Seizure As The Presenting Symptom of

COVID-19: A Retrospective Case Series

Title Seizure As The Presenting Symptom of COVID-19: A Retrospective Case
Series
Journal Elsevier
Years 2020
Writers Pria Anand, Abrar Al-Faraj, Elie Sader, Jonathan Dashkoff, Myriam Abdennadher,
Rubachandran Murugesan, Anna M. Cervantes-Arslanian, Ali Daneshmand
 Background

 Coronavirus Disease 2019 (COVID-19) has rapidly become a global pandemic, with over
5 million confirmed cases worldwide to date.
 Early diagnosis is critical  the consideration of specific treatment and implementation of
appropriate infection control.
 COVID-19 has been described in association with a host of neurologic complications 
acute cerebrovascular events, impaired consciousness, and skeletal muscle.
 minimal literature exists on seizures in patients with COVID-19  this journal describe
the clinical course of 7 patients who presented with seizures as an early manifestation of
COVID-19.
Methods

This observational case series was approved by the Boston University Medical
Center IRB. Cases were identified through a review of admissions and
consultations to the neurology and neurocritical care
services between April 1, 2020 and May 15, 2020.
 Patient Characteristics

1043 patient of Covid 19 in Medical Centre of Boston University

7 patients (0,7 %) presented with seizures (2 males, 5 females)

3 patients with history of well-controlled epilepsy with 4 patient with new onset of seizures
last seizure between 10-17 months ago
2 patient with history of 1 patient with parkinson’s
remote stroke disease
1 patient with post 1 patient with epilepsy
stroke epilepsy following cardiac arrest
1 patient with end stage renal
disease with HD
Features of COVID-19

COVID-19 was identified based on characteristic clinical features and positive

nasopharyngeal polymerase chain reaction (PCR) testing for SARS-CoV-2

4 patients present symptomps of COVID 19  3 patients had no preceding symptoms of COVID-

cough, fatigue, ageusia, fever, shortness of breath, and 19 prior to presentation
emesis

D-dimer, C-reactive protein, and ferritin were elevated in all 7 patients.

Chest imaging was abnormal in all 7 patients

4 patients had severe respiratory failure

1 patient is deceased
requiring intubation
Seizure Onset and Semiology

In all 7 patients, seizures prompted presentation to the emergency department in spite of

prior symptoms of COVID-19. Five patients had generalized tonic–clonic seizures,
while 2 patients had focal seizures characterized by gaze deviation, head version, and
unilateral motor symptoms. Four patients developed focal postictal deficits that
subsequently resolved
Imaging and CSF Findings

Noncontrast enhanced head computed tomography (CT) was obtained in all cases and
showed no new abnormalities in any of the cases.

Arterial or venous vessel imaging was obtained in 3 cases. without cerebral venous
sinus thrombosis or large-vessel occlusion in any of the cases.

MRI brain was obtained in just one case and revealed gyriform restricted diffusion in the cortex of the bilateral
frontal lobes and extensive abnormal fluid attenuated inversion recovery (FLAIR) sequences revealed prominent
FLAIR hyperintensity involving the right frontal lobe and bilateral cerebellar hemispheres

Cerebrospinal fluid (CSF) studies were obtained for one patient (7) and demonstrated a normal
protein and b1 nucleated cell/μL
Axial brain MRI for patient 7. A–D: weighted fluid attenuated inversion recovery (FLAIR) sequences revealed prominent FLAIR hyperintensity involving the
right frontal lobe and bilateral cerebellar hemispheres. E–G: Diffusion-weighted images revealed diffusion restriction involving the right frontal lobe without
associated diffusion restriction of the cerebellum.
 Electrographic Findings

Twenty-four-hour electroencephalography (EEG) was obtained in 2 cases. One patient (patient 6) had
moderately slow background activity, with frequent sharp waves and focal epileptiform discharges in the
right parieto-occipital region and occasional independent sharp waves in the right posterior temporal
region. There were also frequent generalized sharp waves with triphasic morphology and right greater
than frontal predominance. The second patient (patient 7) had moderate to severe encephalopathy, with
frequent short runs of generalized rhythmic delta activity (GRDA). Her clinical status epilepticus had
resolved by the time of EEG.
 Discussion

1. to date, few cases in the literature describe seizures in patients with COVID-19

one in a patient with a history of epilepsy 2 in patients with a COVID-19

one in a critically ill after prior viral encephalitis encephalitis based on SARS-CoV-2
patient detection in the CSF

