16th European Headache Congress

Prof. Dr

Chair

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

Trigeminal neuralgia

Oro-facial and temporomandibular disorders

Abstract text (incl. figure legends and references) Background Patients with multiple sclerosis (MS) are at increased risk of developing trigeminal neuralgia. Medical treatments for trigeminal neuralgia (TN) secondary to MS (MS-TN) is based on weak evidence and have low efficacy and tolerability issues. Patients are often referred to neurosurgery, but the scientific evidence regarding efficacy and complications in these patients is scarce and inconsistent. We aimed to assess outcome and complications after neurosurgical intervention for MS-TN. Methods Patients with MS-TN who underwent microvascular decompression (MVD), glycerol rhizolysis or balloon compression were prospectively included from 2012 to 2019. Preoperatively, we obtained clinical characteristics and performed a 3.0 Tesla MRI in all patients. Postoperative follow-up visits at 3, 6 and 12 months were conducted by independent assessors. Efficacy was assessed using a modified version of the Barrow Neurological Institute score and complications were graded into major and minor complications. Results We included 18 patients with MS-TN. Of seven patients treated with MVD, 5 (71%) patients had an excellent or good outcome, one (14%) patient had treatment failure and one (14 %) patient had a fatal outcome. Three (43%) patients had major complications and two (29%) patients had minor complications. Of eleven patients treated with percutaneous procedures, 6 (55%) patients had an excellent or good outcome. Major complications were seen in two (18%) patients and two (18%) patients had minor complications. Conclusions Our findings shows that surgical treatment with MVD in MS-TN has a higher complication rate and an outcome inferior to MVD in primary TN. Hence, we recommend the use of percutaneous procedures in MS-TN patients and MVD only in selected patients using advanced neuroimaging to maximize the probability of an excellent outcome. Figure. Outcome (top) and complications (bottom) in primary trigeminal neuralgia (TN) and TN in multiple sclerosis (MS-TN).

ePoster

Acute treatment of classic, secondary and idiopathic trigeminal neuralgia in the emergency room. 43 patients series.

Epidemiology

Abstract text (incl. figure legends and references) OBJECTIVES The aim is to describe the acute management of status due to neuralgia in patients with trigeminal neuralgia (TN) who come to the emergency room. METHODS Observational, descriptive, and retrospective study in which all visits to the emergency room due to neuralgia status of all patients with TN followed up in a tertiary hospital were collected. Neuralgia status was defined as TN flares in patients receiving specific pharmacological treatment. For each status episode, the rescue treatment received, the modifications in the basal treatment and the need for hospitalizations and its duration were collected. RESULTS From a sample of 231 patients diagnosed with TN, 43 presented at least one status episode: 16 patients diagnosed with idiopathic TN, 16 with classic TN and 11 with secondary TN (classified according to the ICHD3). The mean age was 44 years old, and the total number of statuses was 89. Concerning the rescue treatment used, 40% of patients received first-step analgesia, 45% opioids, 18% corticosteroids, 11% antiepileptics and 3% gabapentinoids. Opioids seemed to be the more effective ones (75%), followed by antiepileptics (60%) and first-step analgesia (50%). Hospitalization was required in 20% of status patients, with a mean stay of 8.1 days, during which optimization of the basal treatment was performed: the most used drugs being carbamazepine, lamotrigine, lacosamide and gabapentinoids. 8 patients underwent invasive procedures (3 microvascular decompression, 2 percutaneous surgeries, and 3 trigger-point blocks). CONCLUSIONS 18.6% of patients presented at least one status episode. The most administered rescue drugs were first-step analgesia and opioids and the most effective ones seemed to be opioids and antiepileptics. 20% of status required hospitalization and 8 patients required invasive procedures.

