Fatal Familial Insomnia (FFI) is a rare prionopathy with autosomal dominant inheritance. Although it owes its name because insomnia is one of the most frequent and core symptoms, its clinical phenotype can be wide and heterogeneous. This usually makes it necessary to rule out other clinical processes, such as limbic encephalitis or Creutzfeldt Jakob disease, whose symptoms can sometimes overlap. We present the case of a 46-year-old male with a rapidly progressive multidomain cognitive impairment, associated with instability in gait, myoclonus and persistent and progressive insomnia. His mother had died from a genetically determined FFI (D178N mutation). Due to clinical course, an immunomediated encephalopathy was suspected, and immunosuppressive treatment with steroids and immunoglobulins was initiated. The patient showed initial improvement, but later rapidly progressive deterioration until his death 7 months after clinical onset. Cranial magnetic resonance, electroencephalogram and cerebrospinal fluid (CSF) did not show any findings. The antiTPO and antineuronal antibodies were negative. The genetiic study demonstrated the missense mutation c.532G > A (p.Asp178Asn) compatible with FFI. Postmortem study showed synaptic deposits of PrPsc in the entorhinal cortex and in thalamus, which confirmed FFI diagnosis.

中文翻译：

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致死性家族性失眠：免疫治疗早期反应的新病例描述

致死性家族性失眠症 (FFI) 是一种罕见的常染色体显性遗传朊病毒病。虽然它的名字是因为失眠是最常见和最核心的症状之一，但其临床表型可能广泛且异质性。这通常需要排除其他临床过程，例如边缘系统脑炎或克雅氏病，它们的症状有时会重叠。我们介绍了一名 46 岁男性患有快速进展的多域认知障碍的案例，与步态不稳、肌阵挛以及持续和进行性失眠有关。他的母亲死于基因决定的 FFI（D178N 突变）。由于临床病程，怀疑免疫介导性脑病，并开始使用类固醇和免疫球蛋白进行免疫抑制治疗。患者表现出初步改善，但后来迅速进行性恶化，直至临床发病7个月后死亡。颅核磁共振、脑电图和脑脊液 (CSF) 未显示任何发现。抗TPO和抗神经元抗体均为阴性。遗传学研究证明了与 FFI 兼容的错义突变 c.532G > A (p.Asp178Asn)。尸检研究显示内嗅皮层和丘脑中的 PrPsc 突触沉积物，这证实了 FFI 诊断。