DOI: https://doi.org/10.21203/rs.3.rs-1608476/v1
Background
Zoster-associated pain treatment is considered to be difficult worldwide. Presently, the primary treatment methods include oral medications, nerve blocks, nerve radiofrequency (RF), electrical stimulation, etc. We report a peculiar course transition and corresponding treatment for a case of severe herpes zoster-Neuralgia in the Head and Face.
Case Presentation
A 59 year-old Chinese male presented with a severe and variable zoster-associated pain in the head and face. The chief complaint on admission was pain on the right side of his head and face after herpes zoster for 32 days. After pulse RF (PRF) and multiple supraorbital nerve blocks combined with oral analgesics were administered to the patient, the patient rated his resting pain as 4 on the numerical rating scale (NRS) and his paroxysmal pain as 9–10. Specifically, his pain shifted from the right side of his forehead to the right side of his nasal cavity to the right occipital region. Finally, a percutaneous micro balloon compression of the trigeminal ganglion and RF of the second trigeminal nerve, supraorbital nerve, and cervical nerve root were performed consecutively. All the pain was relieved significantly after surgery. Seven months later, there was no recurrence of pain and no oral drugs were taken.
Conclusion
On the premise of not damaging motor function, RF should be used decisively for patients suffering from zoster-associated pain, which is a serious condition and resistant to various treatments.
Zoster-associated pain is the most common sequela of herpes zoster(HZ) [1]. It causes varying degrees of pain and symptoms, frequently causing patients to experience severe negative emotions, including suicidal thoughts [2], which necessitates immediate treatment. The degree of zoster-associated pain in the head and face was extremely severe in this case report and various treatment methods were ineffective. The pain intensity changed throughout the disease. Oral drugs, nerve block, percutaneous micro balloon compression of the trigeminal ganglia, radiofrequency (RF) thermocoagulation of the trigeminal nerve's second branch via the foramen rotundum, RF thermocoagulation of the cervical nerve root and supraorbital nerve were applied sequentially in the treatment. The treatment methods employed in this case may provide a reference for rapid pain relief in patients experiencing severe zoster-associated pain.
A 59 year-old Chinese male patient complained of severe pain after HZ on the right side of his head and face for 32 days. Thirty-two days prior to the onset of the pain, the patient had herpes on the right frontal-parietal and bridge of the nose. He developed scabbing after being administered with intravenous and topical medication at a nearby hospital, and he complained of itching in the painful areas as well as worsening of the paroxysmal pain. The patient scored the numerical rating scale (NRS) as 4 for resting pain and 9–10 for paroxysmal pain. A supraorbital nerve block was performed with 2 mL analgesic mixture (2% lidocaine hydrochloride [0.5 mL] + mecobalamin injection [1 mL] + stroke-physiological saline solution [0.3 mL] + compound betamethasone injection [0.2 mL]), the effect of which only lasted 20 minutes. Multiple intramuscular injections of 5 mg morphine also proved ineffective in alleviating the symptoms. Simultaneously, the patient developed nausea,vomiting, and constipation. The patient was subsequently transferred to Ningbo hospital to undergo pulsed radiofrequency (PRF) of the supraorbital nerve. The patient experienced pain relief only for 1 h, after which the pain restarted with an NRS score of 9–10 for paroxysmal pain. Oral tramadol hydrochloride sustained-release tablets were ineffective in relieving the pain. Because of the severe pain, which flared up 3–4 times every hour, and lasted 3–5 minutes, the patient reported having serious suicidal ideations. He was then escorted overnight to Jiaxing First Hospital, China, and admitted to the pain department as a case of zoster-associated pain.
