Peripheral Neuropathy during Subcutaneous Foslevodopa/Foscarbidopa Infusion in Parkinson's Disease: A Case Series

BACKGROUND: Peripheral neuropathy has been described in Parkinson's disease (PD) patients receiving continuous levodopa delivery. Whether subcutaneous foslevodopa/foscarbidopa (fLD/fCD) infusion carries a similar risk remains unclear. CASES: We report four PD patients treated with continuous subcutaneous fLD/fCD who experienced clinical and electrophysiological worsening of peripheral neuropathy after treatment initiation. At baseline, none reported functional neuropathic symptoms, although electrophysiological evidence of mild subclinical peripheral neuropathy and/or biochemical abnormalities was present. Neuropathic symptoms developed within a few months of fLD/fCD initiation and were associated with vitamin B6 and/or B12 deficiency and persistent hyperhomocysteinemia. In all cases, electrophysiological deterioration accompanied symptoms emergence. CONCLUSIONS: Although causality cannot be established, these cases suggest that fLD/fCD infusion may be associated with aggravation of pre-existing peripheral neuropathy, despite non-enteral administration, supporting a potential systemic metabolic contribution. These findings underscore the importance of baseline assessment and longitudinal monitoring of peripheral nerve function and B-vitamin status in patients receiving fLD/fCD. Optimal vitamin supplementation strategies in this setting remain to be defined.