Oral lacosamide for the treatment of refractory trigeminal neuralgia: a retrospective analysis of 86 patients

Abstract text (incl. figure legends and references) Introduction &amp; Objectives First-line treatment in trigeminal neuralgia (TN) is limited to carbamazepine (CBZ) and oxcarbazepine (OXC), but inefficacy or intolerability is frequent and valid alternatives are scarce. Lacosamide (LCM), a novel sodium channel blocker, has been proposed as an alternative option in a few case reports. Our objective is to describe a series of patients who received oral LCM after first-line treatment failure. Methods In this retrospective analysis, we included patients who were prescribed LCM for TN pain control and were followed at our tertiary hospital. We recorded demographic information, TN characteristics and treatment data. Primary endpoints were pain relief and adverse events. Secondary endpoints were absence of pain and time to pain worsening. Results 86 patients were included, with a mean age of 61.9 ±15.6 years, 62.8% women. Median time since TN diagnosis was 4.44 years (range 48 years). Pain was purely paroxysmal in 66.3%. Etiology was secondary in 18.6%. 88.37% of patients had previously been treated with CBZ or OXC. Mean daily initial LCM dose was 143 ±63.32mg, and mean daily maintenance dose was 228.5 ±113.64mg. 53.49% of patients concomitantly received CBZ or OXC. Pain relief was accomplished in 74.4% of cases, with a 31.4% of adverse events (mainly dizziness in 18.6%, somnolence in 4.65% and instability in 3.48%). One patient presented a first-degree cardiac blockade. Absence of pain was reported in 33.7%. Pain worsening was recorded in 43% or patients, with a mean time of 441.26 ±478.93 days after LCM initiation. Conclusions LCM could be an effective and relatively safe treatment of refractory pain in TN, after first-line treatments failure. Further prospective studies are needed.

Associate Professor

Post COVID-19 Vaccine Trigeminal Neuralgia in a Patient with Melkersson-Rosenthal Syndrome

COVID and headache

Abstract text (incl. figure legends and references) Introduction Melkersson-Rosenthal syndrome (MRS) is a disease characterized by recurrent peripheral facial paralysis, orofacial edema and fissured tongue triad. Cranial neuropathies have also been reported after COVID vaccines. Here, we present a 53-year-old female patient with this rare syndrome who had new-onset trigeminal neuralgia after COVID vaccination. Case Report 53-year-old female patient presented with itchy, burning like pain over the right mandibular region of her face for ten days. Pain was occurring as 10-20 attacks per day lasting seconds. She reported that the new onset pain had started 2 days after the mRNA COVID vaccine. Concerning her medical history, she was diagnosed with MRS which had three previous episodes of peripheral facial paralysis and recurrent orofacial edema. Cranial imaging, serum and cerebrospinal fluid analysis were normal. She was diagnosed as trigeminal neuralgia (TN) and symptomatic treatment with gabapentin 1200 mg/day had started. She was pain-free for the past month. Discussion Cranial nerve involvement in MRS can be seen and the facial nerve is the most commonly involved one. Rarely, other cranial nerves may also be affected with complaints of impaired taste and hearing or trigeminal neuralgia. Cranial neuropathies have also been reported after COVID vaccines, and there are a few cases of post-vaccination trigeminal neuralgia in the current literature. The time interval between vaccination and TN in the reported cases was approximately 7-14 days. However, in our case, the onset of TN was quite rapid, and we interpreted this situation as the combination of MRS and COVID vaccine may facilitate the onset of TN. References 1- Kaya A, Kaya SY. A case of trigeminal neuralgia developing after a COVID-19 vaccination. J Neurovirol. 2022 Feb;28(1):181-182. doi: 10.1007/s13365-021-01030-7. Epub 2021 Dec 6. PMID: 34870807; PMCID: PMC8647511.

Vagoglossopharyngeal neuralgia as cause of syncope due to atrio-ventricular block: one case report

Multidisciplinary clinical assessments

Abstract text (incl. figure legends and references) Question Glossopharyngeal neuralgia is a rare facial pain syndrome characterized by painful paroxysms in the sensory distribution of the glossopharingeal nerve. Association with cardiac syncope is even rarer and when it happens it is termed vagoglossopharyngeal neuralgia (VN). We present a case of idiopatic VN with secondary complete atrio-ventricular (AV) block and symptomatic syncopes Methods A 66-year-old man with no medical history of interest, presented to Emergency department with high intensity pain in left preauricular region and behind mandibular angle. He described the pain as electrical discharges. These attacks were followed by syncopes of 20-30 seconds duration. Furthermore, during some of these episodes he presented limb shaking without tongue bite or sphincter relaxation. Cardiac monitoring showed complete AV block followed by sinus bradycardia at 30 beats per minute and subsequent recovery of heart rate. Between these episodes the patient was asymptomatic. His general and neurological examination was normal. Results He was admitted to Intensive Care Unit for monitoring and treatment with aleudrine was started. Chest radiography, echocardiogram, brain magnetic resonance imaging, computed axial tomography of the neck and electroencephalogram were performed with normal results. Structural heart disease was ruled out. AV-block secondary to increased vagal tone due to NV was diagnosed. Treatment with aleudrine was stopped and carbamazepine was started, after which the patient had no new episodes of neuralgia or cardiac block. He was discharged and after five months he has kept on treatment and has had no new episodes of neuralgia or syncope. Conclusions VN is a rare syndrome. It could be associated with syncopes due to AV-block. Pharmacological therapy is the initial step to the VN treatment, but surgery could be needed in refractory cases. Pacemarker could be required to treat AV-block in selected patients.

