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Frequent Convulsive Seizures in an Adult Patient with COVID-19: A Case Report

March 2020
Iranian Red Crescent Medical Journal In Press(In Press)

DOI:10.5812/ircmj.102828

Authors:

Narges Karimi

Mazandaran University of Medical Sciences

Athena Sharifi Razavi

Mazandaran University of Medical Sciences

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Iran Red Crescent Med J. 2020 March; 22(3):e102828.

Published online 2020 March 28.

doi: 10.5812/ircmj.102828.

Case Report

Frequent Convulsive Seizures in an Adult Patient with COVID-19: A

Case Report

Narges Karimi 1, * , Athena Shariﬁ Razavi2and Nima Rouhani 2

1Immunogenetics Research Center, School of Medicine, Clinical Research Development Unit of Bou Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran

2School of Medicine, Clinical Research Development Unit of Bou Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran

*Corresponding author: Bou Ali Sina Hospital, Pasdararn Blvd, Postal code: 4815838477, Sari, Iran. Tel: +98-1133343018 , Fax: +98-1133344506, Email: drkarimi_236@yahoo.com

Received 2020 March 18; Revised 2020 March 23; Accepted 2020 March 24.

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) is a novel coronavirus that was extracted from patients with respiratory tract

infections. The most common symptoms of patients are fever and respiratory tract involvement. In this report, we describe one

patient with frequent seizures probably due to COVID-19 infection for the ﬁrst time.

Case Presentation: A 30-year-old previously healthy female was admitted with generalized tonic-clonic seizure in the neurology

emergency room. The patient complained of dr y cough ﬁve days before the admission. She had seizures (ﬁve times) approximately

every 8 hours. Brain MRI was normal and chest CT revealed focal ground-glass opacities. The respiratory specimen was positive for

COVID-19 using real-time PCR assay. The symptoms of the patient improved with anticonvulsive and antiviral medications.

Conclusions: Tothe best of our knowledge, this is the ﬁrst case study to report an association between frequent seizures and COVID-

19. In our opinion, there is a hypothesis about this subject that the etiology of seizure may be due to encephalitis and invasion virus

to the brain or toxic eﬀect of inﬂammatory cytokines.

Keywords: Seizure, COVID-19, Novel Coronavirus, Case Report, Convulsion

1. Introduction

Coronavirus disease 2019 (COVID-19) is a novel coron-

avirus that was extracted from patients with respiratory

tract infection of unknown causes on December 31, 2019,

in Wuhan, Hubei, China (1-3). The infected patients’ symp-

toms ranged from asymptomatic to severe (4). The most

common complaints of patients are fever (98%), cough

(76%), dyspnea (55%), myalgia, and fatigue (44%) (5-7). Some

pieces of evidence reported gastrointestinal involvement,

acute cardiac injury, and acute kidney injury due to COVID-

19 (7,8). Mao et al. (9) reported neurological manifesta-

tions of patients with COVID-19. The most common symp-

toms were dizziness, headache, hypogeusia, and hypos-

mia (9). Severe patients had ischemic or hemorrhagic

stroke, and loss of consciousness (9). At this time, the like-

lihood of COVID-19 should be considered primarily in pa-

tients with fever and/or respiratory tract symptoms who

had close contact with a conﬁrmed or suspected patient

of COVID-19 (1). Real-time polymerase chain reaction (real-

time PCR) and next-generation sequencing were used for

deﬁnitive diagnosis of this novel coronavirus (5). To the

best of our knowledge, up to now, no seizure was reported

due to COVID-19. In this report, we describe one patient

with frequent seizures probably owing to COVID19 for the

ﬁrst time.

