Herpes simplex encephalitis following microvascular decompression ...

J Neurosurg 118:530–533, 2013 ©AANS, 2013

Herpes simplex encephalitis following microvascular decompression for trigeminal neuralgia Case report Hon Tang, M.B.B.S., Francisco Falcone, M.B.B.S., and Sam Eljamel, M.B.B.Ch., M.D., F.R.C.S.(Ed), F.R.C.S.(Ir), F.R.C.S.(SN) Department of Neurosurgery, Ninewells Hospital and Medical School, Dundee, United Kingdom The authors present the first reported case of herpes simplex encephalitis (HSE) precipitated by trigeminal nerve microvascular decompression (MVD). The presentation of this specific case together with the pathogenesis and management of HSE are discussed, with a relevant literature review. This 29-year-old woman with treatment-resistant trigeminal neuralgia underwent a successful elective MVD of the right trigeminal nerve. She was discharged but was readmitted 1 week postoperatively with clinical signs and symptoms of meningitis. A CSF sample was obtained through lumbar puncture before she was treated initially with ceftriaxone. The polymerase chain reaction test of CSF was later positive for herpes simplex virus Type 1, at which point the patient was switched to a 2-week course of intravenous acyclovir before being discharged. Although this disease is rare, to avoid a delay in antiviral treatment the authors suggest that HSE should be considered in any patient presenting with a meningoencephalitic picture following MVD. (http://thejns.org/doi/abs/10.3171/2012.11.JNS121386)

Key Words • herpes simplex encephalitis • microvascular decompression • pain

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of HSV-1 is common within the general population, with approximately 90% being seropositive.8 Despite the high percentage of latent HSV-1 carriers, the incidence of HSE remains very low, estimated to be between 0.7 and 13.8 per 100,000 annually.15 Although it is well established that several triggers such as trauma, sunlight, immunosuppression, and irradiation are known to precipitate reactivation of latent HSV in the form of herpes labialis, the exact pathogenesis of HSE remains a much-debated subject.8 The appearance of HSE following neurosurgical intervention is an extremely rare complication, with only a few cases reported in the literature. A recent literature review by Raper et al.13 gathered 13 reported cases of postneurosurgical HSE, of which all except one involved excision of an intracranial tumor. One case occurred following resection of intramedullary ependymoma. Previously, Hengstman et al.5 reported 2 cases of facial nerve revalence

Abbreviations used in this paper: EEG = electroencephalography; HSE = herpes simplex encephalitis; HSV-1 = herpes simplex virus Type 1; LP = lumbar puncture; MVD = microvascular decompression; PCR = polymerase chain reaction; TN = trigeminal nerve.

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neuropathy secondary to HSV reactivation following MVD. We describe the first reported case of HSE following MVD of the TN.

Case Report History. This 29-year-old woman was admitted for an elective MVD of the right TN. She had a 5-year history of right facial pain affecting the first and second divisions of her right TN (V1 and V2) that was refractory to medical therapy. She underwent MVD in the lateral position under continuous auditory evoked potentials. No pre- or postoperative steroids were administered. Her surgery and postoperative recovery were unremarkable, and she was discharged 5 days later with resolution of her trigeminal neuralgia.

Examination. The patient presented to the Emergen cy Department 2 days later with nausea and vomiting, photophobia, neck stiffness, and severe headaches. She was visibly distressed but was alert and oriented, with a Glasgow Coma Scale score of 14. She had pyrexia, tachycardia, and tachypnea. On examination she had no focal J Neurosurg / Volume 118 / March 2013

Herpes simplex encephalitis after microvascular decompression neurological deficit, although she exhibited a positive Kernig sign. There was no wound infection, and a vesicular rash was noted across her torso along the T-4 dermatome distribution.

Treatment. Blood tests revealed leukocytosis with neutrophilia, and monocytosis. Her lymphocyte count was within the normal range and the rest of the blood test results were unremarkable. We suspected that she had postoperative bacterial meningitis in view of her meningitic symptoms and signs. A diagnostic LP was performed and intravenous ceftriaxone and metronidazole were commenced. The results of CSF analysis are shown in Table 1. Microscopy and culture of CSF samples were negative for bacteria, but HSV-1 was detected in the PCR test of her CSF 48 hours later. Tests for HSV-2, varicella zoster virus, and enterovirus were negative. In view of the new findings, she was commenced on intravenous acyclovir (10 mg/kg) thrice daily for 2 weeks and her antibiotics were stopped. On further examination of her medical notes, she had had negative results on an HSV serology test 3 years previously as part of a workup to rule out any gynecological cause of abdominal pain. Her HIV test was also negative. On further questioning, she admitted to suffering from cold sores intermittently in the past 2 years. Posttreatment Course. The patient responded well to treatment; she completed a 2-week course of antiviral drugs and was discharged. A CT head scan demonstrated postsurgical changes at the site of the craniotomy. An MRI study confirmed that there was no focal brain abnormality in the insular region, and the FLAIR sequence demonstrated subtle changes in the medial temporal lobe structures (Fig. 1). The EEG study, however, showed persistent focal slowing over the left frontotemporal area, signs suggestive of focal encephalopathy (Fig. 2).

