Progress in developing disease-modifying therapies in Parkinson’s disease (PD) can only be achieved through reliable objective markers that help to identify subjects at risk. This includes an early and accurate diagnosis as well as continuous monitoring of disease progression and therapy response. Although PD diagnosis still relies mainly on clinical features, encouragingly, advances in biomarker discovery have been made. The cerebrospinal fluid (CSF) is a biofluid of particular interest to study biomarkers since it is closest to the brain structures and therefore could serve as an ideal source to reflect ongoing pathologic processes. According to the key pathophysiological mechanisms, the CSF status of α-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes and markers of neuroinflammation provide promising preliminary results as candidate biomarkers. Untargeted approaches in the field of metabolomics provide insights into novel and interconnected biological pathways. Markers based on genetic forms of PD can contribute to identifying subgroups suitable for gene-targeted treatment strategies that might also be transferable to sporadic PD. Further validation analyses in large PD cohort studies will identify the CSF biomarker or biomarker combinations with the best value for clinical and research purposes.

Neurological manifestations during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are of interest, regarding acute treatment and the so-called post-COVID-19 syndrome. Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorders worldwide. Hence, the influence of SARS-CoV-2 and the COVID-19 syndrome on PD patients has raised many questions and produced various publications with conflicting results. We reviewed the literature, with respect to symptoms, treatment, and whether the virus itself might cause PD during the SARS-CoV-2 pandemic in SARS-CoV-2-affected symptomatic PD patients (COVID-19 syndrome). In addition, we comment on the consequences in non-symptomatic and non-affected PD patients, as well as post-COVID syndrome and its potential linkage to PD, presenting our own data from our out-patient clinic.

(1) Background: Peripheral nerve involvement is increasingly recognized in Parkinson’s disease (PD). Although non-motor symptoms and postural instability are early features of atypical parkinsonian syndromes (APS), peripheral neuropathies in APS have not been addressed in detail thus far. Therefore, the aim of this study was to investigate the prevalence and characteristics of polyneuropathies (PNP) in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), as representative syndromes of APS. (2) Methods: In total, 8 MSA and 6 PSP patients were comprehensively analyzed regarding subjective, clinical (motor and non-motor) and paraclinical PNP features using nerve conduction studies and high resolution nerve ultrasounds (HRUS). (3) Results: A total of 87.5% of MSA and 66.7% of PSP patients complained of at least one neuropathic symptom, with electrophysiological confirmation of PNP in 50.0% of both, MSA and PSP patients. PNP symptom severity in PSP and motor nerve amplitude in MSA were associated with compromised motor function. Morphologic nerve examination by HRUS showed few alterations according to the axonal type of PNP. (4) Conclusions: The overall high PNP symptom burden may be partially credited to the significant prevalence of electrophysiologically diagnosed PNP, and impact motor aspects of APS. The findings of this exploratory study reinforce further investigations on a larger scale, in order to elucidate peripheral nerve involvement and the underlying pathophysiological mechanisms of APS.

Background: Increasing evidence indicates a higher prevalence of polyneuropathy (PNP) in Parkinson’s disease (PD). However, the involvement of large fiber neuropathy in PD still remains poorly understood. Given the lack of longitudinal data, we investigated the course of PNP associated with PD. Methods: In total, 41 PD patients underwent comprehensive clinical evaluation including motor and non-motor assessments as well as nerve conduction studies at baseline and at 2 years of follow-up. The definition of PNP was based on electrophysiological standard criteria. Common causes of PNP were excluded. Results: At baseline, PNP was diagnosed in 65.85% of PD patients via electroneurography. Patients with PNP presented with higher age (p = 0.019) and PD motor symptom severity (UPDRS III; p < 0.001). Over the course of 2 years, PNP deteriorated in 21.95% of cases, and 26.83% remained without PNP. Deterioration of nerve amplitude was most prevalent in the median sensory nerve affecting 57.58% of all PD cases with an overall reduction of median sensory nerve amplitude of 45.0%. With regard to PD phenotype, PNP progression was observed in 33.33% of the tremor dominant and 23.81% of the postural instability/gait difficulties subtype. Decrease of sural nerve amplitude correlated with lower quality of life (PDQ-39, p = 0.037) and worse cognitive status at baseline (MoCA, p = 0.042). Conclusion: The study confirms the high PNP rate in PD, and demonstrates a significant electrophysiological progression also involving nerves of the upper extremities. Longitudinal studies with larger cohorts are urgently needed and should elucidate the link between PD and PNP with the underlying pathomechanisms.

Background: Numerous studies reported a higher prevalence of polyneuropathy (PNP) in patients with Parkinson’s disease (PD) compared to the general population. Importantly, PNP symptoms can aggravate both motor and sensory disturbances in PD patients and negatively impact the disease course. Recent analyses indicate distinct PNP patterns in PD. Main text: This review aims to provide an overview of the current insights into etiological factors, diagnostic methods, and management strategies of large fiber neuropathy in PD. Despite the higher prevalence, the causes of PNP in PD are still not fully understood. A genetic predisposition can underlie PNP onset in PD. Main research attention is focused on long-term levodopa exposure which is suggested to increase PNP risk by depletion of methylation cofactors such as vitamin B12 and accumulation of homocysteine that altogether can alter peripheral nerve homeostasis. Beyond a potential “iatrogenic” cause, alpha-synuclein deposition has been detected in sural nerve fibers that could contribute to peripheral neuronal degeneration as part of the systemic manifestation of PD. Whereas mild axonal sensory PNP predominates in PD, a considerable proportion of patients also show motor and upper limb nerve involvement. Intriguingly, a correlation between PNP severity and PD severity has been demonstrated. Therefore, PNP screening involving clinical and instrument-based assessments should be implemented in the clinical routine for early detection and monitoring. Given the etiological uncertainty, therapeutic or preventive options remain limited. Vitamin supplementation and use of catechol-O-methyltransferase-inhibitors can be taken into consideration. Conclusion: PNP is increasingly recognized as a complicating comorbidity of PD patients. Long-term, large-scale prospective studies are required to elucidate the causative factors for the development and progression of PD-associated PNP to optimize treatment approaches. The overall systemic role of “idiopathic” PNP in PD and a putative association with the progression of neurodegeneration should also be investigated further.

(1) Background: The COVID-19 pandemic impacts healthcare utilization across all care settings and health conditions. The objective of this study was to determine changes in hospital admissions for neurodegenerative diseases (NDD) during the first COVID-19 wave in Germany; (2) Methods: This cross-sectional study used nationwide administrative claims data covering 1468 hospitals. The primary outcome was the year-to-year relative change in case numbers during a four-month study period (16 January–15 May 2020 vs. 2019) during the first pandemic wave. Secondary outcomes included year-to-year relative changes during a four-week peak phase (16 March–15 April) and changes between differential phases of the wave. The analyzed NDD comprised progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and Huntington’s disease; (3) Results: Hospital admissions for any reason decreased by 16.7% in 2020 during the study period and by 36.6% during the peak phase, whereas admissions for NDD decreased by 27.6% and 65.0%, respectively. PSP cases decreased during the study period (−34.7%) and the peak phase (−68.1%) and stayed reduced in a late phase with falling COVID-19 numbers. MSA and ALS cases increased strongest after the peak, with ALS cases being comparatively weakly reduced during the study period (−17.3%) and peak phase (−51.7%); (4) Conclusions: Inpatient care utilization for NDD changed differentially during the first wave of the COVID-19 pandemic in Germany and showed a greater reduction than overall and general neurological admissions. Mitigating long-term health deterioration of this vulnerable subgroup is important to reduce morbidity and mortality in the future.