Background & Aims

Trigeminal neuralgia is characterized by paroxysms of very severe unilateral facial pain. The pain is electric shock-like, shooting, or stabbing in the distribution of one or more branches of the trigeminal nerve (1) and highly debilitating. There is sparse knowledge about trigeminal neuralgia risk factors and comorbidity.(2) Previous studies have used cohorts of limited sizes.(3) By analyzing nationwide disease trajectories, we aim to identify comorbidities temporally associated with trigeminal neuralgia.

Methods

The Danish National Patient Register (DNPR) from 1994 to 2018 has data from 7.2 million unique individuals. Among those individuals we included all persons with trigeminal neuralgia diagnosed in the hospital sector. We identified significantly co-occurring diseases by comparing each individual diagnosed with trigeminal neuralgia with 10,000 matched controls. The sequential disease associations were identified in sex-stratified disease trajectories.(4,5) A Cox-regression analysis investigated whether treatment with carbamazepine or oxcarbazepine, as compared to 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.

Results

We included 7,141 individuals with trigeminal neuralgia with a mean age at diagnosis of 58.7 years, and 64.2% of them were female. We identified 18 diseases that increased the risk of subsequent trigeminal neuralgia, while trigeminal neuralgia increased the risk of later development of nine diseases, including ischemic stroke (relative risk of 1.55). Carbamazepine or oxcarbazepine treatment increased the risk of ischemic stroke (hazard ratio of 1.78 [95% CI: 1.47-2.17]). The polygenic risk of stroke showed no association.

Conclusions

Our population-based study examined trigeminal neuralgia comorbidities demonstrated 27 systematic disease trajectories and allowed us to track the progression of diseases over time in individuals with trigeminal neuralgia. Trigeminal neuralgia itself and its first-line treatments were associated with an increased risk of ischemic stroke. This has important implications for clinical practice. Vascular risk factors should routinely be assessed and optimally treated in individuals with trigeminal neuralgia.

References

1. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.
2. Bendtsen L, Zakrzewska JM, Heinskou TB, et al. Advances in diagnosis, classification,
pathophysiology, and management of trigeminal neuralgia. Lancet Neurol 2020; 19: 784–796.
3. Maarbjerg S, Gozalov A, Olesen J, Bendtsen L. Trigeminal Neuralgia – A Prospective Systematic Study of Clinical Characteristics in 158 Patients. Headache J Head Face Pain. 2014;54(10):1574-1582.
4. Siggaard T, Reguant R, Jørgensen IF, et al. Disease trajectory browser for exploring temporal, population-wide disease progression patterns in 7.2 million Danish patients. Nat Commun. 2020;11(1):1-10.
5. Jensen AB, Moseley PL, Oprea TI, et al. Temporal disease trajectories condensed from population-wide registry data covering 6.2 million patients. Nat Commun. 2014;5(1):4022.

Presenting Author

Jacob Worm

Poster Authors

Jacob Worm

MD

Danish Headache Center, Copenhagen Uni. Hospital and University of Copenhagen

Lead Author

Isabella Friis Jørgensen

PhD

Lead Author

Ólafur Birgir Davídsson

MSc

Lead Author

Henrik Hjalgrim

PhD

Lead Author

Timo Röder

MSc

Lead Author

Sisse Rye Ostrowski

DMSc

Lead Author

Ole Birger Pedersen

PhD

Lead Author

Christian Erikstrup

PhD

Lead Author

Mie Topholm Bruun

MD

Lead Author

Bitten Aagaard Jensen

MD

Lead Author

Erik Sørensen

PhD

Lead Author

Henrik Ullum

PhD

Lead Author

Gyða Björnsdóttir

PhD

Lead Author

Thorgeir Thorgeirsson

PhD

Lead Author

Hreinn Stefánsson

PhD

Lead Author

Ólafur Árni Sveinsson

PhD

Lead Author

Kári Stefánsson

PhD

Lead Author

Henrik Winther Schytz

DMSc

Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet

Lead Author

Lars Bendtsen

DMSc

Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet

Lead Author

Søren Brunak

PhD

Lead Author

Thomas Folkmann Hansen

PhD

Lead Author

Stine Maarbjerg

PhD

Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Orofacial Pain