Apheresis Procedure could Prevent Sequele of Hsv1 Encephalitis-Case Report

The pathogenesis of HSE is not clearly understood. Central Nervous System (CNS) cell damage induces direct action of HSV1 virus and host immune response activity. While many studies are beginning to implicate the immune response to HSV1 and its various cell population (e.g.microglia, CD8+T cells) in causing widespread CNS pathology [5,6], the exact cause of the extensive destruction of CNS is still unclear [7]. Recently, researchers have pointed to signifi cance of immune– mediated post-infectious HSE through identifi cation of antiN-methyl D-aspartate receptor (NMDAR) encephalitis as an autoimmune encephalitis [8].

Citation: Slavic V (2020) Apheresis Procedure could Prevent Sequele of Hsv1 Encephalitis-Case Report. Ann Antivir Antiretrovir 4(1): 010-013. DOI: https://dx.doi.org/10.17352/aaa.000009 produced in Russia, was approved by American Society for Apheresis (ASFA) in 2013. as minimally invasive and safe because it is performed on a single needle and removed plasma is replenished only with saline solution [10]. Nanotechnological processes applied in membrane making have qualitatively improved the process of separation plasma proteins and human blood. More specifi cally, nanomembrane could "capture" the pathological antigens or antigen-antibody complexes, which would induce purifi cation of the blood from disease-causing agents. The most frequently used replacement fl uid is saline solution to avoid adverse complications even when 25% (approximately 700 -750 ml) volume of the circulating plasma is separated [9].
In this paper, we aim to present a case report of the signifi cant impact of a TA procedure consisting of four nanomembrane-based sessions on a Hemophoenix device in the prevention of neurological consequences in a patient suffering from HSE during the fi rst 3 months of onset. Due to the resulting deterioration 2 weeks after treatment onset, he was referred to Infectious Clinic in the Clinical Center of Serbia (CCS) for further treatment and additional diagnostic procedures. LPs were performed 2 times in the next 10 days and obtained results have pointed to a decrease of lymphocytic pleocytosis (fi rst WBC 52, Ly 92 % and second WBC 49, Ly 94 %). MRI brain scan was ordered after completed treatment (21 days) and shown signal alteration zones in the left temporal lobe with engaging of amygdala-hippocampal and parahippocampal regions, olfactory area, piriform cortex, insula and lateral occipito-temporal gyrus. Still, the patient every day was febrile. In mental status prominent memory defi cits, especially retention of new informations, besides language disorders and altered cognition.

Case report
Additionally, serum and CSF NMDAR-antibodies were performed. Obtained results were negative in both samples. In the next 3 days, patient received pulse corticosteroid therapy and fi nally he was afebrile. So, after 49 days of hospital treatment he was discharged home as afebrile but with signifi cant mental disorders. MRI brain scan one month later, corresponds to the condition after HSE in the left temporal lobe basal including hypothalamus and basal frontal lobe to Sylvian fi ssure.
Thus, the patient was referred for TA to the specialized Clinic for Extracorporeal Hemocorrection, at the P. Pavlov First St. Petersburg State Medical University, Russia. The protocol was consisting of 4 session membrane apheresis based on nanotechnological produced membrane applied on Hemophoenix device. In each session plasma has been removed up to 800-900 ml, replaced only with saline solution in continuous infusion. Also, ACD-A or sodium citrate was used as anticoagulants. The whole blood was additionally extracorporeal irradiated with red and infrared Laser beams in every session. Sessions were made every other day. After fi nishing the whole protocol, the patient was signifi cantly improved with regard to both physical as well as mental health. As a fi nal result, the patient returns for full time work only 5 months after fi nishing hospital treatment of HSE.
Six months after fi nishing the TA protocol MRI brain scan indicated good regression and corresponds to the condition after HSE in left temporal lobe, basal. But, one year later MRI brain scan was in complete regression in left temporal lobe, basal with sequelae, gliosis and postencephalitic cyst 16.4 x 14.7 mm to cavernous sinus.

