A 60-Year-Old Woman With Worsening Neuropsychiatric Symptoms

Sridharan Ramaratnam, MD


August 12, 2015

Creutzfeldt-Jakob disease affects approximately 1 person per 1 million per year (approximately 250-300 new cases per year in the United States); this estimate may be low due to difficulty in diagnosing the disease. Approximately 85% of cases are sporadic and 15% are familial. A third type of Creutzfeldt-Jakob disease is acquired Creutzfeldt-Jakob disease, which includes iatrogenic and variant forms. Several cases have occurred from contamination via medical procedures, known as iatrogenic Creutzfeldt-Jakob disease. Variant Creutzfeldt-Jakob disease (vCJD) occurs in young people and has been linked to the ingestion of beef tainted with prions from bovine nervous system tissue. Also called bovine spongiform encephalopathy (BSE), most cases of vCJD have occurred in the United Kingdom.[3,4]

Diagnosing Creutzfeldt-Jakob disease may be difficult because of the nonspecific nature of the disease and the wide range of clinical symptoms. Typical features of Creutzfeldt-Jakob disease include rapidly progressive dementia, generalized myoclonus, and ataxia. The diagnostic criteria used to define patients with sporadic Creutzfeldt-Jakob disease are as follows:

Definite Creutzfeldt-Jakob disease:

  • Characteristic neuropathology

  • Protease-resistant PrP detected by Western blot

Probable Creutzfeldt-Jakob disease:

  • Progressive dementia

  • Typical findings on EEG

  • At least two of the following: myoclonus, visual impairment, cerebellar signs, pyramidal or extrapyramidal signs, or akinetic mutism

Possible Creutzfeldt-Jakob disease:

  • Progressive dementia

  • Atypical findings on EEG or EEG not available

  • At least two of the following: myoclonus, visual impairment, cerebellar signs, pyramidal or extrapyramidal signs, or akinetic mutism

  • Duration of less than 2 years

CT scans of the brain are usually normal or may show atrophic changes that progress rapidly over time. Recent advances in MRI and neurochemical analysis of the CSF have improved the diagnostic accuracy of these examinations.[3,4] MRI may show increased T2 signal intensity in the basal ganglia, thalamus, occipital cortex, or white matter. The sensitivity of increased T2 signal intensity in the basal ganglia has been reported to be only 79%. Diffusion-weighted MRI abnormalities have been shown to be more sensitive than T2-weighted or fluid-attenuated inversion recovery (FLAIR) sequences in detecting lesions in patients who have clinically definite or probable Creutzfeldt-Jakob disease, with a 92.3% specificity and a 93.8% sensitivity.

Diffusion weighting is an MRI technique that provides image contrast dependent on the molecular motion of water. Although most commonly used for the detection of early brain infarction, diffusion-weighted MRI can also detect changes in fluid viscosity caused by other disease processes. Diffusion-weighted images in Creutzfeldt-Jakob disease can demonstrate abnormally high signal intensity in the caudate nucleus, putamen, thalamus, and cortex. The cortex is often most involved in early-stage disease. Basal ganglia involvement is typically most prominent in the caudate. Two characteristic radiologic signs have been described: the "hockey stick" sign, which refers to increased signal in the putamen and head of the caudate nucleus resembling a hockey stick, and the "pulvinar" sign, which corresponds to increased signal in the pulvinar thalamic nuclei, usually bilaterally. The latter sign is more commonly found in patients with vCJD.

Diffusion-weighted imaging is very useful in distinguishing Creutzfeldt-Jakob disease from other neurologic causes of dementia, including Alzheimer disease, vascular dementia, and dementia with Lewy bodies. Other causes of similar diffusion-weighted imaging abnormalities include infectious meningoencephalitis, mitochondrial encephalopathy, lactic acidosis, Wilson disease, venous hypertensive encephalopathy, herpes simplex encephalopathy, and Wernicke encephalopathy. These can be distinguished from Creutzfeldt-Jakob disease based on the clinical and CSF findings. The underlying pathology of these diffusion-weighted imaging lesions in Creutzfeldt-Jakob disease is unknown but may represent spongiform changes or prion protein deposits. These lesions often become less apparent with disease progression.[3,4,5]


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