COVID-19-associated seizure

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mandana Safakhah, MD[2]

Synonyms and keywords:

Overview

Coronaviruses impacts are not always restricted to respiratory system and they have potential for neuroinvasion under specific circumstances. Neurological manifestations such as dizziness,headache ,anosmia as well as case reports with encephalitis ,stroke,epileptic seizures associated with covid-19, have been reported.

Historical Perspective

• two male patients, non-epileptic were hospitalised with covid-19 signs and symptoms, March 2020 ,Ohio, U.S.A. During their hospital stay they developed encephalopathy and seizures, controlled by levetiracetam

• A women with the past medical history of seizure following herpetic encephalitis ,presented with a sudden focal myoclonus and positive test for covid 19 in Italy, 23rd of april 2020.

• Also, a cohort multicentre study was done in China, April 2020, demonstrating that COVID 19 doesn't increase the risk of symptomatic seizure in patients hospitalized with the acute respiratory phase of COVID 19.Although ,some seizure-like reactions are seen because of acute reaction to stress or hypocalcemia .

Classification

There isn't any established classification for covid-19 associated seizure.

Pathophysiology

• Neurological complications caused by COVID-19 are through direct or indirect pathways. This includes hematogenous pathway, neuronal retrograde dissemination through olfactory bulb, entry into to glial cells and neurons via ACE2 receptor and impairment of gas exchange in lungs leading to anemia, hence increasing anaerobic metabolites in brain resulting in cellular and interstitial edema
• Seizures in a patient with COVID-19 may be due to primary virus infection or due to reactivation of the latent virus.
• Infiltration of the brain tissue by the virus and subsequent production of toxins by the virus is one of the several mechanisms that can cause seizures in a COVID-19 patient.
• Production of inflammatory mediators by the brain may also trigger seizures.
• Inflammatory cytokines that are released as a result of inflammatory cascade provoked by COVID-19 include interleukin 2,6,7, and 10, TNF-α and granulocyte colony-stimulating factor. Consequently, activation of glutamate receptors by the cytokines causes neuronal hyperexcitability and development of seizures.

Pathophysiology

Causes

The aetiology of seizure regardless whether it is covid-19 or not ,is divided into two categories:

• 'Provoked seizures : these seizures usually have a temporary trigger such as CNS infection,electrolytes disturbance, withdrawal syndrome,sepsis ,fever, sleep deprivation and stroke.
• Unprovoked seizures: In this catrgory ,there isn't any obvious cause or precipitating factor .

Differentiating COVID-19-associated seizure from other Diseases

Apart from the viral cause of the seizure, the differential diagnosis for this disease is usually based on the presenting symptoms as below:

• Loss of awareness :syncope-Epilepsy-cardiac disorder

• Generalized convulsive movements:Epilepsy-syncope with secondary jerking movement-Involuntary movement disorders and other neurological conditions
• Drop attack:Epilepsy-Cardiac-Brainstem abnormalities-vertebrobasilar ischemia-Idiopathic
• Transient focal motor and sensory attack :tics-tonic spasms of multiple
• Facial muscles and eye movement:partial seizures-movement disorder-Other neurological conditions.

Epidemiology and Demographics

By now there isn't any sufficient evidence for demographic and epidemiologic data about covid- 19 associated seizure.

Risk Factors

There are no established risk factors for covid-19 associated seizure.

Screening

There is insufficient evidence to recommend routine screening for covid-19 associated seizure.

Natural History, Complications, and Prognosis

The global case fatality rate is currently estimated to be 4.6% according to WHO , 9th,June. Also neurological complications of covid-19 .The covid-19 fatality rate depends on several factors such as:

• patient demographics
• availability of health care
• test limitation

Also , the more comorbidities the patient has ,the poorer covid-19 clinical output. Some of the prognostic factor of covid-19 are listed as below:

• Above 65 years old
• smoking
• male sex
• elevated inflammatory markers
• elevated D-Dimer
• elevated interleukin 6
• thrombocytopenia
• high neutrophil to lymphocyte ratio
• higher acute physiology and chronic health evaluation score.

Diagnosis

Diagnostic Study of Choice

The diagnosis of COVID-19-associated seizure is made through:

• Electroencephalogram (EEG, brain waive activity).

Other diagnostic tests include:

• CT scan brain
• MRI brain
• Blood test
• Lumbar puncture
• Toxicology screening

History

• Neurotropism is one common feature of coronaviruses.
• COVID-19 document CNS manifestations in 25% of the patients, headache (13%), dizziness (17%), impaired consciousness (8%), acute cerebrovascular problems (3%), ataxia (0.5), and seizures (0.5%).

Symptoms

• General symptoms or warning signs of a seizure can include:
  • Staring
  • Jerking movements of the arms and legs
  • Stiffening of the body
  • Loss of consciousness
  • Breathing problems or stopping breathing
  • Loss of bowel or bladder control
  • Falling suddenly for no apparent reason, especially when associated with loss of consciousness
  • Not responding to noise or words for brief periods
  • Appearing confused or in a haze
  • Nodding your head rhythmically, when associated with loss of awareness or loss of consciousness
  • Periods of rapid eye blinking and staring

Physical Examination

Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Laboratory Findings

Postictal levels of the following may be elevated in a patient with seizures:

• Prolactin (within 20 minutes after a convulsive event)
• Lactate (within 1 to 2 hours)
• Ammonia (within several hours)
• Creatine kinase (especially 24 to 48 hours postictally)
• To view the laboratory findings on COVID-19, click here.

Electrocardiogram

• There are no typical ECG findings associated with seizures in a COVID-19 patient.
• To view the electrocardiogram findings on COVID-19, click here.
  

X-ray

• There are no x-ray findings associated with COVID-19 associated seizure.
• * To view the x-ray finidings on COVID-19, click here.
  

Echocardiography or Ultrasound

• There are no typical echocardiographic findings for seizure related to COVID-19.
• To view the echocardiographic findings on COVID-19, click here.
  

CT scan

• CT brain may show structural lesions but majority of patients will show nothing.
• To view the CT scan findings on COVID-19, click here.

MRI

• MRI brain may show structural lesions but majority of patients will show nothing.
• To view the MRI findings on COVID-19, click here.
  

Other Imaging Findings

• There are no other imaging findings associated with seizure related to COVID-19.
• To view other imaging findings on COVID-19, click here.
  

Other Diagnostic Studies

• To view other diagnostic studies for COVID-19, click here.
  

Treatment

Medical Therapy

• Development of seizures in a COVID-19 patient requires urgent treatment.
• After the cause of seizure is determined, medical therapy should be aimed at treating the cause immediately (for example, hypoxia, fever, metabolic imbalance).
• Anti-seizure medication (ASM) is often necessary.
• For a single seizure less than 5 min rescue treatment with benzodiazepine is not needed. Intravenous ASM are used with caution in COVID-19 patients due to the adverse effects (e.g., Phenytoin, Phenobarbital and Lacosamide in respiratory and cardiac problems) and drug interactions (e.g., Carbamazepine, Phenytoin, Phenobarbital and Valproic acid).
• Brivaracetam and Levetiracetam have less adverse effects and drug interactions.
• In patients with more than one seizure (either shorter or longer than 5 min) and in status epilepticus rescue treatment with benzodiazepines in addition to ASM is needed.

Surgery

Surgical intervention is not recommended for the management of COVID-19 associated seizure.

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

References

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