Our case is a 12-year-old boy who was transferred to the Bambino Gesu Children's Hospital from another hospital in March 2022, for the management and treatment of severe neurological symptoms. The symptoms began 10 days after asymptomatic SARS-CoV-2 infection. SARS-CoV-2 infection was diagnosed by a nasopharyngeal swab polymerase chain reaction (PCR) test, which was performed after exposition to the virus. Notable neurological symptoms included irritability, headache, and difficulty in urinating. At 2 days after the onset of symptoms, the patient presented with fever, paraplegia, and loss of sensitivity from the T1 level.
His medical history included growth retardation, genetic disorder, community-acquired pneumonia, and angioedema. The individual had been administered all the mandatory vaccines in Italy. However, the SARS-CoV-2 vaccine was not administered.
Upon admission to the hospital, the child was alert and interactive. There was no cranial nerve dysfunction. Lower tendon reflexes and superficial abdominal reflexes were absent. Loss of sensitivity from the T1 level and paraplegia was observed. Dysmetria of the extremities was not present. The patient presented with bladder overdistention and fever.
The cardiorespiratory system was not involved, and O2 saturation was 100% in room air, with stable and autonomous hemodynamics.
At the onset of symptoms, a computed tomography (CT) scan of the brain was performed to exclude neurosurgical emergencies. Brain and spinal cord MRI with contrast revealed "signal alterations corresponding to the pons, the right middle cerebellar peduncle, and the subcortical white substance of the frontal lobes; the alterations at the right middle cerebellar peduncle and pons enhanced after gadolinium" (Figures 1, 2); and "signal alterations from C4 to the conus medullaris, with contrast impregnation at D1 and conus medullaris level" (Figure 3). These images were compatible with that of ADEM with spinal cord involvement. The CSF testing excluded infections, and the result was compatible with an immune-mediated disease (51 mg/dl proteins, 59/mm3 white blood cells, and 6/mm3 red blood cells). CSF and blood cultures were negative.
Band autoantibodies were not detected in the CSF liquor and blood samples, which were anti-MOG-negative and anti-AQP4-negative (measured by enzyme-linked immunosorbent assay). Laboratory tests of blood samples excluded autoimmunity, infections, and immune deficiencies.
In particular, antinuclear antibodies (ANA), extractable nuclear antigens (ENA), anti-smooth muscle antibodies (ASMA), anti-parietal cell antibodies (APCA), endomysial antibodies (EMA IgA), anti-liver-kidney microsome antibodies (LKM), antibodies to double-stranded DNA (Anti Ds-DNA), anti-neutrophil cytoplasmic antibodies (c-ANCA and p-ANCA), anti-cardiolipin antibodies, anti-beta-2-glycoprotein antibodies, and anti-citrullinated protein antibodies (anti-CCP) were negative.
Mycobacterium tuberculosis DNA was not isolated; the nasopharyngeal swab was negative for respiratory viruses. Laboratory tests of blood samples were negative for other infections; in particular, cytomegalovirus (CMV), hepatitis B (antibodies positive for vaccination), hepatitis A (antibodies positive for vaccination), hepatitis C, Treponema pallidum, human immunodeficiency virus (HIV), and saccharomyces cerevisiae, were tested.
Lymphocyte subpopulations were normal.
Electroencephalography (EEG) was normal. The cardiological evaluation did not reveal any problems. Neurophysiological studies revealed normal visual evoked potentials (VEPs), whereas somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were altered.
High-dose steroids (30 mg/kg/day for 3 days) and intravenous immunoglobulin (IVIG; 2 g/kg/day) were administered to the patient without any clinical improvement. The patient received five cycles of plasma exchange therapy, after the parental declaration of informed consent, followed by off-label rituximab infusion (weekly infusion for 4 weeks) as reported in recent pediatric severe cases of ADEM. The patient showed partial clinical improvement along with important radiological improvement.
After the initial therapy with steroids and IVIG, no improvement was observed. Subsequently, plasma exchange therapy and rituximab infusion led to an important improvement that was documented in the brain and spinal cord MRI without contrast, performed 3 months later. At the spinal cord level, a reduction in alteration was observed (Figure 4), and no alterations were observed in the brain (Figures 5, 6). Clinically, the patient reported urinary complications of the neurogenic bladder. Unfortunately, paraplegia persisted, and the patient continued motor physiotherapy.