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A case report in Italy suggests breakthrough seizures may be a sign of COVID-19 infection.

"We describe the first patient to develop a focal status epilepticus as a presenting symptom of SARS-CoV-2 infection," reported Catello Vollono, MD, PhD, of Fondazione Policlinico Universitario Agostino Gemelli in Rome, and co-authors in .

The patient was a woman who had a previous episode of herpes encephalitis with seizures that had been well controlled for 2 years. She developed focal myoclonus suddenly and required hospitalization and intravenous (IV) anti-seizure medications; 12 hours later, she had a fever and tested positive for SARS-CoV-2, the virus that causes COVID-19 infection.

This suggests the patient had an unmasking of her underlying seizures, said Avindra Nath, MD, senior investigator of nervous system infections at the NIH's National Institute of Neurological Disorders and Stroke, who was not involved with the case.

"The importance of this case is that all patients who present with unmasking of seizures in the setting of exposure to the virus should be tested for SARS-CoV-2 during the pandemic and should be isolated until results are available," Nath told MedPage Today.

The report comes on the heels of a retrospective study in of COVID-19 patients in China with no known epilepsy history. In their analysis, Dong Zhou, MD, of West China Hospital of Sichuan University in Chengdu, China, and colleagues found no reports of seizures or status epilepticus among 304 hospitalized COVID-19 patients and only two reports of seizure-like symptoms: one due to acute stress reaction, the other to hypocalcemia. "There was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID‐19," they concluded.

Taken together, the two papers suggest "that mainly those patients who have an underlying seizure disorder may be at greater risk for getting breakthrough seizures," Nath said. "De novo seizures in COVID-19 patients are exceedingly rare."

The Italian case involved a 78-year-old woman presenting in the emergency department (ED) with persistent myoclonic jerks of her right face and right limbs. Her past medical history included herpes simplex virus-1 encephalitis at age 76. She had baseline fluent aphasia and mild right limb weakness due to this, but had been seizure-free for more than 2 years on valproic acid (Depakote) and levetiracetam (Keppra). Her last electroencephalogram (EEG), performed 10 days before she was admitted to the hospital, was normal.

The week before she was admitted to the ED, the patient met her son. Soon after, the son isolated himself because he had been in contact with three people who tested positive for SARS-CoV-2.

The morning the patient was admitted, she developed focal status epilepticus involving her right eyelid and upper lip. She was alert without fever and her EEG showed patterns consistent with focal status epilepticus. She was treated with IV valproic acid followed by IV midazolam and her status epilepticus resolved. She had no acute findings on MRI. Her chest X-ray was normal, but lab results showed lymphopenia and thrombocytopenia.

Twelve hours after being admitted to the ED, the patient developed a fever. She had no respiratory symptoms, but her white cell and platelet counts dropped further. Based on her recent interaction with her son, she had a real-time polymerase chain reaction (RT-PCR) test and was positive for SARS-CoV2.

After treatment with lopinavir-ritonavir (Kaletra) plus hydroxychloroquine (Plaquenil), the patient improved and her fever resolved. A repeat chest X-ray and lung ultrasound were negative for interstitial pneumonia and no other seizures occurred. She was discharged 2 weeks after admission in stable condition with a negative viral PCR.

"Noteworthy, in our patient the disease did not express an important pulmonary involvement; she did not develop pneumonia nor did she require oxygen therapy," Vollono and co-authors wrote.

What happened in this case isn't entirely clear. "Drug levels were not taken at the time of admission to know if she may have been sub-therapeutic, which could itself trigger seizures," Nath said. "There is no evidence to suggest direct infection of the brain with the virus: MRI did not show any new lesions and cerebrospinal fluid was not examined."

But the presence of fever and lymphopenia with a positive PCR "does suggest a systemic infection with the virus," he observed. "It is quite possible that the infection, by triggering immune activation and cytokine release, may have been sufficient to trigger or unmask the seizure."

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