AUTHOR=Erro Roberto , Lazzeri Giulia , Gigante Angelo Fabio , Pilotto Andrea , Magistrelli Luca , Bologna Matteo , Terranova Carmen , Olivola Enrica , Dallocchio Carlo , Moschella Vincenzo , Valentino Francesca , Di Biasio Francesca , Nicoletti Alessandra , De Micco Rosa , Brusa Livia , Sorrentino Cristiano , Matinella Angela , Bertino Salvatore , Paparella Giulia , Modugno Nicola , Contaldi Elena , Padovani Alessandro , Di Fonzo Alessio , Restaino Marialuisa , Barone Paolo ,  TITAN study group , Franco Giulia , De Rosa Anna , di Biase Lazzaro , Esposito Marcello , Chiara Malaguti Maria , Di Giacopo Raffaella , Ceravolo Roberto , Spagnolo Francesca , Bianchi Marta , Vitaliani Roberta , Maria Raglione Laura , Morgante Francesca 

TITLE=Clinical correlates of “pure” essential tremor: the TITAN study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1233524

DOI=10.3389/fneur.2023.1233524

ISSN=1664-2295

ABSTRACT=Background: To date, there are no large studies delineating the clinical correlates of “pure” Essential Tremor (ET) according to its new definition.
Methods: From The ITAlian tremor Network (TITAN) database, we extracted data of patients with a diagno-sis of “pure” ET and excluded those with other tremor classification including ET-plus, focal and task-specific tremors, which were formerly considered parts of the ET spectrum. 
Results: Out of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analysed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by age-at-onset-class of 20 years showed significant differences, with spo-radic cases representing the large majority of the class with age at onset above 60 years. Patients with posi-tive family history for tremor had a younger onset and were more likely to have leg involvement than spo-radic patients, despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggest a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with current pharmacological options.
Discussion: The findings here reported provide new insights especially with regard to a possible inversed sex distribution, with females being more commonly affected by “pure” ET, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies.