A Case of Progressive Multifocal Leukoencephalopathy in a Child with Hyper-Immunoglobulin M Syndrome: The Impact of Missed Care during the COVID-19 Pandemic

Abstract

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal subacute demyelinating disease of cerebral white matter caused by the human polyomavirus 2, commonly known as the John Cunningham virus (JCV) [1]. PML is primarily reported in patients with severe immunosuppression caused by human immunodeficiency virus (HIV) infection, hematologic malignancy, or immunosuppressive therapy, including natalizumab for multiple sclerosis and rituximab for Crohn’s disease [1]. However, PML has also been reported in primary immunodeficiencies (PID), including those with hyper-immunoglobulin M syndrome (HIGM), common variable immunodeficiency, and Wiskott-Aldrich syndrome [2]. In this case study, we describe PML in an immunocompromised child with HIGM during the coronavirus disease 2019 (COVID-19) pandemic. A 6-year-old boy with a history of HIGM was examined after experiencing 3 weeks of left-side weakness in June 2021. The patient had a history of recurrent otitis media and pneumonia since 12 months of age and pertussis at 30 months of age. The patient was diagnosed with HIGM after the pertussis workup. The patient had no family history of immunodeficiency, and his development was normal. The patient had been treated with monthly intravenous immunoglobulin (IVIG) replacement therapy, which had been discontinued 7 months previously because the patient’s parents thought it would be risky to visit a hospital during the COVID-19 pandemic and underestimated the risk of opportunistic infections. The patient had been showing fatigue and poor concentration for 3 weeks prior to the visit and decreased left hand and arm movement for 10 days prior to the visit. The patient did not show signs of upper respiratory or gastrointestinal infection symptoms. The patient was mentally alert; however, a physical examination revealed additional central left facial palsy, urinary incontinence, mutism, and cognitive decline. The patient’s motor grade of the left upper extremity was rated as grade III, and the left lower extremity was rated as grade IV. Right upper and lower motor function was intact. No pathologic reflexes were found. Serum inflammatory markers, including C-reactive protein and the erythrocyte sedimentation rate, were within the normal range. Lymphocyte subset counts were also within the normal range for the patient’s age (Table 1). Serum immunoglobulin (Ig) G and IgA levels were extremely low, with