- Division of Pediatric Neurosurgery, Department of Neurosurgery, Miami Children's Hospital, Miami, FL, USA
Correspondence Address:
Sanjiv Bhatia
Division of Pediatric Neurosurgery, Department of Neurosurgery, Miami Children's Hospital, Miami, FL, USA
DOI:10.4103/2152-7806.153882
Copyright: © 2015 Lo Presti A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.How to cite this article: Presti AL, Weil AG, Niazi TN, Bhatia S. Herpes simplex reactivation or postinfectious inflammatory response after epilepsy surgery: Case report and review of the literature. Surg Neurol Int 25-Mar-2015;6:47
How to cite this URL: Presti AL, Weil AG, Niazi TN, Bhatia S. Herpes simplex reactivation or postinfectious inflammatory response after epilepsy surgery: Case report and review of the literature. Surg Neurol Int 25-Mar-2015;6:47. Available from: http://sni.wpengine.com/surgicalint_articles/herpes-simplex-reactivation-postinfectious-inflammatory-response-epilepsy-surgery-case-report-review-literature/
Abstract
Background:Herpes simplex virus encephalitis (HSVE) is the most morbid clinical syndrome associated with the human herpes virus. Despite treatment with appropriate dosages of acyclovir, neurologic relapse of HSV infection have been reported after cranial surgery. Rarely, neurological deterioration due to postinfectious inflammatory response without demonstrable HSV reactivation may recur following cranial surgery.
Case Description:We report a case of a 17-year-old girl who presented with a HSVE relapse on the 6th postoperative day following resective surgery for medically refractory epilepsy and review the literature. Postinfectious inflammatory reaction may be the underlying mechanism in cases with no HSV identified on cerebrospinal fluid (CSF) or brain polymerase chain reaction (PCR), such as in the current case.
Conclusion:HSVE must be suspected in patients with previous history of HSVE and postoperative fever associated with an altered state of consciousness and/or seizures. Considering the high mortality and morbidity rates associated with HSVE, an adequate prophylactic administration of acyclovir should be considered for patients with previous history of HSVE undergoing neurosurgical procedures, especially when surgery involves the site of a previous herpetic lesion.
INTRODUCTION
Herpes simplex virus encephalitis (HSVE), mostly caused by herpes simplex virus type 1 (HSV-1), is the most morbid clinical syndrome associated with the human herpes virus. Mortality rates of this condition approach 19% in treated patients[
CASE REPORT
History and examination
A 17-year-old immunocompetent girl presented to our service for pharmacoresistant epilepsy. She had a history of HSVE at the age of 6 when she presented with seizures. She was treated with a complete course of acyclovir. She underwent an uneventful recovery and returned to baseline and did not have seizure recurrence until 6 years later. At the age of 12 years, she developed intractable seizures consisting of staring, confusion, face droop, and flushing. Seizures persisted despite multiple antiepileptic drugs (AEDs) and she was brought in for evaluation. Preoperative magnetic resonance image (MRI) showed an area of encephalomalacia involving the anterior and mesial aspect of the right temporal lobe, right frontal operculum, and right insula [
Operation
A right frontotemporal craniotomy was performed, followed by intraoperative recording using a strip over the temporal lobe, a grid over the frontal lobe, and a depth electrode, which was inserted in the insula under magnification. Intraoperative electrocorticography (ECoG) showed that the temporal lobe was extremely active and the frontal lobe also had frequent epileptic discharges. A tailored right temporal lobectomy, amygdalo-hippocampectomy and right frontal lobe disconnection were performed. No intraoperative steroids were used.
