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Valerio et al. Neuroimmunol Neuroinflammation 2021;8:42-9 I http://dx.doi.org/10.20517/2347-8659.2020.30 Page 47

predictive factors, establishing different outcomes. Early EEG alterations suggest a negative prognosis,
supporting the use of aggressive anti-inflammatory neuroprotection therapies [26,27] .

SBCs have been observed in patients with brain inflammations [13,15,28,29] . We have developed an automated
processing method to identify SBCs and we have shown in previous studies a good correlation between
their onset and the severity of encephalitis [14,18] . Here we have focused on the distribution of the sources of
SBCs and their relation with the lesions identified in MRIs.

Two different cases are discussed. In the first, lesions were widespread in the brain, whereas in the second
they were more focused on the left hemisphere. Sources of SBCs were also found more widespread in the
first case and predominantly on the left hemisphere in the second, indicating that the localization of SBC
sources can provide some insights on the location of the lesions.

However, we should notice that SBC sources were identified quite superficial, mostly in frontal location
and not exactly in the sites of the lesions. Notice that the low-frequency activity investigated in this study
(predominantly in the delta range and increased in our patients, due to brain suffering from encephalitis)
is larger in the frontal lobe, even during periods in which SBCs are not present. However, the sources of
SBCs are significantly larger than those producing background activities, indicating that the predominant
identification of SBC sources in the frontal lobe is not a bias.

Possibly, our results could be biased by both the source localization algorithm and the surface EEG
technique in general, which emphasizes cortical contributions. Indeed, the activity of cortical neurons is
recorded with a larger amplitude than that of deeper sources (possibly, even appearing under the noise level
or covered by the synchronous cortical activity of areas also affected by the inflammation). Consider also
that a small number of electrodes was used in our clinical recordings, hampering the identification of deep
[20]
sources . Moreover, lesions affect the activity of cortical neurons connected to the inflamed ones: these
connected neurons could also be far apart from the lesions. Thus, it could be possible to observe altered
activity not only in a contiguous area, but also distant from the lesions, i.e., produced by cortical neurons
in connection with the focal area of inflammation, but located far apart (reflecting a well-known difference
between anatomical and functional correlates in the brain). Notice also that, if the area of inflammation
is located in the white matter, it affects only axons and action potentials propagating along them are less
visible from EEG than post-synaptic potentials. However, as mentioned above, even if the exact locations
of the lesions are not easy to be identified, our results suggest that the spread of the lesions and a possible
asymmetry can be found (indeed, in the first case, the identified SBC sources are widespread and, in the
second case, SBC sources are predominantly found in the same hemisphere in which lesions are located).

Further work is suggested to deepen the promising results found in this pilot study on a few patients. In
particular, using a high-density system for EEG acquisition could allow us to better locate the sources of
[30]
SBCs, to be correlated with MRI results . Moreover, the use of functional MRI in synchronous with EEG
[31]
registration could help in investigating better SBC sources.
As EEG acquisition is cheaper and faster than MRI recording, the possible confirmation of the relation
between SBC sources location and lesions could have relevance in the clinical practice. Specifically, EEG
could support the follow-up of the patient, e.g., with daily monitoring of the effect of the treatment on
the possible reduction of the lesions. This method, if confirmed in an extended study, could support the
clinician in rapid diagnosis, allowing the fast implementation of specific therapy to improve the prognosis
and simple monitoring of the progress of the patient.