Taking the temperature of MS with INO

Many patients with multiple sclerosis (MS) dislike the summer because of the increased fatigue that comes with warm weather.1 Increased body temperature can also lead to temporary reappearance of neurologic symptoms experienced during prior MS exacerbations—Uhthoff's phenomenon.2 Remarkably, an increase in body temperature of less than a degree centigrade can provoke substantial disability, and one of Uhthoff's patients developed symptoms while standing by a hot stove. Cooling may improve such symptoms, although its effectiveness as a clinical treatment in MS (e.g., using cooling vests) is debated.3 Demyelination disrupts normal, saltatory propagation of action potentials in axons to the point that conduction becomes tenuous and may be blocked.4 Thus, conduction in demyelinated axons may fall prey to temperature-induced inactivation of sodium channels, especially during repetitive trains of spikes, when the neural signal is frequency filtered. Conversely, body cooling restores nerve conduction, possibly by prolonging the duration of action potentials, but also by decreasing leukocyte nitric oxide production.4 Study of Uhthoff's phenomenon in patients has required considerable ingenuity because measurement of an observed behavior (e.g., intention tremor) …