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 most 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 impaired mobility and a higher risk of falls. Parkinson’s disease (PD) also causes balance and gait difficulties.
Corrà et al performed this study to determine the type and prevalence of peripheral neuropathy in PD patients and to determine if PD patients with neuropathy demonstrate 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. The authors excluded patients with dementia or with other causes of gait impairment.
After establishing the PD diagnosis, researchers assessed patients 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. Investigators performed labs for other contributing causes, including glucose tolerance. 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. Researchers assessed gait and balance in on and off medication states while the patients used 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. The authors assessed postural control 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. The authors did not observe demyelinating features. Researchers found glucose dysmetabolism in 25% of the PD group with peripheral neuropathy (PD-PNP group) and 20.3% of PD patients without peripheral neuropathy (PD-noPNP group). Investigators saw phospho-alpha-synuclein deposits in 30.7% of small fiber neuropathy participants, more frequently in the proximal thigh than in the distal leg.
Investigators saw significant gait differences in the PD-PNP and PD-noPNP groups across all tasks, but stride length, gait speed, and toe-off angles were particularly worse in peripheral neuropathy patients. The differences were more pronounced in the off state than the on state. PD-PNP patients also struggled more 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 functionally affected 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 optimizing dopaminergic therapy may be even more critical in peripheral neuropathy patients with PD.
In this cohort study of 99 patients with Parkinson’s disease (PD), 40% were found to have peripheral neuropathy, with most meeting criteria for small fiber neuropathy. Gait and balance were worse in PD patients with neuropathy compared to those without.
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