DEAR EDITOR

Trigeminal neuralgia (TN) is an infrequent condition manifested by excruciating unilateral electric shock-like facial pain, with classical abrupt onset and termination ^1-8. TN may be idiopathic, but the etiological factors include vascular nerve compression (classic TN), multiple sclerosis, tumor, trauma, herpes zoster, and temporomandibular dysfunction (secondary TN); arterial hypertension and diabetes are comorbidities ^1,2,5,8. The pains may start by eating, drinking, talking, touching the face, or a puff of wind ². The estimated prevalence is up to 13% yearly,¹ occurring more often among females between from 50 to 70 years of age, and mainly affecting the second or third branches ^1,2. The intensity and persistence of painful episodes cause deleterious effects on the work activities and quality of life of the patients, mainly those presenting refractory pain ^1-5. Consistent literature data have confirmed the high efficacy and tolerability of utilizing gabapentin and other α2δ ligands to control patients with this excruciating pain, carbamazepine and oxcarbazepine are also recommended to first-line pharmacotherapy; additional procedures can include nerve blocks, surgery, or radiofrequency ablation ^1-8. Alvarado Bardales, et al. reviewed the findings of 61 patients with TN in Mexico during the year of 2019; 62.3% were females, the mean age was 60.2 ± 16.8 years, the involved sites were left branch combinations (36.1%), right branch (27.9%), and right maxillary branch (13.1%) ¹. The cornerstone resources for the management of pain during hospital stay was utilizing carbamazepine as gold standard, and gabapentinoids, opioids, and tricyclic or dual-action antidepressants; eight patients underwent some non-pharmacological intervention aiming obtain the best of pain control. With pre-admission use of NSAIDS the pain was severe (96.7%) or moderate; the treatment with carbamazepine (86.8%) and gabapentinoids (60.6%) resulted in the discharges without pain (24.6%), mild pain (57.4%), moderate pain (13.1%), and severe pain (4.9%). The authors commented on the necessity of non-pharmacological intervention utilized for eight of the patients who did not obtain the pain control with solely the drug schedules ¹. In this interesting study there was no reference to the possibility of COVID-19 infection. Since the advent of COVID-19 pandemic, cases of TN associated with infection or vaccination against the SARS-Cov 2 virus have been reported and deserve attention ^9-16.

Chrostowski K, et al. reported a 36-year-old female with episodes of facial pain manifested two months ago, since the next day after the third vaccine for COVID-19 ⁹. She then successfully underwent oxcarbazepine, dexamethasone and pregabalin, and persists without pain episodes for six months after the onset of neurological disorder ⁹. Gárate G, et al. compared the serum levels of a marker of trigeminal vascular activation (CGRP) in 25 COVID-19 inpatients with headache against 15 COVID-19 inpatients without headache, and also 25 matched healthy controls with no headache episode ¹⁰. They detected more elevated CGRP levels both among the COVID-19 patients with headache (55.2 ± 34.3 pg/mL) and among the COVID-19 patients with no headache (43.3 ± 12.8 pg/mL) in comparison with the group of healthy controls (33.9 ± 14.0 pg/mL) ¹⁰. The increased CGRP levels in COVID-19 patients with headache strongly supports the role of trigeminal activation in the pathophysiology of headache in this viral infection ¹⁰. Joshi D, et al reviewed 6 cases of neuropathic pains manifested or exacerbated within weeks or months after COVID-19 infection, and found one TN, which is considered a very recent matter to be better evaluated through further respective medical research ¹¹. Kaya A, et al. reported the case study of a 45-year-old woman presenting typical TN, besides toothache 3 days after the first dose of COVID-19 Pfizer-BioNtech vaccine ¹². NSAIDS and pregabalin were utilized but the symptoms persisted, being later controlled with the use of intravenous methylprednisolone and a 7-day tapering course of steroid; and no recurrence of TN was observed during the outpatient follow-up for 6 months ¹². Lee S, et al. described two patients with consequences of central nervous system demyelination after the Comirnaty (BNT162b2), a mRNA-based COVID-19 vaccine ¹³. One presented typical manifestations of acute disseminated encephalomyelitis; the other had TN and a demyelinating lesion in the pons, and both responded to immunotherapy ¹³. Molina-Gil J, et al. reported a 65-year-old male with COVID-19 infection, who had excruciating episodes of TN on the third day and were not controlled by the use of pregabalin plus diazepam, but completely resolved with the viral disease improvement ¹⁴. O’Neill F, et al. described a 58-year-old female with persistent right facial pain besides in maxillary teeth and right side of tongue after COVID-19 infection 18 months earlier ¹⁵. With stablished diagnosis of TN and the concomitant sixth and eighth cranial nerve neuropathies, she was treated by amitriptyline, nortriptyline, carbamazepine, gabapentin, pregabalin, propranolol, co-codamol, prednisolone, and duloxetine with no response; furthermore, intradermal botulinum toxin A injections were utilized with good a result ¹⁵. Onoda K, et al. reported a 77-year-old female who had acute TN treated by microvascular decompression with success, but one month later she received the first dose of Pfizer-BioNtech vaccine and presented TN that improved by carbamazepine and pregabalin; the authors highlighted the vaccinal etiology of secondary TN in a case of MVD for TN ¹⁶.

