Trigeminal extracranial thermocoagulation along with patientcontrolled analgesia with esketamine for refractory postherpetic neuralgia after herpes zoster ophthalmicus:A case report

lNTRODUCTlON

Varicella-zoster virus infection can cause varicella and latency in the sensory ganglia,and its reactivation causes herpes zoster in the corresponding innervated area.Older adults and those with impaired immune function are prone to the disease[1].The most commonly involved site is the thoracic region,followed by the cranial(especially trigeminal),lumbar,cervical and sacral regions.The first branch of the trigeminal nerve(ophthalmic branch)is the most frequently involved branch of the trigeminal nerve,also known as herpes zoster ophthalmicus(HZO),which accounts for 10%-20% of all cases of herpes zoster[2].This high incidence may be related to long-term ultraviolet exposure[3].HZO can lead to keratitis and even blindness[4].In addition,patients may develop postherpetic neuralgia(PHN),so early intervention is important.

Treatments for herpes zoster mainly includes oral analgesics,nerve block and radiofrequency.Radiofrequency in the trigeminal ganglion is a minimally invasive,quickly effective and safe method for the treatment of HZO[5-7].However,there are still some patients with HZO who cannot be effectively relieved after the above treatment in the clinic.This seriously affects the daily lives of patients.Therefore,it is urgent to explore a new treatment to relieve HZO neuralgia.Ketamine is an Nmethyl-D-aspartate receptor(NMDAR)that has been shown to relieve a variety of neuropathic pain,such as complex regional pain syndrome[8],PHN[9],cancer pain[10]and trigeminal neuralgia[11].We used ketamine for patient-controlled intravenous analgesia(PCIA)for the first time in the treatment of ocular herpes zoster neuralgia,in a new treatment approach for refractory HZO.

Then the prince s servant brought in the three robes, and when the judges saw the mist-gray one which the princess usually wore, they said, Have this robe embroidered10 with gold and silver, and then it will be your wedding robe.

CASE PRESENTATlON

Chief complaints

A 66-year-old woman,weight 46 kg and height 155 cm,was hospitalized with left frontal parietal herpes for 20 d with pain for 3 d.

History of present illness

At the beginning of the disease,the main manifestation was herpes in the left frontal parietal region without pain.Herpes gradually improved after antiviral treatment[valaciclovir capsules(0.3 g bid)was taken orally and acyclovir cream was applied externally for one week].Seventeen days later,pain appeared in the herpes area,which was characterized by paroxysmal,acupuncture-like and electric shock-like pain.The frequency of pain attacks was approximately 1 per hour,and each attack lasted from 30 s to 2 min.The numerical rating scale(NRS)was 9.There was no significant pain relief after oral painkillers,resulting in serious impacts to the patient’s daily life.

All study participants,or their legal guardian,provided informed written consent prior to study enrollment.

When she was fast asleep Vasilissa went into the corner, took the little doll from her pocket, set before it a part of the food that was left and asked its advice. And the doll, when it had become alive, and eaten a little food and sipped36 a little drink, said: Don t worry, beautiful Vasilissa! Be comforted. Do as thou didst last night: say thy prayers and go to sleep. So Vasilissa was comforted. She said her prayers and went to sleep and did not wake till next morning when she heard the old witch in the yard whistling. She ran to the window just in time to see her take her place in the big iron mortar, and as she did so the man dressed all in red, riding on the blood red horse, leaped over the wall and was gone, just as the sun rose over the wild forest.

History of past illness

The patient had a history of diabetes for more than 10 years and was taking metformin sustained release tablets(0.5 g qd)for hypoglycemic treatment.The patient underwent subtotal gastrectomy because of gastric cancer in three years ago.

Personal and family history

There was no significant family history and physical examination was normal.

All the authors have read the CARE Checklist(2016),and the manuscript was revised according to the CARE Checklist(2016).

Physical examination

There was no significant family history and physical examination was normal.

Laboratory examinations

All laboratory investigations and imaging investigations were normal including the liver function.

Please, mister, please, I m sorry. I didn t know what else to do! pleaded the youngster. It s my brother, he said. He rolled off the curb4 and fell out of his wheelchair and I can t lift him up.

Imaging examinations

All laboratory investigations and imaging investigations were normal including the liver function.

FlNAL DlAGNOSlS

Postherpetic neuralgia after herpes zoster ophthalmicus;Diabetes.

