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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 43
[3,4]
subacute, or chronic) and patients frequently report neurological sequelae . The incidence of infectious
[5]
encephalitis is estimated at 1.5-7 cases per 100,000 inhabitants/year in the world , and 10.09 cases per
[4]
100,000 in Italian infants . Encephalitis is a serious problem requiring hospitalization and giving a
significant economic burden on society .
[6]
In more than 50% of cases the etiological cause is unknown and patients are admitted with non-specific
[7]
symptoms at the time of presentation . However, the main manifestations are brain suffering and/or
altered state of consciousness, possibly in addition to fever, focal neurological deficits, epileptic seizures,
abnormalities in the electroencephalogram (EEG) or neuroimaging, and cerebrospinal fluid (CSF)
pleiocytosis. After a rapid evaluation of basic vital functions, serological and instrumental tests, empirical
urgent therapy is usually adopted for symptomatic patients, in association with antiviral, antibiotic, and
steroid drugs . Prognosis is difficult to evaluate, mainly due to the multiple possible aetiologies (for
[8]
example, in the case of herpes simplex encephalitis, which is the most common one, mortality in the range
[9]
of 5%-20% was documented for patients treated with antiviral, 70% in those who did not receive treatment) .

The EEG has a fundamental role in the diagnostic framework. Different aetiologies of encephalitis were
found to be associated with specific EEG patterns: for instance, triphasic waves are pathognomonic of
hepatic encephalopathy and lateralized periodic discharges or periodic lateralized epileptiform discharges
[10]
[11]
are found in herpetic encephalopathy . Moreover, stage II of subacute sclerosing panencephalitis is
characterized by bilaterally symmetrical and synchronous generalized, stereotyped high amplitude delta
[12]
waves, called Radermacker or “R” complexes . Here we are interested in a specific EEG element, called
slow biphasic complex (SBC), described as identical in the first part to the “R” complex even if it has
[13]
different spatial and temporal properties . SBC has been described as associated with the inflammatory
processes of the central nervous system [13-17] . We have recently proposed an automated method to identify
SBCs in an EEG trace, opening the possibility of quantifying them and investigating their origin. In
particular, we have demonstrated that the number and amplitude of complexes reflect the severity of the
[14]
inflammation in pediatric encephalitic patients . Moreover, we have proposed to integrate information
[18]
from different features of SBC to improve the diagnosis .

Herein, we focus on the relation between the location of SBCs and brain lesions found in magnetic
resonance images (MRI). Methods for EEG source detection are applied to the identified SBCs to
localize the brain areas producing them. This could be a promising tool to investigate the topography of
[19]
inflammatory activity . We report the application of this method in two specific cases.

CASE REPORT
[14]
We applied our processing to the EEG recorded from two patients also considered in a previous paper
(to which the reader can refer for details on EEG recordings), for which MRIs were also available. For each
patient, we considered EEG data recorded close to the day in which the MRI was acquired. The two patients
were very different, the first showing diffused lesions due to acute disseminated encephalomyelitis (ADEM)
and the second with inflammatory processes, caused by infectious etiology, focused in one hemisphere. In
this section, we first introduce the processing methods; then the two cases are discussed.

Methods
[14]
An algorithm we introduced before was applied to identify the SBCs . Then, a method for source
localization was used to identify the brain areas involved in the production of the complexes. These
locations were compared to those of lesions identified in the MRIs by an expert neuro-radiologist.

Identification of slow biphasic complexes
SBCs were identified by the method described in a previous paper . In brief, each EEG trace was
[14]