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Background and Objectives: Paraneoplastic neurologic syndrome (PNS) diagnostic criteria were first proposed in 2004 and updated in 2021. The PNS-CARE score, derived from the updated criteria, is a composite model for assigning likelihood for patients with suspected PNS. In this study, we evaluated the utility and applicability of the 2021 PNS-CARE score and present our PNS cohort., Methods: This is a retrospective study. We identified Mayo Clinic patients suspected to have PNS (1/2005-12/2020) and collected relevant information including demographics, PNS presentation, and clinical outcomes. Inclusion criteria were the following: (1) patients with a syndrome consistent with PNS and (2) patients with sufficient information available in charts. Exclusion criteria were the following: (1) evaluation only before 2005, (2) patients not evaluated by neurology, (3) presentation after immune checkpoint inhibitors, and (4) syndromes not included in 2021 criteria. All patients were evaluated for the 2021 and 2004 PNS criteria., Results: We identified 484 patients suspected to have PNS at initial presentation, of whom 212 (44%) were considered to have PNS after completion of evaluation. Among these 212 patients, the most common autoantibodies were PCA1 (Yo)-IgG (17%), KLHL11-IgG (16%), and CRMP5-IgG (14%) and the most common phenotypes were rapidly progressive cerebellar syndrome (29%), brainstem encephalitis (14%), and limbic encephalitis (8%). The 2021 PNS criteria definite/probable categorization (PNS-CARE score ≥ 6) had a sensitivity and specificity of 93% and 100%, respectively, while the 2004 PNS criteria definite categorization had a sensitivity and specificity of 67% and 99%, respectively. We found 15 patients with a PNS-CARE score ≤5 who likely had PNS on our review. The most common presentation among these patients was KLHL11-IgG brainstem encephalitis (7/15, 47%) with likely burned-out testicular tumor., Discussion: Our study validates the PNS-CARE score. A clearer understanding of typical PNS presentation and common underlying malignancies and autoantibodies can aid in earlier and more accurate diagnosis, which is crucial for downstream clinical decisions. Some patients with an intermediate-risk phenotype do not meet probable/definite criteria despite the presence of high-risk antibodies and/or underlying malignancy.

Objectives: Population-based epidemiologic data for paraneoplastic neurologic syndromes (PNSs) in the United States are lacking. Our objective was to evaluate the incidence, prevalence, and associated morbidity of PNS., Methods: We performed a population-based epidemiology study in Olmsted County, Minnesota, with patients identified between January 1, 1987, and December 31, 2018, using the medical records linkage system of the Rochester Epidemiology Project (REP) who met the definite/probable 2021 PNS criteria and 2004 PNS criteria. Patients with dermatomyositis and myasthenia gravis with underlying tumors were included. Age- and sex-specific population counts were obtained from REP resources for January 1, 2014 (prevalence denominator) and annually for 1987-2018 (incidence denominator). Morbidity was estimated using disability-adjusted life years (DALYs; years lived with disability [YLD] plus years of life lost [YLL])., Results: There were 28 patients with PNS identified (50% female) residing in Olmsted County, Minnesota, with median age at diagnosis of 54.5 (IQR 46.5-69.0) years. All patients had a cancer diagnosis, and 18 (64%) patients were neural autoantibody positive including antineuronal nuclear autoantibody type 1 (ANNA-1/anti-Hu; n = 1), ANNA-2/anti-Ri (n = 1), muscle-type acetylcholine receptor (AChR; n = 6), Purkinje cell cytoplasmic antibody type 1 (PCA-1/anti-Yo; n = 1), kelch-like protein 11 (KLH11; n = 3), collapsin response mediator protein 5 (CRMP-5/anti-CV2; n = 2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (n = 1), neurofilament light chain (n = 1), leucine zipper 4 (LUZP4; n = 1), and unclassified neural antibodies (n = 1). PNS incidence was 0.6/100,000 person-years and increased over time from 0.4/100,000 person-years (1987-2002) to 0.8/100,000 person-years (2003-2018) ( p = 0.06). Prevalence was 5.4/100,000 people. The median follow-up period after PNS diagnosis was 3.1 years (IQR, 1.1-9.9 years). Total disability-adjusted life years (DALYs) for 28 patients with PNS were 472.7 years, based on total years of life lost (YLL) for patients dying between 1987 and 2018 (n = 15) of 445.3 years plus years lived with disability (YLD) 27.4 years., Discussion: PNSs are rare neurologic disorders but are associated with severe morbidity and mortality. The estimated number of prevalent PNS cases in the United States is 17,099, and predicted DALY for all US PNS cases is 292,393 years. Their apparent increasing rate of detection is attributable to increasing physician awareness and availability of serologic testing., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To test the hypothesis that myeloneuropathy is a presenting phenotype of paraneoplastic neurologic syndromes we retrospectively reviewed clinical, radiologic, and serologic features of 32 patients with concomitant paraneoplastic spinal cord and peripheral nervous system involvement., Methods: Observational study investigating patients with myeloneuropathy and underlying cancer or onconeural antibody seropositivity., Results: Among 32 patients with paraneoplastic myeloneuropathy, 20 (63%) were women with median age 61 years (range 27-84 years). Twenty-six patients (81%) had classified onconeural antibodies (amphiphysin, n = 8; antineuronal nuclear antibody [ANNA] type 1 [anti-Hu], n = 5; collapsin response mediator protein 5 [CRMP5] [anti-CV2], n = 6; Purkinje cell cytoplasmic antibody type 1 [PCA1] [anti-Yo], n = 1; Purkinje cell cytoplasmic antibody type 2 [PCA2], n = 2; kelch-like protein 11 [KLHL11], n = 1; and combinations thereof: ANNA1/CRMP5, n = 1; ANNA1/amphiphysin, n = 1; ANNA3/CRMP5, n = 1). Cancer was confirmed in 25 cases (onconeural antibodies, n = 19; unclassified antibodies, n = 3; no antibodies, n = 3). Paraneoplastic myeloneuropathies had asymmetric paresthesias (84%), neuropathic pain (78%), subacute onset (72%), sensory ataxia (69%), bladder dysfunction (69%), and unintentional weight loss >15 pounds (63%). Neurologic examination demonstrated concomitant distal or asymmetric hyporeflexia and hyperreflexia (81%), impaired vibration and proprioception (69%), Babinski response (68%), and asymmetric weakness (66%). MRI showed longitudinally extensive (45%), tract-specific spinal cord T2 hyperintensities (39%) and lumbar nerve root enhancement (38%). Ten of 28 (36%) were unable to ambulate independently at last follow-up (median 24 months, range 5-133 months). Combined oncologic and immunologic therapy had more favorable modified Rankin Scale scores at post-treatment follow-up compared to those receiving either oncologic or immunologic therapy alone (2 [range 1-4] vs 4 [range 2-6], p < 0.001)., Conclusions: Paraneoplastic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate early tumor diagnosis and initiation of immunosuppressive treatment., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)