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Eosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare rheumatic immune disease characterized by vasculitis of small- and medium-sized blood vessels. Central nervous system (CNS) involvement frequently consists of cerebrovascular disease; a manifestation with multiple demyelinating lesions has never been reported in detail. This report describes a 38-year-old man, who presented with progressive memory deterioration and underwent microsurgery; EGPA was subsequently confirmed. Unique clinical and radiological features as well as immunohistological outcomes and DNA sequencing revealed a potential disease-associated human leukocyte antigen (HLA) type, and single-nucleotide polymorphisms (SNPs) are described for this uncommon case. Although EGPA rarely involves the CNS, this differential diagnosis should be considered when patients present with a history of nasosinusitis, elevated eosinophil percentage, clinical pulmonitis, and neurological manifestations. Microsurgery is necessary for precise diagnosis and effective treatment.