Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

Importance: In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. Objective: To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. Design, Setting, and Participants: In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Exposures: Chemotherapy agents known to be toxic to peripheral nerves. Main Outcomes and Measures: The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Results: Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 53 of 100 participants (53.0%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 µV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids. Conclusions and Relevance: Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted long term, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.

Neuromuscular disease in the dialysis patient: an update for the nephrologist.

Neuromuscular disease is an extremely common complication of end-stage kidney disease (ESKD), manifesting in almost all dialysis patients, and leading to weakness, reduced exercise capacity, and disability. Recent studies have suggested that hyperkalemia may underlie the development of neuropathy. As such, maintenance of serum K(+) within normal limits between periods of dialysis in ESKD patients manifesting early neuropathic symptoms may reduce neuropathy development and progression. For patients with more severe neuropathic syndromes, increased dialysis frequency or a switch to high-flux dialysis may prevent further deterioration, while ultimately, renal transplantation is required to improve and restore nerve function. Exercise training programs are beneficial for ESKD patients with muscle weakness due to neuropathy or myopathy, and are capable of improving exercise tolerance and quality of life. Specific treatments have recently been evaluated for symptoms of autonomic neuropathy, including sildenafil for impotence and midodrine for intra-dialytic hypotension, and have been shown to be effective and well tolerated. Other important management strategies for neuropathy include attention to foot care to prevent callus and ulceration, vitamin supplementation, and erythropoietin. Treatment with membrane-stabilizing agents, such as amitryptiline and gabapentin, are highly effective in patients with painful neuropathy.