Systematic Literature Review of the Association of Fever and Elevated Temperature with Outcomes in Critically Ill Adult Patients.

Although most commonly associated with infection, elevated temperature and fever also occur in a variety of critically ill populations. Prior studies have suggested that fever and elevated temperature may be detrimental to critically ill patients and can lead to poor outcomes, but the evidence surrounding the association of fever with outcomes is rapidly evolving. To broadly assess potential associations of elevated temperature and fever with outcomes in critically ill adult patients, we performed a systematic literature review focusing on traumatic brain injury, stroke (ischemic and hemorrhagic), cardiac arrest, sepsis, and general intensive care unit (ICU) patients. Searches were conducted in Embase® and PubMed® from 2016 to 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including dual-screening of abstracts, full texts, and extracted data. In total, 60 studies assessing traumatic brain injury and stroke (24), cardiac arrest (8), sepsis (22), and general ICU (6) patients were included. Mortality, functional, or neurological status and length of stay were the most frequently reported outcomes. Elevated temperature and fever were associated with poor clinical outcomes in patients with traumatic brain injury, stroke, and cardiac arrest but not in patients with sepsis. Although a causal relationship between elevated temperature and poor outcomes cannot be definitively established, the association observed in this systematic literature review supports the concept that management of elevated temperature may factor in avoidance of detrimental outcomes in multiple critically ill populations. The analysis also highlights gaps in our understanding of fever and elevated temperature in critically ill adult patients.

Cardiac Oscillations Complicating Brain Death Diagnosis.

Death by neurologic criteria (DNC) or brain death is a clinical diagnosis. It is often complicated by variations in policies as well as confounders on examination. We discuss here the case of a 27-year-old male who had a cardiac arrest following toxic gaseous exposure. He ultimately progressed to brain death but was identified as having cardiac oscillations during clinical assessments that complicated the diagnosis. We discuss the case as well as the maneuvers used to clarify that the "triggered breaths" on the ventilator were indeed cardiac oscillations.

Postanoxia-Induced Chorea Treated with Intravenous Fentanyl.

The case presented is that of a young male with postanoxic brain injury secondary to cocaine overdose who began to exhibit choreiform movements of the left upper extremity. Traditional treatment options for chorea were unsuccessful, leading to the administration of fentanyl, which rapidly resolved the patient's choreiform movements. There is a limited research involving the treatment of chorea in anoxic brain injury as well as fentanyl's role in the movement pathway. We hypothesize that chorea can be caused or exacerbated by opioid withdrawal in a patient with chronic opioid use through modulation of dopamine transmission.

Outpatient EEG in Routine Clinical Care of Patients With Stroke-Related Acute Symptomatic Seizure Concerns.

PURPOSE: Acute symptomatic seizures (ASyS) after stroke contribute the highest risk to poststroke epilepsy (PSE) development. We investigated the use of outpatient EEG (oEEG) among stroke patients with ASyS concerns. METHODS: Adults with acute stroke, ASyS concerns (underwent cEEG), and outpatient clinical follow-up were included (study population). Patients with oEEG (oEEG cohort) were analyzed for electrographic findings. Univariable and multivariable analyses helped identify predictors of oEEG use in routine clinical care. RESULTS: Among 507 patients, 83 (16.4%) underwent oEEG. The independent predictors of oEEG utilization included age (OR = 1.03 [1.01 to 1.05, P = 0.01]), electrographic ASyS on cEEG (OR 3.9 [1.77 to 8.9], P < 0.001), ASMs at discharge (OR 3.6 [1.9 to 6.6], P < 0.001), PSE development (OR 6.6 [3.5 to 12.6], P < 0.001), and follow-up duration (OR = 1.01 [1.002 to 1.02], P = 0.016). Almost 40% of oEEG cohort developed PSE, but only 12% had epileptiform abnormalities. Close to a quarter (23%) of oEEGs were within normal limits. CONCLUSIONS: One in six patients with ASyS concern after stroke undergoes oEEG. Electrographic ASyS, PSE development, and ASM at discharge are primary drivers of oEEG use. While PSE drives oEEG use, we need systematic, prospective investigation of outpatient EEG's role as prognostic tool for PSE development.

Impact of acute symptomatic seizures and their management on patient-reported outcomes after stroke.

