Open-label trial of ranolazine for the treatment of paramyotonia congenita.

INTRODUCTION: Paramyotonia congenita (PMC) is a nondystrophic myotonic disorder that is believed to be caused by a defect in Nav 1.4 sodium channel inactivation. Ranolazine, which acts by enhancing slow inactivation of sodium channels, has been proposed as a therapeutic option, but in vivo studies are lacking. METHODS: We conducted an open-label, single-center trial of ranolazine to evaluate efficacy and tolerability in patients with PMC. Subjective symptoms of stiffness, weakness, and pain as well as clinical and electrical myotonia were evaluated. Baseline measures were compared with those after 4 weeks of treatment with ranolazine. RESULTS: Ranolazine was tolerated well without any serious adverse events. Both subjective symptoms and clinical myotonia were significantly improved. Duration of myotonia was reduced according to electromyography, but this change was not statistically significant in all tested muscles. DISCUSSION: Our findings support the use of ranolazine as a treatment for myotonia in PMC and suggest that a randomized, placebo-controlled trial is warranted. Muscle Nerve 59:240-243, 2019.

Natural history of nonbacterial thrombotic endocarditis treated with warfarin.

We report on the natural history of a cohort of patients presenting with transient ischemic attack or stroke and nonbacterial thrombotic endocarditis treated with warfarin.Patients with valvular vegetations on echocardiography, stroke, or transient ischemic attack presenting to a single neurologist were included. All patients were treated with warfarin until the vegetation resolved or for two years, then were switched to aspirin and had at least one clinical and echocardiographic follow-up.Twenty-nine patients were included and followed for a median of 27 months. Average age was 42 years and 72% were female. Two patients had vegetations on two valves. Five patients (17%) had recurrent strokes, three had systemic lupus erythematosus and antiphospholipid antibodies, one had antiphospholipid antibodies alone and one had neither condition. Three of the five patients did not have resolution of the vegetation at the time of the event. The valvular vegetations resolved in 23 of the 31 affected valves (74%) after a median of 11 months (range 4.5-157.5). Eleven patients had at least one follow-up echocardiogram after resolution of the vegetation and none had recurrent vegetations after warfarin was stopped.This study should serve to provide general recommendations regarding treatment of patients with TIA/stroke with nonbacterial thrombotic endocarditis. Valvular vegetations resolve in most patients and the risk of recurrent stroke is low. Warfarin can safely be switched to aspirin in most patients when the vegetation resolves or after two years if it does not resolve. Prolonged warfarin may be warranted in patients with systemic lupus erythematosus, positive antiphospholipid antibodies, and a persistent vegetation.