HERPES SİMPLEKS VİRÜS ENSEFALİTİ: BİR ÜNİVERSİTE HASTANESİ DENEYİMİ

Abstract

Herpes simpleks virüsü (HSV) ensefaliti sporadik, akut başlangıçlı ve mortal seyredebilen beyin parankimi enfeksiyonudur. Bu çalışmada HSV ensefaliti tanısıyla takip ettiğimiz hastalar literatür eşliğinde incelenmiştir. Çalışmaya 2013-2021 yılları arasında Fırat Üniversitesi Hastanesi Enfeksiyon Hastalıkları kliniğinde takip edilen beyin omurilik sıvısı (BOS) HSV polimeraz zincir reaksiyonu pozitifliği ile tanısı doğrulanmış 18 yaş üstü HSV ensefaliti tanılı hastalar alınmıştır. Hastaların demografik verileri, klinik belirti ve bulguları, laboratuvar sonuçları, tedavi ve prognozları incelenmiştir. Çalışmaya 16 hasta dahil edilmiştir. Hastaların dokuzu (%56.3) kadın, yedisi (%43.7) erkektir. Yaş ortalamaları 55.4±16.3’tür. Bilinç bulanıklığı, ateş, bulantı/kusma ve baş ağrısı en sık görülen klinik semptom ve bulgular olmuştur. BOS mikroskopisinde 15 (%93.8) hastada lenfositik pleositoz, 10 (%62.5) hastada eritrosit saptanmış, bir hastada ise hücre görülmemiştir. Manyetik rezonans görüntülemesi (MRG) yapılan hastaların tamamında patolojik bulguya rastlanmıştır. En sık tutulum görülen bölgeler temporal lob, frontal lob ve insular korteks olmuştur. Elektroensefalografi (EEG) yapılan 11 hastanın ikisinde (%18.2) patolojik bulguya rastlanmazken bir (%9.1) hastada periyodik lateralize epileptiform deşarj, 8 (%72.7) hastada yetersiz temel biyoelektrik aktivite üzerinde keskin dalgalar saptanmıştır. Tüm hastalara intravenöz asiklovir semptom başlangıcından sonra ortalama 3.25 (min-max: 1-13) günde başlanmıştır. İntrakranial basıncı azaltmak amacıyla bir (%6.3) hastaya kortikosteroid tedavisi, iki (%12.5) hastaya dekompresif kraniektomi uygulanmıştır. Üç (%18.8) hasta ölmüştür. HSV ensefalitinin nörolojik belirtilerinden önce gelen sistemik prodromal dönem semptomları, tanıyı zorlaştırmakta ve gecikmeye neden olabilmektedir. COVID-19 döneminde, ateş, takipne ve bilinç değişikliği gibi semptomlar, hipoksi veya COVID-19’un nörolojik komplikasyonları ile karışabilir. Klinik şüphe bulunan hastalarda BOS incelemeleri, kranial MRG ve EEG’nin beraber değerlendirilmesinin önemli tanısal ipucu sağladığı düşünülmüştür.

Keywords

• beyin omurilik sıvısı
• herpes ensefaliti
• herpes simplex virüs
• santral sinir sistemi enfeksiyonu

Herpes Simplex Virus Encephalitis: A University Hospital Experience

Abstract

Herpes simplex virus (HSV) encephalitis is a brain parenchymal infection that starts sporadic, acutely and can result in death. In this study, the patients we followed with the diagnosis of HSV encephalitis were examined in light of the literature.
Patients with a diagnosis of HSV encephalitis over 18 years of age, whose diagnosis was confirmed by cerebrospinal fluid (CSF) HSV polymerase chain reaction positivity, followed in the Infectious Diseases Clinic of Fırat University Hospital between 2013-2021 were included in the study. Demographic data, clinical signs, symptoms, laboratory results and prognosis of the patients were analyzed.
Sixteen patients were included the study. Nine (56.3%) of the patients were female and seven (43.7%) were male. The mean age was 55.4±16.3. Confusion, fever, nausea/vomiting, and headache were the most common clinical symptoms and signs. In CSF microscopy, lymphocytic pleocytosis was detected in 15 (93.8%) patients, erythrocytes were detected in 10 (62.5%) patients, and no cells were detected in one patient. Pathological findings were found in all patients who underwent magnetic resonance imaging (MRI). The most common areas of involvement were the temporal lobe, frontal lobe, and insular cortex. While no pathological findings were found in two (18.2%) of 11 patients who underwent electroencephalography (EEG), periodic lateralized epileptiform discharge was detected in one (9.1%) patient, and sharp waves were detected on an insufficient basic bioelectrical activity in eight (72.7%) patients. Intravenous acyclovir was started in all patients in an average of 3.25 days after symptom onset. Corticosteroid therapy was performed in one (6.3%) patient and decompressive craniectomy was performed in two (12.5%) patients to reduce intracranial pressure. Three (18.8%) patients died.

