Aminergic systems in sleep disorders of neurological diseases

Abstract

INTRODUCTION: Dopamine is a catecholaminergic neurotransmitter. A variety of sleep disorders implicate a dysfunction in the dopaminergic system, particularly REM Behaviour Disorder (RBD), Restless Leg Syndrome (RLS) and Periodic Limb Movements during Sleep (PLMS). PLMS involve stereotyped, rhythmic extension movements of the big toe and dorsiflexion of the foot during sleep. PLMS is particularly frequent in Restless Legs Syndrome (RLS) and other sleep disorders. Few studies have documented a pathological PLMS index in patients with Epilepsy. AIMS: The aims of this study were to evaluate the possibility of an association between Epilepsy and PLMS and to define the polysomnographic characteristics of PLMS. Given the dopaminergic nature of PLMS, the association between PLMS and Epilepsy might have represented an additional, indirect evidence of the involvement of dopamine in the pathogenesis of Epilepsy. Another aim was to evaluate the influence of some dopamine agonists commonly used in the treatment of PLMS on the PLMS pattern of some of the patients constituting our sample, as well as any impact these might have on epileptiform discharges. MATERIALS AND METHOD: We selected all patients referred to our neurological clinic from 2008 to 2012, who had previously been diagnosed with epilepsy based on the ILAE criteria, who showed no signs of Sleep Apnea, RLS, RBD and other degenerative neurologic conditions and who were not being treated with antidopaminergic and/or antidepressant drugs. All patients underwent nocturnal video-polisomnographic recordings . We selected patients who had a PLM index considered as pathological (PLMI>5). Subsequently, 5 patients were randomly selected among those with Epilepsy who had a PLMS index > 5. All 5 patients underwent other two nocturnal video-polisomnographic recordings (before and after administration of a dopamine agonist drug, Pramipexole 0.18 mg). In both recordings, PLMS and epileptiform discharges were also counted and analysed. RESULTS: Eighty-five patients who had been previously diagnosed with Epilepsy met the inclusion criteria for this study. Of these, 17/85 (20%) patients had a pathological PLM index (> 5). Of the 85 patients in our sample, 12/17 (70.6%), were diagnosed with Temporal Lobe Epilepsy, 2/17 (11.8%) with Frontal Lobe Epilepsy and 3/17 (17.6%) with Juvenile Myoclonic Epilepsy. PLMS registered in all 17 patients exhibited a mean PLMS index of 18.78 corresponding to the presence of a periodic nocturnal myoclonus of medium entity. In 58.8% PLMS appeared to be mainly distributed during the first half of the night and in 66.7% PLMS occurred during N2. The analysis of the 5 patients who underwent two VPSG (before and after administration of a dopamine agonist drug) showed a close to 50% reduction of epileptiform discharges in patients with PLMS and Epilepsy after administration of a dopamine agonist, namely Pramipexole. CONCLUSIONS: The study confirms the presence of PLMS in patients with Epilepsy. In our sample, the frequency of PLMS episodes stood at 23%. These movements mainly occurred during the first half of the night, in connection with the N2 stage, with a severity ranging from mild to moderate. They therefore had characteristics and distributions which made them more similar to the PLMS described during RLS than to those associated to neurodegenerative conditions. In addition, the PLMS in our sample were more frequent in patients with Temporal Lobe Epilepsy. Finally, considering the dopaminergic nature of PLMS, their occurrence in association with Epilepsy may serve to strengthen the role of dopamine in the pathophysiology of this disorder. This could have significant repercussions even in the therapeutic field, opening up new possibilities through the employment of dopamine agonists which may well find use in the treatment of some forms of Epilepsy.