In conclusion, the literature data seem to support the possibility of SARS-CoV-2 infection or vaccination constitute an etiology of secondary TN; however, additional case studies and further evidence in the field of research could establish the due relationship.

REFERENCES

1. Alvarado Bardales LM, Salado Ávila MM. Characterization of patients with trigeminal neuralgia in a Mexican hospital, 2009-2019. Rev Méd Hondureña. 2022;90(2), 135-140. https://doi.org/10.5377/rmh.v90i2.15452.

2. Chong MS, Bahra A, Zakrzewska JM. Guidelines for the management of trigeminal neuralgia. Cleve Clin J Med. 2023;90(6):355-362. doi: 10.3949/ccjm.90a.22052.

3. De Stefano G, Di Pietro G, Truini A, Cruccu G, Di Stefano G. Considerations when using gabapentinoids to treat trigeminal neuralgia: A Review. Neuropsychiatr Dis Treat. 2023;19:2007-2012. doi: 10.2147/NDT.S407543. PMID: 37745191.

4. Eskandar E, Kumar H, Boini A, Velasquez Botero F, El Hunjul GN, et al. The Role of Radiofrequency ablation in the treatment of trigeminal neuralgia: A narrative review. Cureus. 2023;15(3):e36193. doi: 10.7759/cureus.36193. PMID: 37065382.

5. Latorre G, González-García N, García-Ull J, González-Oria C, Porta-Etessam J, Molina FJ, et al. Diagnosis and treatment of trigeminal neuralgia: Consensus statement from the Spanish Society of Neurology’s Headache Study Group. Neurologia (Engl Ed). 2023:S2173-5808(23)00027-5. doi: 10.1016/j.nrleng.2023.04.005.

6. Lee JY, Lee GH, Yi SH, Sim WS, Kim BW, Park HJ. Non-surgical treatments of trigeminal neuralgia from the perspective of a pain physician: A narrative review. Biomedicines. 2023;11(8):2315. doi: 10.3390/biomedicines11082315.

7. Rana MH, Khan AAG, Khalid I, Ishfaq M, Javali MA, Baig FAH, et al. Therapeutic approach for trigeminal neuralgia: A systematic review. Biomedicines. 2023;11(10):2606. doi: 10.3390/biomedicines11102606.

8. Rapisarda A, Battistelli M, Izzo A, D’Ercole M, D’Alessandris QG, Polli FM, et al. Outcome comparison of drug-resistant trigeminal neuralgia surgical treatments-an umbrella review of meta-analyses and systematic reviews. Brain Sci. 2023;13(4):530. doi: 10.3390/brainsci13040530.

9. Chrostowski K, Piasecki M, Bielewicz J. Trigeminal neuralgia occurring after the third dose of Pfizer BioNTech COVID-19 vaccine. Complication or coincidence? An illustrative case report and literature review. Cent Eur J Immunol. 2023;48(1):75-80. doi: 10.5114/ceji.2023.125309.

10. Gárate G, Toriello M, González-Quintanilla V, Pérez-Pereda S, Madera J, Pascual M, et al. Serum alpha-CGRP levels are increased in COVID-19 patients with headache indicating an activation of the trigeminal system. BMC Neurol. 2023;23(1):109. doi: 10.1186/s12883-023-03156-z.

11. Joshi D, Gyanpuri V, Pathak A, Chaurasia RN, Mishra VN, Kumar A, et al. Neuropathic pain associated with COVID-19: A systematic review of case reports. Curr Pain Headache Rep. 2022 Aug;26(8):595-603. doi: 10.1007/s11916-022-01065-3.

12. Kaya A, Kaya SY. A case of trigeminal neuralgia developing after a COVID-19 vaccination. J Neurovirol. 2022;28(1):181-182. doi: 10.1007/s13365-021-01030-7.

13. Lee S, Hor JY, Koh KL, Chia YK. Central nervous system demyelination following COVID-19 mRNA-based vaccination: Two case reports and literature review. J Cent Nerv Syst Dis. 2022;14:11795735221102747. doi: 10.1177/11795735221102747.

14. Molina-Gil J, González-Fernández L, García-Cabo C. Trigeminal neuralgia as the sole neurological manifestation of COVID-19: A case report. Headache. 2021;61(3):560-562. doi: 10.1111/head.14075.

15. O’Neill F, De Stefano G, Pridgeon M, Bhargava D, Marshall A, Marshall A, et al. Trigeminal neuropathy presenting secondary to SARS-CoV-2 infection. Pain Rep. 2023;8(6):e1103. doi: 10.1097/PR9.0000000000001103.

16. Onoda K, Sashida R, Fujiwara R, Wakamiya T, Michiwaki Y, Tanaka T, et al. Trigeminal neuropathy after tozinameran vaccination against COVID-19 in postmicrovascular decompression for trigeminal neuralgia: illustrative case. J Neurosurg Case Lessons. 2022;3(16):CASE22101. doi: 10.3171/CASE22101.

Recebido em 7 de Novembro de 2023.
Aceito em 20 de Novembro de 2023.

Conflito de interesses: declaramos não haver conflito de interesses