OBJECTIVE: Acute symptomatic seizures (ASyS) after stroke are not uncommon. However, the impact of ASyS and its management with anti-seizure medications (ASMs) on patient-reported outcome measures (PROMs) remains poorly investigated. The objective of our study is to evaluate the association between PROMs and ASyS and ASMs following stroke. METHODS: We performed a retrospective cohort study of all stroke patients who underwent inpatient continuous EEG (cEEG) monitoring performed due to suspected ASyS, including the ones with observed convulsive ASyS, from 04/01/2012 to 03/31/2018, who completed PROMs within 6 months of hospital discharge. Patient-reported outcome measures, including one Neuro-QoL and six PROMIS v1.0 domain scales, were completed by patients as the standard of care in ambulatory stroke clinics. Since ASMs are sometimes used without clearly diagnosed ASyS, we performed group comparisons based on ASM status at discharge, irrespective of their ASyS status. T-tests or Wilcoxon rank sum tests compared continuous variables across groups and chi-square tests or Fisher's exact tests were used for categorical variables. RESULTS: A total of 508 patients were included in the study [mean age 62.0 ± 14.1 years, 51.6% female; 244 (48.0%) ischemic stroke, 165 (32.5%) intracerebral hemorrhage, and 99 (19.5%) subarachnoid hemorrhage]. A total of 190 (37.4%) patients were discharged on ASMs. At the time of the first PROM, conducted a median of 47 (IQR = 33-78) days after the suspected ASyS, and 162 (31.9%) were on ASMs. ASM use was significantly higher in patients diagnosed with ASyS. Physical Function and Satisfaction with Social Roles and Activities were the most affected health domains. Patient-reported outcome measures were not significantly different between groups based on ASyS (electrographic and/or convulsive), ASM use at hospital discharge, or ASM status on the day of PROM completion. SIGNIFICANCE: There were no differences in multiple domain-specific PROMs in patients with recent stroke according to ASyS status or ASM use suggesting the possible lack of the former's sensitivity to detect their impact. Additional research is necessary to determine if there is a need for developing ASyS-specific PROMs.

Acute Symptomatic Seizure Associated With Chronic Antiseizure Medication Use After Stroke.

Background and Objective: Patients with acute symptomatic seizures (ASyS) after stroke are discharged on antiseizure medications (ASMs) and stay on them for an extended period. We analyzed the current ASM management practice, 6 months, and at the last follow-up after stroke-related ASyS concerns to identify chronic and long-term ASM use predictors. Methods: A single-center, retrospective cohort study of adults who underwent continuous EEG monitoring for ASyS concerns after stroke (April 1, 2012 to March 31, 2018) with at least 6 months of follow-up was performed. ASM use beyond 6 months after the initial ASyS concern was defined as "chronic" among patients discharged on them. "Long-term" ASM use at the last follow-up in all patients with ASyS concerns was analyzed. Logistic regression and Cox regression multivariable modeling to analyze predictors of "chronic" and "long-term" ASM use, respectively, was performed. Results: A total of 465 (mean age 61.7 ± 13.3 years and 52% female patients) patients (41.9% ischemic stroke, 36.1% intracerebral hemorrhage, and 21.9% subarachnoid hemorrhage) were included. Of the 179 (38.5%) patients discharged on ASMs, 132 (73.7%; 28.4% of study population) had chronic ASM use, despite 90% not experiencing any seizure (poststroke epilepsy [PSE]) during this time. The independent predictors of chronic ASM use were electrographic ASyS (odds ratio [OR] = 9.27, 95% CI = 2.53-60.4) and female sex (OR = 2.2, 95% CI = 1.02-4.83). After a median 61-month (5.1 years) follow-up, 101 (21.7%) patients in the study population were on long-term ASM use, including 67 (14.4%) who developed PSE. Long-term ASM use was associated with NIH Stroke Scale Score (OR = 1.5, 95% CI = 1.015-1.98), cortical involvement (OR = 1.28, 95% CI = 1.02-1.6), convulsive ASyS (OR = 1.46, 95% CI = 1.02-2.09), epileptiform findings on outpatient EEG (OR = 4.03, 95% CI = 1.28-12.76), and PSE development (OR = 7.06, 95% CI = 3.7-13.4). Discussion: Chronic ASM use is highly associated with electrographic, rather than convulsive, ASyS. However, long-term ASM use is independently associated with PSE and its risk factors, including convulsive ASyS. With the ubiquity of stroke-related ASyS concerns in routine clinical practice, comparative effectiveness studies to guide ASM management are needed.

