Phd in CLINICAL EXPERIMENTAL NEUROSCIENCE AND PSYCHIATRY

Thesis title: Electroencephalographic alterations in persons with viral infection (HIV, HCV and SARS-CoV2).

Aim of Study • Study the neurophysiological response to viral diseases • Assess brain involvement in viral pathologies • Assess the effectiveness of antiviral therapies on brain health • Validate the electroencephalogram as a routine examination in the evaluation of the patients with viral pathology (both acute and chronic). The infectious diseases analysed in this study are HIV, HCV and COVID19. Our clinical and research experience is based on evaluating the correlation between viral infection and brain damage (chronic and/or acute) using the electroencephalographic technique. This study consists of three research carried out by us over the last 5 years. The HCV study and the Sars-CoV2 study are pilot studies, with a very small sample size compared to the HIV study (in which several research centers participated). METHODS HIV EEG, clinical, and neuropsychological data were collected in 103 treatment-naïve HIV subjects (88 males; mean age 39.8 years ± 1.1 standard error of the mean, SE). An age-matched group of 70 cog- nitively normal and HIV-negative (Healthy; 56 males; 39.0 years ± 2.0 SE) subjects, selected from a local university archive, was used for control purposes. LORETA freeware was used for EEG source estimation in fronto-central, temporal, and parieto-occipital regions of interest. HCV Resting state eyes-closed EEG rhythms were recorded in 6 HCV subjects, asymptomatic for neurocognitive deficits and with liver fibrosis F2-F4 (METAVIR score) before and after new DAAs treatment. As the EEG signals show a superimposition of the physiological alpha activity and of the pathological activity, they were decomposed using Independent Component Analysis (ICA), which allows to separate into distinct signals the different contributions (neural and artefactual) that appear superimposed in the EEG data. SARS-CoV2 EEG data were recorded on individuals in a resting state, with activation tests (SLI and HPN) only for COVID19 patients, through 19 electrodes placed on the scalp, according to the international 10/20 system (electrodes: Fp1, Fp2, F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, O2, linked ears as reference). RESULTS HIV Widespread sources of delta (<4 Hz) and alpha (8–12 Hz) rhythms were abnormal in the treatment-naïve HIV group. Fronto-central delta source activity showed a slight but significant (p < 0.05, corrected) negative correlation with verbal and semantic test scores. So did parieto-occipital delta/alpha source ratio with memory and composite cognitive scores. These sources allowed a moderate classification accuracy between HIV and control individuals (area under the ROC curves of 70–75%). HCV Six patients received new DAAs treatment and all of them reached SVR12. After the treatment, the alpha frequency remains unchanged in 2 subjects, increases in 2 subjects and decreases in 2 subjects. After the treatment, the amount of the pathological activity as quantified by the PRR index decreases in four subjects. SARS-CoV2 The EEG of the 10 persons subjected to the study is result asymmetrical (and therefore is pathological), with a prevalence of signal on the left side of the brain, a condition not in relationship with the respiratory pathology or a poor cerebral blood perfusion, considering the excellent hemodynamic and saturation values of participants. The pattern most represented in this group of patients is characterized by a simultaneous presence of the irritative elements as well as a general slowing of the basic cerebral electrogenesis. CONCLUSION In the HIV study we have shown the involvement of the glia during the infection in persons NAÏVE (not treated with antiretroviral therapy) led to the alteration of cerebral electrogenesis, with the disappearance of the alpha rhythm. Electroencephalographic tracing in HCV patients is generally characterized by a slowed-down underlying rhythm and irritative appearance. In the Sars-CoV2, the evidence deriving from these initial observations leads to identify in this virus a pathogenic element that strongly damages the brain structures capable of causing an inflammation capable on the one hand of altering the physiology of cerebral basal electrogenesis activity. The EEG technique can be considered in all respects as a biomarker capable of providing not only a qualitative assessment of the degree of suffering or hyperexcitability of the cerebral parenchyma, but a reference system capable of quantifying the changes in brain electrogenesis.