Trigeminal neuralgia without neurovascular compression presents earlier than trigeminal neuralgia with neurovascular compression

Abstract

I n 1934, Dandy proposed neurovascular compression (NVC) as an etiology for trigeminal neuralgia (TN).In his series, he reported that the superior cerebellar artery caused NVC in 30.7% of patients. 6 He noted veins, tumors, and vascular and cranial malformations as other "gross findings" causing compression of the trigeminal nerve; nevertheless, in 40% of cases, he observed no evidence of a gross lesion.6 He did document, however, that his posterior fossa approach did not allow for visualization of the entire root entry zone (REZ). After years of observation, and an autopsy series that showed no NVC in cadavers without TN, 13 Jannetta advanced the hypothesis that TN was a "nerve entrapment syndrome," resulting from arteries both lengthened and rendered tortuous by arteriosclerotic cerebrovascular disease. 13 This putative mechanism accounted for recurrence Charts were reviewed, and imaging and operative data were collected for patients with and without NVC. Mean, median, and the empirical cumulative distribution of onset age were determined. Statistical analysis was performed using Student t-test, Wilcoxon and Kolmogorov-Smirnoff tests, and Kaplan-Meier analysis. Multivariate analysis was performed using a Cox proportional hazards model. results The charts of 219 patients with TN were reviewed. There were 156 patients who underwent posterior fossa exploration and microvascular decompression or internal neurolysis: 129 patients with NVC and 27 without NVC. Mean age at symptoms onset for patients with and without NVC was 51.1 and 42.6 years, respectively. This difference (8.4 years) was significant (t-test: p = 0.007), with sufficient power to detect an effect size of 8.2 years. Median age between groups with and without NVC was 53.25 and 41.2 years, respectively (p = 0.003). Histogram analysis revealed a bimodal age at onset in patients without NVC, and cumulative distribution of age at onset revealed an earlier presentation of symptoms (p = 0.003) in patients without NVC. Chi-square analysis revealed a trend toward female predominance in patients without NVC, which was not significant (p = 0.08). Multivariate analysis revealed that age at onset was related to NVC but not sex, symptom side or distribution, or patient response to medical treatment. coNclusioNs NVC is neither sufficient nor necessary for the development of TN. Patients with TN without NVC may represent a distinct population of younger, predominantly female patients. Further research into the pathophysiology underlying this debilitating disease is needed.

A Gain-of-Function Mutation in Nav1.6 in a Case of Trigeminal Neuralgia

“…that TN without NVC is more prevalent in younger individuals (6). These findings suggest contributions of genetic and epigenetic factors to the pathophysiology of classical TN, especially in patients without severe NVC.…”

“…Ultrastructural studies on biopsied trigeminal roots showed axonal a Gain-of-Function Mutation in nav1. 6 …”

“…Intraoperative microneurographic recordings in trigeminal nerve fibers after stimulation of the known trigger zone in a TN patient demonstrated afterdischarges that were absent when unaffected facial areas were stimulated (13), loss, demyelination and dysmyelination consistent with NVC of the trigeminal nerve (2). However, recent studies have suggested that only severe neurovascular contact, causing displacement or atrophy of the nerve, is associated with pain in classical TN (3,4), and some studies have questioned whether NVC is necessary and sufficient for TN, since pain can occur and recur in the absence of nerve compression (5,6). A recent study reported…”

Sodium channels in pain disorders: pathophysiology and prospects for treatment

“…Trigeminal neuralgia (TN) is characterized by paroxysmal facial neuropathic pain along one or more branches of the trigeminal nerve, often triggered by innocuous stimuli, such as light touch, eating, shaving, or applying makeup [30]. Although neurovascular compression of the trigeminal nerve is prevalent in patients with TN, symptoms can occur in the absence of nerve compression or only in a subpopulation of patients with nerve compression [5; 68; 69; 77], which suggests the contribution of other factors in disease manifestation. The sodium channel blockers carbamazepine (CBZ) and oxcarbazepine are the first-line treatment for classical TN [30], which supports involvement of sodium channels in the pathophysiology of TN.…”

Is There a Magnetic Resonance Imaging-Discernible Cause for Trigeminal Neuralgia? A Structured Review

“…[17, 18] Since TN is considered a clinical description disease, magnetic resonance imaging (MRI) is not the standard of care in diagnosis and treatment and, consequently, proof of compression is not required nor often confirmed for treatment or surgery in the majority of cases. A review of autopsy studies shows NVC in 90%–100% of TN patients, yet also in 16%–58% of patients without TN.…”