J Korean Med Sci.  2023 Mar;38(10):e78. 10.3346/jkms.2023.38.e78.

Sudden Death Associated With Possible Flare-Ups of Multiple Sclerosis After COVID-19 Vaccination and Infection: A Case Report and Literature Review

• Jeon YH
• Choi S
• Park JH
• Lee JK
• Yeo NS
• Lee S
• Suh YL

• KMID: 2540428
• DOI: http://doi.org/10.3346/jkms.2023.38.e78

Abstract

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.

Keyword

Multiple Sclerosis; COVID-19; Vaccine; Autopsy

Figure

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  Fig. 1 Timeline of the antemortem medical history of the deceased.BG = basal ganglia, CSF = cerebrospinal fluid, MRI = magnetic resonance imaging, OD = oculus dexter, PCR = polymerase chain reaction, URI sx = upper respiratory infection symptom, WM = white matter.

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  Fig. 2 Gross findings of the brain.(A-F) Coronal sections of the brain revealed multifocal, well-demarcated, gray-tan, demyelinated plaques (indicated by yellow arrows) in the deep white matter (B, C), corpus callosum and periventricular area (E, F). (B, E) are close-up photographs of sections in (A, D) respectively. The demyelinated plaques are different in their size and shape (B, C, E, and F). Sections in (C, F) are formalin-fixed. The venocentric distribution of the demyelinated plaques is grossly identified.

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  Fig. 3 Gross-microscopic correlation of the multifocal lesions of the brain.The demyelinated plaque shown in (A-D) located at periventricular area and abuts basal ganglia. Local infiltrates of macrophages and lymphocytes are present in the plaque (B). LFB stain revealed myelin loss in the plaque, and a finger-like appearance of perivascular demyelination (C). Gliotic fibers are densely condensed within the plaques (D). The demyelinated plaque shown in (E-H) is hypercellular (F), sharply demarcated (G) and contains abundant macrophages and CD45-positive perivascular lymphocytic infiltrations in the plaque (H). The demyelinated plaque shown in (I-L) is a chronic active plaque and consists of central hypocellular inactive center and peripheral rim of macrophage. The macrophage infiltration as shown by CD68 immunostain is not evenly distributed but located preferentially in the peripheral edge of the plaque forming a “rim” (L).Types of staining: (B, F, and J) H&E; (C, G and K) LFB; (D, H, and L) IHC staining for GFAP, CD45 and CD68. Original magnification: (B-D) ×25; (F-H) ×25; (J-L) ×25.H&E = hematoxylin and eosin, LFB = Luxol fast blue, IHC = immunohistochemical, GFAP = Glial fibrillary acidic protein.

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  Fig. 4 Demyelinating plaque of different stages.The upper (A) and upper (D) correspond to the center of the plaques, (black asterisk of B and white asterisk of C) while the lower (A) and lower (D) correspond to the peri-plaque area. The center of the plaque shows diminished but not absent myelin fiber (A) and dense gliotic fiber (D). The lesion shown in (E-H) has abundant and evenly distributed macrophages in the plaque. The myelin loss of the plaque is identified (E). CD68-positive macrophages are abundant in the plaque (F). PAS-positive debris in the macrophage are identified (G). Immunohistochemical stain for phosphorylated NF revealed the relative axonal preservation in the plaque (H). The lesion shown in (I-L) abuts the lateral ventricle. Relatively well-defined demyelination is observed and highlighted on LFB (I-J). A peripheral rim of CD68-positive macrophage is observed (K). CD45-positive lymphocytes are located in the edge of the plaque (L). Perivascular lymphocytic cuffing in the parenchyma was frequently observed (M, N) along with lymphocytic infiltration in the leptomeninges (O, P).Types of staining: (A, B, E, and I) LFB; (C, D) GFAP; (F, K) CD68; (G) PAS; (H) phosphorylated NF; (J, M, N, O, and P) H&E; (L) CD45. Original magnification: (A) ×50; (B, C) ×25; (D) ×50; (E) ×50; (F) ×200; (G) ×400; (H) ×200; (I-L) ×25; (M) ×200; (N, O) ×100; (P) ×400.LFB = Luxol fast blue, GFAP = Glial fibrillary acidic protein, PAS = Periodic acid Schiff, NF = neurofilament, H&E = hematoxylin and eosin.

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