Creutzfeldt-Jakob disease differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2] Twinkle Singh, M.B.B.S. [3]

Overview

Creutzfeldt-Jakob disease must be differentiated from other causes of rapidly progressive dementia, such as variant Creutzfeldt-Jakob disease, Mad Cow disease, Alzheimer disease, Dementia with Lewy bodies, Frontotemporal dementia, Corticobasal degeneration, Normal pressure hydrocephalus, parkinsonian disorder, Paraneoplastic syndrome, Vasculitis, Neurosarcoidosis,Encephalitis, Whipple disease, Rabies, Herpes simplex virus, postinfectious syndrome, Vitamin B12 deficiency, Hypothyroidism, Wernicke-Korsakoff syndrome and urinary tract infections.

Differential Diagnosis of Creutzfeldt-Jakob Disease

• CJD should be differentiated from other diseases presenting with dementia, ataxia, pyramidal/extrapyramidal signs, myoclonus, rigidity and visual hallucinations. The major differentials of CJD include the following:

Disease	Signs and Symptoms										Imaging Findings	Laboratory Findings
	Dementia	Rigidity	Myoclonus	Visual Hallucinations	Parkinsonism	Speech Impairment	Fever	Cerebellar Signs (Ataxia, imbalance, dysdiadochokinesia)	Hyperkinetic Signs	Pyramidal Signs (Spasticity, Hyperreflexia, loss of fine motor skills, upgoing plantars)
Creutzfeldt-Jakob Disease	+ (Rapidly progressive)	+	+	+	-	+	-	+	+	+	On MRI: High signal intensity in the caudate nucleus or putamen at DWI or FLAIR imaging. Focal or diffuse, symmetric or asymmetric involvement (more common) of the cerebral cortex, basal ganglia specially corpus striatum Sparing of peri-rolandic area Cerebellar atrophy Hyperintensity in the globus pallidus on T1-weighted images	On CSF exam: Elevated levels of the 14-3-3 protein On EEG: Periodic sharp wave complexes
Lewy Body Dementia	+	+	+	+	+	+	-	-	-	-
Alzheimer's disease	+ (Slow progression)	+	+	-	-	-/+	-	-	-	-		On CSF exam: Elevated Tau protein Neurofibrillary tangles Senile (neuritic) plaques
Herpes Simplex Encephalitis	-/+	-	-	-	-	+	+	-/+	-	-/+	On MRI: T2-weighted image shows asymmetric bilateral involvement of the temporal lobes with high signal intensity and swelling	On CSF exam: Elevated leukocyte count (mononuclear pleocytosis) Elevated protein levels Normal or decreased glucose levels On EEG: 2–3 Hz periodic lateralised epileptiform discharges originating from the temporal lobes

• Differential diagnosis of Creutzfeldt-Jakob disease includes the following:

Neurodegenerative Diseases

• Alzheimer disease
• Dementia with Lewy bodies
• Frontotemporal dementia
• Corticobasal degeneration
• Normal pressure hydrocephalus
• Parkinsonian disorder

Autoimmune diseases

• Paraneoplastic syndrome
• Vasculitis
• Neurosarcoidosis

Infections

• Encephalitis
• Whipple disease
• Rabies
• Herpes simplex virus
• Postinfectious syndrome

Toxic or metabolic causes

• Vitamin B12 deficiency
• Hypothyroidism
• Adverse drug reaction
• Wernicke-Korsakoff syndrome
• Urinary tract infection

Clinical and pathologic characteristics of classic CJD and variant CJD:

Characteristic	Classic CJD	Variant CJD
Median age at death	68 years	28 years
Median duration of illness	4-5 months	13-14 months
Clinical signs and symptoms	Dementia; early neurologic signs	Prominent psychiatric/behavioral symptoms; painful dysesthesias; delayed neurologic signs
Periodic sharp waves on electroencephalogram	Often present	Often absent
Signal hyperintensity in the caudate nucleus and putamen on diffusion-weighted and FLAIR MRI	Often present	Often absent
Pulvinar sign on MRI	Not reported	Present in >75% of cases
Immunohistochemical analysis of brain tissue	Variable accumulation.	Marked accumulation of protease-resistant prion protein
Presence of agent in lymphoid tissue	Not readily detected	Readily detected
Increased glycoform ratio on immunoblot analysis of protease-resistant prion protein	Not reported	Marked accumulation of protease-resistant prion protein
Presence of amyloid plaques in brain tissue	May be present	May be present

References

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