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Year : 2021  |  Volume : 14  |  Issue : 1  |  Page : 66-68  

A case of herpes simplex encephalitis: Predisposing factors-chemotherapy or chronic alcoholism?

1 Department of Microbiology, Rajarajeshwari Medical College and Research Institute, Bengaluru, Karnataka, India
2 Department of Pathology, Employees' State Insurance Corporation Medical College and PGIMSR, Bengaluru, Karnataka, India

Date of Submission09-Oct-2019
Date of Decision02-Feb-2020
Date of Acceptance02-Jun-2020
Date of Web Publication22-Jan-2021

Correspondence Address:
Panduranga Chikkannaiah
Department of Pathology, Employees' State Insurance Corporation Medical College and PGIMSR, Rajajinagar, Bengaluru - 560 010, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_280_19

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Opportunistic infections acquired during the chemotherapy forms the main limiting factor in the management of acute myeloid leukemia. Bacterial infections are most common, followed by fungal and rarely viral. Alcohol in high doses and long-term consumption also decreases the immunological response. Here, we present a unique case of herpes simplex encephalitis in a 50-year-old male patient who has presented with altered behavior, slurring of speech, disorientation, fever on and off, and confusion for 2 days. He was a known case of acute myeloid leukemia and treated with chemotherapy 5 years back. Moreover, he was also a chronic alcoholic for many years and stopped 1 week before the symptoms. The possible mechanism of immunodeficiency by chemotherapy and alcohol are discussed.

Keywords: Acute myeloid leukemia, alcoholism, chemotherapy, herpes simplex encephalitis

How to cite this article:
Benachinmardi K, Chikkannaiah P. A case of herpes simplex encephalitis: Predisposing factors-chemotherapy or chronic alcoholism?. Med J DY Patil Vidyapeeth 2021;14:66-8

How to cite this URL:
Benachinmardi K, Chikkannaiah P. A case of herpes simplex encephalitis: Predisposing factors-chemotherapy or chronic alcoholism?. Med J DY Patil Vidyapeeth [serial online] 2021 [cited 2021 Mar 9];14:66-8. Available from: https://www.mjdrdypv.org/text.asp?2021/14/1/66/307673

  Introduction Top

The current treatment modalities for acute leukemia are chemotherapy and human stem cell transplant (HSCT). Although there is a significant improvement in the management of bacterial, viral, and fungal infections in immunocompromised patients, these complications still remain the major limiting factor in the management of hematological malignancies.[1],[2] Patients treated with HSCT are at high risk for viral reactivation than chemotherapy. The recorded prevalence of viral infections for post-HSCT range from 2.1% to 14%, while for chemotherapy it is 0.8%. Herpes simplex virus (HSV) is the most common, and mucocutaneous is the common site of involvement.[3],[4] Alcohol in higher dosage and on long-term consumption decreases the immunological responses, increases the chances of opportunistic infections.[5] Here, we present a rare case of herpes simplex encephalitis in a 50-year-old male, who was a chronic alcoholic and treated 5 years back for acute myeloid leukemia by chemotherapy.

