ArticleJournal of neurology2026
Alternative diagnoses of suspected paraneoplastic neurological syndromes: a population-based study.
Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveThe diagnosis of paraneoplastic neurologic syndromes (PNS) requires exclusion of alternative etiologies. However, the spectrum of alternative diagnoses encountered during PNS workup ("better explanations") has not been systematically examined. We aimed to characterize this spectrum.
methodsRetrospective population-based study in Friuli-Venezia-Giulia (Italy). Among 878 consecutive patients tested for PNS antibodies at a centralized tertiary center serving three hospitals (2009-2017), alternative diagnoses were identified. Results of a logistic regression model were used to develop the PNS DDx Score.
resultsAmong 661 patients with alternative diagnoses, median age was 66 years, and 51% were male. CNS involvement predominated in 397 patients (60%), peripheral in 215 (33%), and extra-nervous system in 49 (7%). Etiologic diagnosis was reached in 269 with central involvement, including degenerative (97, 36%), autoimmune (47, 17%), and vascular (37, 14%). In peripheral presentations, a diagnosis was reached in 112 and included autoimmune (51, 45%), toxic-metabolic (40, 36%), and vasculitis (11, 10%). PNS antibody testing increased by 96% from 2009 to 2017; diagnostic yield remained low (7% vs. 8%). Intermediate-risk or other syndromes (OR 7.97, CI95% 3.07-23.80; OR 192.82 CI95%, 66.11-739.59) and low-risk/absence of tumor (OR 6.90, CI95% 2.75-18.92) were associated with alternative diagnoses, whereas increasing age (OR 0.95, CI95% 0.92-0.97) was inversely associated. These variables (age, syndrome, and tumor type) were incorporated in the PNS DDx Score.
conclusionAlternative diagnoses during PNS workup are common in patients < 55 years and those without high-risk syndromes. The PNS DDx Score can be used to identify patients at risk of misdiagnosis.
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