Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes

Kaewpoowat, Quanhathai; Salazar, Lucrecia; Aguilera, Elizabeth; Wootton, Susan H.; Hasbun, Rodrigo

doi:10.1007/s15010-015-0867-6

Cited by 87 publications

(79 citation statements)

References 39 publications

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“…Similarly, even with the increased sensitivity of PCR, HSV was detected in only 6.2% of 6,607 CSF samples at the Mayo Clinic from 1993 to 1997 (35). Cutaneous manifestations of HSV in patients with HSV CNS involvement have been reported to be present in Ͻ10% of cases (36)(37)(38). Therefore, detection of HSV at other sites is not necessarily predictive of CNS involvement.…”

Section: Discussionmentioning

confidence: 99%

Impact of a Rapid Herpes Simplex Virus PCR Assay on Duration of Acyclovir Therapy

et al. 2017

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Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV (dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sampleto-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h; P Ͻ 0.001). Furthermore, 79 patients (43.6%) in the postimplementation group had dHSV PCR results reported Ͻ4 h after specimen collection. The mean time from specimen collection to acyclovir discontinuation was 17.1 h shorter in the postimplementation group (31.1 h versus 14 h; P Ͻ 0.001). The median duration of acyclovir therapy was also significantly reduced in the postimplementation group (29.2 h versus 14.3 h; P ϭ 0.01). Our investigation suggests that implementation of rapid HSV PCR testing can decrease turnaround times and the duration of unnecessary acyclovir therapy.KEYWORDS HSV, acyclovir, encephalitis, herpes simplex virus, meningitis, rapid diagnosis, toxicity H erpes simplex viruses (HSVs) are important causes of meningitis and encephalitis, particularly among children and immunocompromised patients (1). The HSV infection rate among neonates is estimated to be 1 case per 32,000 deliveries, and approximately 1,500 cases of neonatal HSV disease occur annually in the United States (2, 3). Prompt initiation of antiviral therapy is paramount, as mortality rates for disseminated neonatal infections can be as high as 80% if the infections are left untreated; 70% of survivors are left with detrimental neurological sequelae (4-6).Patients with HSV meningitis and encephalitis typically have initial presentations of headache, fever, and altered mental status. However, neonates with HSV central nervous system (CNS) infections may have nonspecific presentations, including lethargy, irritability, poor oral intake, and temperature instability (7). Cutaneous vesicular lesions may be indicative of HSV infections in infants, but the absence of vesicular rash does not preclude neonatal HSV CNS infection in 35% of cases (8). Other infectious etiologies associated with CNS infections can present with similar symptoms (9). Thus, laboratory testing of cerebrospinal fluid (CSF) samples is necessary to confirm the diagnoses.

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Section: Discussionmentioning

confidence: 99%

Impact of a Rapid Herpes Simplex Virus PCR Assay on Duration of Acyclovir Therapy

et al. 2017

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“…Of the infectious causes, HSVE was the most commonly identified agent, followed by tuberculosis and VZV. In the absence of zoster, HSV and VZV can be clinically indistinguishable [94]. More than half of the noninfectious etiologies were immune-mediated, including anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, antivoltage-gated potassium channel complex encephalitis (more precisely anti-leucine-rich glioma-inactivated protein 1 [LGI1] and anti-contactin-associated protein-like 2 [Caspr2] antibodies), and CNS vasculitis.…”

Section: Differential Diagnosismentioning

confidence: 99%

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

2016

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Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be lifesaving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

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“…It has been demonstrated that signs and symptoms alone do not distinguish herpes from other causes of encephalitis (1,5,6). Therefore, an integrative diagnostic approach with the full utilization of neurodiagnostic techniques is a must.…”

Section: Discussionmentioning

confidence: 99%

“…Laboratory findings of encephalitis are characterized with pleocytosis and elevated protein levels (1,2,3,6), with the exception of around 3 to 5 percent of patients with normal CSF analysis despite severe encephalitis, particularly initially (1,2). In our study, CSF pleocytosis was determined in 80.1% of patients, while protein levels were elevated in 57.4% of patients.…”

Section: Discussionmentioning

confidence: 99%

Review of Viral Encephalitis Cases Seen at a Tertiary Care Center in Turkey: Focus on Herpes Simplex Type 1

Kavaklioglu¹,

Çoban²,

Şen³

et al. 2017

Arch Neuropsychiatr

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Introduction: The objective of this study was to determine the incidence of herpes simplex encephalitis (HSE), known as the most common, potentially mortal, and treatable cause of sporadic encephalitis, in a sample Turkish population. Methods:The demographic, clinical, laboratory, imaging, electrophysiology, and polymerase chain reaction (PCR) DNA results of patients examined with a pre-diagnosis of encephalitis were retrospectively examined.Results: A total of 68 patients were included in the study. The most common presenting symptom was altered behavior (67.6%), while temporal T2 hyperintensity was determined in the magnetic resonance imaging (MRI) of 27.9% of the patients and electroencephalography (EEG) abnormalities were determined in 66.2% of the patients. Lymphocytic pleocytosis was determined in the cerebrospinal fluid (CSF) in 35 patients. Fifty-seven patients had been diagnosed with viral encephalitis, 3 with bacterial meningitis, 3 with tuberculous meningitis, 2 with sporadic Creutzfeld-Jakob disease, 2 with acute disseminating encephalomyelitis, and 1 with Brucella encephalitis. Seven (10.2%) cases of viral encephalitis were found to be positive for herpes simplex virus (HSV) DNA by PCR.Conclusion: Viral encephalitis is the most common cause of infectious encephalitis; however, other atypical causes should also be noted. Negative PCR results for HSV DNA should not exclude the need for antiviral therapy in patients with a strong pre-diagnosis of HSE because diagnostic modalities, including PCR, may fail in acute settings and HSE remains the sole treatable cause of infectious encephalitis.

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Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes

Abstract: Alpha herpes CNS infections due to HSV and VZV infections have similar clinical and laboratory manifestations. ACO was observed more frequently in those patients with comorbidities and an encephalitis presentation.

Cited by 87 publications

References 39 publications

Impact of a Rapid Herpes Simplex Virus PCR Assay on Duration of Acyclovir Therapy

Impact of a Rapid Herpes Simplex Virus PCR Assay on Duration of Acyclovir Therapy

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

Review of Viral Encephalitis Cases Seen at a Tertiary Care Center in Turkey: Focus on Herpes Simplex Type 1

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