Trigeminal neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options

Giulia Di Stefano, Stine Maarbjerg, Andrea Truini, Giulia Di Stefano, Stine Maarbjerg, Andrea Truini

Abstract

Background: Trigeminal neuralgia is one of the most characteristic and difficult to treat neuropathic pain conditions in patients with multiple sclerosis. The present narrative review addresses the current evidence on diagnostic tests and treatment of trigeminal neuralgia secondary to multiple sclerosis.

Methods: We searched for relevant papers within PubMed, EMBASE and the Cochrane Database of Systematic Reviews, taking into account publications up to December 2018.

Results: Trigeminal neuralgia secondary to multiple sclerosis manifests with facial paroxysmal pain triggered by typical manoeuvres; neurophysiological investigations and MRI support the diagnosis, providing the definite evidence of trigeminal pathway damage. A dedicated MRI is required to identify pontine demyelinating plaques. In many patients with multiple sclerosis, neuroimaging and surgical evidence suggests that neurovascular compression might act in concert with the pontine plaque through a double-crush mechanism. Although no placebo-controlled trials have been conducted in these patients, according to expert opinion the first-line therapy for trigeminal neuralgia secondary to multiple sclerosis relies on sodium-channel blockers, i.e. carbamazepine and oxcarbazepine. The sedative and motor side effects of these drugs frequently warrant an early consideration for neurosurgery. Surgical procedures include Gasserian ganglion percutaneous techniques, gamma knife radiosurgery and microvascular decompression in the posterior fossa.

Conclusions: The relatively poor tolerability of the centrally-acting drugs carbamazepine and oxcarbazepine highlights the need to develop new selective and better-tolerated sodium-channel blockers. Prospective studies based on more advanced neuroimaging techniques should focus on how trigeminal anatomical abnormalities may be able to predict the efficacy of microvascular decompression.

Keywords: Multiple sclerosis; Neuropathic pain; Secondary trigeminal neuralgia.

Conflict of interest statement

Andrea Truini received consulting fees or payment for lectures from Sigma Tau IFR, Angelini, Gruenenthal and Pfizer. Giulia Di Stefano has no conflicts to declare. Stine Maarbjerg has no conflicts to declare.

Figures

Fig. 1
Fig. 1
Neuroimaging findings in a representative patient with TN secondary to MS possibly due to a double crush mechanism. 3D time-of-flight (TOF) magnetic resonance angiography scans (a) and 3D constructive interference in the steady state (CISS) T2-weighted (b) on the axial plane demonstrate left neurovascular compression (NVC) with associated trigeminal nerve atrophy. T2-weighted image on the axial plane shows a hyperintense pontine lesion at the left trigeminal nerve root entry zone (REZ) (c). The arrow indicates the trigeminal nerve (b) and the arrowhead the demyelinating plaque (c). Reproduced from [16]
Fig. 2
Fig. 2
Voxel-based analysis in patients with TN secondary to MS. Voxel-based brainstem model in patients with TN secondary to MS (TN group, n = 42) and in patients with trigeminal sensory disturbances due to MS (non-TN group, n = 29). The statistical analysis in patients with TN secondary to MS showed an area of very high probability of a lesion (P < 0.0001) centred in the ventrolateral pons between the trigeminal root entry zone and the trigeminal nuclei, i.e. along the intrapontine part of the trigeminal primary afferents. In the non-TN group, the area of high probability of lesion (P < 0.001) corresponded to a more caudal, medial, and dorsal pontine region involving the subnucleus oralis of the spinal trigeminal complex. The axial sections in this figure correspond to the sections 120 and 160 of the Shaltenbrandt atlas. The level of probability is colour-coded. Blue indicates non-significant areas, white the minimum level of significance (P < 0.05), and red the highest level of significance. Reproduced from [15]

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