Trigeminal neuralgia and its comorbidities: A nationwide disease trajectory study

Jacob Worm, Isabella Friis Jørgensen, Ólafur Birgir Davídsson, Henrik Hjalgrim, Timo Röder, Sisse Rye Ostrowski, Ole Birger Pedersen, Christian Erikstrup, Mie Topholm Bruun, Bitten Aagaard Jensen, Erik Sørensen, Henrik Ullum, Gyða Björnsdóttir, Thorgeir Thorgeirsson, Hreinn Stefánsson, Ólafur Árni Sveinsson, Kari Stefansson, Henrik Winther Schytz, Lars Bendtsen, Søren BrunakThomas Folkmann Hansen, Stine Maarbjerg*, Karina Banasik, Jacob Bay, Jens Kjærgaard Boldsen, Thorsten Brodersen, Søren Brunak, Kristoffer Burgdorf, Mona Ameri Chalmer, Maria Didriksen, Khoa Manh Dinh, Joseph Dowsett, Christian Erikstrup, Bjarke Fenstraa, Frank Geller, Daniel Gudbjartsson, Thomas Folkmann Hansen, Lotte Hindhede, Henrik Hjalgrim, Rikke Louise Jacobsen, Gregor Jemec, Bitten Aagaard Jensen, Katrine Kaspersen, Bertram Dalskov Kjerulff, Lisette Kogelman, Margit Anita Hørup Larsen, Ioannis Louloudis, Agnete Lundgard, Susan Mikkelsen, Christina Mikkelsen, Ioanna Nissen, Mette Nyegaard, Sisse Rye Ostrowski, Ole Birger Pedersen, Alexander Pil Henriksen, Palle Duun Rohde, Klaus Rostgaard, Michael Schwinn, Kari Stefansson, Hreinn Stefánsson, Erik Sørensen, Unnur Porsteinsdóttir, Lise Wegner Thørner, Mie Topholm Brun, Henrik Ullum, Thomas Werge, David Westergaard

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

1 Citation (Scopus)

Abstract

There is a limited understanding of risk factors and comorbidities in trigeminal neuralgia, a disease characterized by paroxysms of severe unilateral facial pain and a higher incidence in women. We aim to identify temporally associated comorbidities involving trigeminal neuralgia by analyzing nationwide disease trajectories. Using data from 7.2 million unique individuals in the Danish National Patient Register between 1994 and 2018, each individual diagnosed with trigeminal neuralgia was compared with 10,000 matched controls to identify co-occurring diseases. The sequential disease associations were identified in sex-stratified disease trajectories. A Cox-regression analysis investigated whether treatment with carbamazepine or oxcarbazepine, as compared with gabapentin, pregabalin, or lamotrigine, was associated with stroke risk. Finally, we investigated the stroke polygenic risk score and its association with stroke incidence in a subset of genotyped individuals with trigeminal neuralgia. We included 7141 individuals with trigeminal neuralgia (64.2% female, mean age at diagnosis 58.7 years) and identified 18 diseases associated with subsequent trigeminal neuralgia. After diagnosis, trigeminal neuralgia was associated with 9 diseases, including ischemic stroke (relative risk 1.55). Carbamazepine or oxcarbazepine treatment increased the ischemic stroke risk (hazard ratio 1.78; 95% confidence interval 1.47-2.17); however, the polygenic risk of stroke showed no association. In the Danish population, a trigeminal neuralgia diagnosis is temporally associated with 27 diseases revealed in systematic disease trajectories. Trigeminal neuralgia itself and its first-line treatment, but not a stroke polygenic risk score, was associated with an increased risk of ischemic stroke indicating that vascular risk factors should be routinely assessed in individuals with trigeminal neuralgia.

Original languageEnglish
JournalPain
Volume166
Issue4
Pages (from-to)879-887
Number of pages9
ISSN0304-3959
DOIs
Publication statusPublished - Apr 2025

Keywords

  • Antiseizure medication
  • Cardiovascular disease
  • Cohort study
  • Comorbidity
  • Epidemiology
  • Facial pain
  • Ischemic stroke
  • Neuropathic pain
  • Risk factor

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