Cytotoxic Lesion of the Corpus Callosum in an Adolescent with Multisystem Inflammatory Syndrome and SARS-CoV-2 Infection

Case Presentation

A 13-year-old previously healthy girl, who relocated from New York to Georgia a month prior, presented to the emergency department after 3 days of fever, vomiting, diarrhea, cough, dizziness, and gait instability. The only medications given before admission were aspirin and ibuprofen. On presentation to Egleston Hospital of Children's Healthcare of Atlanta, she had a fever of 39.2°C, hypotension initially requiring pressor support, normal white blood cell count (9780 cells/µL) with increased neutrophils (88%) and lymphopenia (7%), thrombocytopenia (121,000 cells/µL), hyponatremia (128 mmol/L), elevated transaminases (aspartate aminotransferase = 292 U/L, alanine aminotransferase = 336 U/L), acute kidney injury (creatinine = 1.09 mg/dL), elevated inflammatory markers (C-reactive protein = 10.9 mg/dL, erythrocyte sedimentation rate = 63 mm/h, interleukin 6 = 65 pg/mL), and elevated cardiac markers (troponin = 18.2 ng/mL, brain natriuretic peptide = 561 pg/mL). She was admitted to the pediatric intensive care unit for presumed bacterial sepsis and started on ceftriaxone and vancomycin.

On hospital day 1, she began to have hallucinations in addition to urinary retention, prompting neurology consultation. On neurologic examination, she was agitated and combative with a variable rate of speech. She had intermittent auditory hallucinations. Her attention fluctuated. She was able to follow 1- but not 2-step directions. Cranial nerve function was normal without clinical evidence of anosmia. Muscle tone was decreased with symmetric antigravity movement of all extremities. Sensation to light touch was intact throughout. Deep tendon reflexes were 1+ with absent ankle jerks. Contrast-enhanced MR imaging of the brain (Magnetom Avanto, 1.5T; Siemens) on hospital day 1 demonstrated an abnormal focal nonenhancing lesion with increased intensity on T2-weighted sequences and restricted diffusion in the splenium of the corpus callosum (Figure). Findings on MR imaging of the spine were normal. CSF studies were unremarkable (4 white blood cells (WBC)/μL, glucose = 83 mg/dL, protein = 32 mg/dL). The electroencephalogram showed diffuse slowing without epileptiform discharges or seizures. On hospital day 2, the patient developed tachypnea requiring escalation of respiratory support to bilevel positive airway pressure, though no desaturation or hypoxemia was noted. The echocardiogram revealed depressed cardiac function with a left ventricular ejection fraction of 38%. Intravenous immunoglobulin (IVIG), 2 g/kg, was administered on hospital day 2, given concerns for atypical Kawasaki-like multisystem inflammatory state.

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FIGURE.

CLOCC in an adolescent with MIS-C and SARS-CoV-2.. MR image of the brain demonstrates a nonspecific focus of increased signal in the splenium of the corpus callosum on DWI sequences at b=1000 s/mm² (black arrow, A) with associated loss of signal on apparent diffusion coefficient maps (white arrow, B) corresponding to restricted diffusion. The apparent diffusion coefficient for the lesion is 0.44 × 10⁻³mm²/s. This lesion corresponds to a faint focus of abnormal increased signal on T2WI spin-echo sequences (black arrowhead, C). The lesion also demonstrates a lack of contrast enhancement on T1WI postcontrast thin-section image (D) and absent susceptibility, suggesting absent hemorrhage on SWI (E). The imaging findings suggest a cytotoxic lesion of the corpus callosum. Follow-up DWI (F) and ADC maps (G) with T2WI (H), T1WI (I), and SWI sequences (J) after 2.5 months demonstrate resolution of the lesion after therapy.

Extensive infectious and autoimmune investigations were performed. Respiratory viral panel and initial SARS-CoV-2 polymerase chain reaction (PCR) findings on admission were negative. The remainder of infectious evaluation was negative (CSF meningitis panel, CSF and serum arboviral panels, serum viral studies including coxsackie A9 antibody, West Nile virus antibodies, human immunodeficiency virus antigen and antibody, enterovirus PCR, parvovirus B19 PCR, adenovirus PCR, and Epstein-Barr virus PCR). The serum autoimmune encephalopathy panel had a mildly elevated glutamic acid decarboxylase antibody (0.17 nmol/L) in the setting of recent IVIG administration and was thought to likely be a false-positive. Antinuclear antibody titer was elevated to 1:320 with a negative antibody reflex panel. The remainder of autoimmune work-up had negative findings (CSF oligoclonal bands, immunoglobulin G index, CSF autoimmune encephalopathy panel, serum thyroglobulin and antithyroid peroxidase antibodies, myelin oligodendrocyte glycoprotein antibody, aquaporin-4 antibody). Given the high level of suspicion, SARS-CoV-2 PCR was repeated on hospital day 3 and found to be positive. Qualitative COVID-19 immunoglobulin G in serum drawn on hospital day 2 before IVIG administration was also positive.

During the next few days, the patient’s mental status improved gradually; however, she remained weak and tendon reflexes were persistently absent in the ankles. Creatine kinase was elevated (3600 U/L, normal = 50–275 U/L), and the electrodiagnostic study performed on hospital day 5 was unremarkable with no evidence of polyneuropathy or myopathy. On hospital day 6, respiratory support was weaned to nasal cannula, and she was able to stand unassisted. The repeat echocardiogram demonstrated return to normal cardiac function, and laboratory markers normalized. She was transferred out of the intensive care unit and discharged home 12 days following the initial presentation with follow-up in the pediatric neurology clinic scheduled. Furthermore, subsequent research laboratory studies on the CSF did not detect the presence of SARS-CoV-2 by PCR. An indirect enzyme-linked immunosorbent assay for CSF showed increased levels of immunoglobulin M (1:64) for SARS-CoV-2 S1 and E (envelope) proteins (90% sensitivity, 89% specificity; courtesy of the Dr. William Hu Laboratory, Emory University).