Super refractory status epilepticus as a possible manifestation of COVID-19 disease

INTRODUCTION

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus termed as “severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).” The lung is the most commonly affected organ. New-onset seizures and status epilepticus (SE) are infrequently reported among neurological manifestations.^[1]

We hereby report a super-refractory SE (SRSE) case in a patient with COVID-19.

CASE REPORT

A 21-year-old girl presented with complaints of fever, altered sensorium, and two episodes of generalized tonic-clonic seizure over 7 days. There was no previous seizure history in the past. Routine and specific investigations at admission were done including a nasal swab for COVID-19 reverse transcription polymerase chain reaction (PCR) that came positive [Table 1]. As herpes simplex virus (HSV) encephalitis is one of the most common causes of new onset super refractory epilepsy, cerebrospinal fluid PCR was sent for HSV-1 and HSV-2 that came negative. Electroencephalography showed intermittent, generalized, sharp, and slow wave discharges with delta-theta slowing of background with intermittent clinical generalized tonic-clonic activity in between. Magnetic resonance imaging brain had T2/fluid attenuated inversion recovery hyperintensities in the bilateral hippocampus [Figure 1]. There was persistent seizure activity, despite multiple oral and injectable antiepileptic drugs and the ketogenic diet and the patient expired on the 11^th day of admission with more than 1 week of persistent seizure activity [Figure 2, Timeline of events].

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Figure 1:

Axial T2-weighted image (a) and fluid attenuated inversion recovery (b) of brain shows hyperintensity in bilateral hippocampus.

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Figure 2:

Timeline of patient management. PHT: Phenytoin, LEV: Levetiracetam, LCM: Lacosamide, VPA: Valproic acid, CBZ: Carbamazepine, LTG: Lamotrigine, PER: Perampanel, MDZ: Midazolam, KETA: Ketamine, RSE: Refractory status epilepticus, SRSE: Super refractory status epilepticus, D1-D 18: Day 1-18.

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DISCUSSION

There is increasing evidence of neurological involvement in COVID-19 disease, including new-onset seizures.^[2,3] One of the possible explanations for its neuroinvasive property is an expression of Angiotensin-converting enzyme 2 receptors in the brain, particularly in the endothelial cells of cerebral capillaries.[⁴]

In our case, a young female presented with a new-onset seizure without any comorbidity developing into SRSE despite aggressive management and seizure control, and finally succumbed to death. The largest systemic review discussing the association of SE in COVID-19 disease was published by Dono et al. Most of the cases had a good outcome with a resolution of SE, except ten patients who died after a median of 21 days.^[5]

With the correlation of symptoms and no other identified cause, we could hypothesize that SARS-CoV-2 could trigger seizures through a neurotropic pathogenic mechanism, and SE can be a neurological manifestation of SARS-CoV-2 infection.

Our case suggests the importance of considering the possible association between SARS-CoV-2 infection in the patients presented with SRSE.

CONCLUSION

We describe the COVID-19 disease presenting with SRSE with poor outcome. However, more research is needed to confirm its causal association.