Efficacy of surgical treatment in patients with trigeminal neuralgia secondary to multiple sclerosis: A prospective study of 18 cases with evaluation of outcome and complications by independent evaluators.

INTRODUCTION: Medical treatments for trigeminal neuralgia secondary to multiple sclerosis have low efficacy and tolerability and scientific evidence regarding efficacy of neurosurgery is scarce. We aimed to assess neurosurgical outcome and complications in trigeminal neuralgia secondary to multiple sclerosis. METHODS: Patients with trigeminal neuralgia secondary to multiple sclerosis who underwent microvascular decompression, glycerol rhizolysis or balloon compression were prospectively and consecutively included from 2012 to 2019. Preoperatively, we systematically obtained clinical characteristics and performed a 3.0 Tesla MRI. Follow-up at three, six and 12 months was performed by independent assessors. RESULTS: We included 18 patients. Of the seven patients treated with microvascular decompression, two patients (29%) had an excellent outcome (both had neurovascular contact with morphological changes), three patients (43%) had a good outcome, one patient (14%) had treatment failure and one patient (14%) had a fatal outcome. Three patients (43%) had major complications. Of 11 patients treated with percutaneous procedures, seven patients (64%) had an excellent or good outcome with major complications in three patients (27%). CONCLUSION: Percutaneous procedures provided acceptable outcome and complication rates and should be offered to the majority of patients with trigeminal neuralgia secondary to multiple sclerosis who need surgery. Microvascular decompression is less effective and has a higher complication rate in trigeminal neuralgia secondary to multiple sclerosis compared to microvascular decompression in classical and idiopathic trigeminal neuralgia. Microvascular decompression should only be considered in patients with trigeminal neuralgia secondary to multiple sclerosis when they have neurovascular contact with morphological changes.

Microvascular decompression in trigeminal neuralgia - a prospective study of 115 patients.

BACKGROUND: Trigeminal neuralgia is a severe facial pain disorder. Microvascular decompression is first choice surgical treatment of patients with classical TN. There exist few prospective studies with an independent evaluation of efficacy and complications after MVD. OBJECTIVES: We aimed to assess outcome and complications after microvascular decompression from our center. METHODS: We prospectively recorded clinical characteristics, outcome, and complications from consecutive patients with either classical or idiopathic (only patients with a neurovascular contact) trigeminal neuralgia undergoing microvascular decompression. Neurovascular contact was evaluated by 3.0 Tesla MRI. Patients were assessed before and 3, 6, 12, and 24 months after surgery by independent assessors. RESULTS: Of 115 included patients, 86% had a clinically significant outcome (i.e., BNI I - BNI IIIb). There was a significant association between an excellent surgical outcome and the male sex (OR 4.9 (CI 1.9-12.8), p = 0.001) and neurovascular contact with morphological changes (OR 2.5 (CI 1.1-6.0), p = 0.036). Significantly more women (12/62 = 19%) than men (2/53 = 4%) had a failed outcome, p = 0.019. The most frequent major complications were permanent hearing impairment (10%), permanent severe hypoesthesia (7%), permanent ataxia (7%), and stroke (6%). Most patients (94%) recommend surgery to others. CONCLUSION: Microvascular decompression is an effective treatment for classical and idiopathic (only patients with a neurovascular contact) trigeminal neuralgia with a high chance of a long-lasting effect. The chance of an excellent outcome was highest in men and in patients with classical trigeminal neuralgia. Complications are relatively frequent warranting thorough patient evaluation and information preoperatively. TRIAL REGISTRATION: Clinical. TRIALS: gov registration no. NCT04445766 .

Safety and efficacy of erenumab in patients with trigeminal neuralgia in Denmark: a double-blind, randomised, placebo-controlled, proof-of-concept study.

