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herpes viruses are characterized by their ability to infect cells and destroy them or remain inactive without causing cell damage .
herpes simplex virus encephalitis after neurosurgery has been described previously [ 215 ] , including three cases of hsv reactivation following neurosurgery to treat uncontrolled epilepsy in patients with a previous history of hsv encephalitis .
we report a case of hsv-1 encephalitis , confirmed by csf pcr and dna sequencing , following surgical manipulation of the site of a primary hsv-1 infection .
an 11-year - old right - handed caucasian female patient was admitted with fever and confusion after surgery for epilepsy .
her medical history was significant for an episode of hsv encephalitis at twenty months of age , which was diagnosed by positive csf pcr for hsv-1 ( table  1 ) and resulted in developmental delay and epilepsy .
the electroencephalogram ( eeg ) at twenty months showed dysfunction of the right frontotemporal region .
magnetic resonance imaging ( mri ) revealed a signal change in the right temporal , insular , and meningeal arteries , with some bleeding and a lesion in the left hippocampus .
she was treated with intravenous acyclovir ( 30  mg / kg / day for 21  days ) and carbamazepine on discharge from the hospital .
the seizures were controlled for 3  years , but in 2007 , she started having complex partial seizures with secondary generalization . at 11  years of age , her seizures increased in frequency , and the pattern changed , with oculocephalic reflex followed by generalized tonic 
preoperative mri revealed a lesion in the right temporal lobe : a small area of encephalomalacia on the medial anterior pole of the right temporal lobe , involving the temporal amygdala , head of the hippocampus , parahippocampal gyrus , and part of the right insular cortex , suggesting residual findings after a previous ischemic insult .
the patient underwent selective right temporal lobe surgery for epilepsy : 3.5  cm of the anterior temporal lobe was resected , and amygdalohippocampectomy was performed , with no complications during surgery .
anatomopathological study of surgical specimens showed nonspecific changes , segmental neuronal loss within the hippocampal subfields , granule cell dispersion , and the presence of diffuse gliosis associated with pyramidal cell loss , consistent with mesial sclerosis .
immunohistochemical reactions with monoclonal anti - hsv-1 antibody ( dako ) were negative ( fig .  1 ) .
she was discharged from the hospital on the 4th postoperative day ( pod ) in good general condition , with no fever or neurological symptoms .
on the 12th pod , the patient developed fever ( 3940  c ) and severe headache , vomiting , and had deteriorating level of consciousness and worsening of general condition .
neurological examination results were as follows : sleepiness although obeying commands , glasgow coma scale score of 14/15 ( eye opening : 4 , verbal response : 4 , and motor response : 6 ) , pupils bilaterally isochoric and reactive to light , neck stiffness , and spontaneous respiration .
an infectious workup , including lumbar puncture ( table  1 ) and blood and urine cultures , identified no bacteria or fungus .
acyclovir was administered intravenously ( 15  mg / kg / dose ) for 21  days .
magnetic resonance imaging ( mri ) showed sequelae with hyperintense signal , cavitations , volume loss , and disruption of brain parenchyma ( fig .  2 ) .
cerebrospinal fluid ( csf ) analyzed by end - point pcr was positive for hsv and negative for enterovirus ( table  1 ) .
the patient was discharged from the hospital with no clinical or eeg evidence of seizures and was on the following antiepileptic drugs : divalproex sodium ( 13.5  mg / kg / day ; tid ) , carbamazepine ( 15  mg / kg / day ; tid ) , and clobazam ( 0.25  mg / kg / day ; once daily ) .
the patient was monitored in the epilepsy outpatient clinic and maintained on anticonvulsant therapy : divalproex sodium ( 13.5  mg / kg / day ; tid ) and carbamazepine ( 15  mg / kg / day ; tid ) .
an 11-year - old right - handed caucasian female patient was admitted with fever and confusion after surgery for epilepsy .
her medical history was significant for an episode of hsv encephalitis at twenty months of age , which was diagnosed by positive csf pcr for hsv-1 ( table  1 ) and resulted in developmental delay and epilepsy .