  Case Report Top

A 50-year-old male presented with altered behavior, slurring of speech, disorientation, fever on and off, and confusion for 2 days. He was a chronic alcoholic and discontinued for 1 week. On examination, he was conscious, disoriented, talking irrelevantly, and there was the absence of neck stiffness. There was no history of diabetes mellitus or hypertension. History was significant with a diagnosis of acute myelogenous leukemia (AML) 5 years back and was taken treatment (Taxotere and cyclophosphamide) for the same at another center. He had developed bacterial pneumonia during the induction phase and recovered with antibiotic treatment. He continued alcohol after recovery from AML. With these findings, differential diagnoses of alcohol withdrawal syndrome, viral encephalitis, and cerebrovascular accident were made. Routine hematological investigation revealed Hb 13.8%, platelet 1.7 lakh/μl, the total count was 8600 cells/μl, with normal distributions, and no blasts noted. His liver function test, renal function test, and serum electrolytes were within normal limits. Magnetic resonance imaging (MRI) showed large areas of hyperintense signal changes in the left temporal lobe and inferior frontal lobe; similar mild changes were seen on the right side also [Figure 1]. These findings were suggestive of herpes encephalitis. However, cerebrospinal fluid (CSF) analysis revealed nil cells with protein 79 mg/dl. HSV-1 was detected by real-time polymerase chain reaction (PCR) in CSF. Injection acyclovir started 800 mg three times a day, which was continued for a total of 3 weeks. The patient recovered well without any sequel. On follow-up, he developed deficits in the form of loss of memory and dysphasia and dependant on family members for his routine activities. On telephonic follow-up, the patient was found in the same condition, after 2½ years follow-up.
Figure 1: Serial sections of magnetic resonance imaging image showing, large areas of hyperintense signal changes in the left temporal lobe and inferior frontal lobe, similar mild changes were seen on the right side also

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  Discussion Top

Opportunistic infections are the main complication of chemotherapy, and they are the major factor contributing to mortality and morbidity in acute leukemia survivors. The mechanism immunosuppression is due to altered cell-mediated immunity and neutropenia. The infections are common of bacterial origin followed by fungal and rarely viral in origin. Reactivation of latent HSV infections is the most common of all viral infections that occur in AML patients on therapy. The other viruses being cytomegalovirus (CMV), human herpes virus-6 (HHV-6), respiratory syncytial virus, and others.[3],[6]

HSV is known for a variety of illnesses, and clinical manifestations depend on the type of virus, anatomical region, and immune status of the host. In an immune-competent individual mucocutaneous sites such as oro-labial and genitals are commonly involved. However, in immunodeficient individuals, it affects viscera causing necrotizing lesions.[7]

Hanajiri et al.[8] in their extensive study on 353 patients who underwent HSCT for different leukemia, 17 developed central nervous system infections. The common etiology in their series was HHV-6 in six cases followed by enterococcus, staphylococcus, and streptococcus in two cases each, CMV and Toxoplasma in one case each. The median onset of infection was 38 days (10–1028 days) following treatment. The cumulative incidence of central nervous system infections was 4.1% at 1 year and 5.5% at 5 years following HSCT.

Alcohol is known to have dual effects on the immune system, and an effect depends on the type of beverage, sex, and also on drinking habit. In low and moderate doses, it stimulates the immune system. In higher doses, it suppresses the immune system. The key mechanism is due to the decreased function of antigen-presenting cells, other mechanisms being decreased inflammatory response, altered cytokine production, and abnormal reactive oxygen intermediate generation. Hence, in the present case, the immunodeficiency may be due to dual cause such as AML chemotherapy and alcohol abuse.[4],[9]

The common clinical presentation of HSV encephalitis is fever, headache, seizure, and focal neurological deficits. However, rarely atypical presentations such as psychosis, urinary, and fecal incontinence, behavioral syndromes including loss of emotional control, hypomania, and Klver-Bucy syndrome are also recorded.[10]

HSV encephalitis commonly involves a unilateral temporal lobe. Bilateral temporal lobe involvement (as observed in the present case), insular and cingulate gyrus are less frequent.[11]

The diagnosis primarily depends on CSF analysis. CSF analysis shows pleocytosis with high protein and normal glucose levels. However in immunodeficiency patients, CSF may be normal or shows only biochemical alterations without pleocytosis (as observed in our case).The definitive diagnosis is by CSF PCR for HSV.[12] The usual radiological finding of HSV encephalitis is (1) hypointense lesion of temporal lobes and orbitofrontal regions with petechial hemorrhages (2) Hypointensity in T1 and hyperintensity in T2 images.[11]

Wang and Liu,[13] in their study, proposed that MRI images may be more sensitive than HSV PCR, as PCR may be negative after the clinical manifestations. Hence, combination of investigations like MRI, CSF analysis and CSF PCR is recommended for definitive diagnosis of HSV encephalitis.[11]