Personalized model to predict seizures based on dynamic and static continuous EEG monitoring data.

BACKGROUND/OBJECTIVE: Early recognition of patients who may be at risk of developing acute symptomatic seizures would be useful. We aimed to determine whether continuous electroencephalography (cEEG) data using machine learning techniques such as neural networks and decision trees could predict seizure occurrence in hospitalized patients. METHODS: This was a single center retrospective cohort analysis of cEEG data in patients aged 18-90 years who were admitted and underwent cEEG monitoring between 2010 and 2019 limited to 72 h excluding those who were seizing at the onset of recording. A total of 41,491 patients were reviewed; of these, 3874 were used to develop the static model and 1687 to develop the dynamic model (half with seizure and half without seizure in each cohort). Of these, 80% were randomly selected as derivation cohorts for each model and 20% were randomly selected as validation cohorts. Dynamic and static machine learning models (long short term memory (LSTM) and Extreme Gradient Boosting algorithm (XGBoost)) based on day-to-day dynamic EEG changes and binary static EEG features over the prior 72 h or until seizure, which ever was earlier, were used. RESULTS: The static model was able to predict seizure occurrence based on cEEG data with sensitivity and specificity of 0.81 and 0.59, respectively, with an AUC of 0.70. The dynamic model was able to predict seizure occurrence with sensitivity and specificity of 0.72 and 0.80, respectively, and AUC of 0.81. CONCLUSIONS: Machine learning models could be applied to cEEG data to predict seizure occurrence based on available cEEG data. Dynamic day-to-day EEG data are more useful in predicting seizures than binary static EEG data. These models could potentially be used to determine the need for ongoing cEEG monitoring and to prioritize resources.

Acute epileptiform abnormalities are the primary predictors of post-stroke epilepsy: a matched, case-control study.

Stroke patients who underwent continuous EEG (cEEG) monitoring within 7 days of presentation and developed post-stroke epilepsy (PSE; cases, n = 36) were matched (1:2 ratio) by age and follow-up duration with ones who did not (controls, n = 72). Variables significant on univariable analysis [hypertension, smoking, hemorrhagic conversion, pre-cEEG convulsive seizures, and epileptiform abnormalities (EAs)] were included in the multivariable logistic model and only the presence of EAs on EEG remained significant PSE predictor [OR = 11.9 (1.75-491.6)]. With acute EAs independently predicting PSE development, accounting for their presence may help to tailor post-acute symptomatic seizure management and aid anti-epileptogenesis therapy trials.

Seizure Risk in Patients Undergoing 30-Day Readmission After Continuous EEG Monitoring.

PURPOSE: The use of continuous electroencephalographic (cEEG) monitoring has improved the understanding of the seizure risk during acute hospitalization. However, the immediate posthospitalization seizure risk in these patients remains unknown. Patients undergoing 30-day readmission after initial cEEG monitoring were analyzed to fill this knowledge gap. METHODS: A prospectively maintained cEEG database (January 1, 2015-December 31, 2015) was used to identify adults who underwent a repeat cEEG during their 30-day readmission after cEEG during their index hospitalization (index cEEG). Various demographical, clinical, and cEEG variables were extracted including indication for cEEG: altered mental status and clinical seizure-like events. RESULTS: A total of 57 of the 2,485 (2.3%) adults undergoing index cEEG during the study period had concerns for seizures and underwent repeat cEEG during a 30-day readmission. These patients were almost three times more likely to have suffered electrographic seizure on the index admission (odds ratio, 2.82; 95% confidence interval, 1.54-5.15; P < 0.001) compared with non-readmitted patients. Seizure-like events led to the readmission of 40.4% patients. Close to one in five (19.3%) readmitted patients were found to have an electrographic seizure. Only variable predictive of seizure on readmission was seizure-like events (odds ratio, 6.4; 95% confidence interval, 1.2-33.0; P = 0.02). CONCLUSIONS: A small percentage of patients have clinical presentation concerning for seizures with in 30 days after index cEEG. The risk of electrographic seizures in this patient population is higher than patients who have cEEG monitoring but do not undergo a 30-day readmission requiring repeat cEEG. Future research on early identification of patients at risk of 30-day readmission because of concerns for seizure is needed.

