Pregnancy, fertile life factors, and associated clinical course in PRKN early-onset Parkinson's disease.

INTRODUCTION: As the most common cause of autosomal recessive early onset Parkinson's disease (EOPD), parkin type Parkinson's disease (PRKN-PD) may affect female patients in childbearing age. Accordingly, issues related to fertility must be adequately addressed. Here, we landscaped fertile life factors and pregnancy course of a PRKN-PD cohort, including both novel cases directly observed at our center and published ones. METHODS: Six patients with confirmed PRKN-PD were examined by a structured interview on reproductive factors and associated modifications of PD disturbances, including one case followed up throughout pregnancy which was described in greater detail. Six studies reporting fertile life factors of nine PRKN-PD patients were reviewed collecting homogeneous data on fertile life and pregnancy course. RESULTS: PRKN-PD female patients experienced motor fluctuations with the menstrual cycle, pregnancy, and puerperium, which suggests a role for sex hormones in PD clinical burden. In some cases, abortion and miscarriages occurred during the organogenesis phase in patients receiving oral antiparkinsonian therapy; however, levodopa/benserazide monotherapy resulted to be the safest choice in pregnancy. CONCLUSION: Collectively these data disclose the importance of pre-conception counseling in childbearing age PRKN-PD patients and EOPD in general.

Neutrophil-to-lymphocyte ratio and lymphocyte count reflect alterations in central neurodegeneration-associated proteins and clinical severity in Parkinson Disease patients.

INTRODUCTION: Peripheral inflammation has been recently associated to Parkinson disease (PD). However, how the peripheral inflammatory immune response could affect the clinical-pathological features of the disease is not fully understood. In this study, we assessed the peripheral immune profile of a well-characterized PD cohort, examining several correlations with CSF biomarkers of neurodegeneration and the main clinical parameters, aimed at better elucidating the complex dynamics of the brain-periphery interactions in PD. METHODS: The leukocyte populations counts (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) and the neutrophil-to-lymphocyte ratio (NLR) were collected and compared in 61 PD patients and 60 sex/age matched controls (CTRLs). Immune parameters were correlated with CSF levels of total α-synuclein, amyloid-ß-42, total and phosphorylated-tau and main motor and non-motor scores. RESULTS: PD patients had lower lymphocyte and higher NLR counts compared to CTRLs. In PD patients, the lymphocyte count directly correlated with CSF α-synuclein levels, whereas NLR displayed an inverse correlation with the CSF amyloid-ß42 levels. The lymphocyte count also negatively correlated with HY stage, while NLR positively with the disease duration. CONCLUSIONS: This study provided in vivo evidence that, in PD, changes in leukocytes in the periphery, assessed as relative lymphopenia and NLR increase, reflect in central neurodegeneration-associated proteins modifications, especially in α-synuclein and amyloid-ß pathways, and greater clinical burden.

Shaping the course of early-onset Parkinson's disease: insights from a longitudinal cohort.

INTRODUCTION: Early -onset Parkinson's disease (EOPD) labels those cases with onset earlier than fifty. Although peculiarities emerged either in clinical or pathological features, EOPD is managed alike typical, late-onset PD. A customized approach would be, instead, better appropriate. Accordingly, a deeper characterization of the clinical course, with an estimation of the disease progression rate, the therapy flow, and the main motor and non-motor complications occurrence, is needed. METHODS: A longitudinal cohort of 193 EOPD patients (selected on a single-centre population of 2000 PD cases) was retrospectively analysed, providing descriptive statics on a series of clinical parameters (genetics, phenotype, comorbidities, therapies, motor and non-motor complications, marital and gender issues) and modelling the trajectories from diagnosis to 10 years later of both Hoehn and Yahr (H&Y) stage and levodopa equivalent daily dose (LEDD). RESULTS: EOPD had a prevalence of 9.7%, including few monogenic cases. It mostly appeared as a motor syndrome, with asymmetric, rigid-akinetic presentation. H&Y linearly progressed with an increment of 0.92 points/10 years; LEDD flow had a non-linear trend, increasing of 526.90 mg/day in 0-5 years, and 166.83 mg/day in 5-10 years. Motor fluctuations started 6.5 ± 3.2 years from onset, affecting up to 80% of the cohort. Neuropsychiatric troubles interested the 50%, sexual complaints the 12%. Gender-specific motor disturbances emerged. CONCLUSION: We shaped EOPD course, modelling a "brain-first" PD subtype, slowly progressive, with non-linear dopaminergic requirement. Major burden mostly resulted from motor fluctuations, neuropsychiatric complications, sexual and marital complaints, with a considerable gender-effect.