BACKGROUND: Trigeminal neuralgia is a severe facial pain disorder that is difficult to treat. Erenumab, a monoclonal antibody against the calcitonin gene-related peptide (CGRP) receptor, has proven efficacy in migraine. Erenumab modulates sensory processing in peripheral trigeminal pain pathways in mice and was reported to be effective for patients with trigeminal neuralgia in open-label studies. We aimed to evaluate the efficacy of erenumab in patients with trigeminal neuralgia. METHODS: We did a randomised, double-blind, placebo-controlled trial in adults (aged 18-85 years) with idiopathic or classic trigeminal neuralgia as defined by the 3rd edition of the International Classification of Headache Disorders. The trial was based at the Danish Headache Center, Copenhagen University Hospital. Eligible participants had no clinically significant cerebrovascular or cardiovascular disease, had self-reported pain intensity of at least 4 on the 11-point Numeric Rating Scale (0=no pain, 10=worst pain imaginable), and had at least three daily pain paroxysms. After a 1-week pre-screening period, patients entered a 4-week baseline period. Participants who met pain inclusion criteria at the end of the baseline period were randomly assigned (1:1) to receive subcutaneous injections of either erenumab 140 mg or placebo and entered the 4-week follow-up period. Randomisation was done in blocks of 10 using a computer-generated schedule by a third-party company. Participants and assessors were masked to treatment allocation, and erenumab and placebo were packed in identical prefilled syringes. The primary outcome was the number of responders, defined as patients who had a reduction of at least 30% in mean average daily pain intensity during the follow-up period compared with during the baseline period, analysed in the intention-to-treat population. This trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database, EudraCT number 2019-000848-95. FINDINGS: We assessed 860 patients for suitability and excluded 741 between Oct 28, 2019, and Sept 13, 2021. 119 participants entered a 1-week pre-screening period and 26 were excluded, 93 participants entered a 4-week baseline period with 13 excluded before randomisation, and 80 participants were randomly assigned to erenumab 140 mg (n=40) or placebo (n=40). There was no difference between groups in the number of responders at 4 weeks in the intention-to-treat population (14 [35%] of 40 with erenumab vs 18 [45%] of 40 with placebo; estimated effect size -10% [95% CI -31 to 11]; p=0·36). 20 (50%) of 40 participants reported adverse events in each group. The most common adverse events were constipation (28%) and headache (10%) in the erenumab group, and headache (13%), constipation (10%), and abdominal pain (10%) in the placebo group. INTERPRETATION: Erenumab did not reduce pain intensity compared with placebo in patients with trigeminal neuralgia and CGRP probably does not have an important role in paroxysmal pain. Well tolerated, effective treatments in trigeminal neuralgia are still needed. FUNDING: Novartis.

Intravenous fosphenytoin as treatment for acute exacerbation of trigeminal neuralgia: A prospective systematic study of 15 patients.

INTRODUCTION: Intravenous fosphenytoin is widely used for acute exacerbation of trigeminal neuralgia, however, few studies have investigated this treatment. We aimed to examine the efficacy and side effects of initial intravenous fosphenytoin plus oral tapering of phenytoin for exacerbation of trigeminal neuralgia. METHODS: Consecutive patients with primary trigeminal neuralgia were included in this prospective observational 90-days follow-up study. Data were collected using standardized interviews before, at 24 hours, day 7, 30 and 90 post loading dose. The primary outcome was the proportion of responders defined as a 50% reduction in pain intensity 24 hours post loading dose. RESULTS: We included 15 patients. Nine patients (60%) were responders. Pain intensity 24 hours post loading dose was reduced by 5.00 points on the numerical rating scale (p < 0.001), and at day 7 by 5.5 points (p < 0.001). The most common side effects were hypotension and dizziness. CONCLUSION: Intravenous fosphenytoin relieves trigeminal neuralgia pain in most patients and provides a window for titrating prophylactic trigeminal neuralgia medications or planning neurosurgery. The decision to administer intravenous fosphenytoin should be taken with support from trigeminal neuralgia experts and involves considerations of co-morbidities and other treatment options for acute exacerbation of trigeminal neuralgia.Clinical Trial: Preregistered (ClinicalTrials.gov Identifier: NCT03712254.

