Human coronaviruses have the capacity to directly attack the brain via either the haematogenic or retrograde trans-synaptic/peripheral nerve routes.[1] COVID-19 has also been shown to induce systemic alterations that can potentially affect the CNS, such as hypoxia, electrolyte imbalances and, in the worst case, cytokine storm syndromes. These pathogenic mechanisms might potentially result in encephalitic or encephalopathic signs and symptoms in COVID-19 patients.
A case of meningoencephalitis in a 24-year-old man[2] presenting with reduced level of consciousness, neck stiffness and recurrent focal-to-bilateral tonic-clonic seizures (requiring endotracheal intubation and mechanical ventilation) nine days after onset of fever, fatigue and headache. Brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus. Chest CT showed pneumonia and real time polymerase chain reaction (RT-PCR) of CSF was positive for SARS-CoV-2, although a nasopharyngeal swab was negative. Another paper[3] reported the sudden occurrence of focal status epilepticus in a 78-year-old woman with a history of post-HSV encephalitis epilepsy who had previously been seizure-free for over two years. In light of recent exposure to possible SARS-CoV-2 infection, nasopharyngeal and oropharyngeal swabs were obtained, which were RT-PCR-positive for SARS-CoV-2. She developed fever 12 hours after hospital admission, which resolved following antiviral treatment. She did not require oxygen therapy and serial chest imaging with x-ray and ultrasound was negative for interstitial pneumonia. These cases, both with predisposing factors, suggest that seizures may occur in association with SARS-CoV-2, either secondary to a complication of the infection or representing a deterioration in seizure control in people with pre-existing epilepsy. Firm conclusions about underlying mechanisms cannot be drawn without a significantly larger series of patients with similar symptoms. Neurologists are encouraged to be vigilant, to add patients to the upcoming EAN COVID-19 registry and to discuss cases in the COVID-19 forum, once these services are launched.
However, in four cohort studies[4–7] investigating the occurrence of seizures and other disorders associated with SARS-CoV-2 infection, only one patient out of 689 had confirmed seizures, suggesting that this complication is a rare feature of COVID-19. This could be an underestimate of the true prevalence explained by the fact that severe COVID-19 cases were intubated and therefore treated with propofol or midazolam, both potent anticonvulsive anaesthetics.
Possibly the highest risk during this COVID-19 pandemic for people with epilepsy is related to the discontinuation of antiseizure medicines. Lai[8] reported that drug withdrawal during the SARS outbreak – as a result of either patient choice or loss of contact with the attending physician – significantly increased seizure frequency and severity.
Key points:
- At this moment, it is uncertain whether SARS-CoV-2 infection can cause isolated, de novo seizures.
- Seizures seem to be a rare feature of COVID-19. However, anaesthetic agents used along with endotracheal intubation for severe COVID-19 cases have potent anti-convulsive properties.
- The COVID-19 pandemic may be associated with unintentional antiseizure medicine withdrawal in some people with epilepsy.
References:
Bohmwald K, Gálvez NMS, Ríos M, et al. Neurologic Alterations Due to Respiratory Virus Infections. Front Cell Neurosci 2018;12. doi:10.3389/fncel.2018.00386
Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55–8. doi:10.1016/j.ijid.2020.03.062
Vollono C, Rollo E, Romozzi M, et al. Focal status epilepticus as unique clinical feature of COVID-19: A case report. Seizure 2020;78:109–12. doi:10.1016/j.seizure.2020.04.009
Lu L, Xiong W, Liu D, et al. New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study. Epilepsia 2020;:epi.16524. doi:10.1111/epi.16524
Helms J, Kremer S, Merdji H, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med 2020;:NEJMc2008597. doi:10.1056/NEJMc2008597
Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 2020;:m1091. doi:10.1136/bmj.m1091
Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol Published Online First: 10 April 2020. doi:10.1001/jamaneurol.2020.1127
Lai S-L, Hsu M-T, Chen S-S. The impact of SARS on epilepsy: The experience of drug withdrawal in epileptic patients. Seizure 2005;14:557–61. doi:10.1016/j.seizure.2005.08.010