Cortical ribbon sign: Initial sign of Creutzfeldt–Jakob disease

Abstract

A 72-year-old woman with a history of hypertension and hyperlipidemia presented with difficulty in speaking and writing. She noticed she became reluctant to do calculations 3 months earlier. The symptoms of aphasia and agraphia had gradually worsened over the prior 3 weeks; thus, she visited our hospital. Physical examinations showed motor aphasia, agraphia, and a positive Barre sign on the right side; however, tendon reflexes and the finger-to-nose test were normal, and there was no decrease in temperature, pain, or touch sensation. Laboratory data and head computed tomography showed no abnormalities. She subsequently underwent brain magnetic resonance imaging (MRI), showing high signal intensity areas on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR), predominantly in the right frontal lobe region and in the bilateral occipitotemporal lobes (cortical ribbon sign) (Figure 1A,B). As the differential diagnoses included encephalitis, epileptic seizures, and Creutzfeldt–Jakob disease (CJD), she was admitted for further evaluation. The cerebrospinal fluid (CSF) was clear, with a white blood cell count of 6/μL, total protein level of 18.9 mg/dL, and glucose concentration of 63 mg/dL. Electroencephalography performed on Day 2 revealed no abnormalities, which made the diagnosis of epileptic seizures less likely. One week after admission, the patient became unable to say her name, and ataxic symptoms worsened. Given the possibility of autoimmune encephalitis, steroid pulse therapy was initiated; however, it was ineffective. Polymerase chain reaction testing for herpes simplex virus, as well as tests for anti-NMDA receptor antibody and paraneoplastic antibodies, submitted upon admission, later returned negative results, thereby ruling out encephalitis. By the third week of hospitalization, the patient had developed akinetic mutism, and myoclonus emerged on Day 25. Follow-up brain MRI one month after admission demonstrated extensive high signal intensity in the bilateral cerebral cortex and left striatum (Figure 1C,D), raising high suspicion for CJD. Electroencephalography revealed periodic sharp wave complexes (PSWC) (Figure 2). Moreover, additional CSF analysis revealed positive findings for T-Tau protein, 14-3-3 protein, and real-time quaking-induced conversion (RT-QuIC), confirming the diagnosis of CJD. Brain MRI 2 months after admission demonstrated high signal intensity in the bilateral cerebral cortex, as well as the bilateral striatum (Figure 1E,F), which was also characteristic of CJD. She was transferred to the rehabilitation hospital on Day 92.

CJD is a rare and fatal prion disease characterized by progressive dementia, typically over a period of a few weeks to months.¹ Although the diagnosis of CJD is challenging due to its non-specific manifestations, it is based on a combination of clinical symptoms, electroencephalography, CSF analysis, and MRI findings. Key clinical findings include rapidly progressive cognitive decline, ataxia, and myoclonus. Typical electroencephalography may show PSWC, whereas CSF biomarkers, such as 14-3-3 and tau proteins, are useful for diagnosis, with the RT-QuIC assay providing high sensitivity and specificity for detecting abnormal prion proteins. Moreover, brain MRI is the most useful imaging tool in assisting the antemortem diagnosis of CJD.² A characteristic MRI finding in CJD is the presence of restricted diffusion in at least two cortical regions, known as cortical ribbon sign, along with restricted diffusion predominantly in the caudate nucleus, followed by the putamen and thalamus.³ Consequently, the cortical ribbon sign could serve as a key radiological finding for the early diagnosis of CJD, and its presence should prompt physicians to consider CJD in the differential diagnosis.

Shiori Nakamichi: Conceptualization; methodology; investigation; validation; visualization; writing – original draft. Ryohei Ono: Conceptualization; methodology; investigation; validation; formal analysis; visualization; writing – original draft; writing – review and editing. Michihiro Kudo: Conceptualization; methodology; investigation; validation; visualization; writing – original draft. Shigeto Horiuchi: Conceptualization; methodology; investigation; validation; visualization; writing – original draft. Izumi Kitagawa: Conceptualization; methodology; validation; visualization; writing – review and editing; supervision.

The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Ethical approval statement: We confirm that informed consent was obtained from the patient's next of kin for publication of the clinical images and accompanying text. The patient's next of kin was informed that the images and text would be published in a journal accessible to the public, and anonymity was ensured by omitting identifiable information.

Patient consent statement: As the patient had progressive dementia, informed consent was obtained from the patient's next of kin, and patient anonymity was preserved.

Clinical trial registration: None.