Herpes simplex virus type 1 (HSV-1) infects approximately 90% of the population, resulting in a variety of disorders.1 Acute infection may be initiated in the cornea, nose, or mouth. After primary infection, the virus travels retrograde along the ophthalmic (V1), maxillary (V2), or mandibular (V3) division of the trigeminal nerve. Once it reaches the Gasserian ganglion, it establishes lifelong latency in sensory neurons.2,3 The primary infection is controlled by the initial innate immune response, and latency is maintained by T cells and cytokines in the Gasserian ganglion.4 Reactivation of HSV-1 from latency in sensory neurons leads to viral anterograde axonal transport towards the periphery and clinical manifestation of the disease.
We describe the case of a 17-year-old boy with dermatologic HSV-1 outbreaks with incapacitating facial pain requiring multiple hospitalizations. Gasserian ganglion block for trigeminal neuralgia was described by Harris in 1912,5 and these blocks have been performed for managing facial pain associated with herpes zoster virus; however, a literature search performed on PubMed and Medline found no references for using Gasserian ganglion block in the treatment of HSV-1 infection. Dexamethasone–lidocaine Gasserian ganglion block under computed tomography (CT)–scan guidance was used in the present case to completely resolve the facial pain complaints. This is the first reported use of Gasserian ganglion block for treatment of HSV-1 infection of the trigeminal nerve.
A 17-year-old male—with a remote history of eczema, viral meningitis, and Varicella–zoster virus (VZV) infection at age 3 years—was completely healthy until spontaneously developing small ulcerative lesions on the left nasal filtrum and left forehead, crossing the midline, 18 months before presenting to our pain center. After 4 days the rash became painful and was soon intolerable, with a numeric rating pain score 10/10.
Vesicular skin lesions were positive for HSV type-1 and negative for VZV by polymerase chain reaction. The patient had low VZV-specific immunoglobin (Ig)G, and anti-VZV IgM was undetectable. The patient had a low total number of T-cells (CD4 and CD8), natural killer (NK) cells, and T lymphocytes. An infectious disease specialist diagnosed the patient with HSV-1, and treatment with acyclovir IV (followed by P.O. use) and valacyclovir IV was begun.
Even after resolution of the skin lesions, the patient suffered from intractable pain, located in the left right supraorbital area, persisting for 18 months. The pain was unresponsive to interventional therapies performed at 6 different university hospitals, including stellate ganglion blocks using fluoroscopic guidance (times 3) and supraorbital and supratrochlear nerve blocks using extended-duration local anesthetics. Pain regimens included acetaminophen, naproxen, tramadol, pregabalin, hydromorphone IV, amitriptyline, topiramate, topical lidocaine 5% patch, and topical over-the-counter capsaicin cream, each of which provided either no relief or only temporary pain relief.
The patient presented to our pain clinic for persistent, unremitting pain. He and his parents were desperately seeking a long-term strategy to manage the pain because he had become habituated to hydromorphone, using 8-mg tablets every 3 to 4 hours to reduce his numeric rating scale pain score from 10/10 to 8/10. The patient failed to complete his senior year of high school, was essentially bed-ridden because of pain, and had lost 25 pounds. A discussion was undertaken with the parents concerning the theoretical benefits of performing CT-guided injection of corticosteroid and local anesthetic to target the Gasserian ganglion. Because the procedure had never been done for this indication, the appropriate warnings were provided, including the unknown risk of viral dissemination and the unknown effect of dexamethasone injected into the cerebrospinal fluid.
After obtaining informed, written consent, IV sedative hypnotic medications were administered so that the patient would be calm, but still able to provide verbal feedback regarding the presence of paresthesias, using 2 mg of midazolam and 50 mcg of fentanyl. The patient was placed into the CT scanner in the supine position with the head and neck extended. After performing skin prep and draping, a skin wheal was made approximately 3 cm lateral to the angle of the mouth with ropivacaine 0.5%, 3 mL total, using a 27-gauge 1½ inch needle. Next, a 25-gauge Whitacre-type subarachnoid needle with a curve at its distal tip was advanced from the lateral corner of the mouth on the left side toward the zygoma with CT imaging to delineate the location of the foramen ovale. Once the needletip was located in the foramen ovale on the left side (Figs. 1A, 2A, and 3 A), 0.5 mL of iopamidol-200 contrast was injected (Figs. 1B, 2B, and 3B). The contrast outlined Meckel's cave, depicting all 3 branches of the trigeminal nerve (Fig. 2B). Noting the absence of cerebrospinal fluid and without producing paresthesias, 2 mg of dexamethasone sodium phosphate and 1 mL of 1% lidocaine plain was subsequently slowly injected (total volume 1.5 mL). The needle was flushed with 0.5 mL normal saline, restyletted, and withdrawn. The patient tolerated the procedure well with no immediate side effects or complications. He stated immediately upon the completion of the injection that his pain was totally gone. An additional CT scan of the brain confirmed that contrast was not spreading into the subarachnoid space or brain. The patient was observed for >3 hours in the postanesthesia care unit, and he had no delayed onset side effects or complications apparent from the procedure.
