Author Response: Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes
FrancescGraus, Emeritus investigator, Institut d'Investigacions Biomèdiques August Pi i Sunyer. Barcelona, Spain
Submitted November 14, 2021
We are pleased to clarify the cancer level from the PNS-care score in our article for Zhang et al.1 As explained in the “Cancer Associated With PNS and Cancer Screening” section of the updated criteria, consistent cancers are those with well-known epidemiological and antibody associations (Tables 1-3).1 These tumors score 4. Non-consistent cancers are therefore those lacking these epidemiological/antibody associations, and they only score 4 with antigen expression. Tumors that are not consistent, as in colon cancer in an anti-Hu positive patient, or an unknown antigen expression status should score as 0, or 1 if follow-up is <2 y for this item. The time cutoff should principally apply to patients without a detectable cancer to account for the likelihood of the presence of an underlying tumor despite initial negative screenings. Thus, for the clinical scenario proposed, polyradiculoneuropathy is an intermediate-risk phenotype (score 2), Ma2 is a high-risk antibody (score 3), and during the first 2 years of follow-up without a cancer found, the cancer level would score 1, resulting in a total of 6, probable PNS. The third year of follow-up until the tumor diagnosis, the score would decrease until 5 (2+3+0), possible PNS, but would increase again up to 6 (2+3+1), probable PNS, with the non-Hodgkin lymphoma diagnosis, which is a non-consistent cancer for the phenotype-antibody association proposed.2,3 We acknowledge that the updated criteria are stricter and may fail to diagnose as ‘definite’ a few true PNS cases. On the other hand, using these updated criteria, the risk is reduced of defining as true PNS neurological syndromes in which the temporal association with the underlying cancer does not reflect a pathogenic link.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Graus F, Vogrig A, Muñiz-Castrillo S, et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurol Neuroimmunol Neuroinflammation. 2021;8(4):e1014.
Vogrig A, Joubert B, Maureille A, et al. Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome. J Neurol. 2019;266:398–410.
Vogrig A, Fouret M, Joubert B, et al. Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors. Neurol Neuroimmunol Neuroinflammation. 2019;6(6):e60.
We are pleased to clarify the cancer level from the PNS-care score in our article for Zhang et al.1 As explained in the “Cancer Associated With PNS and Cancer Screening” section of the updated criteria, consistent cancers are those with well-known epidemiological and antibody associations (Tables 1-3).1 These tumors score 4. Non-consistent cancers are therefore those lacking these epidemiological/antibody associations, and they only score 4 with antigen expression. Tumors that are not consistent, as in colon cancer in an anti-Hu positive patient, or an unknown antigen expression status should score as 0, or 1 if follow-up is <2 y for this item. The time cutoff should principally apply to patients without a detectable cancer to account for the likelihood of the presence of an underlying tumor despite initial negative screenings. Thus, for the clinical scenario proposed, polyradiculoneuropathy is an intermediate-risk phenotype (score 2), Ma2 is a high-risk antibody (score 3), and during the first 2 years of follow-up without a cancer found, the cancer level would score 1, resulting in a total of 6, probable PNS. The third year of follow-up until the tumor diagnosis, the score would decrease until 5 (2+3+0), possible PNS, but would increase again up to 6 (2+3+1), probable PNS, with the non-Hodgkin lymphoma diagnosis, which is a non-consistent cancer for the phenotype-antibody association proposed.2,3 We acknowledge that the updated criteria are stricter and may fail to diagnose as ‘definite’ a few true PNS cases. On the other hand, using these updated criteria, the risk is reduced of defining as true PNS neurological syndromes in which the temporal association with the underlying cancer does not reflect a pathogenic link.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References