These two patients developed a new headache within 1 to 6 days after COVID-19 vaccination. The first case had a previous history of headaches and the second had a migraine that was clearly different from the present headache. None of the patients accepted the third dose of vaccination, and a causal relation can only be established by the close temporal association.
The most common adverse effects of the BNT162b2 mRNA COVID-19 vaccine are injection site reactions (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%) and fever (14.2%) (5). These are usually mild or moderate and remitted within a few days after vaccination (2). According to the data available, the most common neurological symptom is a headache that occurs in over 50% of vaccinated (5) and is even more common after the second dose (2). From the analysis of a multicenter observational study of 2349 participants that had headaches after vaccination against COVID-19 with the BNT162b2 (Pfizer) mRNA vaccine (3) between 8 January 2021 and 26 February 2022, it was found that the onset of the headache had a mean of 18.0 h ± 27.0 h. In less than 10% of the participants, the headaches began more than two days after the vaccination. The mean headache duration was 14.2 ± 21.4 h, and in 10% of the participants, the headache lasted longer than 36 h. The most common characteristic of the pain was dull pain (40,7%).
Nevertheless, two cases of trigeminal neuralgia after vaccination against COVID-19 had already been reported (4, 12), both after the first dose of BNT162b2 (Pfizer) and starting on the same day of the administration. An immune-mediated inflammatory response was assumed in both cases.
Moreover, it had been described as a series of seven cases of patients with cluster headache that was clinically stable for a long time and had a new crisis of pain within a few times after the administration of COVID-19 vaccination (from a few minutes to 7 days after). In these cases, an inflammation of the trigeminovascular system with calcitonin gene-related peptide (CGRP) release had been postulated. Alternatively, the authors assumed the vaccine's possible direct central (inflammatory) role (6).
Occipital neuralgia is described as a unilateral or bilateral paroxysmal described like a shooting, stabbing, electric, shock-like or sharp pain in the posterior part of the scalp, involving the greater, lesser, and third occipital nerve distribution, with sudden onset, and immediately spreading toward the vertex (7). It can sometimes be accompanied by diminished sensation or dysesthesia in the affected area and commonly associated with tenderness over the involved nerves (7, 8).
The paroxysms of the pain may start spontaneously or be triggered by brushing the hair, exposure to cold, or neck movements. A dull occipital discomfort may be present during periods between painful paroxysms (9). On examination, pressure, palpation, or percussion over the occipital nerve trunks may reveal local tenderness, trigger painful paroxysms, worsen the dull pain, or elicit paresthesias along the distribution of the affected nerve (7).
The pathophysiology of occipital neuralgia is yet uncertain but can result from an injury to the C2-C3 nerve roots and occipital nerves through different mechanisms (chronic instability, entrapment, trauma, inflammation) (10). Most often, occipital neuralgia is idiopathic (13).
The diagnosis of occipital neuralgia is considered when typical clinical features are present, based on the diagnostic criteria for occipital neuralgia from the International Classification of Headache Disorders, 3rd edition (ICHD-3) (8), and can be confirmed when pain is transiently relieved by a local occipital anesthetic block (11).
Relative to both patients, all the criteria for occipital neuralgia are fulfilled, and in the second patient, no characteristic of migraine headache had been detected.
The fact that both cases had developed within 1 to 6 days after the second dose of the vaccine for COVID-19 raises the hypothesis that it is a consequence of this vaccination, which was partially later corroborated by an imaging study that does not show any type of lesion at the root level of C2-C3 and the territory of the occipital nerves.
Although according to a recent systematic review and meta-analysis (14), post-vaccination headache tends to develop within 24-h from injection and usually resolves in less than 24 h, our cases highlight the possibility of persistent symptoms after COVID-19 vaccination.
After COVID-19 vaccinations, the exact mechanism for the neurologic involvement is not fully elucidated and attributed to molecular mimicry and immune-mediated inflammatory response. The first one often requires 10–14 days to be developed, but the last requires less time (12). In both of our cases, we hypothesize that occipital neuralgia had been consequent to an immune-mediated inflammatory response. Also, bilateral pain is unusual in primary occipital neuralgia and the fact that it was bilateral in the first case can corroborate the fact that there was an underlying systemic inflammatory reaction. However, more studies are required to clarify controversial aspects of the pathophysiology of this unknown disease.