Clinical, Electrophysiological, and Neuropathological Features of Peripheral Neuropathies in People With T-Cell Lymphoproliferative Disorder.

Abstract

Peripheral neuropathies (PNs) associated with T-cell lymphoproliferative disorders (T-Ly) are exceptionally rare and poorly characterized. Whether their mechanisms, clinical features, and outcome differ from PN associated with B-cell lymphoproliferative disorders (B-Ly) remains unclear. We aimed to characterize the clinical, electrophysiologic, and pathologic spectrum of T-Ly-associated PN, evaluate treatment responses, and compare these findings with B-Ly-associated PN. We conducted a retrospective multicentric cohort study across 17 PN reference centers in France and Switzerland. Adult patients with confirmed PN and T-Ly were included after exclusion of alternative PN etiologies and isolated CNS involvement. Clinical, electrophysiologic, imaging, and histopathologic data were collected. PN were classified as neurolymphomatosis or dysimmune neuropathy based on multidisciplinary consensus. Functional outcomes were assessed using the modified Rankin Scale (mRS) and Overall Neuropathy Limitations Scale. The results were compared with a reference cohort of B-Ly-associated PN. Nineteen patients were included (mean age 67.0 ± 11.4 years, 52.6% female) with a median follow-up of 22 months (interquartile range 11.5-30.5). Neurolymphomatosis accounted for 11 cases (58%) and typically presented with multifocal, predominantly axonal neuropathy, including meningoradiculitis and multiple mononeuropathies. Eight patients (42%) had dysimmune neuropathy, most often demyelinating and strongly associated with angio-immunoblastic T-cell lymphoma. Neurologic improvement occurred in 72% of treated patients; however, most patients with neurolymphomatosis showed only partial recovery and persistent disability. IV immunoglobulins were uniformly ineffective, whereas corticosteroids yielded the greatest PN-specific benefit. Compared with B-Ly-associated PN (n = 33), T-Ly-associated PN were associated with more severe disability (median mRS 3 vs 2, <i>p</i> = 0.014), more frequent motor involvement, pain, cranial nerve involvement, and a higher prevalence of neurolymphomatosis. T-Ly-associated PN are predominantly driven by neurolymphomatosis and exhibit more severe clinical profiles and poorer neurologic outcomes than B-Ly-associated PN. Dysimmune neuropathies represent a substantial subset, particularly in angioimmunoblastic T-cell lymphoma. Limitations include the retrospective design and heterogeneity of diagnostic investigations. These findings underscore the need for early recognition and mechanism-specific therapeutic strategies.