Clinical Features,Bio-fluid Alpha-synuclein And SNCA-Rep1 Polymorphism In Patients With Restless Legs Syndrome

PART I: CLINICAL FEATURES AND SUBTYPES IN PATIENTS WITH RESTLESS LEGS SYNDROMEBackground and objective: The clinical spectrum of Restless Legs Syndrome(RLS)has not been described in a Chinese population.We aim to evaluate the detailed clinical profile in a cohort of unselected RLS patients in China.Methods: We enrolled RLS patients continuously according to the diagnostic criteria.Laboratory examinations were performed to exclude mimics and notable comorbidities.Results: 359 patients with RLS were enrolled.RLS symptom is mostly symmetrical(65.2%),purely unilateral RLS is not common(5.6%),however unilateral dominant RLS is relatively more common.Only 1.1% RLS patients reported no unpleasant sensations in the legs.The largest proportion of RLS patients described their uncomfortable sensation as indescribable(43.5%)and soreness(40.4%).8.9% RLS patients described their abnormal sensation as painful.34.5% RLS patients reported their symptoms fluctuated with seasonal trends.This population had a higher likelihood of a RLS family history.RLS patients with summer exacerbation had younger age at RLS onset and longer disease duration(P<0.01).Iron deficiency without anemia is common in Chinese RLS patients.Early onset RLS are more likely to have a positive family history(P<0.01),more summer worsening of symptoms(P<0.01),more severely disturbed peripheral iron status(P<0.01)and more iron deficiency(P<0.01) when compared to late onset RLS patients.Conclusion: The subjective description is somewhat different with more “soreness” and less pain reported in Chinese RLS patients from western countries.Seasonal fluctuation and iron deficiency without anemia are frequently seen in Chinese RLS patients and predict some other features.Differentiating these various subtypes can facilitate optimal management.PART II: BIO TISSUE ALPHA-SYNUCLEIN LEVEL AND SNCA-Rep1 POLIMORPHISM IN RESTLESS LEGS SYNDROMEBackground and objective: There is a role of α-synuclein on dopaminergic synaptic transmission and dopamine homeostasis and maybe involved in restless legs syndrome(RLS).We investigate whether α-synuclein levels are altered in serum and saliva in patients with RLS and explore influence of the SNCA-Rep1 microsatellite repeat on RLS.Methods: We enrolled RLS patients according to the IRLSSG criteria.A unified semi-structured questionnaire was used to record demographic information and leg restlessness symptoms.Blood and saliva samples were collected to detect α-synuclein protein levels and to genotype the SNCA Rep1 marker.Laboratory examinations were performed to exclude secondary RLS.We also enrolled healthy controls.Results: 71 patients with RLS as well as 56 age and gender matched healthy controls underwent analyses of serum α-synuclein concentration.RLS patients showed decreased serum α-synuclein level compared to age and gender matched controls(10.4±6.2 vs 38.6±9.9ng/ml,p<0.0001).RLS patients without medication demonstrated even lower serum α –syn level than RLS patients with medication(8.8±5.1 vs 14.5±7.1ng/ml,Z=-3.156,P=0.002).Lower serum α-synuclein level was associated with shorter duration of RLS(P<0.05).Levels of α-syn in saliva was similar in RLS patients and controls(P>0.05).201 RLS patients and 218 healthy controls underwent genotypies.Frequencies of SNCA Rep1 0/0 genotype and allelic 0 variant were significantly lower in RLS patients compared to controls(OR=0.344,95% CI=0.173-0.684,P=0.002;and OR=0.681,95% CI=0.512-0.905,P=0.008,respectively).Frequencies of SNCA Rep1 2/2 genotype and allelic 2 were significantly higher(OR=5.186,95% CI=1.395-19.273,P=0.007;and OR=1.913,95%CI=1.212-3.021,P=0.005),while Rep1 0/1 genotype and allelic 1 were significantly lower in RLS patients with iron deficiency compared to RLS patients without iron deficiency(OR=0.467,95%CI=0.239-0.912,P=0.024;and OR=0.649,95%CI=0.421-0.998,P=0.049).RLS patients with at least one allele 2 showed lower serum α-synuclein level compared to RLS patients without any allele 2(P<0.05).Conclusion: Serum α-synuclein level was significantly decreased in patients with RLS and dopaminergic drug therapy may have an impact on the level of serum α-synuclein in RLS patients.SNCA Rep1 polymorphism is associated with RLS and its phenotype.