Postoperative course
Postoperative MRI showed expected postoperative changes with no complication [
On the 6th postoperative day (POD) she presented with two consecutive episodes of generalized tonic-clonic seizures and three episodes of mouth twitching with unresponsiveness, associated with postictal left facial weakness and fever. The computerized tomography (CT) of the brain performed at another medical center did not show significant findings. The following day, she was transferred to the pediatric intensive care unit of our center for further management. Physical examination revealed mild left facial palsy and fever. Rest of the neurological examination was otherwise unremarkable. There were no signs of wound infection. A new brain MRI confirmed no significant changes compared with prior postoperative MRI. There were no extra-axial collections suggestive of empyema. The patient continued with persistent fever and partial seizures involving the face despite AEDs that included her usual medication with the addition of clobazam, levetiracetam, phenytoin, benzodiazepine drip, and corticosteroids. The patient was placed on continuous VEEG and a lumbar puncture was performed. Cerebrospinal fluid (CSF) testing showed 2 white blood cells/ml (differential: 2 lymphocytes, 0 polymorph), 26.9 mg/dl of protein, normal glucose levels and a negative gram stain. CSF, blood, and urine samples were sent for culture (all were eventually negative) and empiric treatment with vancomycin and ceftazidime was started. On the 10th POD, the patient's condition gradually worsened. A repeat CSF study was normal but follow-up MRI showed extensive cytotoxic edema with restricted diffusion in the right fronto-orbital, insular, and posterior frontal cortex [
Figure 3
(a-b) Postoperative axial MRI on the 10th POD showing extensive cytotoxic edema with restricted diffusion in the right fronto-orbital, insular, and posterior frontal cortex. (c-d) Serial postoperative axial MRI showed extensive cytotoxic edema involving the right fronto-parietal-temporal and insular cortex, right thalamus, and left fronto-insular cortex
The final pathology report from surgical resection revealed encephalomalacia of cortex characterized by cystic degeneration/cavitation, astrocytic gliosis with gemistocytic astrocytes and perivascular lymphocytic monocyte cuffing. There were no viral inclusion bodies and in situ hybridization for HSV DNA was negative. These findings were consistent with chronic encephalitis [
Figure 5
Pathology revealing encephalomalacia of cortex characterized by cystic degeneration/cavitation (a), astrocytic gliosis with microglial nodules (b), perivascular lymphocytic monocyte cuffing (c) and reactive gliosis (d). There are no viral inclusion bodies. There is pyramidal neuronal loss in hippocampus
At follow-up 1 year after surgery in an outpatient clinic, the patient is seizure-free. However, she has left hemiparesis, severe difficulty in swallowing requiring jejunostomy tube, dysphasia, and flat affect. She also has mild behavioral impairment and emotional lability manifested by fluctuations in level of cooperation from quiet and smiling to marked irritability.
DISCUSSION
Six prior cases of postcraniotomy HSVE in children have been reported in the literature, of which four have occurred following resective surgery for medically refractory epilepsy and two followed tumor resection [Tables
CSF analysis reveals variable findings in cases of HSVE. Although CSF in HSVE usually has a raised white cell count with lymphocyte predominance and raised protein, findings can be variable and protein or white cell counts have been reported as normal. This supports the idea that CSF PCR testing should not be restricted to patients with abnormal basic CSF findings (glucose, cell count, protein level).[
Neuroimaging is of great diagnostic importance in cases of suspected HSVE, specially MRI[
Although the above-mentioned diagnostic tests all highly suggest postcraniotomy HSVE as the underlying process in our patient, other diagnoses must be considered in the setting of new onset neurological deterioration in association with persistent seizures and fever. Postoperative bacterial central nervous system (CNS) infection was considered, but laboratory test and images findings did not support that theory. In addition, the patient's condition worsened despite antibiotic treatment. The diffusion-weighted MRI changes may have been secondary to status epilepticus, however, this would not have explained the fever nor the radiological progression and persistence for months despite improvement of seizures. Although the lesions may theoretically have been caused by arterial ischemia, the presence of fever and the lesion location involving multiple vascular territories (right Middle Cerebral Artery, right Posterior Cerebral Artery, left Middle Cerebral Artery) render this unlikely. Finally, clinical presentation with rapid progression of fever, seizures and functional deterioration, the previous history of HSVE, the improvement following acyclovir therapy all support postcraniotomy HSVE diagnosis. In addition, thalamus involvement had been previously reported in HSVE.[
Regarding pathology findings in the brain tissue, microscope appearance of HSVE differs between the acute to chronic phase. In the acute phase, earliest lesions contain scanty parenchymal inflammation but at a more advanced stage lesions usually contain sheet of necrotic cells, foci of hemorrhage and an intense perivascular and interstitial infiltrate of lymphocytes and macrophages. Nuclear inclusions are sparse at this later stage and viral DNA can usually be detected in frozen or paraffin sections by in situ hybridization or PCR. In the chronic phase, the normal gray and white matter is replaced by cavitated glial scar tissue and occasional cluster of lymphocytes are still seen in the meninges and brain parenchyma.[
The pathogenic mechanisms underlying HSVE relapses in general include reactivation of a latent herpes virus and postinfectious immune inflammatory response. Reactivation from a herpes virus that has previously established latent infection within the CNS affected by herpes encephalitis is the most commonly proposed mechanism after surgery and this is supported by the detection of DNA HSV in CSF or in brain tissue, along with the appearance of a new typical herpetic cortical lesion.[
The specific stimuli responsible for triggering a HSVE relapse remain unclear. Associated factors include immunodeficiency states, trauma, bacterial infections, and radiation, but no clear evidence of surgery as trigger factor has been proved. In the current case, relapse could have been triggered by surgical manipulation of brain parenchyma at the previous site of herpes infection, as has been proposed in three of the prior postcraniotomy for epilepsy HSVE relapse cases. However, we have to keep in mind that these patients may have a temporary immunodeficiency as a result of surgical stress and corticosteroid administration, which could act as triggers as well.[
HSVE is a highly morbid condition. Of the six reported cases of postcraniotomy HSVE, two died and two remained with significant neurological deficits. The other two patients had good outcome with mild impairments. The patient with the most benign clinical evolution received prophylactic acyclovir therapy of 20 mg/kg/dose every 8 h starting the day of surgery. Based on the morbidity of HSVE reactivation, we have adopted this strategy of covering epilepsy surgery patients with a history of encephalitis with prophylactic perioperative acyclovir starting the day prior to surgery and continuing for 10 days.
