**5.1 CSF findings**

There are only a few reports with CSF findings in COVID-19 patients, as it is not systematically accessed for every patient. One systematic review reported CSF findings in COVID-19 patients who presented seizures in infection setting, including 69 patients. They found that only 13% had positive CSF SARS-CoV-2 PCR. Pleocytosis was found in one-third of them, and nearly half had increased proteinorachia. Postictal pleocytosis and hyperproteinorachia were already described, so these findings may be secondary to seizures itself as opposed to an intrathecal process related to SARS-CoV-2. Autoimmune antibodies were tested in 11 patients and were positive in only two (NMDA antibodies and Caspr2 antibodies). It remained unclear if these findings were related to COVID-19 (as some cases of autoimmune encephalitis can be preceded by infection that works as a trigger of autoimmunity) or if it was purely coincidental [57].

## **5.2 Electroencephalographic findings**

There are some reports of electroencephalogram (EEG) findings in patients with SARS-CoV-2 infection. Altered mental status and seizures are the most common indication for EEG. Most of patients performed routine EEG, with a few cases submitted to continuous video-EEG monitoring [42, 58]. A systematic review found that continuous EEG studies reported more abnormalities than routine EEG [59].

Even though EEG abnormalities are frequent, none of available studies showed specific findings in COVID-19 patients. The most commonly described abnormalities are diffuse slow activity (accounting for 60% of findings in these patients) and, less frequently, focal slow activity [56]. One study showed that brain reactivity was reduced or absent more often in COVID-19 patients with poor prognosis [27, 60]. Confusion and seizures seem to be the most frequent predictors of encephalopathy [58].

According to available literature, epileptiform abnormalities and periodic patterns account for 13–20% of EEG findings in COVID-19 patients, more often found in critically ill patients and in those whose presented seizures [42, 56, 59]. Several EEG patterns were reported in status epilepticus (SE) associated to COVID-19, including periodic discharges (lateralized, bilateral, and generalized) and rhythmic discharges, but no single pattern appears to be specific. EEG findings localized to frontal lobe were described in almost half of SE [59].

Just a few patients had focal abnormalities explained by structural focal lesions as ischemic stroke, encephalitis, and unspecified gliosis [56].

One report found severity of EEG findings may be correlated with oxygen saturation at admission and with severity of COVID-19 [59]. It is difficult to relate EEG findings with CSF and neuroimaging findings as just a few patients underwent a complete screening for all modalities. One study was able to obtain records of thoracic CT scan, CSF SARS-CoV-2 PCR, and EEG of a subgroup of 13 patients, and no correlations were found between those variables [58].

There are some limitations to obtain information in this field. Timing of EEG is difficult to recall, as it is usually performed according to onset of neurological complication and not COVID-19 classical symptoms. Information about disease severity and anti-seizure medication and sedatives at time of EEG is not always clear [56].

#### **5.3 Neuroimaging findings**

Neuroimaging findings in COVID-19 patients are heterogeneous, varying according to disease severity and neurological concomitant complications [42]. Available cases and reviews suggest more than two-thirds of COVID-19 patients, who undergo brain imaging (CT or MRI), do not show abnormalities presumably associated to infection [61].

Among those who present abnormalities, the most common findings were unspecific diffuse white matter (WM) abnormality (accounting for about 75% of reported findings) and acute or subacute ischemic strokes. WM signal abnormality is usually described as subcortical and periventricular, in association with microhemorrhages. Cerebellar, midline, and deep brain structures involvement is uncommon [61, 62]. Leukoaraiosis is one important finding attributable to aging, and one review suggested its prevalence was higher in COVID-19 patients than expected for age. However, relationship between COVID-19 infection and structural brain lesions is not clear yet. Cortical FLAIR signal abnormality was described in a vast differential diagnosis, including patients with encephalitis, post-ictal state, PRES, and acute ischemia [61].

In a cohort of patients with SE, MRI revealed abnormalities in about 43% of patients, mainly inflammatory lesions, and lesions suggestive of PRES, brain atrophy, cerebral hemorrhage, and brain tumor. Inflammatory lesions did not reveal a specific localization nor a specific cortical involvement in most of cases [55].

## **6. Conclusions**

SARS-CoV-2 seems to have neurotropism and neuroinvasion mechanisms, similar to previous known human coronavirus infections, and neurological complications are frequent [22]. Despite of all new information constantly being published about this issue, robust and complete data are lacking about seizures in patients with COVID-19.

Systemic infection may be a trigger for breakthrough seizures in patients with a history of epilepsy and respiratory infection in particular is a well-known precipitant of acute symptomatic seizures in such individuals [27]. Severe systemic illness, metabolic derangements, emotional stress, the eventual inability to obtain anti-seizure drugs (as patients may avoid hospitals and pharmacies and have more difficulty to get their medications), or gastrointestinal symptoms impeding absorption of oral medications are just examples of the diversity of ways through which COVID-19 may be associated with recurrence of seizures in the epileptic population [25, 27]. As any other infectious disease, COVID-19 can present with significant electrolytic and metabolic imbalance, as hyponatremia or uremic state, both potentially responsible for lowering the seizure threshold in susceptible, non-epileptic, patients. Acute symptomatic seizure can also occur in the context of cerebrovascular disease [27].

Nevertheless, seizure occurrence in COVID-19 is uncommon. Most of the available reviews report an incidence lower than 1% of SARS-CoV-2 infections, even lower than that described in previous human coronaviruses. Higher risk is appointed for patients with poor general condition and severe COVID-19 symptoms [26, 27].

## *COVID-19 and Seizures DOI: http://dx.doi.org/10.5772/intechopen.102540*

Regardless of etiology, COVID-19 should be considered in the differential diagnosis for patients presenting with seizures during the pandemic, as early consideration may lead to earlier detection and appropriate precautions [27]. Particular attention should rise for patients with altered mental status and the risk of nonconvulsive status epilepticus.