2. Case Presentation

A 30-year-old previously healthy female was admit-

ted with generalized tonic-clonic seizure in the neurol-

ogy emergency room in Bou Ali Sina Hospital, Mazandaran

Province, Iran. The patient had no history of drug and alco-

hol abuse. She complained of dry cough ﬁve days before

admission. Three days prior to admission, she had fever

(T = 38°C axillary) and fatigue. The ﬁrst generalized tonic-

clonic seizure (GTC) of the patient occurred in the sleep,

two days before the admission. Then, recurrent seizures

(ﬁve times) happened approximately every 8 hours. Also,

one seizure attack arose in the hospital, at the admission

time. As the seizure ended, the patient was sleepy and con-

fused for thirty minutes to one hour. The patient was con-

scious between attacks. She neither had a history of epilep-

tic seizures nor a family history concerning seizure disor-

ders. At the time of hospitalization in the Emergency De-

partment, the body temperature was 38.8°C, blood pres-

sure 130/70 mmHg, heart rate 98 beats/minute, respiratory

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Karimi N et al.

rate 20/minute and oxygen saturation of 96% on room air.

The bedside serum glucose level was 108 mg/dL. In terms

of neurological examination, the patient was drowsy with

disorientation to time. The cranial nerves were intact.

Pupils were midsize and reactive to light and accommo-

dation. There was no optic disc swelling bilaterally. The

patient was able to move all four extremities and there

was no stiﬀ neck and nuchal rigidity. Deep tendon reﬂexes

were normal. Considering general examination, no skin

rash was observed and other systems, including cardiac

and abdominal examination, were normal. Primary labo-

ratory tests discovered a normal blood sugar, electrolytes,

calcium, phosphor, magnesium, liver function test, urea,

and creatinine. The blood sample revealed the following

results: white blood cell count 5,500 cells per microliter

with 26% lymphocytes and 70% neutrophils, mildly ele-

vated erythrocyte sedimentation rate (ESR = 35 mm/hour),

and normal C-reactive protein (CRP). Lumbar puncture was

done and the cerebrospinal ﬂuid (CSF) showed normal pro-

tein, glucose, with ﬁve cell counts (all of them were lym-

phocytes). There was no bacterial growth after 48 hours of

incubation. Brain MRI was normal. Given that the patient

had cough and fever, the chest computed tomography (CT)

was done and revealed focal ground-glass opacities (Fig-

ure 1). Respiratory specimens, including nasal and phar yn-

geal swabs, and CSF sample were tested for COVID-19 using

real-time PCR in the Health Center no. 5 (Shahid Ghasemi)

Laboratory. This center is under the supervision of Mazan-

daran University of Medical Sciences. Nasal and pharyn-

geal samples were positive for COVID-19. The CSF sample

was unremarkable for COVID-19 infection. The patient was

treated with intravenous phenytoin and levetiracetam. In

addition, the patient received chloroquine 200 mg BD and

Lopinavir-ritonavir 400/100 mg bd. The patient was mon-

itored for one week. Fever and seizure of the patient were

controlled.

3. Discussion

Coronavirus disease 2019 (COVID-19) is beta coron-

aviruses, similar to severe acute respiratory syndrome

coronavirus (SARS-CoV) in 2003 but with a diﬀerent mono-

phyletic group. Both viruses bind to receptor angiotensin-

converting enzyme 2 (ACE2) to enter the cell (10,11). The

most well-known clinical symptoms of this virus are respi-

ratory symptoms. Moreover, Mao et al. (9) described neu-

rological presentations of infected patients with COVID-19.

The most common reported symptoms were headache and

dizziness. In this report, we reported a case with COVID-19

and frequent seizures, with no past medical history. There

are many diﬀerent viruses that play a role in the develop-

ment of seizures and convulsions (12). The causes of seizure

Figure 1. Chest computer tomography in the patient with COVID-19 is shown

may be due to a primary infection or due to reactivation of

the latent virus. There are several mechanisms for the eti-

ology of seizure in the patients who suﬀer from viral infec-

tions, including direct inﬁltration of brain tissue and pro-

duction of toxins by the virus or production of inﬂamma-

tory mediators by the brain (13). Huang et al. (2) reported

that COVID-19 provokes the inﬂammatory cascade and as

a result, releases inﬂammatory cytokines, including inter-

leukins 2, 6, 7, and 10, tumor necrotizing αand the granu-

locyte colony-stimulating factor. Previous studies reported

that TNF-αand IL-6 cytokines and C3 of the complement

system are the main factors of stimulating the immune sys-

tem. Consecutively, these cytokines can drive neuronal hy-

perexcitability via activation of glutamate receptors and

play a role in the development of acute seizures(14-16).

