Epidemiology of paraneoplastic neurological syndromes: a population-based study.

BACKGROUND: The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-based incidence study and report the clinical spectrum and antibody profile of PNS in a large area in Northeastern Italy. METHODS: We performed a 9-year (2009-2017) population-based epidemiological study of PNS in the provinces of Udine, Pordenone and Gorizia, in the Friuli-Venezia Giulia region (983,190 people as of January 1, 2017). PNS diagnosis and subgroups were defined by the 2004 diagnostic criteria. Age- and sex-adjusted incidence rates were calculated. RESULTS: We identified 89 patients with a diagnosis of definite PNS. Median age was 68 years (range 26-90), 52% were female. The incidence of PNS was 0.89/100,000 person-years. PNS incidence rates increased over time from 0.62/100,000 person-years (2009-2011), 0.81/100,000 person-years (2012-2014) to 1.22/100,000 person-years (2015-2017). The prevalence of PNS was 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in every 334 cancers in our region. Statistically significant associations were observed between cancer type and Ab-specificity (P < 0.001), and between neurological syndrome and Ab-specificity (P < 0.001). CONCLUSIONS: This first population-based study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.

Human mitochondrial DNA with large deletions repopulates organelles faster than full-length genomes under relaxed copy number control.

Partially-deleted mitochondrial DNA (DeltamtDNA) accumulates during aging of postmitotic tissues. This accumulation has been linked to decreased metabolic activity, increased reactive oxygen species formation and the aging process. Taking advantage of cell lines with heteroplasmic mtDNA mutations, we showed that, after severe mtDNA depletion, organelles are quickly and predominantly repopulated with DeltamtDNA, whereas repopulation with the wild-type counterpart is slower. This behavior was not observed for full-length genomes with pathogenic point mutations. The faster repopulation of smaller molecules was supported by metabolic labeling of mtDNA with [3H]thymidine during relaxed copy number control conditions. We also showed that hybrid cells containing two defective mtDNA haplotypes tend to retain the smaller one as they adjust their normal mtDNA copy number. Taken together, our results indicate that, under relaxed copy number control, DeltamtDNAs repopulate mitochondria more efficiently than full-length genomes.