Creutzfeldt-Jakob Disease (CJD): Causes, Pathophysiology, Imaging, and Clinical Insights

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Keywords: Creutzfeldt-Jakob Disease, Prion Disorders, Rapidly Progressive Dementia, MRI Cortical Ribboning, Transmissible Spongiform Encephalopathy

Introduction

Creutzfeldt-Jakob disease (CJD) is a rare, fatal, and rapidly progressive neurodegenerative disorder classified under transmissible spongiform encephalopathies (TSEs). The disease is caused by misfolded prion proteins that accumulate in the brain, leading to neuronal death and spongiform degeneration. Although rare, with an incidence of 1–2 cases per million annually, its devastating progression and lack of treatment make it a critical subject for clinicians, researchers, and public health experts.

This article provides a comprehensive overview of CJD, covering its cause, etiology, pathophysiology, epidemiology, clinical presentation, imaging features, treatment, and prognosis, while incorporating figures and case data from the provided case study.

Case Presentation

A 56-year-old woman presented with several months of behavioral disturbances, depressed consciousness, and seizure-like activity. Neurological examination revealed myoclonus.

Imaging Findings

CT Findings (Figure 1):
Axial non-contrast CT scan demonstrated no evidence of mass, hemorrhage, or hydrocephalus. Acute infarction was not observed. Essentially, a normal CT examination.

Figure 1. Axial non-contrast CT of the brain in a CJD patient.

  • MRI Findings (Figure 2):
    MRI demonstrated restricted diffusion in the bilateral basal ganglia and cerebral cortex, with mild T2 hyperintensity. DWI abnormalities extended into the thalamus, showing classic cortical ribboning and the hockey stick sign.

Figure 2. Axial MRI showing diffusion restriction and cortical ribboning in CJD.

Diagnosis was confirmed as Creutzfeldt-Jakob disease.

Etiology and Pathophysiology

CJD results from the accumulation of misfolded prion proteins (PrP^Sc) that induce conformational change in normal cellular prion proteins (PrP^C). This process triggers aggregation, neuronal loss, and the spongiform changes that characterize the disease.

Subtypes of CJD

  1. Sporadic CJD (sCJD): Accounts for ~85% of cases, arising spontaneously without an identifiable cause.

  2. Familial CJD (fCJD): Caused by PRNP gene mutations; accounts for 10–15% of cases.

  3. Iatrogenic CJD: Transmitted via contaminated neurosurgical instruments, dura mater grafts, or human pituitary-derived hormones (<5% of cases).

  4. Variant CJD (vCJD): Linked to bovine spongiform encephalopathy (“mad cow disease”), often affecting younger individuals.

Epidemiology

  • Incidence: 1–1.5 cases per million population annually.

  • Age of onset: Typically between 50–70 years.

  • Geographic variation: Sporadic CJD occurs worldwide; variant CJD cases have clustered in the UK and Europe due to BSE exposure.

Clinical Presentation

CJD is distinguished by rapidly progressive dementia combined with neurological signs:

  • Cognitive decline: Memory impairment, executive dysfunction.

  • Behavioral changes: Depression, psychosis, irritability.

  • Neurological symptoms: Ataxia, myoclonus, visual disturbances, pyramidal/extrapyramidal signs.

  • Seizures: Occasionally observed.

Median survival is less than one year after symptom onset.

Imaging Features

CT

  • Often normal in early stages.

  • Rarely shows cerebral atrophy or non-specific white matter changes.

MRI

  • Cortical ribboning: Hyperintensity along cortical gyri on DWI/FLAIR.

  • Basal ganglia involvement: Especially the caudate and putamen.

  • Thalamic signs:

    • Hockey stick sign – hyperintensity in dorsomedial thalamic nuclei.

    • Pulvinar sign – hyperintensity in the posterior thalamus (seen in vCJD).

  • Cerebellar atrophy: Seen in late stages.

PET/SPECT

  • It can reveal hypometabolism in affected regions, though less routinely used.

Diagnosis

  • EEG: Periodic sharp wave complexes (PSWCs) in ~74% of patients.

  • CSF biomarkers: The Presence of 14-3-3 protein and RT-QuIC assay is highly specific.

  • Definitive diagnosis: Post-mortem neuropathology.

Treatment

Currently, no curative therapy exists. Management focuses on:

  • Supportive care: Symptom relief, palliative management.

  • Seizure control: Anticonvulsants may be required.

  • Experimental therapies: Immunotherapy and prion-protein-targeting strategies are under investigation but remain unproven.

Prognosis

  • Median survival: 4–12 months after onset.

  • 90% of patients die within one year.

  • Outcome is universally fatal despite supportive interventions.

Quiz Section


Q1: What did the CT scan in this patient reveal?

A. Normal examination

B. Diffuse cerebral edema

C. Chronic subdural hematoma

D. Normal pressure hydrocephalus

E. Acute transcortical infarction


Q2: Which imaging sign is most characteristic of CJD?

A. Cortical ribboning

B. Hot cross bun sign

C. Butterfly glioma pattern

D. Ring-enhancing lesion


Q3: Which type of CJD is linked to bovine spongiform encephalopathy (BSE)?

A. Sporadic CJD 

B. Familial CJD

C. Iatrogenic CJD

D. Variant CJD


Q4: Which biomarker in CSF is strongly associated with sporadic CJD?

A. Tau protein

B. Beta-amyloid

C. 14-3-3 protein

D. S100 protein


Q5: What is the median survival time after onset of CJD symptoms?

A. 1–2 months

B. 4–12 months

C. 2–3 years

D. >5 years


Answer & Explanation

1. Answer: A. Normal examination. Explanation: Most CJD cases have unremarkable CT findings in early disease.

2. Answer: A. Cortical ribboning. Explanation: DWI/FLAIR cortical hyperintensity is a hallmark of CJD.

3. Answer: D. Variant CJD. Explanation: Variant CJD is transmitted through the consumption of BSE-contaminated beef.

4. Answer: C. 14-3-3 protein. Explanation: CSF 14-3-3 is highly specific for sporadic CJD.

5. Answer: B. 4–12 months. Explanation: CJD is rapidly progressive, with most patients dying within a year.


References

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[2] D. C. Fragoso, A. L. Gonçalves Filho, F. T. Pacheco, et al., “Imaging of Creutzfeldt-Jakob disease: Imaging patterns and their differential diagnosis,” Radiographics, vol. 37, no. 1, pp. 234–257, 2017.
[3] Y. Iwasaki, “Creutzfeldt-Jakob disease,” Neuropathology, vol. 37, no. 2, pp. 174–188, 2017.
[4] S. Mead, “Prion disease genetics,” European Journal of Human Genetics, vol. 14, pp. 273–281, 2006.
[5] P. Gambetti, M. Cali, and W. Q. Zou, “Sporadic and familial CJD: classification and characterization,” British Medical Bulletin, vol. 66, pp. 213–239, 2003.
[6] J. Collinge, “Prion diseases of humans and animals: their causes and molecular basis,” Annual Review of Neuroscience, vol. 24, pp. 519–550, 2001.
[7] M. Zeidler, R. J. Ironside, and R. G. Will, “Variant Creutzfeldt-Jakob disease,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 68, no. 6, pp. 727–733, 2000.

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