The main treatment is intravenous acyclovir. In patients with HSCT and in leukemia patients on chemotherapy screening for HSV is advised, those who are seropositive should receive acyclovir prophylaxis for 6 weeks.[7]

HSV encephalitis is having high mortality being 35.7% in immunodeficiency patients and 6.7% in an immunocompetent patient. The mortality can be reduced by timely treatment with acyclovir, which should be started within 2 days of onset of neurological symptoms.[4] The morbidities observed are neurological deficits, abnormal behavior, memory disturbances, dysphasia, seizure, and naming defects (as observed in our case).[14]

  Conclusion Top

A rare case of HSV encephalitis with a dual mechanism of immunodeficiency has been described. Although CSF white cell count is misleading by showing no alteration or being within the normal limits, the combined approach of MRI, CSF analysis, and CSF PCR for HSV is essential for definitive diagnosis and better patient management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ahmadzadeh A, Varnasseri M, Jalili MH, Maniavi F, Valizadeh A, Mahmoodian M, et al. Infection pattern of neutropenic patients in post-chemotherapy phase of acute leukemia treatment. Hematol Rep 2013;5:e15.  Back to cited text no. 1
Pagano L, Caira M, Nosari A, Rossi G, Viale P, Aversa F, et al. Etiology of febrile episodes in patients with acute myeloid leukemia: Results from the Hema e-chart registry. Arch Intern Med 2011;171:1502-3.  Back to cited text no. 2
Busca A. Viral infections in patients with hematological malignancies. Leuk Suppl 2012;1:S24-5.  Back to cited text no. 3
Lin R, Liu Q. Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation. J Hematol Oncol 2013;6:94.  Back to cited text no. 4
Romeo J, Wärnberg J, Nova E, Díaz LE, Gómez-Martinez S, Marcos A. Moderate alcohol consumption and the immune system: A review. Br J Nutr 2007;98 Suppl 1:S111-5.  Back to cited text no. 5
Yoo JH, Choi SM, Lee DG, Choi JH, Shin WS, Min WS, et al. Prognostic factors influencing infection-related mortality in patients with acute leukemia in Korea. J Korean Med Sci 2005;20:31-5.  Back to cited text no. 6
Gold D, Corey L. Acyclovir prophylaxis for herpes simplex virus infection. Antimicrob Agents Chemother 1987;31:361-7.  Back to cited text no. 7
Hanajiri R, Kobayashi T, Yoshioka K, Watanabe D, Watakabe K, Murata Y, et al. Central nervous system infection following allogeneic hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther 2017;10:22-8.  Back to cited text no. 8
Szabo G. Consequences of alcohol consumption on host defence. Alcohol Alcohol 1999;34:830-41.  Back to cited text no. 9
Modak J, McMahon K, Prasad A. Diagnostic delay in a case of HSV encephalitis. Neurology 2014;82:314.  Back to cited text no. 10
Patoulias D, Gavriiloglou G, Kontotasios K, Tzakri M, Keryttopoulos P, Koutras C. HSV-1 encephalitis: High index of clinical suspicion, prompt diagnosis, and early therapeutic intervention are the triptych of success-report of two cases and comprehensive review of the literature. Case Rep Med 2017;2017:5320839.  Back to cited text no. 11
Tan IL, McArthur JC, Venkatesan A, Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology 2012;79:2125-32.  Back to cited text no. 12
Wang WS, Liu CP. The clinical presentation, diagnosis, treatment, and outcome of encephalitis: Five years of experience at amedical center in northern Taiwan. Int J Gerontol 2011;5:9-12.  Back to cited text no. 13
Panagariya A, Jain RS, Gupta S, Garg A, Sureka RK, Mathur V. Herpes simplex encephalitis in North West India. Neurol India 2001;49:360-5.  Back to cited text no. 14
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