the electroencephalogram ( eeg ) at twenty months showed dysfunction of the right frontotemporal region .
magnetic resonance imaging ( mri ) revealed a signal change in the right temporal , insular , and meningeal arteries , with some bleeding and a lesion in the left hippocampus .
she was treated with intravenous acyclovir ( 30  mg / kg / day for 21  days ) and carbamazepine on discharge from the hospital .
the seizures were controlled for 3  years , but in 2007 , she started having complex partial seizures with secondary generalization . at 11  years of age , her seizures increased in frequency , and the pattern changed , with oculocephalic reflex followed by generalized tonic 
preoperative mri revealed a lesion in the right temporal lobe : a small area of encephalomalacia on the medial anterior pole of the right temporal lobe , involving the temporal amygdala , head of the hippocampus , parahippocampal gyrus , and part of the right insular cortex , suggesting residual findings after a previous ischemic insult .
the patient underwent selective right temporal lobe surgery for epilepsy : 3.5  cm of the anterior temporal lobe was resected , and amygdalohippocampectomy was performed , with no complications during surgery .
anatomopathological study of surgical specimens showed nonspecific changes , segmental neuronal loss within the hippocampal subfields , granule cell dispersion , and the presence of diffuse gliosis associated with pyramidal cell loss , consistent with mesial sclerosis .
immunohistochemical reactions with monoclonal anti - hsv-1 antibody ( dako ) were negative ( fig .  1 ) .
she was discharged from the hospital on the 4th postoperative day ( pod ) in good general condition , with no fever or neurological symptoms .
on the 12th pod , the patient developed fever ( 3940  c ) and severe headache , vomiting , and had deteriorating level of consciousness and worsening of general condition .
neurological examination results were as follows : sleepiness although obeying commands , glasgow coma scale score of 14/15 ( eye opening : 4 , verbal response : 4 , and motor response : 6 ) , pupils bilaterally isochoric and reactive to light , neck stiffness , and spontaneous respiration .
an infectious workup , including lumbar puncture ( table  1 ) and blood and urine cultures , identified no bacteria or fungus .
acyclovir was administered intravenously ( 15  mg / kg / dose ) for 21  days . magnetic resonance imaging ( mri ) showed sequelae with hyperintense signal , cavitations , volume loss , and disruption of brain parenchyma ( fig .  2 ) .
cerebrospinal fluid ( csf ) analyzed by end - point pcr was positive for hsv and negative for enterovirus ( table  1 ) .
the patient was discharged from the hospital with no clinical or eeg evidence of seizures and was on the following antiepileptic drugs : divalproex sodium ( 13.5  mg / kg / day ; tid ) , carbamazepine ( 15  mg / kg / day ; tid ) , and clobazam ( 0.25  mg / kg / day ; once daily ) .
the patient was monitored in the epilepsy outpatient clinic and maintained on anticonvulsant therapy : divalproex sodium ( 13.5  mg / kg / day ; tid ) and carbamazepine ( 15  mg / kg / day ; tid ) .
the present study reports a patient with a recurrence of hsv-1 encephalitis , following temporal lobe surgery for epilepsy .
postoperative infections that occur as complications of neurosurgical procedures are usually bacterial in origin and include meningitis , subdural empyema , and cerebral abscess .
viral encephalitis complicating the early postoperative course is rare , and diagnosis of postoperative hsv encephalitis is difficult because the clinical features can mimic other more common postoperative complications .
review of the literature revealed three cases of reactivation of hsv following epilepsy surgery in patients with a previous history of hsv encephalitis   very similar to the case reported in the present study .
neurosurgery was performed at the site of the previous encephalitis , which raises the possibility that surgical manipulation caused reactivation of the infection .
cases of hsv reactivation without a previous history of hsv encephalitis have also been reported [ 47,10,13 ] .
