Large-fiber neuropathy in Parkinson's disease: a narrative review.

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.

Longitudinal evaluation of polyneuropathy in Parkinson's disease.

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.

Psychophysical dual-task setups do not measure pre-saccadic attention but saccade-related strengthening of sensory representations.

Visual attention and saccadic eye movements are linked in a tight, yet flexible fashion. In humans, this link is typically studied with dual-task setups. Participants are instructed to execute a saccade to some target location, while a discrimination target is flashed on a screen before the saccade can be made. Participants are also instructed to report a specific feature of this discrimination target at the trial end. Discrimination performance is usually better if the discrimination target occurred at the same location as the saccade target compared to when it occurred at a different location, which is explained by the mandatory shift of attention to the saccade target location before saccade onset. This pre-saccadic shift of attention presumably enhances the perception of the discrimination target if it occurred at the same, but not if it occurred at a different location. It is, however, known that a dual-task setup can alter the primary process under investigation. Here, we directly compared pre-saccadic attention in single-task versus dual-task setups using concurrent electroencephalography (EEG) and eye-tracking. Our results corroborate the idea of a pre-saccadic shift of attention. They, however, question that this shift leads to the same-position discrimination advantage. The relation of saccade and discrimination target position affected the EEG signal only after saccade onset. Our results, thus, favor an alternative explanation based on the role of saccades for the consolidation of sensory and short-term memory. We conclude that studies with dual-task setups arrived at a valid conclusion despite not measuring exactly what they intended to measure.