[1] WHO. Coronavirus disease 2019 (COVID-19) situation report-61; 2020

[2] Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study.
medRxiv. 2020.
[7] Lau K-K, Yu W-C, Chu C-M, Lau S-T, Sheng B, Yuen K-Y. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis. 2004;10:342–4.
[8] Vollono C, Rollo E, Romozzi M, Frisullo G, Servidei S, Borghetti A, et al. Focal status epilepticus as unique clinical feature of COVID-19: a case report. Seizure. 2020;78: 109–12.
 Discussion

2. One large cohort from China's Hubei Province  304 patients with COVID-19

84 patients with brain insults or metabolic imbalances, none had seizures

and 2 had “seizure-like symptoms” in the setting of hypocalcemia,
concluding that the virus does not carry an increased risk of seizure

[2] Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study.
medRxiv. 2020.
Discussion

3. By contrast, the 7 patients here presented with either new-onset or breakthrough seizure as an
early symptom of COVID-19.

4 of the patients presented had 3 had no preceding symptoms to

preceding respiratory or suggest a diagnosis of
gastrointestinal symptoms COVID-19.

In all cases, seizure was the symptom that prompted presentation to the hospital. In
endemic areas with community spread of COVID-19, clinicians should be vigilant for
the infection in patients who present with seizures.
 Discussion

4. Three of the patients described presented with significant metabolic derangements.

One patient developed seizures

One presented with shortly after undergoing
One patient was uremic
hyponatremia hemodialysis.

Preliminary reports suggest that hyponatremia and early renal failure may be common features of COVID-19

Hyponatremia, uremia, and related metabolic derangements can both cause encephalopathy and lower the seizure
threshold in susceptible patients.

These cases demonstrate that COVID-19 should be considered in patients who present with seizure in
the setting of metabolic derangements.
Discussion

5. In one case, valproic acid levels were found to be subtherapeutic, which may have precipitated
seizures in conjunction with infection.

Although the etiology for subtherapeutic levels was unclear, reports from prior coronavirus
epidemics suggested that breakthrough seizures may occur at higher rates in the pandemic
setting, as patients may avoid hospitals and pharmacies and have more difficulty obtaining
their prescribed antiepileptic therapies

[4] Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-
coronavirus-2. Int J Infect Dis. 2020; 94:55–8. https://doi.org/10.1016/j.ijid.2020.03.062.
 Discussion

6. Experience with prior pandemic ribonucleic acid (RNA) viruses suggests that both new-onset and
breakthrough seizures may be a common presenting manifestation of viral illness. In some cases,
these may be a manifestation of encephalitis, while in others, they may reflect metabolic derangements,
severe systemic illness, an inability to obtain medications, or gastrointestinal symptoms impeding
absorption of oral medications.

Because of prior reports regarding thromboembolic and hemorrhagic events in patients with
COVID-19, seizures may also represent the presenting symptom of cerebral venous sinus
thrombosis or intracerebral hemorrhage in some cases.

[9] Asadi-Pooya AA. Seizures associated with coronavirus infections. Seizure. 2020;79: 49–52.
Conclusion

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.
 Rerefences

[1] WHO. Coronavirus disease 2019 (COVID-19) situation report-61; 2020.

[2] Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a
retrospective case series study. medRxiv. 2020
[3] Li M. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Lancet. 2020;19.
[4] Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-coronavirus-2. Int J
Infect Dis. 2020; 94:55–8. https://doi.org/10.1016/j.ijid.2020.03.062.
[5] Kaddumukasa M, Kaddumukasa M, Matovu S, Katabira E. The frequency and precipitating factors for breakthrough seizures among patients with epilepsy in
Uganda. BMC Neurol. 2013;13:182.
[6] Lu L, Xiong W, Liu D, Liu J, Yang D, Li N, et al. New-onset acute symptomatic seizure and risk factors in corona virus disease 2019: a retrospective
multicenter study. Epilepsia. 2020;61(6):e49–53. https://doi.org/10.1111/epi.16524.
[7] Lau K-K, Yu W-C, Chu C-M, Lau S-T, Sheng B, Yuen K-Y. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis. 2004;10:342–
4.
[8] Vollono C, Rollo E, Romozzi M, Frisullo G, Servidei S, Borghetti A, et al. Focal status epilepticus as unique clinical feature of COVID-19: a case report.
Seizure. 2020;78: 109–12.
[9] Asadi-Pooya AA. Seizures associated with coronavirus infections. Seizure. 2020;79: 49–52.