CONCLUSION
HSVE in neurosurgical patients is a rare but potentially life-threatening complication that must be particularly suspected in patients with previous history of HSVE and unexplained postoperative fever associated with an altered state of consciousness and/or seizures. Whether or not prophylactic acyclovir therapy can avoid relapses or at least minimize the expression of the disease remains unclear. Based on this review and considering the high mortality and morbidity rates associated with HSVE, an adequate prophylactic administration of acyclovir should be considered for patients with previous history of HSVE undergoing neurosurgical procedures, especially when surgery involves the site of a previous herpetic infection.
References
1. Aldea S, Joly LM, Roujeau T, Oswald AM, Devaux B. Postoperative herpes simplex virus encephalitis after neurosurgery: Case report and review of the literature. editors. Clin Infect Dis. 2003. 36: 96-9
2. Barthez-Carpentier MA, Rozenberg F, Dussaix E, Lebon P, Goudeau A, Billard C. Relapse of herpes simplex encephalitis. editors. J Child Neurol. 1995. 10: 363-8
3. Bourgeois M, Vinikoff L, Lellouch-Tubiana A, Sainte-Rose C. Reactivation of herpes virus after surgery for epilepsy in a pediatric patient with mesial temporal sclerosis: Case report. editors. Neurosurgery. 1999. 44: 633-5
4. De Tiège X, De Laet C, Mazoin N, Christophe C, Mewasingh LD, Wetzburger C. Postinfectious immune-mediated encephalitis after pediatric herpes simplex encephalitis. editors. Brain Dev. 2005. 27: 304-7
5. De Tiège X, Rozenberg F, Burlot K, Gaudelus J, Ponsot G, Héron B. Herpes simplex encephalitis diagnostic problems and late relapse. editors. Dev Med Child Neurol. 2006. 48: 60-3
6. Ellison D, Love S, Chimelli L, Harding B, Lowe J, Vinters H. Neuropathology. A Reference Text of CNS Pathology. editors. Philadelphia: Elsevier – Mosby; 2013. p. 308-12
7. Fearnside MR, Grant JM. Acute necrotizing encephalitis complicating bifrontal craniotomy and pituitary curettage. Report of two cases. editors. J Neurosurg. 1972. 36: 499-502
8. Filipo R, Attanasio G, De Seta E, Viccaro M. Post-operative Herpes simplex virus encephalitis after surgical resection of acoustic neuroma: A case report. editors. J Laryngol Otol. 2005. 119: 558-60
9. Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D. Causes of encephalitis and differences in their clinical presentations in England: A multicentre, population-based prospective study. editors. Lancet Infect Dis. 2010. 10: 835-44
10. Gong T, Bingaman W, Danziger-Isakov L, Tuxhorn I, Goldfarb J. Herpes simplex virus reactivation after subtotal hemispherectomy in a pediatric patient. editors. Pediatr Infect Dis J. 2010. 29: 1148-50
11. Ihekwaba UK, Battersby RD. Type 2 herpes simplex reactivation after craniocervical decompression for hind brain hernia and associated syrinx. editors. Br J Neurosurg. 2009. 23: 326-8
12. Ito Y, Kimura H, Yabuta Y, Ando Y, Murakami T, Shiomi M. Exacerbation of herpes simplex encephalitis after successful treatment with acyclovir. editors. Clin Infect Dis. 2000. 30: 185-7
13. Jalloh I, Guilfoyle MR, Lloyd SK, Macfarlane R, Smith C. Reactivation and centripetal spread of herpes simplex virus complicating acoustic neuroma resection. editors. Surg Neurol. 2009. 72: 502-4
14. Kennedy PG, Steiner I. Recent issues in herpes simplex encephalitis. editors. J Neurovirol. 2013. 19: 346-50
15. Kim SH, Lee SG, Kim SH, Kim DS, Kim HD. Relapsed herpes simplex virus encephalitis after epilepsy surgery. editors. J Epilepsy Res. 2013. 3: 28-31
16. Kimura H, Aso K, Kuzushima K, Hanada N, Shibata M, Morishima T. Relapse of herpes simplex encephalitis in children. editors. Pediatrics. 1992. 89: 891-4