Discussion
HSV1 is the most common cause of lethal sporadic encephalitis. Despite improved therapy with intravenous Acyclovir, HSE is associated with persistent severe neurological defi cits [11]. So, it is understandable need to establish a diagnosis of HSE as early as possible in order to minimize sequelae that greatly impair quality of life. Fever and abnormal mental status are the primary signs and symptoms of HSE, occurring in >90% of patients [12]. In our case the fi rst symptoms were fever and mental alteration which make him suspected for viral brain infection. CT brain scan is not the imaging modality of choice in suspected viral encephalitis considering that abnormal fi ndings have been observed in 25-80% of patients with HSE imaged soon after admission [13]. But normal CT brain scan cannot rule out the diagnosis [14]. The patient in our case had inconclusive fi nding of CT brain scan.
Clinical presentation and normal or inconclusive CT brain scan demand the next diagnostic step by performing a LP and CSF testing. Typical CSF profi le in HSE includes moderate lymphocytic pleocytosis (10-200/mm3), may demonstrate elevated erythrocytes (normal minimally elevated counts are common), moderately elevated protein (50-100 mg/dL) and normal glucose [15]. According to literature, CSF analysis was abnormal in our case with remarkable high lymphocytic pleocytosis (715/mm3, 98%Ly).
RT PCR for HSV in CSF is the gold standard for the diagnosis of HSE and has high sensitivity (96%) and specifi city (99%) [16]. Although, in our case RT PCR performed to a broader specter of pathogens, positivity was gained only for HSV-1.
According to guidelines for HSE treatment the patients started with Acyclovir by scheme (10mg/kg body weight/8 h).
The current guidelines recommend intravenous Acyclovir for 14-21 days in HSE (17) in order to avoid immune mediated relapse. So, in our case patient received 21 days of Acyclovir.
Even more, he has become RT-PCR negative for HSV1 in CSF within 14 therapy days. However, he begins to show signs of clinical relapse. He has fever again and worsening of mental status (depressed level of consciousness, confusion, memory lost, language diffi culties). According to literature clinical relapse is not seldom but has been reported in range 5-27%.
Many of these reported cases have no evidence of HSV1 activity in CSF (negative RT-PCR) and poor clinical response to antiviral medication [18]. For the most authors this was a proof that underlying mechanism is not mediated by direct viral cytotoxicity, but it is about immune mediated process. Lately, published studies that have demonstrate that many patients suffering HSE relapse develop autoimmune encephalitis known as anti-NMDAR [19,20]. Clinical presentation of anti-NMDAR encephalitis among other symptoms includes mental alteration such as progress of memory defi cits and language disintegration [21]. In our case clinical relapse was not caused by producing antibodies to NMDAR since these antibodies were negative in serum and CSF. Further, our patient had a good response to pulse corticosteroid therapy which was one more proof of post-HSV-1 immune-mediated encephalitis.
Once viral reactivation or persistence have been excluded, treatment with immunomodulatory therapy should be strongly considered [8]. The fi rst-line immunomodulatory treatment includes corticosteroids and/or intravenous immunoglobulins or plasma exchange. By Armague this treatment resulted in substantial improvement in all analyzed patients in the series [22]. In our case, the patient received only pulse corticosteroid therapy before being discharged from the hospital.
In conditions of immunosuppression because of the HSE treatment, it is necessary to correct the quality of the immune response by improving its regulatory component in order to correct and re-establish immune and rheological response.
Laser irradiation of blood during apheresis is aimed to restore energy homeostasis in the cells through reactivation of antioxidant protection as well as normalized erythrocyte rheological properties for improving tissue oxygenation. For this purpose, red and infra-red Laser beams are used as extracorporeal treatment through PVC blood lines. Published studies have shown that extracorporeal blood irradiation results in greater immunomodulatory and anti-infl ammatory benefi ts characterized by activation of lymphocytes and macrophages, increased synthesis of IL-2, gamma-interferon, and beta2 microglobulin, in addition to improving microcirculation and tissue oxygenation [23].
The whole procedure consists of 4 sessions of membrane apheresis with extracorporeal Laser irradiation with red and infra-red beams in order to eliminate fi rstly pathological products from blood, later from interstitial body spaces and fi nally from cells.
In our case patient received whole procedure conducted on Hemophenix device which turned out to be a very effective for the best possible recovery. Primarily, the patient returns for full time work only 5 months after fi nishing hospital treatment of HSE. Even more, after one year his MRI brain scan shows good regression of post-infl ammatory changes.

Conclusion
HSV1 encephalitis as the most common sporadic encephalitis can cause serious neurological and mental disorders that severely impair quality of life. The apheresis procedure in combination with extracorporeal Laser blood irradiation could be a very effective therapeutic tool in the prevention of brain damage caused by HSV1 encephalitis.