Normocellular CSF in herpes simplex encephalitis

Abstract

BackgroundHerpes simplex virus (HSV) is the most common cause of sporadic encephalitis worldwide. The high mortality rate (70–80 %) of herpes simplex encephalitis (HSE) can be reduced to 20–30 % by antiviral therapy. However, normocellular CSF can lure physicians to look for non-infectious causes, resulting in delayed treatment. This study aimed to investigate, characterize and differentiate HSE patients, with normocellular and pleocytosis CSF, according to neuroimaging patterns, underlying disease, CSF viral load and clinical outcome. Patients with proven (by PCR positive CSF) or presumed viral infections of the CNS admitted to King Chulalongkorn Memorial Hospital between January 2002 and 2011 were analyzed.ResultsHSV was detected in the CSF of 43 patients but only 23 patients had encephalitis. Among these 23 patients, 6 cases (26.1 %) had normal CSF WBC (<5 cells/mm3). One patient in this normocellular CSF group had HIV infection. Although this patient had low CD4 counts (<200 cells/mm3), the peripheral WBC counts showed only mild leukopenia. The CSF HSV viral load in the pleocytosis group was higher than the normocellular group, with an average of 12,200 vs 3027 copies/ml respectively. There was no correlation between the viral load and the clinical outcome. With respect to neuroimaging, 4 (66.7 %) patients in the normocellular group had unremarkable/non-specific results.ConclusionsNormocellular CSF in HSE is not rare, and can be seen in normal as well as immunocompromised hosts. Clinicians should not exclude CNS infection, especially HSE, merely based on the absence of CSF pleocytosis and/or unremarkable neuroimaging study.

CSF in acute and chronic infectious diseases

“…If the clinical presentation is highly suspicious for encephalitis, a spinal fluid analysis returning with only borderline elevated cells should be repeated as, especially in HSE, a normal CSF can be seen in the first hours of infection. This can cause a treatment delay, worsening the prognosis of the encephalitis or leading to an alternative wrong diagnosis (de Toledo et al, 2001;Benninger et al, 2013;Desena et al, 2014;Saraya et al, 2016). In HSE at least 10% have normal cell counts within a week of onset of illness, usually, but not always, increasing later (Koskiniemi et al, 1984).…”

Missing Cases of Herpes Simplex Virus (HSV) Infection of the Central Nervous System When the Reller Criteria Are Applied for HSV PCR Testing: a Multicenter Study

“…In this context, the Reller criteria (4), which are based on previously reported data (2, 3), have been validated by another group (5). The finding of normocellular CSF fluids in patients with confirmed HSV encephalitis in some series is not extraordinary (15)(16)(17); nevertheless, very few cases of patients with CNS HSV infection who do not meet the Reller criteria have been documented (15). In our view, previous studies assessing the validity of the Reller criteria were hindered by their single-center design (2)(3)(4); in this sense, the strength of this current study stems from its multicenter design, including a large number of patients.…”

Acute encephalitis – diagnosis and management

“…However, early in the illness neutrophils can predominate, or occasionally the white cell count may be normal. 9 Protein is normal to moderately raised and glucose is normal. Polymerase chain reaction (PCR) for the most frequent viral causes should yield results within 24-48 hours from most laboratories.…”