key: cord-034156-adcnahpn
authors: Kim, Michael G.; Stein, Alan A.; Overby, Philip; Kleinman, George; Nuoman, Rolla; Gulko, Edwin; Al-Mufti, Fawaz; Pisapia, Jared M.; Muh, Carrie R.
title: Fatal Cerebral Edema in a Child with COVID-19
date: 2020-10-22
journal: Pediatr Neurol
DOI: 10.1016/j.pediatrneurol.2020.10.005
sha: 
doc_id: 34156
cord_uid: adcnahpn

nan

Many patients with the pediatric multisystem inflammatory syndrome (PMIS) associated with COVID-19 present without respiratory symptoms. [1, 2] We present a pediatric patient with COVID-19 who experienced rapid neurologic deterioration, diffuse cerebral edema, and ultimately brain death secondary to PMIS.

A 7-year-old male with no significant past medical history presented with three days of fever up to 102.4F, headaches, abdominal pain, and intractable emesis. He denied neck stiffness, photophobia, diarrhea, rhinorrhea, cough, and dyspnea. His parents had tested positive for SARS-CoV-2 four weeks prior with subsequent symptom resolution. A nasopharyngeal swab tested positive for SARS-CoV-2 RNA by PCR. His serum inflammatory labs showed a normal procalcitonin, ferritin, and white blood cell count, but had an elevated C-reactive protein of 13 mg/dL (0.00-0.50 mg/dL), erythrocyte sedimentation rate of 38 mm/hr (0-15 mm/hr), and Ddimer of 6.54 mg/L (<0.59 mg/L). An electrocardiogram was normal. A computed tomography (CT) venogram of his head was negative for any intracranial pathology.

On his second day of admission, he developed severe neck pain and headache. He received one dose of hydroxychloroquine and soon after developed a facial rash, altered mental status, expressive aphasia, and pinpoint but reactive pupils. He then became unresponsive with left gaze deviation, a positive Brudzinski's sign, and decreased neck range of motion. A noncontrast CT and CT angiography of the brain revealed no intracranial pathology. The patient received levetiracetam, lorazepam, vancomycin, and ceftriaxone. He was transferred to the pediatric intensive care unit and an electroencephalogram (EEG) showed no evidence of paroxysmal activity. Over the following seven hours, the EEG developed intermittent polymorphic delta activity in the right temporal region, then loss of fast activity over the right hemisphere with increased delta activity in the left hemisphere, and then bilateral generalized voltage attenuation. He was found to be extensor posturing with fixed and dilated pupils and absent brainstem reflexes. He was intubated and a CT scan of the head revealed new loss of gray-white differentiation with diffuse cerebral edema. Repeat lab results were consistent with severe inflammation, including procalcitonin 6.68 ng/mL (0.15-2.00 ng/mL), ferritin 1601.2 ug/L (18.0-370.0 ug/L), C-reactive protein 22 mg/dL, and D-dimer 17.65 mg/L. However, his erythrocyte sedimentation rate was 14 mm/hr and his white blood cell count was 6.5 k/mm 3 (5.3-15.0 k/mm 3 ). An intracranial pressure monitor was placed and revealed pressures greater than 76 mmHg, which remained refractory despite aggressive medical therapy. His neurologic exam became consistent with brain death and his family elected to withdraw life-sustaining treatment. Pathology slides showed diffuse cerebral edema in both the gray and white matter with perivascular mononuclear infiltrates, consistent with diffuse inflammation (Figure 1 ). There were no microglial nodules or neuronophagia, which would have been suggestive of viral encephalitis. Cerebrospinal fluid and brain parenchyma did not have evidence of SARS-CoV-2 on PCR testing. There was no immunohistochemical, molecular, or electron microscopic evidence of SARS-CoV-2. No vasculitis was seen.

The exact etiology of PMIS is unknown. Pediatric patients present with signs of inflammation in multiple organ systems causing features such as fatigue, neck pain, abdominal pain, diarrhea, vomiting, kidney injury, rash, conjunctivitis, extremity edema, myocarditis, and cardiogenic shock. Laboratory biomarkers are consistent with inflammation, often similar to late stage severe COVID-19 in adults with cytokine storms, hyperinflammation, and multiorgan damage. [3, 4] An overproduction of pro-inflammatory cytokines can cause vascular injury, cell death, and increased vascular permeability, which could account for the cerebral edema in our patient. It is unclear why PMIS presents in a delayed fashion in pediatric patients who otherwise J o u r n a l P r e -p r o o f Kim 4 did not manifest the early stages of COVID-19. Children with suspected PMIS and neurologic symptoms should be closely monitored and anti-inflammatory therapies should be considered.

J o u r n a l P r e -p r o o f

Health Alert #13: Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID

Hyperinflammatory shock in children during COVID-19 pandemic

Pediatric COVID-associated Multi-system Inflammatory Syndrome (PMIS)

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

COVID-19 and Kawasaki Disease: Novel Virus and Novel Case

Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

The surrounding cortex is edematous and the neurons are hyperchromatic. Immunostains for CD 3, a T-cell lymphocyte marker (B), and CD 163, a histiocyte marker (C), show a mixed inflammatory infiltrate consisting of T-cells and histiocytes within both the meninges and cerebral cortex. An electron micrograph reveals vesiculo-vacuolar organelles within the cerebral endothelial cells with no evidence of virions (D)