Intravenous lidocaine infusions for trigeminal neuralgia acute exacerbations – preliminary results from a prospective study

Abstract text (incl. figure legends and references) Question: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder. Some patients experience severe acute exacerbations, often requiring therapeutic escalation. The efficacy of intravenous (IV) lidocaine infusions in this setting was reported in few small studies, however, there is not a uniform protocol of administration. Our aim was to evaluate the efficacy of IV lidocaine infusion for TN acute exacerbations based on a predefined protocol in a Chronic Pain Outpatient Clinic. Methods: We included all adult patients admitted to our Outpatient Clinic for treatment of acute exacerbation of TN with IV lidocaine. IV lidocaine (1mg/kg) was infused over 60 minutes in each session. Vital signs were measured during and after each infusion. Pain was evaluated before initiating treatment and after the last infusion using the Numeric Pain Scale (NPS), the Pain Catastrophizing Scale (PCS), the Pain Disability Index (PDI) and the Hospital Anxiety and Depression Scale (HADS). Patient scores were compared using the paired-samples t-test and Wilcoxon. P-values &lt;0.05 were considered statistically significant. Results: Eight patients completed 12 sessions (3/week), 5 (62.5%) female, with a mean age of 61 ± 14 years. Significant differences were found between baseline and the end of the IV lidocaine treatment in NPS (before 9 ± 5 vs after 4.13 ± 2.42, p=0.02). No significant differences were found in PCS (40.88 ± 9.08 vs 38.88 ± 6.79, p=0.41), PDI (45 ± 24 vs 30.88 ± 22.71, p=0.40) and HADS (anxiety 10.50 ± 4.24 vs 9.50 ± 3.59, p=0.51; depression 11.50 ± 2.56 vs 10 ± 4.44, p=0.26). No adverse effects were reported. Conclusion: Patients showed improved scores in all applied scales after IV lidocaine treatment, although not statistically significant except for the NPS. In order to confirm these preliminary results we are still recruiting patients to enlarge our sample.

Descriptive study of a series of patients diagnosed with secondary trigeminal neuralgia. 39 patients series.

Abstract text (incl. figure legends and references) Objectives The aim of the study is to describe the most frequent etiologies and the pain qualities in a sample of patients with secondary trigeminal neuralgia (TN). Methods Observational, descriptive, retrospective, and single-center study that includes all secondary TN followed up for a mean of 5 years in the Headache Unit of a tertiary hospital. Results 39 patients diagnosed with secondary TN with a mean age of 54 years were included. The main etiologies found in our sample were tumors 41% (meningioma 38%, squamous cell tumor 25%, schwannoma 25% and glioma 13%) and multiple sclerosis (MS) 41% (88% due to pontine plaques, only 8% active plaques). The remaining 18% were related to nonspecific demyelinating lesions without MS criteria, ischemic lesions, post-surgery, pachymeningitis, hemangioma, and Arnold-Chiari malformation. Regarding the pain pattern, most of the patients suffered Burchiel type 1 neuropathic pain (77%) and the involvement of more than one branch predominated: 2 branches in 41% of the patients and three branches in 21%. The most affected branch was V3 (77%), followed by V2 (67%). The most used drugs were carbamazepine and its derivatives (79%), with an effectiveness of 45% for more than two years, followed by gabapentinoids (67%), with an effectiveness of 11%, and lacosamide (41%), with an effectiveness of 0%. 28% of the patients underwent percutaneous surgery and 10% underwent microvascular decompression surgery. Conclusions The most frequent causes of secondary TN were intracranial tumors and MS. Secondary TN more often affects 2 or more trigeminal branches. The most effective drugs were carbamazepine and its derivatives.