herpes simplex virus-1 was identified in the present case , which is common in most reported cases of postoperative hsv encephalitis , with only one case reporting hsv-2 . in some of the abovementioned cases , surgical manipulation occurred far from the previous encephalitis site , which leads us to hypothesize that stress due to surgery or use of corticosteroids
reported cases with a previous history of hsv encephalitis , including the case reported here , the elapsed time after hsv encephalitis varied from 14  months to 10  years .
the appearance of the early signs of encephalitis in the postoperative period usually occurs in the first two weeks ( mean    sd , 10    7 ; median , 9 ; iqr , 516.5 ; range : 121  days ) .
the immunohistochemical reactions with monoclonal anti - hsv-1 antibody in the surgical specimens were negative , indicating later reactivation of the infection following the surgical manipulation .
risk factors include stress , trauma , bacterial infections , exposure to ultraviolet radiation , and menstruation . in the case
reported here , the right temporal lobe was the site previously affected by hsv , and surgical manipulation could have been the main trigger , although stress due to surgery or use of corticosteroids might also be implicated .
herpes simplex virus establishes a latent infection within sensitive neurons that innervate the site of the primary infection .
transcription of the viral genome depends on a specific cellular protein of octameric structure known as oct-1 that is present in most human cells . however , some neurons express the oct-2 protein , which restrains the transcription of specific purinic and pyrimidinic bases , preventing the reactivation of latent strains of hsv .
herpes simplex virus recurrence after tissue injury can be caused by a decrease in the level of ngf in neurons expressing oct-2 , allowing oct-1 to prevail and , consequently , the transcription of the hsv genome .
herpes simplex virus encephalitis must be considered in neurosurgery patients with postoperative altered state of consciousness , seizures , and fever .
polymerase chain reaction ( pcr ) is the method of choice for diagnosis of hsv encephalitis .
it is positive 2448  h after the commencement of symptoms and remains positive 25  days after treatment .
the sensitivity of conventional pcr is 98% , specificity 94% , positive predictive value 95% , and negative predictive value 98% .
its mechanisms of action include competitive inhibition of viral dna polymerase , incorporation into and subsequent termination of the growing viral dna chain , and inactivation of dna polymerase .
adequate prophylactic administration of acyclovir has been proposed by some authors for neurosurgery that involves the site of a previous herpetic lesion ; however , the following points should be considered : reactivation following neurosurgery is a very rare event , acyclovir only acts on replicating viruses and not latent viruses , and acyclovir crosses the blood 
plasma protein binding is relatively low ( 933% ) , and drug interactions involving binding site displacement are not anticipated .
although it is a very safe drug , side effects have been described , including neurological symptoms .
it is usually only seen in immunocompromised patients with multiple recurrent herpes lesions and past treatment with acyclovir and results from changes in viral thymidine kinase or dna polymerase .
a primary genetic immunodeficiency can predispose individuals to hsv infection . identifying those at risk could help to select patients with previous hsv encephalitis who would benefit from prophylactic therapy when undergoing neurosurgery .
the potential risk of reactivation of hsv encephalitis after intracranial surgery must be considered in neurosurgery patients with postoperative altered state of consciousness , seizures , and fever .
the prophylactic use of acyclovir needs further evaluation , and research and consensus in this area are needed to delineate best practice for prophylaxis .
purposethe present study reports a case of encephalitis due to herpes simplex virus-1 ( hsv-1 ) , following surgical manipulation of the site of a primary infection.methodsherpes simplex virus-1 infection was confirmed by csf pcr and dna sequencing.resultsthe patient was an 11-year - old girl who required temporal lobe surgery for epilepsy . 
 she had meningoencephalitis due to hsv at the age of 20  months , and she was treated with acyclovir . 
 three years later , the patient developed uncontrolled seizures that became more frequent and changed in character at 11  years of age . on the 12th postoperative day , she developed fever and seizures , and she was diagnosed with hsv-1 by positive csf pcr . 
 she was treated with acyclovir ( 30  mg / kg / day for 21  days ) . in this report 
 , we describe the patient and review the relevant literature.conclusionthe authors stress the potential risk of reactivation of hsv encephalitis after intracranial surgery . herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever .