Purpose: Infectious spongiform encephalopathy, also known as prion disease (PrD), is a rare, fatal central nervous system degenerative disease with hereditary, infectious, and sporadic features, and PrD is both neurodegenerative and infectious. In this paper, we summarize the clinical manifestations, imaging and pathological features, as well as biopsy precautions and instrument sterilization techniques, in relation to the data of eight patients with pathologically confirmed stereotactic brain tissue biopsies in our department. METHODS: The clinical and imaging and pathological data of the eight patients biopsied in our department were retrospectively analyzed. RESULTS: The age of the patients in this group ranged from 23 to 59 years old, with an average of 47.6 years old, 6 males and 2 females, with a short disease duration of 4.2 months on average. The initial stage of the disease was mostly characterized by general symptoms such as general fatigue, visual disturbances, depression, and insomnia, and the patients rapidly progressed to mental or cognitive disorders within a short period of time. The early symptoms of mental confusion and progressive memory loss accounted for 70% of the cases. 5 cases in this group had the typical “triad” of progressive dementia, ataxia and myoclonus. Pathology showed vacuolization of neurons and astrocytes, sponge-like degeneration of neurons and their synapses; amyloid plaque formation; no inflammatory reaction and inflammatory cell infiltration. The spongy changes are mainly located in the neocortex, inferior hippocampal peduncle, caudate nucleus, shell nucleus, thalamus, and molecular layer of cerebellar cortex, with amyloid plaque deposition on top of this in 50% of cases. characteristic MRI changes are mainly characterized by high signal in the head of shell nucleus and caudate nucleus, ribbon-like high signal in the cerebral cortex; extensive ribbon-like high signal in the cerebral cortex (at least 3 cerebral cortexes), with normal white matter in the corresponding subcortex, and TIWI was normal. Conclusion: CJD is most common with spongy degeneration in the cortex and striatum, and the biopsy target should be selected at the most obvious lesion, but the cortex is difficult to retrieve and bleeds easily, and the striatum is in the functional area, so the biopsy path and target design are crucial, and a needle path can be designed with the assistance of advanced planning software for multi-point retrieval and subcortical gray-white matter intersection to ensure the positive rate of biopsy. Prion is very persistent and super infectious, we must strengthen prevention and eliminate medical transmission; try to use stereotactic guided brain biopsy, not open biopsy; surgical dressings, biopsy needles, and guiding clips combined with the guiding frame are disposable, and avoid biopsy needles touching any guiding equipment other than guiding clips during surgery; all used dressings and disposable instruments are collected uniformly; specimens should be sent to the professional pathology department with detection All used dressings and disposable instruments are collected uniformly; specimens should be sent to professional pathology departments with CJD qualification, and sectioning and staining equipment should be dedicated to specific diseases to prevent cross-transmission.