Medical Cannabis in Senior Patients: Therapeutic Effects/Side Effects. Behavioral and Imaging Correlations

Headache in the elderly

Abstract text (incl. figure legends and references) BACKGROUND Cannabinoid receptors CB1 and CB2 upregulation occurs in pain processing, CB2 agonists suppress neuropathic symptoms. Trigeminal neuralgia (TN), a pain syndrome of neuropathic origin, can be or become refractory to anticonvulsants. Observation concerns cannabinoids in refractory TN of senior patients. METHOD Drug: fixed combination 22%Tetrahydrocannabinol (THC), a CB1 CB2 receptor partial agonist +&gt;1%Cannabidiol (CBD) trafficking with CB1 and CB2 receptors THC/CBD Dose finding: 200 mg/day effective dose Administration Route: Sublingual to circumvent gastrointestinal adaptation, hepatic first-pass metabolism and producing higher plasma concentration. Non decarboxylated form was chosen to allow entourage effect Plan: Explanatory-Controlled partly Covered, 3-months treatment, 1-month follow-up Participants suffered from TN refractory (less than 25% relief) to anticonvulsants. They are part of an observation regarding refractory TN. Hereinafter observation concerns Group A (23 males, 5 females; 57.3+2.2SD) receiving fixed combination THC-/CBD and Group B (20 males, 6 females; 56.9+1.9SD) re-testing carbamazepine 900mg/day. Rescue treatment: lidocaine 2% 10 ml i.v. RESULTS Theraputic Effects, Side effects Pain relief THC/CBD vs Baseline and Carbamazepine treatment p&lt;0.0001 Rescue n=13 Carbamazepine, n=1 THC/CBD Withdrawal n=7 Carbamazepine, n=2 THC/CBD Relapse during follow-up n=4 THC/CBD, n=8 Carbamazepine Somnolence, Drowsiness n=9 Carbamazepine, n=11 females THC/CB first week Memory (Randt Memory Battery) impairment n=20 Carbamazepine p&lt; 0.5 vs baseline Retrieval amelioration: THC/CBD n=27 p&gt;0.01 vs baseline Cerebral fMRI changes within the temporal lobe n=3 males Carbamazepine Sexual intercourses increase n=3 males THC/CBD CONCLUSIONS Outcomes suggest either effectiveness and safety of 22%THC+&gt;1%CBD in refractory TN sufferers 50-65 years old or a role for CB1, CB2 receptors in TN. Larger casuistry is needed to guarantee efficacy

Prof.

Differential expression of the calcitonin receptor, CGRP and amylin in the trigeminal and dorsal root ganglia

Neuropeptides, channels in headache

Basic science, animal models in headache research

Abstract text (incl. figure legends and references) Objective: The trigeminal ganglia (TG) and dorsal root ganglia (DRG) are anatomically important sites for pain, containing neuropeptides and receptors that modulate pain transmission. The neuropeptides, calcitonin gene-related peptide (CGRP) and amylin have been linked to migraine. They are potent agonists of the AMY1 receptor, a heterodimer of the calcitonin receptor (CTR) and RAMP1. Co-expression of the CTR and CGRP has been reported in the TG, with little or no amylin observed. In the DRG, both peptides have been reported; however, their distribution relative to the CTR is unknown. This suggests that there may be differences in the relative abundance of each peptide between these two ganglia and which peptides might signal via CTR in each location. This study aimed to determine the relative distribution of the CTR with CGRP and amylin in the DRG and compare this to the TG. Methods: In combination with neural markers, specific antibodies against CTR, CGRP and amylin were applied to mouse, rat, and human C1/2 DRG to investigate distribution. Data were compared to our prior TG data using the same conditions. Results: In the DRG, CGRP-like immunoreactivity (LI) and amylin-LI were present in distinct and overlapping neurons, indicating occasional co-expression of the peptides. CTR-LI was present in neurons which expressed CGRP or amylin alone, as well as neurons which expressed both peptides. Co-staining was uncommon with an A-fibre marker, NF200, indicating that CTR-LI, CGRP-LI and amylin-LI were primarily in C-fibre neurons. Conclusions: The expression of CGRP and CTR were similar between the DRG and TG. However, unlike the TG, abundant amylin expression and co-localisation with CTR was observed in the DRG. These data suggest that distinct local agonists may activate CTR-based receptors, such as the AMY1 receptor, in C-fibre neurons in the DRG and TG. This highlights that local amylin may play a more important role in DRG-mediated pain responses than in the TG.