TREATMENT

At the beginning of pain(on the 17 d after HZO),the patient was treated with gabapentin capsules(0.3 g bid)and paracetamol oxycodone tablets(5 mg tid)to control the pain,but the pain persisted.After computed tomography(CT)-guided trigeminal nerve pulse radiofrequency procedure,the pain was relieved for 2 h after the procedure,and severe pain later appeared again.A single subcutaneous injection of morphine hydrochloride(5 mg)temporarily relieved pain,but there was still repeated touch-induced pain and spontaneous pain.After obtaining the patient's consent,percutaneous radiofrequency thermocoagulation was performed under the guidance of CT to completely destroy the ophthalmic branch of the trigeminal nerve(Figure 1A and B).After the procedure,the sensation of the innervation area of the ophthalmic branch of the left trigeminal nerve decreased(manifested as numbness),and the touch-induced pain disappeared,but there was no relief of paroxysmal spontaneous pain.On the second day,the patient was given esketamine for PCIA for continuous analgesia.The PCIA formula was esketamine hydrochloride injection(550 mg)combined with midazolam injection(5 mg)diluted in 275 mL(that is,the concentration of esketamine was 2 mg/mL).Parameter settings were as follows: maintenance dose 8 mg/h,additional dose 10 mg,and additional interval time 30 min.The parameters were adjusted according to the pain and tolerance of the patient.The patient was given oxygen inhalation,and vital signs were monitored.

OUTCOME AND FOLLOW-UP

The pain was significantly relieved after two courses of PCIA,and the NRS score was reduced to 2 points,compared with that before treatment,the difference was statistically significant(

＜ 0.05).There was no spontaneous pain and allodynia.During the use of PCIA,the patient developed lethargy,nausea,hypotension and abnormal liver enzymes.After positive treatment,the above adverse reactions were improved.The patient was discharged after no adverse reactions were observed.

After discharge,the patient was followed up by telephone or outpatient services every week.During the 2-month follow-up,the pain was relieved continuously,and no spontaneous pain or allodynia was reported.The NRS score was ≤ 3,and the Pittsburgh Sleep Quality Index score was 5,which was significantly different from that before treatment(

＜ 0.05).No adverse events were observed.Figure 2 shows the changing trend of NRS score at admission and during follow-up after discharge.

DlSCUSSlON

Ketamine is an NMDAR antagonist.NMDARs are excitatory glutamate receptors in the spinal cord and are involved in the transmission of pain signals.Persistent pain receptor stimulation leads to activation and upregulation of synaptic NMDARs in the spinal dorsal horn,which leads to enhanced and amplified transmission of pain signals to the brain(central sensitization).In addition,ketamine can enhance the descending inhibition of the central site and anti-inflammatory effects[15].It can relieve all kinds of neuropathic pain[16,17].Esketamine is the dextral form of ketamine and has a higher affinity for NMDARs[10].Therefore,the dose needed to produce analgesia is lower.Ketamine has been used in the treatment of PHN[9,18].In this case,PCIA with esketamine was used for the treatment of refractory herpetic neuralgia after HZO for the first time,and the pain was significantly relieved.Previous studies have shown that the duration of relief from neuropathy is related to the total infusion dose and infusion duration of ketamine[19].Furthermore,intravenous ketamine infusion in the treatment of refractory pain is within the guidelines of the American Society of Anesthesiology and Pain[20].Therefore,in this case chose the PCIA mode.The PCIA mode can accurately control the infusion speed and infusion dose and achieve continuous analgesia.In addition,when an outbreak of pain occurs,patients can automatically control the additional dose to relieve the pain symptoms in time.The peak effect of ketamine is after 15 to 20 min and hence the lockout time was set to 30 min.The combined use of midazolam can reduce the side effects of unpleasant pseudomental disorders to some extent.There were no psychedelic,paranoid or other mental side effects in this case.

This case shows that trigeminal thermocoagulation combined with esketamine PCIA can effectively relieve refractory herpetic neuralgia after HZO.In addition,the pain relief lasted at least 2 mo.Primary trigeminal neuralgia can achieve satisfactory curative effects through drug and surgical intervention[12,13].However,neuralgia caused by varicella-zoster virus infection of the trigeminal nerve is not satisfactorily managed through drugs and surgical treatment,and these methods are ineffective in some patients.This may be related to the mechanism of central sensitization after herpes zoster virus infection.Untimely treatment may lead to keratitis and even permanent visual impairment.Besides,7%of patients suffer from post herpetic neuralgia after HZO which may last from 30 days to 6 mo[14].Antiviral treatment,steroids and anti-inflammatory drugs will prevent the complications.

On the second day after treatment with esketamine PCIA,the patient showed drowsiness and nausea,and her blood pressure dropped to 82/53 mmHg.After lowering the dose and rehydration,the patient's drowsiness improved,and blood pressure returned to normal.On the 3

day,the patient’s liver enzyme index was significantly higher than that before treatment.The liver enzyme decreased after liver protection treatment and returned to normal at discharge.Dizziness and lethargy are common central nervous system symptoms of ketamine.Ketamine is mainly metabolized by the liver,and heavy use of ketamine will damage liver function.Therefore,when using ketamine,we should pay attention to the changes in patients' consciousness,monitor vital signs and review liver function regularly.No myocardial inhibition,cystitis or other adverse reactions were found in this case.

This case was followed up for 2 mo after treatment.Long-term follow-up,large sample size and prospective studies are needed to verify the long-term efficacy of ketamine in the treatment of intractable herpes zoster.

CONCLUSlON

By the time I graduated from college, I was ready to spread my wings. I got a job teaching special education at a school in Coachella, California, a desert town about 170 miles from home. It was no dream job. Low-income housing across the street from the school was a haven3 for drug users. Street gangs hung around the school after dark. Many of my charges, emotionally disturbed 10-to 14-year-old boys, had been arrested for shoplifting, car theft or arson4.

FOOTNOTES

Tao JC performed the literature research and drafted the manuscript;Xin BY and Zhang ZQ collected the data;Luo G analyzed the data Huang B and Yao M conceived the study design and revised the manuscript in depth;All authors have read and approved final version of this manuscript for publication.

One Sunday, he followed me to my car and asked me to go to lunch with him. I think we both knew we felt something special for each other before that lunch was finished. Less than a month later, he proposed. I accepted but with much fear in my heart. I was determined5 not to ever be abused again. Three years of marriage to this wonderful man has brought me immense（，） joy as he has showered me with his love, compassion6 and caring. He has become my husband, my lover, my companion, and my best friend. I have learned the difference between self-serving, abusive（，） love and the real, true, self-sacrificing kind of love. The best thing I can think to say about this big, bald（） Texan is that he enables me to find the best in myself and loves me as I am. Sometimes, love is sweeter the second time around.

All authors declare that they have no conflicts of interest.

In conclusion,trigeminal extracranial thermocoagulation combined with esketamine PCIA may be a safe and feasible method for the treatment of refractory herpetic neuralgia after herpes zoster ophthalmicus.This may be a new treatment method for refractory ocular herpes zoster neuralgia.

My sister has become my dearest friend, and today I am ashamed of the names I called her and the fits I pitched. If they still sold white-white, I d buy her a lifetime supply. All the same, I can t help gloating that she ll be forty before I will.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial(CC BYNC 4.0)license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See: https://creativecommons.org/Licenses/by-nc/4.0/

29. Cast off the form of a beast: Shapeshifting is a common motif56 in folklore and found in almost every culture around the world, often attributed to gods and mythical85 creatures, but sometimes practiced by humans. The change can either be voluntary or imposed through enchantment, as it is here. The most common types of shapeshifting for humans usually involves changing into a bear or wolf, especially for men. Shapeshifting is often instigated86 by the rising or setting of the sun or moon. Return to place in story.

China

Jia-Chun Tao 0000-0002-0135-7680;Bing Huang 0000-0001-5714-3860;Ge Luo 0000-0001-6681-9308;Zhi-Qiang Zhang 0000-0002-0747-7755;Bing-Yue Xin 0000-0003-2232-069X;Ming Yao 0000-0002-3014-0560.

Zhang H

A

Oh, all right, Mrs. Katrinka said. If you d like to take home some of the 60 foot crane you left in my back yard, it s sitting right over there in those six sculptures.

Zhang H

1 Shiraki K,Toyama N,Shiraki A,Yajima M;Miyazaki Dermatologist Society.Age-dependent trigeminal and femalespecific lumbosacral increase in herpes zoster distribution in the elderly.

2018;90: 166-171[PMID:29395575 DOI: 10.1016/j.jdermsci.2018.01.009]

2 Liesegang TJ.Herpes zoster ophthalmicus natural history,risk factors,clinical presentation,and morbidity.

2008;115: S3-12[PMID: 18243930 DOI: 10.1016/j.ophtha.2007.10.009]

3 Zak-Prelich M,Borkowski JL,Alexander F,Norval M.The role of solar ultraviolet irradiation in zoster.

2002;129: 593-597[PMID: 12558343 DOI: 10.1017/s0950268802007793]

4 Li JY.Herpes zoster ophthalmicus:Acute keratitis.

2018;29: 328-333[PMID: 29794881 DOI:10.1097/ICU.0000000000000491]

5 Zhang H,Ni H,Liu S,Xie K.Supraorbital Nerve Radiofrequency for Severe Neuralgia Caused by Herpes Zoster Ophthalmicus.

2020;2020: 3191782[PMID: 33062083 DOI: 10.1155/2020/3191782]

6 Liu DY,Chen JS,Fang ZZ,Liu SY,Wan L.Pulsed Radiofrequency of the Trigeminal Ganglion for Treating Postherpetic Neuralgia of the Ophthalmic Branch.

