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Zuo et al. Herpes simplex encephalitis in adults

With the development of the diagnosis, and antiviral standard method for the diagnosis of HSE. However,
therapies, the management of patients with HSE has there is evidence of pseudo-negative result influenced
improved rapidly in recent years. However, acyclovir by the time of CSF sample collection: the PCR may
resistance and a better understanding of pathogens be negative for HSV-1 during the first 3 days of the
and pathogenesis also represent new challenges. illness, however, if the CSF is re-examined after a
[12]
few days, the PCR may then become positive. The
Here, we review the current status of diagnosis and European consensus report recommends repeating
[21]
therapies for HSE and discuss current controversies the CSF PCR routinely after 14 days of treatment,
and expectations for the treatment of this disease. although this does not guarantee a positive result at 10-
14 days after illness. In particular, it has been previously
DIAGNOSIS shown that PCR positive result most commonly occurs
during the first week of infection, even in the case of
Current status of diagnosis concurrent treatment with acyclovir. In light of these
[22]
HSE is a medical emergency and correct and immediate data, clinicians should give full consideration to the
diagnosis is fundamental for the prognosis and patient’s clinical manifestations and curative effects to
therapeutic interventions. At patient’s first presentation determine if the PCR test on CSF should be repeated.
a meticulous medical history and a careful neurological
examination are critical. Peripheral blood count and THERAPY
cellular morphology, such as lymphocytosis, are also
helpful in differential diagnosis. Cerebrospinal fluid (CSF) Current status of therapy
typically shows a lymphocytosis of 10-200/mm (or more) Correct immediate introduction of specific therapies
3
and increased protein of 0.5-1.0 g/L or more. During could reduce the extent of injury and impact on survival.
[7]
the early stage of the disease, electroencephalography
(EEG) with the evidence of spike and slow wave Antiviral therapy
localization to the temporal lobe might suggest HSE, Acyclovir (ACV), a guanosine analogue, targets viral
however, EEG has a sensitivity of approximately 60% DNA replication and is the most efficient drug for the
and a specificity of 80%. [11] treatment of HSE. The recommended dose is 10 mg/kg IV
every 8 h for 14 days. In immunocompromised patients
Virus isolation in cell culture, serological tests for specific or children under 12 years, the treatment usually lasts
antigen or antibody production and brain biopsy play for at least 21 days. Therapy should begin as soon
a crucial role for the etiology and diagnosis of HSE. as HSE is suspected, in fact treatment delays are
However, all have been now replaced by the detection usually associated with a significantly poorer disease
of HSV using polymerase chain reaction (PCR) in the outcome. Renal toxicity, caused by crystallization of
[3]
CSF, that shows a sensitivity of approximately 96%, ACV in the kidneys, can be prevented by hydration and
and a specificity of approximately 99%. [12] slow infusion rates, however kidney function should be
monitored and any sign of renal impairment should be
Neuroimaging is also importance in suspected HSE considered. [23]
cases. Magnetic resonance imaging (MRI) is more
specific and sensitive than computed tomography Valacyclovir (VCV), an L-valyl ester prodrug of ACV,
(CT), because of its non-ionizing radiation, multiplanar which is converted to ACV by the hepatic enzyme
imaging capability, improved contrast of soft tissue, VCV hydrolase has been shown to have a better oral
and high anatomic resolution. [13,14] Usually MRI shows bioavailability than ACV. A recent study indicated that
the abnormalities characteristic of edema and/or the administration of VCV at 1,000 mg three times daily
enhancement in temporal and frontal lobes, the insular result in adequate acyclovir concentrations in the CSF
cortex, and the angular gyrus. [15-17] Nowadays, the use and could be considered an acceptable early treatment
of DWI and FLAIR imaging is strongly encouraged, for suspected HSE in resource-limited settings. [24]
[18]
as approximately 5% HSE patients show a normal MRI
at presentation. However, it is worth noting that the Corticosteroids
[19]
sensitivity of a new CT post-processing tool based on Corticosteroids as an adjunct treatment for HSE are still
frequency-selective nonlinear blending (best-contrast controversial. One study showed that corticosteroids
CT) seems to be equal to that of DWI and FLAIR, as increase patient benefit but they are not routinely
[25]
suggested in a recent study. [20] recommended [3,16,26] as a large prospective randomised
trial is still needed. However, steroid administration is
Unresolved issues in diagnosis recommended in situations where HSE patients show
PCR-based test in CSF has been established as a gold severe cerebral edema that could result in severe brain
Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ February 20, 2017 25