Cognitive impairment without altered levels of cerebrospinal fluid biomarkers in patients with encephalitis caused by varicella-zoster virus: a pilot study

Abstract

Varicella-zoster virus (VZV) is one of the most common agents causing viral infections of the central nervous system (CNS). VZV encephalitis is associated with severe neurological sequelae, despite antiviral treatment. Cognitive impairment has been reported and VZV has been associated with dementia. Our aim was to investigate the cognitive impairment and cerebrospinal fluid biomarkers in a follow-up study of patients with VZV encephalitis. Thirteen patients with VZV encephalitis, diagnosed by detection of VZV DNA in cerebrospinal fluid (CSF) by PCR and concomitant symptoms of encephalitis, were included. Neuropsychological assessment in parallel with a lumbar puncture to obtain CSF was performed 1.5-7 years after acute disease. The CSF biomarkers neurofilament light chain (NFL), S100B, glial fibrillary acidic protein (GFAP), amyloid-β (Aβ) 40 and Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) were analysed and compared to controls (n = 24). Cognitive impairment was shown in the domains of executive functions and speed/attention and to a minor degree in the domains of learning/memory and language, indicated by a significantly poorer performance on seven neuropsychological test variables. No convincing evidence of alterations in concentrations of biomarkers in the CSF were shown. Our results indicate that patients with VZV encephalitis suffer from cognitive impairment long time after acute disease. Importantly, these impairments do not seem to be accompanied by biomarker evidence of ongoing neuronal or astrocytic injury/activation or induction of dementia-related brain pathologies by the infection.

Figure 1

(a–e) Concentrations of cerebrospinal fluid biomarkers in patients with encephalitis caused by reactivated varicella-zoster virus (n = 12), 41 months (range: 19–85) after acute disease, and their controls (n = 24) (a) neurofilament light chain (NFL), (b) glial fibrillary acidic protein (GFAP), (c) S-100B, (d) amyloid-β 40 (Aβ40), (e) amyloid-β 42 (Aβ42), f) phosphorylated tau (p-tau), g) total tau (t-tau).

Figure 2

Neuropsychological test results for the total study group, presented as T-scores. P-values indicate difference between study group and normative scores.

Figure 3

(a–e) Neuropsychological test results within five cognitive domains (a) executive functions, (b) learning and memory, (c) speed and attention, (d) language, (e) visuospatial functions, plotted as individual T-scores.  oper circle = younger ages (24; 28; 32; 34; 35 years); filled circle = older ages (52, 74, 76, 82, 85 years). Significant group differences compared to normal data (Fig. 2) are indicated by * (p < 0.05) or ** (p < 0.001). BNT Boston naming test, BVMT-R Brief visuospatial memory test revised, Cat. Category, CPT continuous performance test, CVLT California verbal learning test, SD standard deviation, SDMT Symbol digit modalities test, seq. sequencing; TMT Trail making test, VOSP Visual object and space perception.