Neurology · Dementia
The facts most likely to be tested
Creutzfeldt-Jakob disease is caused by the accumulation of misfolded prion proteins (PrPSc) that induce a spongiform degeneration of the brain.
The classic clinical presentation is rapidly progressive dementia associated with myoclonus triggered by startle.
Electroencephalogram (EEG) findings typically demonstrate periodic sharp wave complexes on a background of slowing.
Magnetic resonance imaging (MRI) of the brain shows cortical ribboning and hyperintensity in the caudate nucleus and putamen on diffusion-weighted imaging (DWI).
Cerebrospinal fluid (CSF) analysis is often positive for the 14-3-3 protein and the tau protein.
The RT-QuIC (real-time quaking-induced conversion) assay is the most specific diagnostic test for detecting prion protein seeding activity in the CSF.
Creutzfeldt-Jakob disease is uniformly fatal, with most patients succumbing to the illness within one year of symptom onset.
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A 68-year-old male is brought to the clinic by his daughter due to a 4-month history of rapidly worsening memory loss and personality changes. She reports that he has recently developed involuntary, jerky muscle movements in his arms whenever a loud noise occurs. On physical examination, the patient is disoriented to time and place and exhibits myoclonus. An MRI of the brain reveals cortical ribboning and hyperintensity in the basal ganglia on DWI sequences.
What is the most likely diagnosis?
Creutzfeldt-Jakob disease
The patient's presentation of rapidly progressive dementia and myoclonus, combined with the pathognomonic MRI findings of cortical ribboning, is diagnostic for Creutzfeldt-Jakob disease.
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High yield triage
Etiology / Epidemiology
Rapidly progressive dementia caused by misfolded prion proteins (PrPSc). Most cases are sporadic (sCJD).
Clinical Manifestations
Rapidly progressive dementia, myoclonus, and startle response. Look for ataxia and visual disturbances.
Diagnosis
EEG shows periodic sharp wave complexes. CSF analysis for 14-3-3 protein and RT-QuIC.
Treatment
No curative therapy exists. Focus on supportive care and palliative management.
Prognosis
Universally fatal. Median survival is <1 year from symptom onset.
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Epidemiology & Etiology
CJD is a rare, fatal neurodegenerative disorder caused by the accumulation of misfolded prion proteins. While most cases are sporadic, iatrogenic transmission can occur via corneal transplants or contaminated neurosurgical instruments. Genetic forms exist due to mutations in the PRNP gene.
Pertinent Anatomy
The disease primarily targets the cerebral cortex and basal ganglia, leading to widespread neuronal loss. Involvement of the cerebellum explains the prominent ataxia seen in many patients.
Pathophysiology
Normal cellular prion protein (PrPc) undergoes a conformational change into the infectious, protease-resistant isoform (PrPSc). This triggers a template-directed misfolding cascade, resulting in spongiform degeneration of the brain parenchyma. The accumulation of these proteins leads to rapid neuronal death and glial proliferation.
Clinical Manifestations
Patients present with rapidly progressive dementia and cognitive decline. Classic features include myoclonus (often triggered by startle response), ataxia, and visual field deficits. Rapidly progressive dementia in a patient with new-onset motor symptoms is a major red flag.
Diagnosis
The gold standard for definitive diagnosis is brain biopsy or autopsy, though rarely performed. Clinical diagnosis relies on EEG showing periodic sharp wave complexes and CSF testing for 14-3-3 protein. The most specific diagnostic test is RT-QuIC (Real-Time Quaking-Induced Conversion).
Treatment
There is no disease-modifying treatment. Management is strictly supportive care to address psychiatric symptoms and myoclonus. Avoid antipsychotics if possible, as they may exacerbate motor symptoms. Focus on palliative care and family counseling.
Prognosis
The disease course is aggressive, with median survival of 6 months. Most patients succumb to aspiration pneumonia or secondary infections within one year of diagnosis.
Differential Diagnosis
Alzheimer's disease: slower progression, lacks myoclonus
Lewy Body Dementia: visual hallucinations, parkinsonism
Viral encephalitis: fever, CSF pleocytosis
Hashimoto encephalopathy: elevated TPO antibodies
Paraneoplastic syndrome: associated with underlying malignancy