key: cord-0730556-prsoqugl
authors: Shenker, Jennifer; Trogen, Brit; Schroeder, Laura; Ratner, Adam J.; Kahn, Philip
title: Multisystem Inflammatory Syndrome in Children Associated with Status Epilepticus
date: 2020-07-24
journal: J Pediatr
DOI: 10.1016/j.jpeds.2020.07.062
sha: 94056f2cc5625250fb0095ef813d0bcd8248c70e
doc_id: 730556
cord_uid: prsoqugl

nan

multisystem inflammatory syndrome in children (MIS-C). After clinical stabilization following treatment with antibiotics, remdesivir, and anakinra, the patient was noted to have episodes of altered mentation. Video EEG revealed status epilepticus, which was subsequently controlled with antiepileptic medications.

A 12-year-old male with no prior medical problems presented to the emergency department with four days of fever up to 39.5°C and two days of worsening right-sided neck swelling. The patient reported trismus, loss of smell and taste, as well as difficulty swallowing. The patient's mother reported her own loss of smell several weeks prior to presentation. Physical examination was notable for dry, cracked lips, tender right-sided neck and jaw swelling, and bilateral conjunctival injection, as well as a blanching, macular abdominal rash. Fluid resuscitation improved his tachycardia and hypotension. Initial laboratory results demonstrated leukocytosis, thrombocytopenia, acute kidney injury, and elevated inflammatory markers (Table) . SARS-CoV-2 PCR from a nasopharyngeal swab sample was positive. Neck CT showed a retropharyngeal fluid collection. The patient was started on enoxaparin, vancomycin, ampicillin-sulbactam, and clindamycin.

During initial hospitalization, the patient required supplemental oxygen and was transferred to the pediatric ICU. Retropharyngeal exploration under anesthesia revealed no discrete abscess. Post-operatively, the patient failed extubation due to acute respiratory failure, and was started on furosemide for fluid overload. On hospital day 3, the patient was given intravenous immunoglobulin (2 g/kg) for treatment of possible MIS-C, after which he became hypotensive and required an epinephrine infusion. On hospital day 6, remdesivir and anakinra were initiated, and antibiotics were narrowed to ampicillin-sulbactam. On hospital day 7, the patient was successfully extubated, and inflammatory markers began to decrease. The boy was weaned off epinephrine and furosemide infusions. He completed a 5-day course of remdesivir and continued to show improvement in laboratory findings. Serum SARS-CoV-2 IgG sent on hospital day 9 was positive.

Following extubation, the patient began to display brief, waxing and waning episodes of rapid, tangential speech, hyperactivity, and emotional lability while undergoing wean from sedation medications. Serial physical examinations identified no focal findings on neurologic examination. On hospital day 11, the patient developed an episode of altered mental status overnight, during which he became agitated and pulled out his arterial catheter. He had no memory of this event the following morning. The consulting neurologist recommended video EEG, which revealed six subclinical seizures over a 3-hour period ranging from 20 seconds to 8 minutes in duration, and the patient was treated with a loading dose of levetiracetam. Over the next 24 hours, the patient had twelve additional seizures, three of which lasted over 10 minutes.

The patient was given lorazepam and fosphenytoin with improvement in seizure frequency. He subsequently displayed a decreased level of consciousness with minimal responsiveness to commands. Video EEG indicated focal epilepsy arising in the central region with diffuse bifrontal spread and evidence for non-specific cerebral dysfunction over the frontocentral region. This evolving syndrome has been characterized by persistent fevers, elevated inflammatory laboratory markers, and single-or multi-organ dysfunction. We report MIS-C-associated status epilepticus, as defined by the Neurocritical Care Society criteria of 5 minutes or more of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery to baseline between seizures (2).

Neurologic involvement during the acute phase of SARS-CoV-2 infection has been documented among adults, with widespread reports of headache, disturbed consciousness, loss of smell and taste, paresthesias, seizures, and stroke (3, 4) . Prior studies of other severe coronavirus infections have also found central nervous system (CNS) involvement, and following the 2003 SARS outbreak, pathology reports of infected individuals identified signs of cerebral edema, meningeal vasodilation, neuronal ischemia, and demyelination, with monocytic and lymphocytic infiltration in brain vasculature (4, 5) . SARS-CoV particles were also detected in brain tissue (4, 5) .

Previous reports of MIS-C suggest a pattern of exposure to the novel coronavirus several weeks before the development of new, Kawasaki-like symptoms and rising inflammatory markers. In this case, the history of loss of olfaction in the patient's mother several weeks prior to presentation suggests a similar timeline. Although the presence of SARS-CoV-2 IgG antibodies has been reported as early as four days after symptom onset, seroconversion more frequently occurs after the second week of infection (6) . This patient's seizure activity may therefore represent a complication of the hyperinflammatory response of MIS-C rather than acute COVID-19. However, the exact etiology of his seizures remains unknown given the inability to detect viral particles in CSF, normal cell counts and protein in the CSF, and the absence of gross 6 findings of arteritis or other abnormalities on brain imaging. Status epilepticus has not been identified with use of anakinra or remdesivir.

Other hyperinflammatory syndromes are known to manifest with severe neurologic findings. Neurologic involvement has been reported in hemophagocytic lymphohistiocytosis and macrophage activation syndrome, including seizures, stroke, myelopathy, altered consciousness, nerve palsies, and demyelination (7, 8) . Kawasaki disease can rarely present with CNS findings, including decreased consciousness, seizures, and hemiplegia (9) . As an acute systemic vasculitis, some have speculated that cerebral hypoperfusion may play a role in these symptoms.

The current case illustrates the importance of recognizing potential CNS involvement during MIS-C. Clinicians treating affected patients should be highly attentive to subtle changes in clinical and mental status. Given the severity of illness in patients with MIS-C, acute changes in mental status may be masked by the use of sedating medications, and many of these patients are also at risk of delirium. Because of these confounding factors, it is even more critical that clinicians maintain a high index of suspicion for severe neurologic complications as we continue to investigate the underlying pathophysiology of this emerging clinical entity. 

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Central nervous system (CNS) involvement is a critical prognostic factor for hemophagocytic lymphohistiocytosis

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Kawasaki disease with predominant central nervous system involvement