Peripheral neuropathy is a common problem in patients with Parkinson’s disease. Peripheral neuropathy’s prevalence in Parkinson’s disease varies between 4.8% - 55%, compared to 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson’s disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson’s disease patients, and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson’s disease patients assessed by Movement Disorders’ specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and Quantitative Sensory Testing) and neuropathological (Intraepidermal nerve fiber density in skin biopsies’ punches) evaluation, to characterize peripheral neuropathy’s type and etiology with a cross-sectional design. Gait and balance were characterized using wearable health-technology at OFF and ON medication states and the main parameters were extracted using validated algorithms. A total of 99 Parkinson’s disease participants with a mean age of 67.2 (±10) years-old and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation we found that 40.4% of Parkinson’s disease patients presented peripheral neuropathy, with a predominance of small fiber neuropathy (70% of the group). At OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. At ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson’s disease patients with and without peripheral neuropathy were observed at OFF medication state during stance with closed eyes on a foam surface. At ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson’s disease, and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve Parkinson’s disease patient’s gait and minimize balance related disability, targeting individualized medical care.
Congenital ataxias are a heterogeneous group of disorders characterized by congenital or early‐onset ataxia. Here, we describe two siblings with congenital ataxia, who acquired independent gait by age 4 years. After 16 years of follow‐up they presented near normal cognition, cerebellar ataxia, mild pyramidal signs, and dystonia. On exome sequencing, a novel homozygous variant (c.1580‐18C > G ‐ intron 17) in ATP8A2 was identified. A new acceptor splice site was predicted by bioinformatics tools, and functionally characterized through a minigene assay. Minigene constructs were generated by PCR‐amplification of genomic sequences surrounding the variant of interest and cloning into the pCMVdi vector. Altered splicing was evaluated by expressing these constructs in HEK293T cells. The construct with the c.1580‐18C > G homozygous variant produced an aberrant transcript, leading to retention of 17 bp of intron 17, by the use of an alternative acceptor splice site, resulting in a premature stop codon by insertion of four amino acids. These results allowed us to establish this as a disease‐causing variant and expand ATP8A2‐related disorders to include less severe forms of congenital ataxia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.