The patient had a history of ankylosing spondylitis for 30 years and diabetes for 5 years without regular treatment. The patient had no history of smoking or substance abuse.Routine blood coagulation, urine, and stool results were normal. The erythrocyte sedimentation rate was 16 mm/h. For the routine blood test, the white blood count was 20*10/L, neutrophil ratio was 86.6%, procalcitonin level was 0.05 ng/mL, blood glucose level was 15 mmol/L, and glycosylated hemoglobin score was 13.9%. A chest computed tomography (CT) showed inflammation of the right lower lung, while an abdominal CT revealed fatty liver, liver calcification foci, and double kidney stones. A head magnetic resonance imaging showed no obvious abnormality.The patient was diagnosed with zoster-associated pain (secondary trigeminal neuralgia of the V1 branch), type 2 diabetes mellitus, ankylosing spondylitis, and pneumonia.
Treatment:
Intravenous antibiotics were given to the patient to prevent infection, and an endocrinology consultation stabilized his blood sugar levels. The patient continued to take oral analgesic drugs. Pregabalin was increased from 75 mg to 150 mg every 12 h and tramadol sustained-release tablets of 100 mg were administered every 12 h to the patient. A supraorbital nerve block was also performed. Lidocaine cataplasms were applied externally on the patient, using one patch per day. A day after the abovementioned medications were administered, serious side effects were observed, including dizziness, nausea, and vomiting. The pain, however, was not well controlled, and the patient refused to increase the dose of the medications any further. In addition, the patient had experienced nausea, vomiting, and constipation as a result of being injected with morphine in the previous hospital he was admitted to; hence, he refused to upgrade the current oral drugs to opioids.
With the consent of patients and their families, a CT-guided percutaneous micro balloon compression (PMC) [3] of the semilunar ganglion was performed under local anesthesia 3 days after admission to Jiaxing First Hospital. Because the patient had a history of ankylosing spondylitis and could not lie on his back, he was assisted by multiple body pads (Fig. 1-a), which made it difficult to plan the puncture path before operation (Fig. 1-b). According to the classic Hartel approach [4], the foramen ovale was punctured (Fig. 1-c), the needle core was withdrawn, and the balloon catheter was placed so that the distal mark point was flush with the tip of the rock cone (Fig. 1-d). The balloon was filled by being injected with 0.6 mL of 30% iohexol contrast agent for 200 s(Fig. 1-e). The balloon's three-dimensional CT image revealed that it was pear-shaped (Fig. 1-f). The patient reported that the skin on the right side of his face felt slightly numb and the pain had subsided; therefore, the NRS score was reduced to 2. Following that, the contrast agent in the balloon was released, and the balloon catheter and puncture needle were removed to finish the procedure. During ward rounds the following day, the patient reported that the original pain in the right side of his forehead had subsided but he was experiencing severe burning pain in the nasal cavity on the same side, with an NRS score of 7. The pain was in the distribution area of the second branch of the trigeminal nerve (V2); thus, a CT-guided percutaneous puncture of the second branch of the trigeminal nerve was performed with local anesthesia[5], and the treatment was successful. The needle tip was placed at the external orifice of the foramen rotundum(Fig. 2). RF thermocoagulation was performed at 95°C for 300 s.
The patient reported that the pain on the right side of his face had been alleviated (with an NRS score of 1–2). 5 days after the second operation, but he complained of severe pain in the right occipital region, which is the distribution area of the cervical nerve 2(C2). Meanwhile, the original right frontal pain returned, with a paroxysmal NRS score of 6. The patient reported having unbearable attacks of pain dozens of times a day; hence, a new course of treatment was urgently required. We emphasized to the patient and his family members that RF thermocoagulation of C2 would cause numbness in the occipital region and that of the supraorbital nerve would cause numbness on the frontal region on the same side. However, the patient complained of intolerable pain and rejected increasing the dose of oral drugs,and repeatedly requested continued RF thermocoagulation. Therefore, CT-guided percutaneous RF thermocoagulation of C2 [6] and supraorbital nerve [7] was performed with local anesthesia. The RF thermocoagulation of the C2 was performed in the left lateral decubitus position. The puncture route was planned before the operation, and the puncture needle reached the target point (Fig. <link rid="fig5">3</link>-a,3-b). The puncture needle was pulled out after RF thermocoagulation at 95°C for 300 s. Then, the right supraorbital nerve RF was performed in the supine position and the puncture needle reached the supraorbital hole (Fig. 3-c). The RF thermocoagulation was then performed at 95°C for 300 s. After the operation, the right occipital region and the top of the forehead were numb, the pain disappeared (with an NRS score of 0–1), and slight involuntary tears were observed in the patient’s right eye.