The patient stated that it was the first time in almost 2 years that he had absolutely no pain. Opioid medications were completely discontinued on the day of the procedure and were not reinstated during any of the follow-up visits. The patient followed up in our pain clinic every 30 days for 6 months, and he remained pain free, on no opioids whatsoever. He was able to complete his high school senior year and earn a diploma.
Current management of HSV-1 infection does not target eradication of the virus at the site of latency. Virus shedding and clinical complications at end-organ sites are treated with acyclovir or valacyclovir for inhibiting viral replication and minimizing epithelial damage.2,6,7 Daily prophylaxis with systemic antiviral drugs is indicated for eczema herpeticum, ocular herpes, and immunocompromised patients.7 During latent HSV-1 infection, viral expression is limited to the latency-associated transcript (LAT), and the virus is usually undetectable.8 LAT products regulate the neuronal genome to prevent apoptosis, viral replication, and recurrent viral disease.1,3,9,10 Stress, cold, heat, intense light, trauma, or immune suppression influence recurrent herpetic disease.1 Stress stimulates release of epinephrine and glucocorticoids from the adrenal gland, which act on LAT through respective receptor-mediated signaling cascades.
Our patient had CD8+ and NK cell deficiencies, and NK cells are responsible for mounting the initial immune response to HSV-1.1,3,9 Frequency and extent of recurrent herpetic disease depends on the initial viral load presented to sensory neurons of the Gasserian ganglion after primary infection.1,2 NK cell deficiency would theoretically predispose this patient to a larger load of LAT. CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. HSV-1–specific CD8+ T cells block reactivation of virus from latency by producing interferon (IFN)–γ, tumor necrosis factor-α, and other cytokines providing active surveillance of viral gene expression.11 We believe that low CD8+ T cells rendered suppression of the virus in this patient unlikely.2
Dexamethasone is widely used as therapy for inflammatory, autoimmune, and allergic diseases because of its role in suppression of innate and cellular immune responses. It is also used in neurological trauma as a first-line drug to reduce cerebral edema and brain swelling.12 Dexamethasone inhibits Th1 and enhances Th2 cytokine secretion. It inhibits interleukin-12-induced IFN-γ secretion and IFN regulatory factor-1 expression in both NK and T cells, shifting immunity toward the Th2 humoral immune response.3,13 Humoral immune response is mediated by plasma cells of the B cell lineage, which produce antibodies. Antibodies cause agglutination and precipitation of antibody–antigen products, prepare viruses for phagocytosis by macrophages, block viral receptors, and stimulate the complement pathway. We believe that local injection of dexamethasone into Meckel's cave inhibited the Th1 cell– mediated immune response and stimulated the Th2-mediated humoral immune response.13,14 Alternatively, there could have been local immunization of the ganglion by allowing HSV-1 to emerge from latency long enough to produce antigens for immunity, while not causing clinical manifestation of disease.3
CT guidance for Gasserian ganglion block is recommended, because needle malposition may result in serious complications when using conventional fluoroscopy.15–17 Potential side effects and complications of dexamethasone and lidocaine Gasserian block include bleeding, hematoma, hypoesthesias, paresthesias, dysesthesias, weakness of the muscles of mastication, facial asymmetry, Horner's syndrome from blockade of sympathetic fibers, infection, postdural puncture headache, nerve injury, paralysis, stroke, and infarction.18
Finally, steroids themselves may reactivate latent HSV-1 in animal models.19,20 Although we did consider this viral reactivation a possibility, we also recognized that intentional, direct application of glucocorticoids (i.e., methylprednisolone) into the spinal subarachnoid space in patients suffering from intractable pain due to herpes zoster virus did not result in clinical sequelae consistent with viral reactivation.21,22
Patients infected with HSV-1 complain of pain in or near the region of skin lesions. In 70%–80% of patients, pain occurs shortly before skin lesions appear.23 Our patient complained of pain even after resolution of skin lesions. Takasaki et al.23 showed that HSV-1 infection in mice induces allodynia and hyperalgesia. HSV-1 may be a cause of Bell's palsy, especially in cases with persistent severe facial paralysis and pain.24 However, antiviral drugs were not more effective than placebo in treating Bell's palsy.25 Omura26 hypothesized that chronic intractable pain without any discernible causes is often due to unrecognized presence of viral or bacterial infection. Muneshige et al.27 showed that patients with complex regional pain syndrome had more than twice IgG antibody titers for HSV-1 than did a healthy control group.
We present the first case report of Gasserian ganglion injection for recalcitrant pain due to HSV-1 infection of the trigeminal nerve under CT guidance. We believe that Gasserian ganglion injection of dexamethasone with lidocaine may be useful in the treatment of HSV-1 infections of the trigeminal nerve in select individuals suffering from recurrent severe pain, who have failed to demonstrate a response to noninterventional therapies or to nontargeted or peripheral treatments, including stellate ganglion blocks and supraorbital or supratrochlear nerve blocks. Such blocks may be less risky than Gasserian ganglion block but do not address the underlying pathophysiology of facial pain due to HSV-1, and their use, as in the present case, may potentially delay the timely implementation of the targeted (i.e., Gasserian ganglion block) treatment.
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