Glibenclamide posttreatment does not inhibit levcromakalim induced headache: A randomized clinical trial

Migraine

Abstract text (incl. figure legends and references) Objective: ATP-sensitive potassium (KATP) channel opener levcromakalim causes headache in humans. Whether KATP channel blocker glibenclamide inhibits levcromakalim-induced headache has not yet been elucidated. Methods: In a double blind, randomized, three-arm, placebo-controlled study, 20 healthy participants were assigned to receive 20 mL of levcromakalim (0.05 mg/min (50 mg/mL) or placebo (saline) intravenously over 20 minutes followed by oral administration of 10 mg glibenclamide or placebo. The primary endpoint was the difference in incidence of headache (0–12 hours) between glibenclamide and placebo. Results: Fifteen participants completed all three study days. More participants developed headache on levcromakalim-placebo day (15/15, 100%) and levcromakalim-glibenclamide day (13/15, 86%) compared to placebo-placebo day (7/15, 46%) (P &lt; 0.05). We found no difference in headache incidence between levcromakalim-placebo day and levcromakalim-glibenclamide day (P &gt; 0.05). The AUC0-12h for headache intensity was significantly larger in levcromakalim-placebo day and levcromakalim-glibenclamide day compared to placebo-placebo day (106.3± 215.8) (P &lt; 0.01). There was no difference in the AUC0-12h for headache intensity between the levcromakalim-placebo (494 ± 336.6) day and the levcromakalim-glibenclamide day (417 ± 371.6) (P &gt; 0.05). Conclusion: Non-specific KATP channel inhibitor glibenclamide did not attenuate levcromakalim-induced headache in healthy volunteers. Future studies should clarify the involvement of the distinct isoforms of sulfonylurea receptor subunits of KATP channels in the pathogenesis of headache and migraine.

Monthly occipital nerve blocks in chronic tension-type headache – a tertiary centre results

Tension type headache

Neuromodulation and nerve blocks

Abstract text (incl. figure legends and references) Question: Peripheral nerve blocks are used in the acute and preventive treatment of primary headaches. Few studies have studied its effectiveness in tension-type headache (TTH), with contradictory results. Methods: Observational study of patients followed in a headache-intervention consultation of a tertiary hospital (01/2021-04/2022), submitted to monthly greater and lesser occipital nerve blocks (GON, LON) with lidocaine 2% (2.5mL GON, 1.0mL LON). Results: Peripheral nerve blocks were performed in 75 patients, median of 46 years (P25=36.0, P75=57.0), 63 (84.0%) were female. The most prevalent type of headache was migraine (38.7%), followed by cTTH (20.0%). Of the patients with cTTH (n=15), 13 (86.7%) were female and 10 (66.7%) were older than 50 years-old. Five (33.3%) had concomitant medication-overuse headache. Twelve patients (80.0%) were receiving concomitant prophylactic treatment. In 33.3% the block was performed due to refractory course, and in 33.3% due to treatment intolerance. Overall, in this group, there was a decrease in the number of headache days with treatment [p&lt;.001; 23.9 (sd 8.6) pre-treatment vs. 10.0 (sd 11.1) post-one treatment]; only 4 (14.8%) had no response. An interaction with age (≤50/&gt;50) (p=.001) was observed, with a higher reduction in headache frequency in patients &gt;50y (Mprevious=22.7±9.1; Mpost-blockade=8.1±9.5), compared to ≤50y (Mprior=15.4±10.0; Mpost-block=9.2±9.6). There was an interaction with follow-up time (0-6/7-24/&gt;24) (p=.029), with a greater reduction in frequency in the group with a follow-up time of up to 6months. Conclusions: Patients with cTTH had a good response to monthly occipital nerve blocks. Treatment responsiveness seemed to be better in older patients and those that started this intervention earlier.

Poster session 8

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