Jakob-Creutzfeldt Disease

A 68-year-old man presented to our clinic for evaluation of a five-month history of memory problems. Memory loss, feeling “funny,” and loss of appetite were initial symptoms. At the first visit the daughter reported that the problems appeared to be accelerating, and were much worse over the last two weeks. He now had difficulty getting dressed, using the toilet, and finding his way around his own house. He had emotional lability and paranoia. He complained of blurry vision and was noted to be very drowsy at times.

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Jakob–Creutzfeldt Disease

Definition	• Jakob–Creutzfeldt disease (JCD) is one of several prion transmissible neurodegenerative diseases characterized by a rapid cognitive decline that can progress to akinetic mutism over weeks. • Jakob–Creutzfeldt disease is the most common type of prion disease; prion diseases are also called transmissible spongiform encephalopathies. • Prion diseases have a specific neuropathology characterized by spongiform changes, neuronal death, astrocytosis, and accumulation of a pathological protein (PrP ^Sc) in the brain and sometimes other organs. • Other forms of Jakob–Creutzfeldt disease include genetic and acquired. Acquired forms include iatrogenic and variant. • Variant Jakob–Creutzfeldt disease is similar biochemically and histopathologically to bovine spongiform encephalopathy (aka “mad cow disease”).
Prevalence	• Sporadic Jakob–Creutzfeldt disease has an incidence of approximately 1 to 1.5 per million. • The usual age of onset of sporadic Jakob–Creutzfeldt disease is from 45 to 75 years; variant Jakob–Creutzfeldt disease often presents in younger individuals.
Genetic risk	• Prion diseases are transmissible because an inoculation with the pathological protein can cause the disease in another individual. • There are a number of mutations of the gene PRNP (located on the short arm of chromosome 20), which codes for the pathological protein (PrP ^Sc), leading to familial, autosomal dominant Jakob–Creutzfeldt disease.
Cognitive, behavioral, and other symptoms	• Cognitive and behavioral changes include impairment of memory and executive function, as well as depression and sometimes personality changes. • Cerebellar signs and myoclonus are frequent, and can worsen over a period of days.
Diagnostic criteria	1. Progressive dementia 2. At least two of the following four features: a. Myoclonus b. Visual or cerebellar disturbance c. Pyramidal or extrapyramidal signs d. Akinetic mutism 3. And one or more of the following: a. Periodic discharges on the EEG b. A positive 14-3-3 CSF assay and death <2 years c. High signal abnormalities in caudate nuclei and putamen or at least two cortical regions (temporal-parietal-occipital, but not frontal, cingulate, insular, or hippocampal) either in DWI or FLAIR MRI d. No alternative diagnosis on routine investigations.
Treatment	• Treatment for Jakob–Creutzfeldt disease is supportive.
Top differential diagnoses	• Slow progression: common degenerative diseases • Dementia with Lewy bodies • Frontotemporal dementia • Corticobasal degeneration • Progressive supranuclear palsy • Alzheimer’s disease (particularly when associated with cerebral amyloid angiopathy). • Rapidly progressing dementias • Cerebrovascular disease • Vasculitis • Autoimmune disease • Collagen vascular and granulomatous disease • Infectious disease • Malignancies • Paraneoplastic disorders • Toxic and metabolic disorders • Psychiatric disorders.

His neurologic exam was notable for myoclonus and a coarse intention tremor in both upper extremities due to ataxia. He had perseveration, anomia, and apraxia. He was unable to complete the Montreal Cognitive Assessment (MoCA) due to perseveration. Cerebrospinal fluid 14-3-3 was within normal limits. EEG showed diffuse slowing and occasional triphasic complexes. MRI showed significant atrophy, along with abnormal diffusion signal in the thalami and bilateral parietal lobes. He died seven months after symptom onset.

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