The systemic prodromal symptoms that precedes the neurological manifestations of HSV encephalitis complicates the diagnosis and causes delay. During the COVID-19 period, symptoms such as fever, tachypnea, and altered consciousness can be confused as hypoxia or a neurological complication of COVID-19. When CSF examinations, cranial MRI, and EEG were evaluated together in patients with clinical suspicion, it was thought to provide an important diagnostic clue.

Keywords

• central nervous system infection
• cerebrospinal fluid
• herpes encephalitis
• herpes simplex virus

References

1. Aurelius E, Johansson B, Skoldenberg B, et al. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid Lancet. 1991;337:189–192
2. AK AK, Mendez MD. Herpes Simplex Encephalitis, StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK557643/ (erişim tarihi: 20.02.2022)
3. Beckham JD, Tyler KL. Encephalitis, Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 10. baskı, s.1226-47, Churchill Livingstone Elsevier (2020).
4. Bradshaw MJ, Venkatesan A. Herpes Simplex Virus-1 encephalitis in adults: pathophysiology, diagnosis, and management. Neurotherapeutics. 2016;13(3):493-508. doi: 10.1007/s13311-016-0433-7.
5. Cag Y, Erdem H, Leib S, et al. Managing atypical and typical herpetic central nervous system infections: results of a multinational study. Clin Microbiol Infect. 2016;22(6):568.e9-568.e17.
6. Dagsdóttir HM, Sigurðardóttir B, Gottfreðsson M, Kristjánsson M, Löve A, Baldvinsdóttir GE, Guðmundsson S. Herpes simplex encephalitis in Iceland 1987-2011. Springerplus. 2014;3:524.
7. Dodd KC, Michael BD, Ziso B, et al. Herpes simplex virus encephalitis in pregnancy - a case report and review of reported patients in the literature. BMC Res Notes. 2015;8:118.
8. Domingues RB, Tsanaclis AM, Pannuti CS, et al. Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples. Clin Infect Dis. 1997;25(1):86-91.

9. Durmaz-Çetin B, Hasman H. Herpes ensefalitleri. Klimik Derg. 2004;17(2):68-71.
10. Gnann JW Jr, Whitley RJ. Herpes Simplex Encephalitis: an Update. Curr Infect Dis Rep. 2017;19(3):13.
11. Hjalmarsson A, Blomqvist P, Sköldenberg B. Herpes simplex encephalitis in Sweden, 1990-2001: incidence, morbidity, and mortality. Clin Infect Dis. 2007;45(7):875-80.
12. Kremer S, Lersy F, de Sèze J et al. Brain MRI findings in severe COVID-19: a retrospective observational study. Radiology. 2020;297(2):242-51.
13. Lovati C, Osio M, Pantoni L. Diagnosing herpes simplex-1 encephalitis at the time of COVID-19 pandemic. Neurol Sci. 2020;41(6):1361-4. doi:10.1007/s10072-020-04461-y
14. Maraite N, Mataigne F, Pieri V, Dang T, Diederich NJ. Early decompressive hemicraniectomy in fulminant herpes simplex encephalitis. Bull Soc Sci Med Grand Duche Luxemb. 2009;(2):131-3.
15. Nadelman CM, Newcomer VD. Herpes simplex virus infections. Postgrad Med 2000;107(3):189-200.
16. Sabah M, Mulcahy J, Zeman A. Herpes simplex encephalitis. BMJ. 2012;344:e3166.
17. Safain MG, Roguski M, Kryzanski JT, Weller SJ. A review of the combined medical and surgical management in patients with herpes simplex encephalitis. Clin Neurol Neurosurg. 2015;128:10-6.
18. Sagmak-Tartar A, Ozer-Balin S, Akbulut A, Gonen M, Demirdag K. A case of Herpes Simplex Virus encephalitis without pleocytosis in cerebrospinal fluid and complicated with intracranial hematoma. Klimik Derg. 2020;33(3):327-8.
19. Sauerbrei A. Acyclovir resistance in herpes simplex virus type I encephalitis: a case report. J Neurovirol. 2017;23(4):640-1.
20. Sili U, Kaya A, Mert A; HSV Encephalitis Study Group. Herpes simplex virus encephalitis: clinical manifestations, diagnosis, and outcome in 106 adult patients. J Clin Virol. 2014;60(2):112-8.
21. Singh TD, Fugate JE, Hocker S, Wijdicks EFM, Aksamit AJ Jr, Rabinstein AA. Predictors of outcome in HSV encephalitis. J Neurol. 2016;263(2):277-89. Stone KM, Reiff-Eldridge R, White AD, et al. Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999. Birth Defects Res A Clin Mol Teratol. 2004;70(4):201-7.
22. Traynor R, Shanahan B, Walsh J, Ryan A and Pope G. Stroke, COVID-19 infection or herpes simplex encephalitis: a diagnostic dilemma. Ulster Med J. 2022;91(1): 56-7.
23. Tunkel AR, Glaser CA, Bloch KC, et al. Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47(3):303-27.
24. Weil AA, Glaser CA, Amad Z, et al. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis. 2002 15;34(8):1154-7. doi: 10.1086/339550.