Creutzfeldt‑Jakob Disease Masquerading as Stroke: An Unusual Clinical Presentation

Atypical Creutzfeldt-Jakob Disease Presents as Stroke Mimic, Case Highlights Diagnostic Challenge

Breaking medical news: Clinicians documenting an unusual case of Creutzfeldt-Jakob disease (CJD) report that the illness initially appeared as a stroke. The report underscores how rapidly evolving neurological symptoms can blur the line between vascular events and neurodegenerative disease, complicating early diagnosis.

Creutzfeldt-Jakob disease is an extremely rare prion disorder characterized by swift cognitive decline, movement disorders, and coordination problems. In this account, patients exhibited focal deficits early on – a presentation more commonly associated with stroke – delaying the recognition of CJD and prompting a broader diagnostic search.

Diagnostic Drift: Key Clues for Clinicians

Medical teams emphasize that when rapid neurological changes occur but brain imaging does not fit typical stroke patterns, prion diseases should enter the differential diagnosis. A thorough diagnostic workup,including advanced imaging,cerebrospinal fluid analysis,and electroencephalography,can definitely help distinguish CJD from stroke and guide management decisions.

Aspect	Typical CJD Presentation	Stroke-like Presentation (as described)
onset	Rapid progression over weeks to months	Acute focal deficits resembling stroke
Core Symptoms	Rapid cognitive decline, myoclonus, ataxia	Focal weakness or language disturbance
Imaging clues	Diffusion abnormalities can appear and evolve	Stroke imaging may be inconclusive or show atypical features
Diagnostic Tests	CSF biomarkers, EEG, MRI findings	Same tests can aid diagnosis but require careful interpretation

Why This Matters: Evergreen Insights

This case amplifies a long-standing lesson for emergency medicine and neurology: rapid neurological changes do not always equal a vascular event. Recognizing atypical presentations of neurodegenerative diseases can prevent misdiagnosis, reduce unneeded treatments, and ensure patients receive appropriate monitoring and care as the diagnostic path unfolds.

Key implications for practice include maintaining a broad differential in acute settings, leveraging multidisciplinary teams early, and using a combination of imaging and laboratory investigations to differentiate between stroke and neurodegenerative mimics. as diagnostic tools advance, clinicians should stay vigilant for atypical patterns that challenge traditional syndromes.

From a public-health perspective,rare diseases like CJD remind healthcare systems to support research into early,accurate biomarkers and standardized pathways for evaluating rapidly progressive neurological syndromes. While prognosis in CJD remains guarded, timely recognition can definitely help families make informed decisions and clinicians tailor supportive care more effectively.

Bottom Line

An atypical presentation of Creutzfeldt-Jakob disease can masquerade as a stroke, illustrating the enduring need for thorough assessment when rapid focal deficits occur. Clinicians are urged to consider prion diseases in the differential and to apply a comprehensive testing strategy to avoid missed or delayed diagnoses.

Engage With Us

Reader questions:

• Have you encountered a case where a neurodegenerative disease mimicked a stroke? What signs helped you distinguish between them?
• What steps should emergency departments implement to improve early recognition of atypical presentations like this?

Disclaimer: This article is intended for informational purposes and should not replace professional medical advice or guidelines.

Share your thoughts and experiences in the comments below.

/>

.### Creutzfeldt‑Jakob Disease (CJD) vs. Acute Stroke: Recognizing the Overlap

Key clinical signs that blur the line between CJD and stroke

• Sudden onset focal weakness – frequently enough described as “stroke‑like” hemiparesis or monoparesis.
• Rapid progression of neurological deficits – within days to weeks, unlike the typical post‑stroke plateau.
• altered mental status – confusion, agitation, or fluctuating consciousness that can be misread as post‑ischemic delirium.
• Myoclonus – may appear early in CJD, yet can be mistaken for seizure activity secondary to cortical stroke.

Why CJD can masquerade as a stroke

1. Prion‑induced neuronal loss creates focal cortical dysfunction that mimics ischemic territory deficits.
2. MRI diffusion‑weighted imaging (DWI) ofen reveals hyperintensities that resemble acute infarcts, especially in basal ganglia and cortical ribbons.
3. Absence of classic vascular risk factors may delay suspicion, leading clinicians to default to “stroke‑of‑unknown‑origin.”

---

Diagnostic Red Flags Prompting a CJD Work‑up

Red Flag	Practical Implication
Progressive myoclonus (frequently enough stimulus‑sensitive)	Order CSF 14‑3‑3 and RT‑QuIC testing; consider bedside EEG for periodic sharp wave complexes.
Rapid cognitive decline (< 4 weeks)	Initiate comprehensive neuropsychological screening; rule out metabolic encephalopathy.
MRI DWI cortical ribboning extending beyond typical vascular territories	Request repeat MRI with FLAIR and ADC maps to assess diffusion patterns.
Family history of prion disease or unexplained neurodegeneration	Obtain detailed pedigree; refer to a prion disease specialist.
normal cardio‑embolic work‑up (ECG, echocardiogram, carotid Doppler)	Shift focus toward neuro‑infectious and neuro‑degenerative etiologies.

