Post-operative Herpes Simplex Virus Encephalitis after Surgical Resection of Meningioma: A Case Report and Review of the Literature

Background: Herpes Simplex Virus (HSV) encephalitis is a rare but life threatening complication in neurosurgical patients. Diagnosis of Herpes Simplex Encephalitis (HSVE) is based on the detection of the herpes simplex virus (HSV) DNA in patient`s CSF samples. A low threshold for both investigations with CSF PCR and empirical treatment with intravenous acyclovir is warranted. Methods and materials: In this case we discussed a 55year-old man with HSVE after surgical resection of meningioma. We represent a rare case of HSV encephalitis. The appearance of a high grade fever (40°C) and altered consciousness and spastic quadriparesia complicated the post-operative course in a 55-year-old man who underwent surgical removal of a meningioma on the second postoperative day. Brain MRI detected brain abnormalities on the fourth day after onset of symptoms, and polymerase chain reaction (PCR) identification of HSV 1 DNA confirmed the diagnosis. Result: A positive prognosis was achieved due to the decision to start specific, high-dose antiviral therapy based on clinical suspicion, before a firm diagnosis was established. . Treatment with acyclovir was maintained for 8 weeks and patient die after severe sepsis. Conclusion: There are only few case reports of postoperative HSV1 encephalitis. These reports suggest that this rare postoperative complication is associated with a poor prognosis, with high mortality and morbidity. Neurosurgical interventions involving peripheral nerve root or ganglia have been reported to cause re-activation of cutaneous herpes simplex infection. Factors compromising the immune system may also increase susceptibility to herpes simplex infection.


Introduction
Herpes Simplex Virus (HSV) encephalitis is the most common form of sporadic viral encephalitis [1]. It can manifest at any time of the year, in patients of all ages, and is associated with significant morbidity and mortality [2][3][4][5]. HSV usually begins as a febrile illness with symptoms of diffuse and focal cerebral involvement, such as headaches, personality changes, obtundation, focal seizures and paresis [6,7]. Postoperative herpes simplex encephalitis has been rarely described. HSV encephalitis is an extremely life-threatening consequence of the HSV infection of the central nervous system. It is said that the HSV encephalitis is extremely rare, and only a minority of individuals return to normal functions. Antiviral therapy is most effective when early, necessitating prompt diagnosis started.
Actually, preventing the inflammation of spreading from a small area of the brain inflammation to a bigger involved area is an extremely important issue. In fact, of all different types of viral encephalitis, HSV encephalitis is one of the few viral causes of diseases for which we actually have accurate diagnostic tests and relatively cheap treatments already available [8].
The necessity for treatment is dictated by factors such as age, the immune system function, the type and severity of the disease, or mild cases-the amount of stress the condition causes [9]. The occurrence of HSV encephalitis after neurosurgery is rare and only a small number of cases have been reported in the literature. In this report we represent a rare case of HSV encephalitis in a 55-year-old man.

Case report
Intracranial infections following neurosurgery are most commonly caused by bacteria. Postoperative herpes simplex encephalitis has been described rarely before. Herpes simplex virus encephalitis is a life-threatening consequence of HSV infection of the central nervous system. Only a minority of individuals return to normal functions when faced by this  Table 1). Antiviral therapy is most effective when early, necessitating prompt diagnosis is started. In this study we represent a rare case of HSV encephalitis. After diagnosing convexity meningioma in a 55-year-old man, the patient underwent uneventful surgery for the removal of meningioma (Figure 1).
The patient was awoken and was responsive after the surgery. The appearance of a high grade fever (40°C) and altered consciousness and spastic quadriparesis complicated the post-operative course 48 hours after surgery. Neurological exam was done, but there was not any specific finding. Laboratory findings were normal. The brain MRI detected brain abnormalities on the fourth day after the onset of symptoms, signal changes in left insula and temporal lobe and also in both sides of basal ganglia were detected as a sign of infarction (Figure 2).

Discussion
Herpes simplex virus-1 is the most common cause of lethal sporadic encephalitis. HSV-1 encephalitis is associated with persistent severe neurological deficits, although improved therapy with intravenous acyclovir has been adopted recently [2][3][4]. Encephalitis caused by HSV is not common. In fact the estimated incidence, derived from large series, is 2 to 4 cases per million populations per year [10]. The differential diagnosis of HSV encephalitis is extensive [11]. It includes such infectious conditions as bacterial abscess, empyema, listeriosis, mycobacterial infection, fungal infection (especially Cryptococcus), parasitic infection (toxoplasmosis, amoebic infection), other viral infections (Epstein-Barr virus, lymphocytic choriomeningitis virus, influenza virus, enterovirus, rabies, subacute sclerosing panencephalitis, arboviruses, adenovirus, rubella virus), and noninfectious conditions such as vascular malformations, tumors, and Reye syndrome [10,12]. This wide range of possibilities makes it impossible to treat empirically without more definitive diagnostic evaluations.
It has also been mentioned that postoperative infections that occur as complications of neurosurgical procedures are originally bacterial and include meningitis, subdural empyema, and cerebral abscess [2]. It has also been proven that HSV infection has a genetic immune etiology in which a deficiency exists in a protein or a toll-like receptor that helps mediate an immune response [3].
Finally it can be said that there are only few case repots of postoperative HSV 1 encephalitis. These reports suggest that this rare postoperative complication is associated with a poor prognosis, with high mortality and morbidity. Neurosurgical interventions involving peripheral nerve root or ganglia have been reported to cause reactivation of cutaneous herpes simplex infection. Factors compromising the immune system may also increase susceptibility to herpes infection, so does previous HSV infection.

Conclusion
To conclude, the most significant factor affecting the HSV encephalitis outcome is starting effective antiviral treatment as early as possible [13]. Although HSV encephalitis is rare, mortality rates reach 70% in the absence of therapy and only a minority of individual's return to normal functions. So considering the possibility of HSV encephalitis in case of decreased level of consciousness and high grade fever after neurosurgical operations is logical. Owing to the lifethreatening nature of the disease, if there is a delay in diagnostic test results therapy should not be withheld until they become available. It means empirical acyclovir treatment is strongly recommended when encephalitis is suspected [4,14]. After the completion of therapy, PCR of the CSF can confirm the elimination of replicating virus, aiding further management of the patient. Unfortunately, despite all the improvements in the diagnosis and treatment of this disease, but there is still many failures. Actually, about 30% of patients with HSV encephalitis result in poor prognosis [15,16].