Discussion

Encephalitis is the inflammation of the brain parenchyma, with HSV-1 the most common causative organTABLE 1: Results of CSF sample testing in a patient with HSE who was readmitted for treatment* Investigation glucose in CSF (mmol/L) glucose in serum (mmol/L) protein (mg/L) white blood cells lymphocytes (%) polymorphs (%) red blood cells lactate microscopy/culture HSV-1

1st Admission 2.1 5.5 1133 282 90 10 294 5.2 no growth detected

* — = not measured.

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2nd Admission — — 784 103 100 0 4 — no growth not detected

Fig. 1. Coronal FLAIR MRI scan demonstrating subtle changes in the medial temporal lobes in a patient with HSE.

ism in the West. It carries a high mortality rate unless treatment is initiated promptly. Encephalitis usually pre sents with a constellation of clinical features such as fever, altered mental status, severe headaches, nausea, and vomiting as well as seizures. Common impairments of mental functions include disorientation, speech disturbances, and behavioral changes. It is important to note that the Glasgow Coma Scale score can be normal at presentation.15 There is often a potential overlap of clinical features in patients with suspected encephalitis and suspected meningitis or both (meningoencephalitis), because an active CNS viral infection can result in meningeal irritation and disruption of brain parenchyma function. Nevertheless, subsequent investigations and initial management are very similar. The fact that our patient had a positive PCR (which is 99% specific for HSE), negative Gram stain, negative CSF and blood cultures for bacteria, a lack of response to broad-spectrum antibiotics, a fast response to antiviral therapy, and slowing of EEG activity supports the diagnosis of HSE rather than meningitis. Previous studies have shown that latent HSV reactivation is not uncommon after neurosurgical TN decompression, with a positive HSV culture from oropharyngeal secretions and throat wash in up to 50% of patients.12 Cutaneous herpetic lesions were reported in 38%–94% of patients after TN decompression.1,2,4,12 Surgical manipulation of cranial nerves is most likely the etiology behind reactivation of latent HSV-1 in these patients.7,10,12 A histo531

H. Tang, F. Falcone, and S. Eljamel

Fig. 2. The EEG readings obtained in a patient with HSE; the bottom 4 strips represent the left side of the brain, with focal slowing.

ry of recurrent herpes labialis infection is also associated with an increased risk of reactivation postoperatively.12 Prophylactic acyclovir has been shown to possibly reduce the incidence of reactivation.14 Although reactivation of latent HSV is a frequent complication, especially after MVD, there were no reported cases of HSE as a result of viral reactivation. For this particular case of HSE, it may be more than just simply a reactivation of latent HSV-1, but also perhaps an underlying immunodeficiency disorder, thus increasing the risk of developing encephalitis. Our patient underwent extensive investigations including complete blood count, immunoglobulin, and complement levels, and she did not have immune deficiency. Evidence-based guidelines on management of viral encephalitis have been published in recent years.15,16,18 The gold standard method of diagnosis formerly was a brain biopsy; however with the advent of modern viral PCR, the choice of investigation would be a diagnostic LP for CSF analysis, provided that there are no contraindications to LP. This should be performed as soon as the patient is stable, ideally before initiating any antibiotic or antiviral drugs. In suspected viral encephalitis, CSF samples should be tested for HSV-1, HSV-2, varicella zoster virus, and enterovirus, because these would identify 90% of cases of viral pathogens.15 The PCR test has a sensitivity and specificity of 96% and 99%, respectively, when performed between 48 hours and 10 days from onset of symptoms, even after antiviral drugs have been commenced.9,17 Patients should be started on intravenous acyclovir (10 mg/kg 3 times daily) once initial CSF analysis has indicated a viral infection or if there is any contraindication or delay (> 6 hours) in performing an LP. Recommended duration of treatment is 14–21 days.15 Steroids are currently not recommended until results of an ongoing randomized trial prove otherwise.11 Other investigative modalities include MRI because it has higher sensitivity than CT in detecting HSE, although CT scans are often performed initially due to the acute nature of presentation.3,10 An EEG study can be a useful investigation. Typical EEG abnormalities in encephalitis include slowing of background activity with periodic localized delta discharges, especially in the temporal lobe, although these are not pathognomonic of HSE.6 532

Conclusions

This is the first reported case of HSE following MVD for TN. This is an extremely rare complication, despite studies showing that the rate of latent reactivation of HSV can be very high following neurosurgical procedures. Although HSE is rare and its presenting features might resemble meningitis, there should be a low threshold for suspecting HSE because prompt treatment in the form of intravenous acyclovir can prevent an otherwise fatal condition. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Eljamel. Acquisition of data: all authors. Analysis and interpretation of data: Eljamel, Tang. Drafting the article: Tang. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Eljamel. Study supervision: Eljamel. Acknowledgments The authors acknowledge the contribution of the staff on the neurosurgical high-dependency unit and the microbiology department for the excellent care they have provided to these patients. References 1. Carton CA: Effect of previous sensory loss on the appearance of herpes simplex following trigeminal sensory root section. J Neurosurg 10:463–468, 1953 2. Carton CA, Kilbourne ED: Activation of latent herpes simplex by trigeminal sensory-root section. N Engl J Med 246:172– 176, 1952 3. Domingues RB, Fink MC, Tsanaclis AM, De Castro CC, Cerri GG, Mayo MS, et al: Diagnosis of herpes simplex encephalitis by MRI and PCR essays of CSF. J Neurosci 157:148–153, 1996 4. Ellison SA, Carton CA, Rose HM: Studies of recurrent herpes simplex infections following section of the trigeminal nerve. J Infect Dis 105:161–167, 1959 5. Hengstman GJ, Gons RA, Menovsky T, Lunel FV, van de Vlasakker CJ, de Vries J: Delayed cranial neuropathy after neuro-


Herpes simplex encephalitis after microvascular decompression surgery caused by herpes simplex virus reactivation: report of three cases. Surg Neurol 64:67–70, 2005 6. Illis LS, Taylor FM: The electroencephalogram in herpessimplex encephalitis. Lancet 229:718–721, 1972 7. Jalloh I, Guilfoyle MR, Lloyd SK, Macfarlane R, Smith C: Reactivation and centripetal spread of herpes simplex virus complicating acoustic neuroma resection. Surg Neurol 72:502– 504, 2009 8. Kennedy PGE, Chaudhuri A: Herpes simplex encephalitis. J Neurol Neurosurg Psychiatry 73:237–238, 2002 9. Lakeman FD, Whitley RJ: Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. J Infect Dis 171:857–863, 1995 10. Marchbank ND, Howlett DC, Sallomi DF, Hughes DV: Magnetic resonance imaging is preferred in diagnosing suspected cerebral infections. BMJ 320:187–188, 2000 11. Openshaw H, Cantin E: Corticosteriods in herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry 76:1469, 2005 12. Pazin GJ, Ho M, Jannetta PJ: Reactivation of herpes simplex virus after decompression of the trigeminal nerve root. J Infect Dis 138:405–409, 1978 13. Raper DM, Wong A, McCormick PC, Lewis LD: Herpes simplex encephalitis following spinal ependymoma resection: case report and literature review. J Neurooncol 103:771–776, 2011 14. Schädelin J, Schilt HU, Rohner M: Preventive therapy of herpes labialis associated with trigeminal surgery. Am J Med 85 (2A):46–48, 1988


15. Solomon T, Michael BD, Smith PE, Sanderson F, Davies NW, Hart IJ, et al: Management of suspected viral encephalitis in adults—Association of British Neurologists and British Infection Association National Guidelines. J Infect 64:347–373, 2012 16. Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, et al: Viral encephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 12:331–343, 2005 17. Tebas P, Nease RF, Storch GA: Use of the polymerase chain reaction in the diagnosis of herpes simplex encephalitis: a decision analysis model. Am J Med 105:287–295, 1998 18. Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, et al: The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 47:303–327, 2008 Manuscript submitted July 15, 2012. Accepted November 30, 2012. This paper was given as a platform presentation during the World Congress of Skull Base Surgery held in Brighton, England, in May 2012. Please include this information when citing this paper: published online January 4, 2013; DOI: 10.3171/2012.11.JNS121386. Address correspondence to: Sam Eljamel, M.B.B.Ch., M.D., Department of Neurosurgery, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom. email: m.s.eljamel@ dundee.ac.uk.

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