Paradoxical and Retrograde Air Embolism from Pressurized Peripheral Bolus.

INTRODUCTION: Cerebral air embolism is a rare, yet serious neurological occurrence with unclear incidence and prevalence. Here, we present a case of fatal cerebral arterial and venous cerebral gas embolism in a patient with infective endocarditis and known large right-to-left shunt and severe tricuspid regurgitation following pressurized fluid bolus administration. Case Presentation. A 32-year-old female was admitted to the medical intensive care unit from a long-term acute care facility with acute on chronic respiratory failure. Her medical history was significant for intravenous heroin and cocaine abuse, methicillin-sensitive Staphylococcus aureus tricuspid valve infective endocarditis on vancomycin, patent foramen ovale, septic pulmonary embolism with cavitation, tracheostomy with chronic ventilator dependence, multifocal cerebral infarction, hepatitis C, nephrolithiasis, anxiety, and depression. After intravenous fluid administration, she became unresponsive with roving gaze, sluggish pupils, and hypotensive requiring vasopressors. CT of the brain showed diffuse arterial and venous cerebral air embolism secondary to accidental air administration from fluid bolus. Magnetic resonance imaging of the brain showed diffuse global anoxic injury and flattening of the globe at the optic nerve insertion. Given poor prognosis, her family chose comfort measures and she died. CONCLUSIONS: Fatal cerebral air embolism can occur through peripheral intravenous routes when the lines are inadequately primed and fluids administered with pressure. Caution must be exercised in patients with right-to-left shunting as air may gain access to systemic circulation.

Timing of Acute Stroke in COVID-19-A Health System Registry Study.

BACKGROUND AND PURPOSE: The association between SARS-CoV-2 infection and stroke remains unknown. We aimed to compare the characteristics of stroke patients who were hospitalized with Coronavirus Disease 2019 (COVID-19) based on the timing of stroke diagnosis. METHODS: We performed a retrospective analysis of adult patients in a health system registry of COVID-19 who were hospitalized and had imaging-confirmed acute stroke during hospitalization. Baseline characteristics and hospital outcomes were collected and analyzed. RESULTS: Out of 882 COVID-19 patients who were hospitalized between March 9 to May 17, 2020, 14 patients (2% of all COVID-19 patients and 21% of those who underwent imaging) presented with stroke or developed stroke during hospitalization. Eleven had acute ischemic stroke (AIS) and 3 had acute hemorrhagic stroke. Six patients (43%) presented to the hospital with acute stroke symptoms and were found to have SARS-CoV-2. Compared to patients who presented with AIS, more patients with AIS during hospitalization were male, of older age, had pneumonia and acute respiratory distress syndrome, were severely ill, and had high inflammatory and thrombotic markers (including C reactive protein, D dimer, ferritin, and fibrinogen). Among all patients, hospital mortality was high (50%) and the majority of patients who were discharged had poor neurological outcome. CONCLUSIONS: A distinction should be made between patients who present with acute stroke with concurrent SARS-CoV-2 infection and those who develop stroke as a complication of severe COVID-19. It is likely that a subset of stroke patients will incidentally test positive for the virus given the widespread pandemic.

Characterization of Postanoxic Tonic Eyelid Opening: A Poorly Recognized Prognostic Sign.

BACKGROUND: Postanoxic myoclonus is a known poor prognostic sign, and other postanoxic spontaneous movements have been reported but poorly described. We aim to describe the electroclinical phenomenon of postanoxic eyelid openings in context of its possible prognostic value. METHODS: We collected clinical data on postcardiac arrest patients with suspicious eyelid movements noted on continuous EEG monitoring. The eyelid movements captured on the video were correlated with the EEG findings and final clinical outcome. Neuroimaging data were reviewed when available. We also conducted a thorough literature review on this topic. RESULTS: A total of 10 patients (5 females) with average age of 56.1 (±14.4) years were included. The mean cardiopulmonary resuscitation duration was 18.9 (±11.3) minutes. Postanoxic eyelid-opening movements occurred at variable intervals (0.5-570 seconds) in each individual. Close examination of eyelid opening (available in 6 patients) revealed them to be tonic movements, lasting an average of 3 (±0.8) seconds and always succeeded the onset of burst of EEG activity in a burst-suppression background. This is a transient phenomenon, lasting a median duration of 30 (interquartile range 7.75-36) hours. MRI findings in 3 patients demonstrated diffuse cortical ischemic injury with relative sparing of the brainstem. All patients died within 2-7 days following cardiac arrest. CONCLUSIONS: Contrary to previous descriptions, the postanoxic tonic eyelid openings (PATEO) are repetitive but nonperiodic, nonmyoclonic movements. Their close and specific temporal correlation with the burst of EEG activity suggests that this could be considered an ictal phenomenon requiring an intact midbrain based on MRI findings.