17. Koelfen W, Freund M, Gückel F, Rohr H, Schultze C. MRI of encephalitis in children comparison of CT and MRI in the acute stage with long-term follow-up. editors. Neuroradiology. 1996. 34: 490-3
18. Koenig H, Rabinowitz SG, Day E, Miller V. Post-infectious encephalomyelitis after successful treatment of herpes simplex encephalitis with adenine arabinoside: Ultrastructural observations. editors. N Engl J Med. 1979. 300: 1089-93
19. Kwon JW, Cho BK, Kim EC, Wang KC, Kim SK. Herpes simplex encephalitis after craniopharyngioma surgery. Case report. editors. J Neurosurg Pediatr. 2008. 2: 355-8
20. Livorsi D, Anderson E, Qureshi S, Howard M, Wang YF, Franco-Paredes C. Brainstem encephalitis an unusual presentation of herpes simplex virus infection. editors. J Neurol. 2010. 257: 1432-7
21. Lund M. Herpes simplex virus reactivation and encephalitis after topectomy. editors. J Pediatr Health Care. 2011. 25: 323-7
22. Navin P, Delanty N, Brennan P, Looby S. Herpes simplex virus encephalitis involving the right thalamus. editors. BMJ Case Rep. 2013. p.
23. Perry JD, Girkin CA, Miller NR, Kerr DA. Herpes simplex encephalitis and bilateral acute retinal necrosis syndrome after craniotomy. editors. Am J Ophthalmol. 1998. 126: 456-60
24. Ploner M, Turowski B, Wöbker G. Herpes encephalitis after meningioma resection. editors. Neurology. 2005. 65: 1674-5
25. Prim N, Benito N, Montes G, Pomar V, Molet J, Rabella N. Human herpesvirus 1 meningoencephalitis after trigeminal neuralgia surgery. editors. J Infect. 2013. 67: 79-81
26. Schleede L, Bueter W, Baumgartner-Sigl S, Opladen T, Weigt-Usinger K, Stephan S. Pediatric herpes simplex virus encephalitis: A retrospective multicenter experience. editors. J Child Neurol. 2013. 28: 321-31
27. Sköldenberg B, Aurelius E, Hjalmarsson A, Sabri F, Forsgren M, Andersson B. Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults. editors. J Neurol. 2006. 253: 163-70
28. Spacca B, Mallucci C, Riordan A, Appleton R, Thorp N, Pizer B. HSV encephalitis in a child with brain stem glioma: A rare complication of therapy Case report and review of the neurosurgical literature. editors. Childs Nerv Syst. 2007. 23: 1347-50
29. Spiegel R, Miron D, Yodko H, Lumelsky D, Habib A, Horovitz Y. Late relapse of herpes simplex virus encephalitis in a child due to reactivation of latent virus: Clinicopathological report and review. editors. J Child Neurol. 2008. 23: 344-8
30. Spuler A, Blaszyk H, Parisi JE, Davis DH. Herpes simplex encephalitis after brain surgery: Case report and review of the literature. editors. J Neurol Neurosurg Psychiatry. 1999. 67: 239-42
31. Steiner I, Schmutzhard E, Sellner J, Chaudhuri A, Kennedy PG. European Federation of Neurological Sciences, European Neurologic Society. EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system. editors. Eur J Neurol. 2012. 19: 1278-91
32. Tyler LK. Herpes simplex virus infections of the central nervous system: Encephalitis and meningitis, including Mollaret’s. editors. Herpes. 2004. 11: 57-64A
33. Uda T, Koide R, Ito H, Hosono A, Sunaga S, Morino M. Relapse of herpes simplex virus encephalitis after surgical treatment for temporal lobe epilepsy: Rare complication of epilepsy surgery. editors. J Neurol. 2013. 260: 318-20
34. Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. editors. N Engl J Med. 1986. 314: 144-9
35. Whitley RJ. Viral encephalitis. editors. N Engl J Med. 1990. 323: 242-350
36. Yamada S, Kameyama T, Nagaya S, Hashizume Y, Yoshida M. Relapsing herpes simplex encephalitis: Pathological confirmation of viral reactivation. editors. J Neurol Neurosurg Psychiatry. 2003. 74: 262-4