A 2-year-old Japanese female with no history suggestive of any immune system or metabolic disorder visited our institute before the coronavirus disease (COVID-19) outbreak. She presented with fever 2 days before admission (day 1) and manifested cervical lymphadenopathy on day 2. On day 3, it was observed that she had a persistently high fever, numerous coalescent red spots on the trunk and limbs, peripheral edema, conjunctival injection, and a strawberry tongue. The initial laboratory evaluation showed leukocytosis (24,200/muL) and an elevated C-reactive protein (CRP) level (11.6 mg/dL). A diagnosis of KD was made, and she was admitted to our hospital where she was treated with intravenous immunoglobulin (IVIG), a dose of 2 g/kg/day, and oral aspirin. The recrudescent fever required another IVIG treatment (2 g/kg/day) on day 7. A high fever recurred on day 11, but no other clinical features of KD were present. Laboratory data revealed a decreased white blood cell (WBC) count (6,610 /muL) and CRP level (0.70 mg/dL).
On day 12, the patient experienced episodes of vomiting and a cluster of generalized tonic-clonic seizures without recovery of consciousness. The seizures resolved with multiple intravenous infusions of midazolam. The patient's body temperature was 40.1 C, and her blood pressure 107/58 mmHg. She did not have any upper respiratory tract symptoms or diarrhoea. Laboratory data showed a normal WBC count (7,620/muL), moderately increased CRP level (3.24 mg/dL), and mild hyponatremia (131 mEq/L). Serum glucose was 173 mg/dL, and alanine transaminase and aspartate aminotransferase levels were elevated at 110 and 185 IU/L, respectively. Cerebrospinal fluid (CSF) analysis did not show pleocytosis, but the protein level was elevated to 90 mg/dL. Blood and CSF culture were negative. The FilmArray  Meningitis and Encephalitis Panel (BioFire Diagnostics/Biomerieux, Salt Lake City, Utah), a pathogen-specific polymerase chain reaction testing of CSF capable of simultaneously detecting 6 bacteria, 7 viruses and a yeast, yielded negative results. Cranial computed tomography (CT) revealed no abnormalities. After convulsive status epilepticus, electroencephalography (EEG) showed a high-amplitude diffuse slowing background without ictal activity. During the interictal period, the patient could communicate with her parents and drink water.
Several convulsive seizures were observed on day 13. Moreover, the patient's mental status started to worsen and she became lethargic. MRI T2-weighted images (T2WI) showed bilateral symmetrical hyperintensities in the cerebral white matter and thalamus. The white matter lesions were observed predominantly in the subcortical white matter and sparsely in the internal capsule and corpus callosum (Figure 1). Linear radial hyperintensities parallel to the cerebral vessels of the periventricular space were also observed (Figure 1C). The white matter lesions were isointense on a T1-weighted image (T1WI), and there were hyperintense signals on fluid-attenuated inversion recovery (Figures 2A,B). The lesions showed no gadolinium enhancement (Figure 2C). The cerebral white matter displayed iso-intensity on diffusion-weighted images (Figure 2D), with high intensity on the apparent diffusion coefficient map (Figure 2E). These findings suggested vasogenic edema. Susceptibility-weighted images did not show any hemorrhages.
Eight hours after the MRI examination, the patient had abrupt cessation of spontaneous breathing that required intratracheal intubation and mechanical ventilation. Her pupillary light reflexes were absent, and her EEG showed diffuse low activity. Head CT demonstrated diffuse swelling of the cerebrum, cerebellum, and brainstem, with sulcal and cisternal effacement, suggesting brain herniation (Figure 2F). We diagnosed the patient with acute encephalitis related to KD based on the clinical manifestations, such as high fever, a cluster of seizures, vomiting, altered mental status, and neuroradiological abnormalities. We started intensive treatment with intravenous methylprednisolone, plasma exchange, mannitol, inotropic agents, and target temperature monitoring, but these were not effective for the brain swelling. The patient developed neurogenic pulmonary edema and central diabetes insipidus. The background activity on the EEG remained severely depressed, and the brainstem reflexes did not recover, and the patient died due to septic shock on day 41. Echocardiography was performed on days 3, 5, 6, 8, 11, and 13, and it did not show any coronary artery lesions. The additional laboratory tests for serum anti-myelin oligodendrocyte glycoprotein antibody and anti-N-methyl-D-aspartate receptor antibody in the CSF were negative.