2021;2021: 6638392[PMID: 34122683 DOI:10.1155/2021/6638392]

7 Wan C,Dong DS,Song T.High-Voltage,Long-Duration Pulsed Radiofrequency on Gasserian Ganglion Improves Acute/Subacute Zoster-Related Trigeminal Neuralgia: A Randomized,Double-Blinded,Controlled Trial.

2019;22: 361-368[PMID: 31337167]

8 Sigtermans MJ,van Hilten JJ,Bauer MCR,Arbous SM,Marinus J,Sarton EY,Dahan A.Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1.

2009;145: 304-311[PMID:19604642 DOI: 10.1016/j.pain.2009.06.023]

9 Kim YH,Lee PB,Oh TK.Is magnesium sulfate effective for pain in chronic postherpetic neuralgia patients comparing with ketamine infusion therapy?

2015;27: 296-300[PMID: 25792176 DOI: 10.1016/j.jclinane.2015.02.006]

10 Culp C,Kim HK,Abdi S.Ketamine Use for Cancer and Chronic Pain Management.

2020;11: 599721[PMID: 33708116 DOI: 10.3389/fphar.2020.599721]

11 Rabben T,Skjelbred P,Oye I.Prolonged analgesic effect of ketamine,an N-methyl-D-aspartate receptor inhibitor,in patients with chronic pain.

1999;289: 1060-1066[PMID: 10215688]

12 Sterman-Neto H,Fukuda CY,Duarte KP,Aparecida da Silva V,Rodrigues ALL,Galhardoni R,de Siqueira SRDT,de Siqueira JTT,Teixeira MJ,Ciampi de Andrade D.Balloon compression

radiofrequency for primary trigeminal neuralgia:a randomized,controlled trial.

2021;162: 919-929[PMID: 32947541 DOI: 10.1097/j.pain.0000000000002070]

13 Ren H,Zhao C,Wang X,Shen Y,Meng L,Luo F.The Efficacy and Safety of the Application of Pulsed Radiofrequency,Combined With Low-Temperature Continuous Radiofrequency,to the Gasserian Ganglion for the Treatment of Primary Trigeminal Neuralgia: Study Protocol for a Prospective,Open-Label,Parall.

2021;24: 89-97[PMID:33400432]

14 Schmader K.Herpes Zoster.

2018;169: ITC19-ITC31[PMID: 30083718 DOI: 10.7326/AITC201808070]

15 Niesters M,Martini C,Dahan A.Ketamine for chronic pain: risks and benefits.

2014;77: 357-367[PMID: 23432384 DOI: 10.1111/bcp.12094]

16 Marchetti F,Coutaux A,Bellanger A,Magneux C,Bourgeois P,Mion G.Efficacy and safety of oral ketamine for the relief of intractable chronic pain: A retrospective 5-year study of 51 patients.

2015;19: 984-993[PMID:25381898 DOI: 10.1002/ejp.624]

17 Pickering G,Pereira B,Morel V,Corriger A,Giron F,Marcaillou F,Bidar-Beauvallot A,Chandeze E,Lambert C,Bernard L,Delage N.Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized,Double-blind,Crossover Trial.

2020;133: 154-164[PMID: 32384291 DOI: 10.1097/ALN.0000000000003345]

18 Sawynok J,Zinger C.Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain.

2016;17: 601-609[PMID: 26809783 DOI: 10.1517/14656566.2016.1146691]

19 Maher DP,Chen L,Mao J.Intravenous Ketamine Infusions for Neuropathic Pain Management:A Promising Therapy in Need of Optimization.

2017;124: 661-674[PMID: 28067704 DOI: 10.1213/ANE.0000000000001787]

20 Schwenk ES,Viscusi ER,Buvanendran A,Hurley RW,Wasan AD,Narouze S,Bhatia A,Davis FN,Hooten WM,Cohen SP.Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine,the American Academy of Pain Medicine,and the American Society of Anesthesiologists.

2018;43: 456-466[PMID: 29870457 DOI: 10.1097/AAP.0000000000000806]