Case Report Intermittent Atrioventricular Block following Fingolimod Initiation E. Gialafos, S. Gerakoulis, A. Grigoriou, V. Haina, C. Kilidireas, E. Stamboulis, and E. Andreadou Department of Neurology, Athens National and Kapodistrian University, “Aeginition” Hospital, 11528 Athens, Greece Correspondence should be addressed to E. Andreadou; eandread@med.uoa.gr Received 13 April 2014; Accepted 14 July 2014; Published 5 August 2014 Academic Editor: Isabella Laura Simone Copyright © 2014 E. Gialafos et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 47-year-old female patient with multiple sclerosis (MS) developed symptomatic intermittent 2nd degree atrioventricular block (AVB) of ive-hour duration, ive hours ater the irst two doses of ingolimod, that resolved completely. Frequency domain analysis of heart rate variability (HRV) revealed increased parasympathetic activity and decreased sympathetic tone, while modiied Ewing tests were suggestive of impaired cardiac sympathetic function. We hypothesize that expression of this particular arrhythmia might be related to autonomic nervous system (ANS) dysfunction due to demyelinating lesions in the upper thoracic spinal cord, possibly augmented by the parasympathetic efect of the drug. 1. Background Fingolimod is an oral sphingosine-1-phosphate (S1P) receptor modulator used for the treatment of relapsing-remitting form of multiple sclerosis (RRMS). Although the drug is safe, certain side efects exist, with cardiac abnormalities, macular edema, and elevation of liver enzymes being the most severe [1, 2]. he mechanism possibly attributed to cardiac abnor- malities seems to be the activation of G-protein-coupled inwardly rectifying potassium (GIRK) channels mediated by S1P on atrial myocytes [3]. In clinical trials, ingolimod induces a transient decrease in heart rate, reaching maximum plasma concentration at 4-5 h ater the irst dose and attenuat- ing over time with continued dosing [4]. In the FIRST study, a 4-month, open-label, phase 3b, multicenter study evaluating mainly cardiac safety during treatment initiation in a real word population with RRMS, palpitations and bradycardia were the most common cardiac abnormalities, with second- degree AVB being rare [2]. We report a female MS patient who developed reversible symptomatic Weckenbach type of AVB ater the irst two doses of ingolimod and discuss the underlying mechanisms possibly involved in the pathophysiology of this adverse event. 2. Case Report A 47-year-old female with RRMS diagnosed 8 years ago presented with an acute relapse characterized by numbness of the right leg, which started from the toes and ascended up to the right knee. he patient had been discontinuously treated with interferon beta-1b for two separate semesters in the past and had decided to stop treatment on her own 4 years ago, because of lu-like symptoms. he patient is a smoker and her family history revealed MS in her 48-year-old sister and her cousin. Neurological examination revealed impairment of vibra- tion and joint position sense in both lower extremities and decreased sensation of pain and light touch in the right leg. Brain MRI showed demyelinating lesions in T2- weighted images in the cerebral hemispheres and one T1 gadolinium-enhancing lesion located at the right upper and middle cerebellar peduncle (Figure 1(a): (A)–(C)). Spinal cord imaging revealed lesions opposite to C6-C7 and C7- C8 vertebral discs and one gadolinium-enhancing lesion located opposite the T1-T2 vertebra (Figure 1(a): (D)–(F)). he patient was treated with intravenous methylprednisolone 1 g daily for 5 days with clinical improvement. hereater, treatment initiation with ingolimod was decided, because Hindawi Publishing Corporation Case Reports in Neurological Medicine Volume 2014, Article ID 191305, 4 pages http://dx.doi.org/10.1155/2014/191305