Epidural administration of local anesthetic and methylprednisolone is significantly more effective in preventing PHN at 12 months compared to intravenous acyclovir and prednisolone.

Levodopa-induced dyskinesias (LID) negatively impact on the quality of life of patients with Parkinson’s disease (PD). We assessed the risk factors for LID in a cohort of de-novo PD patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI). This retrospective cohort study included all PD patients enrolled in the PPMI cohort. Main outcome was the incidence rate of dyskinesia, defined as the first time the patient reported a non-zero score in the item “Time spent with dyskinesia” of the MDS-UPDRS part IV. Predictive value for LID development was assessed for clinical and demographical features, dopamine transporter imaging (DaTscan) pattern, cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau, phosphorylated tau, total α synuclein) and genetic risk score for PD. Overall, data from 423 PD patients were analyzed. The cumulative incidence rate of LID was 27.4% (95% CI = 23.2–32.0%), with a mean onset time of 5.81 years from PD diagnosis. Multivariate Cox regression analysis showed several factors predicting LID development, including female gender (HR = 1.61, 95% CI = 1.05–2.47), being not completely functional independent as measured by the modified Schwab & England ADL scale (HR = 1.81, 95% CI = 0.98–3.38), higher MDS-UPDRS part III score (HR = 1.03, 95% CI = 1.00–1.05), postural instability gait disturbances or intermediate phenotypes (HR = 1.95, 95% CI = 1.28–2.96), higher DaTscan caudate asymmetry index (HR = 1.02, 95% CI = 1.00–1.03), higher polygenic genetic risk score (HR = 1.39, 95% CI = 1.08–1.78), and an anxiety trait (HR = 1.02, 95% CI = 1.00–1.04). In PD patients, cumulative levodopa exposure, female gender, severity of motor and functional impairment, non-tremor dominant clinical phenotype, genetic risk score, anxiety, and marked caudate asymmetric pattern at DaTscan at baseline represent independent risk factors for developing LID.

Parkinson's disease (PD) is the second most common neurodegenerative disease and the most common synucleinopathy, as alpha-synuclein (α-syn), a prion-like protein, plays an important pathophysiological role in its onset and progression. Although neuropathological changes begin many years before the onset of motor manifestations, diagnosis still relies on the identification of the motor symptoms, which hinders to formulate an early diagnosis. Since α-syn misfolding and aggregation precede clinical manifestations, the possibility to identify these phenomena in PD patients would allow us to recognize the disease at the earliest, premotor phases, as a consequence of the transition from a clinical to a molecular diagnosis.Seed amplification assays (SAAs) are a group of techniques that currently support the diagnosis of prion subacute encephalopathies, namely Creutzfeldt Jakob disease. These techniques enable the detection of minimal amounts of prions in cerebrospinal fluid (CSF) and other matrices of affected patients. Recently, SAAs have been successfully applied to detect misfolded α-syn in CSF, olfactory mucosa, submandibular gland biopsies, skin and saliva, of patients with PD and other synucleinopathies. In these categories, they can differentiate PD and dementia with Lewy bodies (DLB) from control subjects, even in the prodromal stages of the disease. In terms of differential diagnosis, SAAs satisfactorily differentiated PD, DLB, and multiple system atrophy (MSA) from non-synucleinopathy parkinsonisms. The kinetic analysis of the SAA fluorescence profiles allowed the identification of synucleinopathy-dependent α-syn fibrils conformations, commonly referred to as strains, which have demonstrated diagnostic potential in differentiating among synucleinopathies, especially between Lewy body diseases (PD, DLB) and MSA. In front of these highly promising data, which make the α-syn seeding activity detected by SAAs as the most promising diagnostic biomarker for synucleinopathies, there are still preanalytical and analytical issues, mostly related to the assay standardization, which need to be solved. In this review, we discuss the key findings supporting the clinical application of α-syn SAAs to identify PD and other synucleinopathies, the unmet needs, and future perspectives.