Long-term electro-clinical profile of sudden cardiac arrest survivors.

OBJECTIVE: Recent research has explored the use of continuous EEG (cEEG) monitoring for prognostication of spontaneous cardiac arrest (SCA). However, there is limited literature on the long-term (post-hospital discharge) electrographic findings among SCA survivors and their clinical correlates. Our study aims to fill this critical knowledge gap. METHODS: We retrospectively used our EEG database to identify adults (≥18 years) with SCA history who underwent an outpatient laboratory-based EEG between 01/01/2011 and 12/31/2018. After electronic medical records (EMR) review, patients with epilepsy history and unclear/poorly documented SCA history were excluded. Outpatient EEGs were reviewed by authors. Acute EEG findings were extracted from the EEG database and EMR. In addition, we extracted data on acute and long-term neuroimaging findings (CT/MRI), post-SCA seizures, and anti-seizure medications (ASM) status. Descriptive analysis and Fisher's exact test were performed. RESULTS: We included 32 SCA survivors (50% women; mean age = 52.1 ± 13.6 years) in the study. During a median clinical follow-up of 28.2 months, 3 patients suffered only clinical seizures, 3 only chronic post-hypoxic myoclonus, and 5 had both [11 (34.4%) in total]. Interictal epileptiform discharges (IEDs) were noted in one-third of the patients, which localized to vertex and frontocentral regions in all but one patient. Five (15.6%) of them did not suffer a clinical seizure despite the presence of EAs. Patients who developed epilepsy were significantly more likely to have abnormal neuroimaging findings [10/11 (90.9%)] during the follow-up compared to the rest of the patients [OR = 25 (95% CI 2.6->100, P = .002)]. Half of the study cohort was taking ASM at the last follow-up. SIGNIFICANCE: Our small study reveals a signature location of IEDs in SCA survivors. Neuroimaging abnormalities seem to be a better indicator of epilepsy development, while EEG may reveal markers of potential epileptogenicity in the absence of clinical seizures. Future, larger studies are needed to confirm our findings.

COVID-19 Disease and Hypercoagulability Leading to Acute Ischemic Stroke.

INTRODUCTION: SARS-Coronavirus-2 infection leading to COVID-19 disease presents most often with respiratory failure. The systemic inflammatory response of SARS-CoV-2 along with the hypercoagulable state that the infection elicits can lead to acute thrombotic complications including ischemic stroke. We present 3 cases of patients with COVID-19 disease who presented with varying degrees of vascular thrombosis. CASES: Cases 1 and 2 presented as cerebral ischemic strokes without respiratory failure. Given their exposure risks, they were both tested for COVID-19 disease. Case 2 ultimately developed respiratory failure and pulmonary embolism. Cases 2 and 3 were found to have simultaneous arterial and venous thromboembolism (ischemic stroke and pulmonary embolism) as well as positive antiphospholipid antibodies. CONCLUSION: Our case series highlight the presence of hypercoagulability as an important mechanism in patients with COVID-19 disease with and without respiratory failure. Despite arterial and venous thromboembolic events, antiphospholipid and hypercoagulable panels in the acute phase can be difficult to interpret in the context of acute phase response and utilization of thrombolytics. SARS-CoV-2 testing in patients presenting with stroke symptoms may be useful in communities with a high case burden or patients with a history of exposure.

Ipsilateral Reversible Cerebral Vasculopathy Secondary to Carotid Artery Revascularization: A Case Report.

