The Effect of Peripheral Neuropathy in Parkinson’s Disease on Gait and Balance

By Jennifer Langsdorf, MD

Assistant Professor of Neurology, Peripheral Neuropathy Center, Weill Cornell Medical College

SYNOPSIS: In this cohort study of 99 patients with Parkinson’s disease (PD), 40% were found to have peripheral neuropathy, with the majority meeting criteria for small fiber neuropathy. Gait and balance were worse in PD patients with neuropathy compared to those without.

SOURCE: Corrà MF, Vila-Chã N, Sardoeira A, et al. Peripheral neuropathy in Parkinson’s disease: Prevalence and functional impact on gait and balance. Brain 2023;146:225-236.

Peripheral neuropathy occurs with increasing incidence with age. It can affect balance and gait, causing decreased mobility and an increased risk of falls. Parkinson’s disease (PD) also causes balance and gait difficulties. Past studies have shown the prevalence of peripheral neuropathy in PD patients to be between 5% and 55%, compared to 9% of the general population of similar age.

This study was performed to determine the type and prevalence of peripheral neuropathy in PD patients and to determine if PD patients with neuropathy have more significant motor impairment than PD patients without it. It involved a cohort of 99 consecutive PD patients diagnosed in an outpatient movement disorders clinic. The mean age was 67.2 years (± 10 years) and 39.4% of participants were women. Patients with dementia or with other causes of gait impairment were excluded.

After the diagnosis of PD was established, patients were assessed for peripheral neuropathy in the following ways: neuropathy symptom scales, electromyography (EMG)/nerve conduction studies (NCS), quantitative sensory testing (QST), skin biopsies for epidermal nerve fiber (ENF) density, and pathological evaluation of skin biopsy samples for the presence of alpha-synuclein by immunofluorescence. Labs for other contributing causes, including glucose tolerance, also were performed. Patients were diagnosed with large-fiber neuropathy if NCS were abnormal. Patients were diagnosed with small-fiber neuropathy if at least two of the following were found: abnormal ENF density, abnormal QST, and/or abnormal neuropathy scales and sensory exam.

Gait and balance were assessed both in on and off medication states while using wearable health technology (Reha-Gait inertial measurement units, which include accelerometer and gyroscope) on the lower back and lateral parts of both feet. Gait tests included a 20-meter straight walking test, a 1080º circular walking test, and the Timed Up and Go test. Postural control was assessed with 30-second trials of side-by-side stance on the floor and foam with eyes opened and eyes closed, and with tandem stance on the floor.

Testing resulted in a diagnosis of peripheral neuropathy in 40.4% of patients. Small fiber neuropathy was the predominant neuropathy type diagnosed, comprising 70% of the neuropathy patients. Twelve percent showed axonal large fiber neuropathy. No demyelinating features were observed. Glucose dysmetabolism was found in 25% of the PD group with peripheral neuropathy (PD-PNP group) and 20.3% of the PD patients without peripheral neuropathy (PD-noPNP group). Phospho-alpha-synuclein deposits were seen in 30.7% of the small fiber neuropathy participants, more frequently in the proximal thigh than in the distal leg.

Significant gait differences were seen in the PD-PNP and PD-noPNP groups across all tasks, but stride length, gait speed, and toe-off angles were particularly worse in the patients with peripheral neuropathy. The differences were more pronounced in the off state than the on state. PD-PNP patients also had more difficulty with static balance tasks, especially standing on foam with eyes closed.

COMMENTARY

This study demonstrates a higher incidence of peripheral neuropathy in PD patients than in age-matched controls. This difference had a functional effect on gait and balance and was more notable in the off-medication state. Loss of sensory input from the lower extremities because of peripheral neuropathy can worsen balance and gait in patients without PD, and the effects may cause an even more significant functional impairment in PD patients, increasing the risk of falls. Since the effects were more significant in the off state, this suggests that optimizing dopaminergic therapy may be even more critical in peripheral neuropathy patients with PD.