Neurovascular contact plays no role in trigeminal neuralgia secondary to multiple sclerosis.

INTRODUCTION: A demyelinating plaque and neurovascular contact with morphological changes have both been suggested to contribute to the etiology of trigeminal neuralgia secondary to multiple sclerosis (TN-MS). The aim of this study was to confirm or refute whether neurovascular contact with morphological changes is involved in the etiology of TN-MS. METHODS: We prospectively enrolled consecutive TN-MS patients from the Danish Headache Center. Clinical characteristics were collected systematically. MRI scans were done using a 3.0 Tesla imager and were evaluated by the same experienced blinded neuroradiologist. RESULTS: Sixty-three patients were included. Fifty-four patients were included in the MRI analysis. There was a low prevalence of neurovascular contact with morphological changes on both the symptomatic side (6 (14%)) and the asymptomatic side (4 (9%)), p = 0.157. Demyelinating brainstem plaques along the trigeminal afferents were more prevalent on the symptomatic side compared to the asymptomatic side (31 (58%) vs. 12 (22%), p < 0.001). A demyelinating plaque was highly associated with the symptomatic side (odds ratio = 10.6, p = 0.002). CONCLUSION: The primary cause of TN-MS is demyelination along the intrapontine trigeminal afferents. As opposed to classical trigeminal neuralgia, neurovascular contact does not play a role in the etiology of TN-MS. Microvascular decompression should generally not be offered to patients with TN-MS.The study was registered at ClinicalTrials.gov (number NCT04371575).

Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia.

Trigeminal neuralgia is a very painful neurological condition with severe, stimulus-evoked, short-lasting stabbing pain attacks in the face. The past decade has offered new insights into trigeminal neuralgia symptomatology, pathophysiology, and treatment, leading to a change in the classification of the condition. An accurate diagnosis is crucial because neuroimaging interpretation and clinical management differ among the various forms of facial pain. MRI using specific sequences should be a part of the diagnostic workup to detect a possible neurovascular contact and exclude secondary causes. Demonstration of a neurovascular contact should not be used to confirm a diagnosis but rather to facilitate surgical decision making. Carbamazepine and oxcarbazepine are drugs of first choice for long-term treatment, whereas microvascular decompression is the first-line surgery in medically refractory patients. Advances in neuroimaging techniques and animal models will provide further insight into the causes of trigeminal neuralgia and its pathophysiology. Development of more efficacious treatment options is highly warranted.

Favourable prognosis of trigeminal neuralgia when enrolled in a multidisciplinary management program - a two-year prospective real-life study.

BACKGROUND: Prognosis of medically treated trigeminal neuralgia patients is assumed to be poor, but the evidence is lacking. Thus, prospective real-life studies of medical management of trigeminal neuralgia are warranted. METHODS: This was an observational study. Patients were consecutively enrolled in a structured management program at a specialist centre for facial pain. Optimisation of medical treatment, physiotherapy, psychotherapy, and advice from trained nurses, were parts of the program. Medically intractable patients were referred for neurosurgery. Data-collection was prospective using standardised schemes and patient surveys. The aim was to describe the two-year outcome of medical treatment at the specialist centre. The primary outcome was a 50% reduction in the overall burden of pain according to a Numerical Rating Scale (NRS) after two years. RESULTS: A total of 186 primary TN patients were enrolled in the program of which 103 patients remained medically managed and completed the two-year follow-up. Fifty patients were treated surgically within the first two years of follow-up. Half of the medically managed patients (53 (51%)), had more than a 50% reduction in the overall burden of pain over the two-year period. The overall burden of pain on NRS decreased from mean 5.34 to 3.00, p < 0.01. There was no significant association between primary outcome and sex, depression and/or anxiety, concomitant persistent pain, or neurovascular contact with morphological changes of the trigeminal nerve. CONCLUSIONS: Patients with trigeminal neuralgia improve over a two-year period when enrolled in a structured medical management program. Optimisation of drug treatment, continuous advice and education and support by the multidisciplinary team, referral of the medically intractable patients for surgery or the natural history of the disease, can be some of the reasons for the improvement. The favourable prognosis provides hope and optimism for medically managed TN patients. TRIAL REGISTRATION: Current study was observational, and patients were offered standard clinical care and laboratory workups according to current American Academy of Neurology and European Federation of Neurological Societies treatment guidelines. The study has been registered at ClincalTrials.gov. ID: NCT03838393 .