BACKGROUND: The emergence of neurologic symptoms after carotid revascularization is not uncommon and typically caused by perioperative ischemic stroke or hyperperfusion. Postoperative vasculopathy, including reversible cerebral vasoconstriction syndrome (RCVS) is a rare complication of carotid intervention and may be an under-identified cause of neurologic deficit after revascularization. We report a case of reversible postoperative vasculopathy following carotid revascularization as well as its management. CASE PRESENTATION: A 74 year old right-handed woman presented to the emergency department with sudden onset left arm weakness and episodic shaking while hypotensive. Computed tomography angiography revealed total occlusion of her right internal carotid artery. Transcranial Doppler monitoring demonstrated active embolic events in her right middle cerebral artery raising concern for continued stump embolization. She underwent carotid revascularization with carotid endarterectomy, mechanical thrombectomy, and carotid angioplasty and initially did well postoperatively. On postoperative day 5, she developed a fixed right gaze and left hemiparesis. Computed tomography revealed new right frontal lobe and basal ganglia infarcts, and angiography showed new right internal carotid, middle cerebral, and anterior cerebral artery vasoconstriction consistent with postoperative vasculopathy. Despite treatment with pressure augmentation and vasodilator therapy, her symptoms persisted resulting in left hemiplegia at discharge. DISCUSSION: This case highlights postoperative vasculopathy (including RCVS) as a rare potential complication after carotid revascularization that should be considered in a patient with persistent acute neurologic symptoms. Information regarding incidence and predisposing risk factors is limited. Multiple diagnostic and therapeutic modalities may be necessary in the recognition and treatment of postoperative vasculopathy.

Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes.

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.

Lighting Strikes Twice: Recurrent Guillain-Barré Syndrome (GBS) after Influenza Vaccination.

Guillain-Barré syndrome (GBS) is a rare acute demyelinating syndrome of the peripheral nervous system that is commonly preceded by infection. Vaccinations have also been associated with an increased incidence of GBS, though the risk is low. Caution with revaccination is recommended in patients with a history of GBS. Risks of revaccination compared with the risks of influenza complications should be considered. Patients who experience GBS after vaccination have not been shown to have an increased incidence of recurrent GBS after the influenza vaccine, though evidence is limited. We report a case of recurrent GBS in a patient following the influenza vaccine.

Acute Symptomatic Seizures in Critically Ill Patients with COVID-19: Is There an Association?

BACKGROUND: The coronavirus disease of 2019 (COVID-19) emerged as a global pandemic. Historically, the group of human coronaviruses can also affect the central nervous system leading to neurological symptoms; however, the causative mechanisms of the neurological manifestations of COVID-19 disease are not well known. Seizures have not been directly reported as a part of COVID-19 outside of patients with previously known brain injury or epilepsy. We report two cases of acute symptomatic seizures, in non-epileptic patients, associated with severe COVID-19 disease. CASE PRESENTATIONS: Two advanced-age, non-epileptic, male patients presented to our northeast Ohio-based health system with concern for infection in Mid-March 2020. Both had a history of lung disease and during their hospitalization tested positive for SARS-CoV-2. They developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures. Resolution of seizures was achieved with levetiracetam. DISCUSSION: Patients with COVID-19 disease are at an elevated risk for seizures, and the mechanism of these seizures is likely multifactorial. Clinical (motor) seizures may not be readily detected in this population due to the expansive utilization of sedatives and paralytics for respiratory optimization strategies. Many of these patients are also not electrographically monitored for seizures due to limited resources, multifactorial risk for acute encephalopathy, and the risk of cross-contamination. Previously, several neurological symptoms were seen in patients with more advanced COVID-19 disease, and these were thought to be secondary to multi-system organ failure and/or disseminated intravascular coagulopathy-related brain injury. However, these patients may also have an advanced breakdown of the blood-brain barrier precipitated by pro-inflammatory cytokine reactions. The neurotropic effect and neuroinvasiveness of SARS-Coronavirus-2 have not been directly established. CONCLUSIONS: Acute symptomatic seizures are possible in patients with COVID-19 disease. These seizures are likely multifactorial in origin, including cortical irritation due to blood-brain barrier breakdown, precipitated by the cytokine reaction as a part of the viral infection. Patients with clinical signs of seizures or otherwise unexplained encephalopathy may benefit from electroencephalography monitoring and/or empiric anti-epileptic therapy. Further studies are needed to elucidate the risk of seizures and benefit of monitoring in this population.