Abstract
While trigeminal neuralgia (TN) is relatively uncommon, the symptoms associated with the condition are well known to both the public and the medical profession and have been documented for many years. A Google search of TN yields almost two million ‘hits’, and the severe pain associated with the condition was formally documented by John Fothergill in a presentation to the Medical Society in London in 1773 and probably first documented almost 2000 years ago in the writings of Galen (1). Although the clinical characteristics of TN are well known, there is a paucity of information regarding the epidemiology of the condition. There is only one population-based study of the incidence of TN and its possible risk factors (2). This study assessed the population of Rochester, Minnesota, between 1945 and 1984, and found an overall annual incidence rate TN of 4.3 per 100,000 population. The investigators also documented that the incidence was higher among women, increased with increasing age, and that patients with TN had an elevated risk of having hypertension.
On the basis of the potential link between hypertension and TN, Pan et al. (3) hypothesized that TN may be linked to an increased risk of stroke, and conducted an age- and sex-matched cohort design study to assess whether there is an association between TN and stroke. The study found that, after adjusting for demographic characteristics and the presence of hypertension and other vascular risk factors, there was a significantly increased 2-year hazard ratio of stroke (both infarction and haemorrhage) for the TN cohort of 1.76 (95% CI, 1.41–2.45; p < 0.0001). This finding suggests that TN may be an independent predictor of stroke, and raises the intriguing question whether TN is an independent risk factor for stroke, and if so, what is the mechanism. However, there are limitations in this study which caution us against jumping to conclusions too hastily regarding whether a causative relationship between TN and stroke might exist. As the authors acknowledge, there are problems with this study regarding the accuracy of diagnoses, the absence of information about vascular risk factors such as smoking, and a short period of observation (only 2 years). There are potentially other problems with the study that need be considered. First, it is unclear whether case ascertainment was complete. The authors have not documented whether every patient in the study was evaluated at the end of the 2-year period of observation to insure that data acquisition was complete. Also, in order to be sure that all cases of stroke during a 2-year period are identified, it is necessary to evaluate a period of at least 3 years because strokes which occur in the latter stages of the study may be identified at clinic visits which occur after the 2-year period of observation. Second, it is possible that case ascertainment bias occurred. Patients with TN would be likely to have more clinic visits than non-TN patients, so the occurrence of stroke would be more likely identified in the TN cohort. Finally, important data, such as the prevalence of atrial fibrillation, the severity of hypertension, and how well hypertension was managed, is missing.
However, if TN is truly associated with a higher risk of stroke, a number of mechanisms could explain the relationship between the two diseases. Hypertension is a risk factor for stroke, and is thought to be a risk factor for TN. It is possible that hypertension occurs at an earlier age in patients with TN, which could then lead to premature atherosclerosis or other cardiac problems such as atrial fibrillation, which could lead to earlier occurrence of stroke. The average age of persons in the two cohorts was 56 years, so the number of strokes in the non-TN cohort would be expected to be low. If hypertension develops at an earlier age in TN patients leading to strokes developing prematurely, that could explain the higher incidence of stroke in the TN cohort in the study. Another more speculative mechanism is that the increased afferent trigeminal nerve activity in patients with TN could have effects on the trigeminovascular system leading to vascular changes which could be associated with an increased risk of stroke. Basic science studies could be designed to assess mechanisms by which TN could lead to an increased risk of stroke. However, before embarking on such research, appropriately designed studies need to be conducted to confirm that the chance of stroke is increased in TN patients, and the findings in the study of Pan et al. are not due to chance.