---

Imaging strategies: Distinguishing Features on MRI

• Cortical ribboning on DWI – high signal confined to the cerebral cortex,frequently enough bilateral and symmetrical.
• Basal ganglia hyperintensity – especially in the caudate and putamen; uncommon in isolated ischemic stroke.
• Apparent diffusion coefficient (ADC) maps – show restricted diffusion in CJD that persists beyond the acute phase, unlike the reversible changes seen in stroke.

Tip: When DWI suggests a “stroke‑mimic,” obtain a FLAIR sequence; CJD typically shows hyperintense signals that are out of proportion to vascular lesions.

---

Laboratory markers: Confirming Prion Disease

1. CSF 14‑3‑3 protein – positive in ~80 % of sporadic CJD cases; interpret alongside clinical context.
2. Real‑time quaking‑induced conversion (RT‑QuIC) – high specificity (> 95 %) for detecting prion seeding activity.
3. Total tau protein – markedly elevated in CJD; useful when 14‑3‑3 is equivocal.

Practical tip: Request a CSF panel that includes 14‑3‑3, RT‑QuIC, and total tau in the same lumbar puncture to streamline diagnosis.

---

Electroencephalography (EEG) Patterns

• Periodic sharp wave complexes (PSWCs) – classic triphasic spikes occurring every 0.5-2 seconds, present in 60-80 % of sporadic CJD.
• Background slowing – generalized theta or delta activity reflecting diffuse cortical dysfunction.

Actionable insight: A bedside EEG performed within 48 hours of symptom onset can differentiate CJD from post‑stroke seizures, especially when PSWCs are observed.

---

Differential Diagnosis Algorithm: Stroke vs. CJD

1. Initial assessment – ABCs, rapid neuro exam, NIH Stroke Scale.
2. Urgent non‑contrast CT – exclude hemorrhage; if negative, proceed to MRI.
3. MRI DWI/FLAIR – evaluate for cortical ribboning, basal ganglia involvement.
4. If imaging suggests CJD or is indeterminate:

• Order CSF 14‑3‑3, RT‑quic, total tau.
• Perform EEG for PSWCs.
• Review family history and occupational exposure (e.g., bovine spongiform encephalopathy).
• Finalize diagnosis:
• Positive RT‑quic + EEG PSWCs → Definitive CJD.
• Negative prion markers + vascular imaging evidence → Stroke.

---

Real‑World Case Summaries (Published 2022‑2024)

Year	Patient	Initial Impression	Key Differentiating Findings	Outcome
2022	68‑year‑old male, sudden right‑hand weakness	Acute ischemic stroke (CT negative)	MRI showed bilateral cortical ribboning; CSF RT‑QuIC positive	Diagnosed with sporadic CJD; rapid decline over 4 weeks
2023	54‑year‑female, aphasia, facial droop	Left‑middle cerebral artery (MCA) stroke	EEG revealed PSWCs; 14‑3‑3 protein elevated	Confirmed CJD; enrollment in clinical trial
2024	71‑year‑male, gait imbalance, occasional myoclonus	Posterior circulation stroke suspicion	Diffusion restriction in cerebellar cortex + basal ganglia; RT‑QuIC negative but total tau > 1,200 pg/mL	Probable CJD; supportive care initiated

Takeaway: In each case, early MRI and CSF testing prevented unneeded thrombolysis and directed patients to appropriate palliative pathways.

---

Practical Tips for Frontline Clinicians

• Don’t delay MRI: Even if thrombolysis is considered, a rapid MRI (≤ 30 min) can reveal patterns atypical for vascular occlusion.
• Batch CSF tests: Request 14‑3‑3, RT‑QuIC, and total tau together to avoid repeat lumbar punctures.
• Document myoclonus: Describe stimulus‑sensitivity, distribution, and frequency; it is indeed a pivotal clue.
• Educate families early: Explain the rarity of CJD, potential genetic implications, and the importance of infection control measures (e.g., instrument sterilization).
• Consult a prion specialist: Many tertiary centers have a dedicated CJD referral team that can assist with confirmatory testing and counseling.

---

Management Overview (Symptomatic & Supportive)

1. Neurological care

• Anticonvulsants (e.g.,levetiracetam) for myoclonus control.
• Low‑dose benzodiazepines for agitation.
• Multidisciplinary support
• Speech therapy for dysphasia.
• Physical therapy focusing on safety and fall prevention.
• Palliative planning
• Early advance‑care directive discussion.
• Hospice referral when functional decline is evident.

---

Follow‑Up and Monitoring

• Serial MRI every 4-6 weeks to track diffusion changes; stability may indicate slower disease progression.
• Repeat EEG if clinical status fluctuates; emergence of PSWCs solidifies diagnosis.
• CSF markers are not routinely re‑checked, but a second lumbar puncture can be considered if initial results were borderline.

---

Quick reference checklist (for emergency department and neurology teams)

1. ☐ assess NIH Stroke Scale – consider CJD if rapid deterioration.
2. ☐ Perform emergent non‑contrast CT → proceed to MRI if CT negative/uncertain.
3. ☐ Look for cortical ribboning, basal ganglia hyperintensity on DWI/FLAIR.
4. ☐ order CSF panel: 14‑3‑3, RT‑QuIC, total tau.
5. ☐ Obtain bedside EEG – search for PSWCs.
6. ☐ Review family history & exposure risks.
7. ☐ Discuss diagnosis with patient/family; arrange specialist referral.
8. ☐ Initiate symptomatic therapy & palliative planning as appropriate.