Teaching Case

75-years-old lady presented with rapidly progressive dementia. Within two months she was unable to walk and communicate. Myoclonic jerks were also present. Lumbar puncture was performed and 14-3-3 protein was detected in high concentration in the cerebrospinal fluid. A month later she became comatose and finally passed away.

During patient’s hospitalization two brain MRI examinations were performed. The first MRI revealed on FLAIR and DWI source images a slight cortical hyperintensity in the parietal lobes. The T2-weighted images were normal (Fig. 1). A follow-up MRI one week after demonstrated on FLAIR images and DWI a more extensive cortical hyperintensity and again almost normal appearance on T2-weighted images (Fig. 2, 3).

Creutzfeldt-Jakob disease (CJD) is a rare but invariably fatal neurodegenerative illness caused by accumulation of an abnormal form of a PrP, or prion, in the brain parenchyma. Multiple forms of CJD have been described, with the sporadic form being the most commonly documented (85% of cases) [1]. Other forms of CJD are variant, familial, and iatrogenic. Variant CJD in humans caused by the transmission of bovine spongiform encephalopathy has caused renewed interest in the disease. Familial CJD is exceedingly rare and is inherited as a germline mutation in the human prion protein gene. Iatrogenic causes include ingestion of contaminated human hormone supplements, corneal transplantation, and transplantation of cadaveric dura mater. Creutzfeldt-Jakob disease occurs worldwide in late middle age and usually manifests as a rapidly progressive dementia, but the clinical symptoms are relatively nonspecific and overlap with other dementia disorders. There are often myoclonic jerks and the disease is typically associated with periodic sharp wave discharges on EEG. Detection of 14-3-3 protein in the cerebrospinal fluid (CSF) can support the diagnosis and is positive in over 90% of patients with CJD [1]. The presence of this protein should not be considered pathognomonic, however, as it can also be detected in the setting of encephalitis, hypoxic brain injury, and Alzheimer's disease; all these causes were excluded in our case. Brain biopsy is required for a definitive diagnosis but in the present case there is none because the patient's family refuse it. Most patients with suspected CJD are studied with MRI during the course of the disease to exclude other possibly treatable diseases or to support the diagnosis of CJD. Early in the disease course, brain MRI may be without any abnormality. The large majority of patients with CJD demonstrate early imaging features, when fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences are employed as part of the imaging protocol [2-3]. FLAIR images show high signal in the basal ganglia (head of the caudate nucleus, putamen, and thalamus) and in the cerebral cortex. Sometimes DWI is more sensitive than FLAIR in the detection of early CJD parenchymal abnormalities [3-5]. A recent study showed DWI abnormalities in 24 of 26 (92.3%) patients with a subacute clinical presentation. These DWI abnormalities included linear lesions with reduced water diffusivity in the cerebral cortex (41.7%), and the basal ganglia (45.8%) [6]. These early findings in CJD represent direct "prion-related injury", causing "spongiform degeneration"; late in the course of the disease [5].