3.1. Conclusions

To the best of our knowledge, this is the ﬁrst case study

that reports an association between frequent seizures and

COVID-19. In our opinion, there is a hypothesis about this

subject that the etiology of seizure may be encephalitis

and the invasion of the virus to the brain or toxic eﬀect of

inﬂammatory cytokines.

Acknowledgments

We thank the patient for her consent to publish the

case report.

2Iran Red Crescent Med J. 2020; 22(3):e102828.

Karimi N et al.

Footnotes

Authors’ Contribution: Study concept and design:

Narges Karimi and Nima Rouhani. Interpretation of

data: Narges Karimi and Athena Shariﬁ Razavi. Drafting

of the manuscript: Narges Karimi. Critical revision of

the manuscript for important intellectual content: Nima

Rouhani and Athena Shariﬁ Razavi.

Conﬂict of Interests: No conﬂict of interest was reported

regarding this case report.

Ethical Approval: Mazandaran University of Medical Sci-

ences approved the publication of this case report.

Funding/Support: Not applicable.

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Jan 2020

Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study

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Jan 2020

Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia

Article

Feb 2020

Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.

Emerging Coronavirus 2019-nCoV Pneumonia

Article

Feb 2020

Background The chest CT findings of patients with 2019 Novel Coronavirus (2019-nCoV) pneumonia have not previously been described in detail.PurposeTo investigate the clinical, laboratory, and imaging findings of emerging 2019-nCoV pneumonia in humans.Materials and Methods Fifty-one patients (25 men and 26 women; age range 16-76 years) with laboratory-confirmed 2019-nCoV infection by using real-time reverse transcription polymerase chain reaction underwent thin-section CT. The imaging findings, clinical data, and laboratory data were evaluated.ResultsFifty of 51 patients (98%) had a history of contact with individuals from the endemic center in Wuhan, China. Fever (49 of 51, 96%) and cough (24 of 51, 47%) were the most common symptoms. Most patients had a normal white blood cell count (37 of 51, 73%), neutrophil count (44 of 51, 86%), and either normal (17 of 51, 35%) or reduced (33 of 51, 65%) lymphocyte count. CT images showed pure ground-glass opacity (GGO) in 39 of 51 (77%) patients and GGO with reticular and/or interlobular septal thickening in 38 of 51 (75%) patients. GGO with consolidation was present in 30 of 51 (59%) patients, and pure consolidation was present in 28 of 51 (55%) patients. Forty-four of 51 (86%) patients had bilateral lung involvement, while 41 of 51 (80%) involved the posterior part of the lungs and 44 of 51 (86%) were peripheral. There were more consolidated lung lesions in patients 5 days or more from disease onset to CT scan versus 4 days or fewer (431 of 712 lesions vs 129 of 612 lesions; P < .001). Patients older than 50 years had more consolidated lung lesions than did those aged 50 years or younger (212 of 470 vs 198 of 854; P < .001). Follow-up CT in 13 patients showed improvement in seven (54%) patients and progression in four (31%) patients.Conclusion Patients with fever and/or cough and with conspicuous ground-glass opacity lesions in the peripheral and posterior lungs on CT images, combined with normal or decreased white blood cells and a history of epidemic exposure, are highly suspected of having 2019 Novel Coronavirus (2019-nCoV) pneumonia.© RSNA, 2020.

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Article

Jan 2020

Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding: National Key R&D Program of China.

A novel coronavirus outbreak of global health concern

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