Headache disorders are prevalent and debilitating, affecting 21% of women and 10% of men.1 Etiologies are broad and include primary headache disorders, such as migraine headaches, and secondary headaches disorders, such as those due to infections or hypertensive emergencies. Headaches caused by infections are typically separated into 2 categories: those due to systemic infections, such as influenza, and those due to central nervous system infections caused by viral meningitis or encephalitis.2 Viral infections such as herpes simplex virus (HSV) often cause headaches in the setting of meningitis and encephalitis, which typically present with altered cognition, fever, headache, nuchal rigidity, and focal neurologic symptoms.2 The viruses can cause migraine-like syndromes in the absence of the classic meningeal and encephalitis symptoms due to their close association with the trigeminal and sphenopalatine ganglion, where viruses such as HSV reside following primary infection.3

Migraine headaches are one of the most common causes of headache disorders and can typically be managed through conservative pharmacological methods, such as nonsteroidal anti-inflammatory drugs and triptans for acute management of symptoms, and beta blockers, tricyclic antidepressants, and anticonvulsants for symptom prevention.4 Interventional techniques can be considered for cases of headache disorder that are refractory to conservative treatment protocols.5 Examples of these techniques include peripheral nerve of trigeminal nerves branches or occipital nerves, trigger point injections, and sphenopalatine ganglion blocks.

The incidence of reactivation of a latent virus associated with nerve blocks is rare. While there are a limited number of cases reporting this occurrence, most are associated with intrathecal or intraarticular administration.6 Subclinical infection, transient immunosuppression from steroid injection, and local ganglion trauma may play a role in the reactivation of dormant viruses. However, the underlying cause of reactivation remains unknown.7 In this case report, we discuss a patient who developed reactivation of HSV following a sphenopalatine ganglion nerve block.

CONSENT

The patient has completed a written consent form and a Health Insurance Portability and Accountability Act form for use of data for publication of this case report and for scientific research. This article adheres to the applicable Enhancing the Quality and Transparency of Health Research (EQUATOR) guideline.

CASE DESCRIPTION

A 36-year-old woman with no significant past medical history was referred to the pain clinic for further management of a 17-year history of migraine headaches. She typically had 3 to 4 severe migraines per month that lasted between 3 and 7 days on each occurrence. Her typical migraine headache symptoms included a visual aura, described as gray-white spots followed by pain behind the right eye with right-sided facial pain and radiation to the right frontal, temporal, and suboccipital regions. The patient was previously treated with acetaminophen, ibuprofen, rizatriptan, methylprednisolone, prednisone, and dexamethasone, with minimal relief. However, the migraines were successfully treated with sumatriptan.

In January 2023, the patient developed a right-sided migraine headache that localized to the right orbital and medial cheek area. It was accompanied by pain radiating through the right lateral jaw extending to the right ear, and down the right suboccipital region of the head. She initially received ketorolac, rizatriptan, and a 7-day dexamethasone taper that involved taking 4 mg 3 times per day for 3 days, 4 mg twice daily for 2 days, and finally 4 mg once daily for 2 days. These medications failed to resolve her symptoms. She subsequently developed a metallic taste and blurry vision, which prompted referral to a neurology clinic. Her neurologist prescribed a regimen of naratriptan, prochlorperazine, acetaminophen, ibuprofen, and diphenhydramine, which also failed to mitigate the migraine. Magnetic resonance imaging of her brain was unremarkable.

Given that her symptoms failed to disappear with medical management, the patient became a candidate for sphenopalatine ganglion nerve block. The procedure was subsequently completed under ultrasound guidance, wherein a volume of 4 mL of bupivacaine 0.25% and 1 mL of dexamethasone 4 mg/mL were injected. This treatment also failed to resolve her symptoms. One day following the procedure, she developed an erythematous and edematous rash on her right thumb which subsequently cultured positive for HSV. She was prescribed valacyclovir, which provided relief of her headache symptoms and rash within 48 hours. One week later, her migraine symptoms disappeared and did not recur.

DISCUSSION

Migraine headaches have been reported to affect up to 12% of the world population, with chronic migraines affecting up to 2% of the population.8 Sphenopalatine ganglion blocks are becoming an increasingly popular method for interventional treatment of intractable migraine headaches due to ease of administration and their role in the trigeminal-autonomic reflex pertaining to the underlying pathophysiology of migraine headaches.4,5 Lidocaine and dexamethasone have also been used to reduce migraine pain by desensitization of intracranial nociceptors and suppression of inflammatory mediators that stimulate the nociceptors that produce migraines.8,9

Several case reports have linked dormant HSV infections and migraine symptomology to the relationship between the trigemino-vascular system and HSV infection of trigeminal ganglion. Although the underlying etiology in this case is not known, there are multiple factors to consider. It is theorized that the HSV infection may have occurred due to immunosuppression caused by previous steroid use along with the steroid contained in the nerve block injection. The patient completed a 7-day taper of dexamethasone following the onset of her migraine in January. She had previously completed two 3-day courses of prednisone 20 mg and one 5-day course of prednisone 50 mg from July 2022 to November 2022. Hypothalamic-pituitary-adrenal (HPA) axis suppression occurs following the use of prednisone in doses greater than 20 mg per day for longer than 2 weeks.10 There are limited data on the effects of repeated short-term use of glucocorticoids. However, 1 study showed evidence of HPA axis suppression following repeated 7-day courses of prednisone with varying doses between 5 mg and 60 mg.10

It is also possible the patient’s headache was secondary to an underlying HSV-1 infection, which would explain the intractable nature of the headache and development of a different pattern of her headache pain distribution, as well as the thumb erythema and edema. Furthermore, the patient became headache-free following treatment with valacyclovir. In another case report, a migraine headache was successfully treated with famciclovir, suggesting that the etiology of the migraine was due to a preexisting HSV infection.11

It is also possible the sphenopalatine nerve block led to reactivation of HSV. There are several reports of reactivation of HSV following neuraxial anesthesia in obstetric patients, with reactivation occurring in 38% of patients.6 HSV reactivation in the form of herpes labialis has also been reported following microvascular decompression of the trigeminal nerve as HSV commonly resides in the trigeminal ganglion.12 Corticosteroids and catecholamines have been shown to alter immune response to HSV infection.13 Another consideration is that with any injection of local anesthesia, there is the possibility of systemic extravasation of the agents along with local trauma and immune response at the injection site.7

The development of HSV following sphenopalatine ganglion block is exceedingly rare. It is important to consider the timeline of symptomology and response to treatment in these patients. The underlying cause of this patient’s presentation is most likely multifactorial due to transient immunosuppression, underlying HSV infection, and local trauma to the nerve injection site. For patients who present with migraines that are resistant to the typical treatment regimen, reactivation of HSV should be on the list of differential diagnoses.

DISCLOSURES

Name: Nicholas I. Koenig, BS.

Contribution: This author helped in formatting and writing the overall article, conducted the literature review, and submitted the article.

Name: Joseph A. McGuire, MD.

Contribution: This author helped in formatting and writing the overall article and provided edits for the article.

Name: Violet P. Shackleford, MD.

Contribution: This author helped in providing edits for the article.

Name: Kelsey Bauer, MD.

Contribution: This author helped in providing edits for the article.

This manuscript was handled by: Mark C. Phillips, MD.

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