Prognostic factors for outcome of microvascular decompression in trigeminal neuralgia: A prospective systematic study using independent assessors.

INTRODUCTION: There is a lack of high-quality prospective, systematic studies using independent assessors of outcome of microvascular decompression as treatment for trigeminal neuralgia. METHODS: Clinical characteristics and outcome data were recorded prospectively from consecutive classical trigeminal neuralgia patients, using standardized interviews. Degree of neurovascular contact was evaluated by a 3.0 Tesla MRI blinded to symptomatic side. Patients were assessed before and 12 months after surgery by a neurologist. RESULTS: Twenty-six men and 33 women completed 12 months follow-up. Forty-one patients (69%) had an excellent outcome (no pain, no medication). Ten (18%) patients had a good outcome. Eight (12%) patients had no improvement or had worsening of pain. MRI showed neurovascular contact with morphological changes in 34 patients (58%). Odds ratio between neurovascular contact with morphological changes and excellent outcome was 4.4 (Cl 1.16-16.26), p = 0.029. Odds ratio between male sex and excellent outcome was 11.38 (Cl 2.12-59.52), p = 0.004. No significant association was found between excellent outcome and concomitant persistent pain, current age or disease duration. CONCLUSION: Neurovascular contact with morphological changes and male sex are positive predictive factors for outcome of microvascular decompression. The findings enable clinicians to better inform patients before surgery.

Persistent idiopathic facial pain - a prospective systematic study of clinical characteristics and neuroanatomical findings at 3.0 Tesla MRI.

Introduction Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical characteristics and neuroimaging findings in PIFP. Methods Data collection was prospective and standardized in consecutive PIFP patients. All patients underwent 3.0 MRI. Results In a cohort of 53 PIFP patients, the average age of onset was 44.1 years. PIFP was found in more women 40 (75%) than men 13 (25%), p < 0.001. There was a high prevalence of bilateral pain 7 (13%), hypoesthesia 23 (48%), depression 16 (30%) and other chronic pain conditions 17 (32%) and a low prevalence of stabbing pain 21 (40%), touch-evoked pain 14 (26%) and remission periods 10 (19%). The odds ratio between neurovascular contact and the painful side was 1.4 (95% Cl 0.4-4.4, p = 0.565) and the odds ratio between neurovascular contact with displacement of the trigeminal nerve and the painful side was 0.2 (95% Cl 0.0-2.1, p = 0.195). Conclusion PIFP is separated from trigeminal neuralgia both with respect to the clinical characteristics and neuroimaging findings, as NVC was not associated to PIFP.

[Diagnostics and treatment of trigeminal neuralgia].

Trigeminal neuralgia (TN) is characterized by unilateral evoked short-lasting intense pain paroxysms in the face. A concomitant persistent background pain is frequently present. Neurovascular contact causing displacement or atrophy of the trigeminal nerve is important to TN aetiology. TN can also be secondary to a space-occupying lesion or multiple sclerosis. Early high-quality magnetic resonance imaging is mandatory as a part of the work-up. First-choice treatment is medical. Medically refractory patients are referred to neurosurgery. Nationwide in Denmark, there is a need for structured and uniform treatment of TN.