Clinical and Neuropathological Variability in Clinically Isolated Central Nervous System W hipple's Disease

Central nervous system Whipple's disease ( CNS ‐ WD ) with clinically isolated neurological involvement is a rare condition fatal without an early diagnosis. We aimed to present clinical and neuropathological features of three cases of pre‐ or post‐mortem polymerase chain reaction confirmed CNS ‐ WD with distinct clinical presentation, outcome and pathological findings. One patient had an acute onset with spinal and brainstem involvement and died without CNS ‐ WD diagnosis after 14 weeks. Neuropathology showed extensive inflammatory and necrotizing lesions with abundant foamy periodic‐acid‐ S chiff ( PAS )+ macrophages. The second patient had a subacute evolution with late CNS ‐ WD diagnosis and death occurring 18 months after onset despite antibiotic treatment. Brain examination showed inflammatory lesions in the brainstem, thalamus and cerebellum, and abundant foamy PAS + macrophages. The third case was diagnosed within 4 weeks of onset and treated with an excellent response. He died after a disease‐free period of 24 months of unrelated causes. Neuropathology showed cystic residual lesions devoid of microorganisms without inflammatory reaction. CNS ‐ WD may have an acute or subacute course with variable response to treatment. Accordingly, subjacent lesions may be those of a severe acute necrotizing encephalitic process or subacute inflammatory lesions involving diencephalic, brainstem, cerebellar and spinal regions. Chronic, cavitary brain lesions may be sequelae of a successful treatment. Early diagnosis should allow appropriate treatment and improve prognosis.