key: cord-0827736-i10jvfuw
authors: Gómez-Enjuto, Sara; Hernando-Requejo, Virgilio; Lapeña-Motilva, José; Ogando-Durán, Gonzalo; Fouz-Ruiz, Daniel; Domingo-García, Julio; Rodríguez-García, Elena; Cemillán-Fernández, Carlos Alberto
title: Verapamil as treatment for refractory status epilepticus secondary to PRES syndrome on a SARS-Cov-2 infected patient
date: 2020-06-06
journal: Seizure
DOI: 10.1016/j.seizure.2020.06.008
sha: e296e5134829af1f01ad5840af7a619ecd199aea
doc_id: 827736
cord_uid: i10jvfuw

nan

Verapamil as treatment for refractory status epilepticus secondary to PRES syndrome on a SARS-Cov-2 infected patient. We present the case of a 74-year-old male with an 18-year history of IgG kappa multiple myeloma who received multiple lines of treatment, including carfilzomibdexamethasone every three weeks for the last 8 months.

On April 1 th , 2020, the patient presented to the outpatient clinic with asthenia, dry cough, and fever, so carfilzomib-dexamethasone was not administered. He was diagnosed with severe bilateral pneumonia due to SARS-CoV-2 infection. Laboratory tests showed ferritin of 4242 ng/ml (30 -400), IL-6 of 85,97 pg/ml (0-7) and lymphocytes of 130 cels/µL (900-5200). He was hospitalized initiating treatment with hydroxichloroquine 200 mg/12 hours, lopinavir/ritonavir 400-100 mg/12 hours, ceftriaxone 2g/24 hours, dexamethasone 20 mg/12 hours and enoxaparin at a prophylactic dose of 40mg/24h. Initially he remained stable, but despite the treatment his condition worsened quickly, developing severe lymphopenia (30-40 cels/µL) and severe anemia with haemoglobin of 7,5 g/dl.

On the 15th day of hospitalization, once the infection had partially improved, he suffered two focal aware motor seizures, described as left oculocefalic deviation and clonic movements of the upper left limb, that ceased spontaneously. At that moment his systolic blood pressure was of 140-150 mmHg, higher than his usual levels of 110-120 mmHg. Following this episode, he presented a new focal motor onset seizure with impaired awareness. As he did not recover, progressive doses of antiepileptics were After reviewing the case, infection due to SARS-Cov-2 was proposed as the etiology of the PRES. The new coronavirus can induce endothelial dysfunction [1] that can damage the blood-brain barrier, making it highly permeable and subsequently causing cerebral edema, the underlying mechanism of PRES. This endothelial dysfunction determines a microvascular disturbance that may produce vasoconstriction, which can influence the development of PRES. In addition, the infection by SARS-CoV-2 can lead to a systemic inflammatory response mediated by proinflamatory cytokines, including TNF alpha.

This motivates endothelial activation, increases vascular permeability and ultimately the cerebral interstitial edema [2] . Finally, carfilzomib has been described as an etiological factor in the appearance of PRES [3] , and probably played a role in our case despite not receiving the last prescribed dose.

To our knowledge, this is the first reported case of PRES on a SARS-CoV-2 infected patient. This case has a probable multifactorial origin: the basal treatment with carfilzomib and the elevation of arterial blood pressure, although not substantial, could have created a susceptible environment in which the disease caused by the new coronavirus acted as a trigger.

On the other hand, verapamil, used mainly as a vasodilator, has reported good results on drug-resistant epilepsy as it inhibits P-glycoprotein, increasing the availability of antiepileptic drugs [4] . Moreover, similar drugs such as nimodipine have been used on the prevention of vasospasm secondary to SVCR and PRES [3] .The use of verapamil in J o u r n a l P r e -p r o o f this instance was prompt by the CT images, suggestive of PRES, ceasing the focal status epilepticus with an unequivocal temporal correlation between the administration and the clinical response.

We believe this is the first reported case of verapamil as treatment for refractory epilepsy secondary to PRES. The effectiveness of the prescription in this case may be explained by its vasodilator effect, its adjuvant effect on refractory epilepsy, or a combination of both. Further research is crucial to confirm the results.

Declarations of interest: none.

Endothelial cell infection and endotheliitis in COVID-19

TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib

Management of Posterior Reversible Encephalopathy Syndrome Induced by Carfilzomib in a Patient With Multiple Myeloma