFN-γ production of CD56(bright)CD16(-) NK cells but not of their CD56(dim)CD16(+) counterparts were substantially diminished in MS. Impaired expansion of CD56(bright)CD16(-) NK cells was cell intrinsic because the observed effects could be reproduced with purified NK cells in an independent cohort of patients and controls. In contrast, cytolytic NK-cell activity toward the human erythromyeloblastoid leukemia cell line K562, the allogeneic CD4(+) T cell line CEM and allogeneic primary CD4(+) T-cell blasts was unchanged. Thus, characteristic functions of CD56(bright)CD16(-) NK cells, namely cytokine-induced NK cell expansion and IFN-γ production, are compromised in the NK cell compartment of MS patients.

New therapies, along with variations of currently available treatments, may prove more efficacious and tolerable than the available arsenal of treatments. Nevertheless, as the treatment horizon broadens, choosing first-line therapies will become more complicated, with greater influence of risk-to-benefit ratios in light of premature safety data. Patient's clinical, paraclinical and biomarker fingerprint profiles may help elucidate disease subtypes as well as response to therapy in an effort to individualize treatment choice. A complete discussion of all studies currently underway is beyond the scope of this review, which will highlight recent promising therapeutic strategies under investigation in the field of multiple sclerosis.

We studied a patient with ophthalmoparesis and pupillary areflexia 2 weeks after a viral syndrome. Miller Fisher syndrome was suspected but GQ1b antibodies were not detected. To define neuromuscular involvement we performed electrodiagnostic studies. Single-fiber electromyography (SFEMG) in the extensor digitorum communis (EDC) showed abnormal jitter and axonal blocking, suggesting terminal axon dysfunction. Subsequent GQ1b antibody titers were elevated to borderline levels. Clinical symptoms gradually resolved. SFEMG may help characterize neuropathies associated with antibodies to neuronal ganglioside and identify involvement of the terminal axon and neuromuscular junction.