Outcome and follow-up
The patient's pain basically disappeared, NRS:0–1, and the original pain area was numb. The oral drug dose was reduced following these treatments. Tramadol was discontinued, and pregabalin was reduced to 75 mg every 12 h. The patient was discharged from the hospital after 7 days of observation because he was deemed to be in a stable condition. Pregabalin was discontinued after a month. A month later, there was no obvious discomfort in the original pain area, no adverse reaction to cold, wind, and heat stimulation, and the involuntary tears had ceased. Seven months later, there was no recurrence of pain and no oral drugs were taken. The patient and his family were very satisfied with the treatment results.
At present, zoster-associated pain is still notoriously difficult to treat. It is more strongly associated with certain conditions [8], such as advanced age, female sex, severe prodromal symptoms, severe herpetic pain, associated immune diseases, and herpes in specific areas (trigeminal nerve distribution, especially in the eyes, perineum, and brachial plexus). In this case, there were several co-occurring factors: older age, diabetes, severe pain in the herpetic stage, a history of ankylosing spondylitis, and lesions in the trigeminal distribution area. Therefore, the patient was at high risk for zoster-associated pain.
Analysis of patient course transition
The patient's initial symptom was herpes, with severe pain in the first distribution of the trigeminal nerve. After the V1 pain subsided, the symptoms progressed to severe pain in the V2 distribution area. The pain then migrated to the occipital region of the C2 after RF thermocoagulation of the V2. This disease shift is most likely explained by the theory of overspeed inhibition of the heterotopic excitatory sites of the nerve [9], which states that in the presence of the strongest ectopic excitement, other excitement points are inhibited. When the strongest excitement is eliminated, secondary excitement occurs level by level, until all are eliminated. The shift of disease may also be related to the body's perception of pain. When there is more than one area of pain, the area with the most intense pain gets the most attention. After this area is treated, the areas with a lower pain level are immediately upgraded to the most painful areas. In this case, the dominated areas of the V1, V2, and C2 became the most painful areas in sequence, and thus the patient's clinical symptoms continued to change.
Analysis of the reasons for choosing PMC and its curative effects
PMC as a treatment for trigeminal neuralgia was first reported by Mullan in the 1980s [10]. The technique has been shown to be less invasive and more effective [11] than RF thermocoagulation, causing significantly less postoperative facial numbness [12]. PMC has also been shown to be effective in treating trigeminal neuralgia caused by HZ and multiple sclerosis [13]. Due to the short duration of the disease in this case, we determined that PMC was less damaging to the nerves than RF thermocoagulation, and hence chose it as the first treatment option. However, the pain returned 5 days following PMC, and the clinical analgesic effect was insufficient. This case, combined with our team's previous clinical experience using PMC to treat trigeminal neuralgia, demonstrates that the efficacy of PMC for trigeminal neuralgia secondary to HZ is not exact. It may be that the degree of compression cannot destroy the afferent nerve and cut off the peripheral signal.
