Anti-uhthoff effect of hypothermia on multiple sclerosis patients previously affected by optic neuritis: Clinical, electrophysiological and biochemical results

Objective and Hypothesis: The symptoms with elevated body temperature (Uhthoff phenomennon-UF) in multiple sclerosis due to conduction block in demyelinated and transected axons. Therapeutic effects of lowering body temperature have been reported to some studies. This study aimed to assess the effects of body cooling on clinical parameters (neuroofthalmologicial examination, Sloan Letter Test-SLT, Expanded Disability Status Scale-EDSS, Fatigue scales, Multiple Sclerosis Functional Composite-MSFC and Multiple Sclerosis International Quality of Life-MUSIQOL), on electrophysiological measures (Visual evoked potentials-VEP) and on free radicals and proinflamatory cytokines (Nitrite/Nitrate and TNF-alfa, IFN-gamma) in patients with multiple sclerosis (MS) previously affected by optic neuritis.Methods: Twenty patients describes UF or anti-Uhthoff effect with diagnosis of definite MS according to McDonald and Poser criteria were participated. All patients had a history of optic neuritis at least once. Before the cooling process, all patients were examined clinical, electrophysiological (VEP) and biochemical (Nitric oxide, TNF-alfa, IFN-gamma) parameters. Body cooling was provided by using `Medivance Arctic Sun Temperature Management System?. After the body temperature was decreased approximately 1°C, all tests and evaluations repeated again. Serum IFN-gamma and TNF-alfa levels measured by using Invitrogen human IFN-gamma, TNF-alfa antigen kits and `sandwich? ELISA methods. Leukocyte nitric oxide (NO) level measured spectrophotometrically by using `Assay Designs? NO evaluation kits.Results: Mean body temperature was decreased 0.89±0.13°C. After the cooling process, P100 latency shortened significantly at 1st, 6th and 24th hours (p<0.001, p<0.001, p<0.001). A significant improvement in EDSS was detected after the cooling process (<0.001). Significant improvement in visual acuity and colour vision of the affected and unaffected eyes were detected. Improvements in contrast level 100%, 2.5% and 1.25 of SLT were detected (p<0.001, p=0.001and p<0.001, respectively). Fatigue severity and fatigue impact scale scores were also improved (p<0.001). After the cooling process, increase in PASAT points was detected. Duration of 9 Hole Pag Test (HPT) and Timed 25 Foot Walk (T25FW) were shortened. A significant improvement in MUSIQOL points were observed after the cooling process (p<0.001). Both leukocyte NO levels and proinflamatory cytokine levels were decreased. It was significant for NO levels (p=0.002).Conclusion: Our results demonstrated that cooling process had beneficial effects on disability scores, quality of life and mainly visual system on the bases of clinical, electrophysiological and biochemical parameters in patients with MS.Key words: Multiple sclerosis, Uhthoff phenomennon, Anti-Uhthoff effect, Cooling, Hypothermia, Visual evoked potentials, Nitric oxide, Cytokines.