Management of restless legs syndrome in chronic liver disease:A challenge for the correct diagnosis and therapy

AIM To investigate the association between restless legs syndrome(RLS) and well-defined chronic liver disease, and the possible therapeutic options. METHODS Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment(PSQI), Epworth sleepiness scale(ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity(IRLS) scoring system. Ironfree level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood testoccurred at the beginning of the therapy, after 2 wk, and at the 28^(th), 75 th, 105 th, 135 th, 165 th and 205 th day. Regarding therapy, pramipexole or gabapentin were used.RESULTS Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS s yndrome had not be e n c ons ide re d be fore t he neurological visit. All(211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients(135 th day), and more frequent(35%) than previous data(8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our study.CONCLUSION RLS is a common disorder, requiring rapid diagnosis and treatment. Further research is therefore fundamental.

Bilirubin and inflammation in neurodegenerative and other neurological diseases

Inflammation links neurodegenerative,neuropsychiatric and other neurological diseases(NDs)with acute brain events.It is responsible for the alteration of neurotransmission and circuity,brain architecture,and cell fate,affecting mood and personality(anxiety,depression and schizophrenia)and behavior(decline in cognitive,motor and speech abilities,altered sleep,fatigue,pain sensitivity and dementia).Inflammation is also a key component in systemic chronic diseases(cardiovascular disease,cancer,diabetes,and metabolic syndrome),in which bilirubin has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule,and where the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started.While altered serum bilirubin levels have been reported in ND patients,the potential activity of bilirubin in the brain is vague.This review summarizes the available fragmentary information on the interplay of bilirubin with neuroinflammation,aiming to elucidate the pigment's role in the central nervous system environment.