Analysis of the possible causes of C2 involvement
The varicella-zoster virus invades the body, lurking in the sensory ganglia. In this case, the virus was latent in the trigeminal nucleus. When immunity is compromised, the virus becomes active [14] and spreads through the trigeminal nucleus to the trigeminal spinal tract. The caudal of the trigeminal spinal tract continues with the posterior horn of the cervical spinal nerve root at the C1 and C2 Levels crossing to form the “trigemino–cervical complex” [15]. Therefore, the abnormal signals of the trigeminal and C2 spinal nerves often appear converged in the interference, and are manifested as paresthesia of the cervical nerve distribution area. This case can confirm the anatomic convergence theory between the trigeminal nucleus and cervical spinal nerve. In line with our team’s previous studies, this case indicates that neuralgia induced by HZ is intermixed with electrical excitation [16]. Based on this theory, the best treatment option is to alleviate the pain from the level of the trigeminal nucleus [17]. However, the risks associated with operation are currently relatively high. As a result, for patients such as the one in this case,who cannot increase their oral dose, the symptomatic treatment of the peripheral branches was used to alleviate the patient's clinical symptoms and severe pain. Electrical stimulation may be more effective for such patients if regulatory electrodes are placed in the medulla oblongata plane near the trigeminal nucleus, and this option will be investigated further in future studies by our team.
Analysis of the feasibility and timing of RF thermocoagulation for zoster-associated pain
It is generally believed that RF thermocoagulation is not to be performed in the acute stage of HZ neuralgia [18], and the recovery of nerve function is mainly promoted by PRF. Nerve RF thermocoagulation treatment can be a consideration for zoster-associated pain when indications are strictly controlled, if other treatments fail, and informed consent is obtained.
In this case, the pain was excruciating, large doses of oral medication were ineffective, and PRF and multiple nerve block treatments were unsuccessful. Despite the continuous elevation of oral drug doses, the NRS score remained 9–10, and breakthrough pain was extremely frequent, which seriously affected the quality of life of the patient and his family members. The patient was suicidal, so after communicating with him, we decided to choose RF thermocoagulation therapy. After this treatment, the pain disappeared and the patient was very satisfied with the outcome. There was no recurrence, painless numbness, impaired muscle strength, or other adverse reactions during the one-month follow-up,and there was no recurrence of pain 7 month later. Therefore, our team believes that on the premise of not affecting motor function, RF thermocoagulation should be decisively chosen to alleviate stubborn pain and severe zoster-associated pain, as in this case.
We believe that RF should be used decisively for patients suffering from zoster-associated pain that is severe and resistant to various treatments, on the basis of not causing motor function damage.
RF: radiofrequency; PRF: pulse radiofrequency; NRS: numerical rating scale; HZ: herpes zoster; V1: the first branch of the trigeminal nerve; CT: chest computed tomography ; PMC: percutaneous micro balloon compression; V2: the second branch of the trigeminal nerve; C2: area of the cervical nerve 2.
Acknowledgements
We thank our patient for his permitting us to tell his story. We would like to show our gratitude to Wensheng Zhao for their valuable wisdom of advice and insights into this piece of research.
Author contributions
Xindan Du, drafting and revising the manuscript, retrieval of relevant literature. Lulu Xu, acquisition of data and collection patient information. Bing Huang, the corresponding author, project leader, conception or design of this case, revising the manuscript in depth; All authors have read and approved final version of this manuscript for publication.
Funding
Hangzhou Science and Technology Bureau biomedical and health industry development support technology special(2021WJCY325);General Project of Hangzhou Agriculture and Social Development (20201203B173);Public welfare research project of Jiaxing city(2022AY30040);Zhejiang Social Public Welfare Research and Development Project (LGF20H090021);Zhejiang Health Science and technology plan project(2022ZH012);Key Discipline Fund of Pain Medicine Co-established by Zhejiang Province and Municipality (2019-ss-ttyx);
Availability of data and materials
This article has no datasets available during the current study.
Ethics approval and consent to participate
Trigeminal nerve extracranial radiofrequency therapy techniques and awake computed tomography-guided percutaneous balloon compression of trigeminal ganglion techniques have been reviewed and approved by the ethics committee (Medical Ethics Committee of The First Hospital of Jiaxing: 2015-081; LS2019-134). Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Institutional review board approval is not required for this case report. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
Competing interests
All authors declare no conflict of interest in this study.