Creutzfeldt-Jakob Disease (CJD) is a rare and universally fatal neurodegenerative disorder that impacts the brain. This condition causes rapid damage, leading to severe neurological decline. Approximately 350 cases are diagnosed annually in the United States.
Nature of Creutzfeldt-Jakob Disease
CJD is categorized as a prion disease, caused by abnormal proteins called prions. These prions are misfolded versions of normal proteins found on the surface of many cells, especially in the brain and nervous system. When misfolded prions accumulate, they induce normal prion proteins to also misfold. This chain reaction leads to the formation of clumps and deposits in the brain, damaging and destroying brain cells. The destruction of brain tissue results in a sponge-like appearance under a microscope, a characteristic feature of these conditions.
Acquisition Pathways
Creutzfeldt-Jakob Disease can arise through several distinct pathways.
Sporadic CJD (sCJD)
Sporadic CJD (sCJD) is the most common form, accounting for about 85% of cases. This type occurs spontaneously, without a known genetic predisposition or external cause. The misfolding of prion proteins in sporadic CJD is hypothesized to occur as a result of the aging process affecting cellular machinery, typically appearing in individuals around age 60.
Familial CJD (fCJD)
Familial CJD (fCJD) is a rare, inherited form, making up about 10-15% of cases. It results from a specific mutation in the prion protein gene (PRNP) located on chromosome 20. This mutation is usually inherited in an autosomal dominant pattern, meaning only one mutated gene from a parent is sufficient for the disease to develop.
Iatrogenic CJD (iCJD)
Iatrogenic CJD (iCJD) is an acquired form resulting from accidental transmission during medical procedures, accounting for less than 1% of cases. Historically, this has included cases linked to contaminated neurosurgical instruments, corneal transplants, or dura mater grafts. Cases were also associated with human growth hormone derived from cadaveric pituitary glands before synthetic alternatives became available, with some cases still being identified decades later.
Variant CJD (vCJD)
Variant CJD (vCJD) is a distinct acquired form with a clear link to bovine spongiform encephalopathy (BSE), commonly known as “mad cow disease.” This connection was established through the consumption of beef products contaminated with prions from infected cattle. Strict controls implemented since the mid-1990s, such as banning meat-and-bone meal in animal feed and removing high-risk parts of carcasses, have significantly reduced the risk of BSE entering the human food chain.
Symptoms and Disease Progression
Symptoms of Creutzfeldt-Jakob Disease generally reflect a rapid decline in brain function. Initial signs often include memory problems, changes in behavior, and difficulties with coordination and balance.
As the disease progresses, symptoms quickly intensify. Patients often develop rapidly worsening dementia, leading to severe cognitive impairment. Involuntary muscle jerks, known as myoclonus, are common. Individuals also experience a progressive loss of motor control, speech difficulties, and can eventually become blind. Most people die within a year of symptom onset, often within four to eight months for sporadic CJD.
Diagnosis, Treatment, and Prevention
Diagnosing Creutzfeldt-Jakob Disease definitively typically requires examination of brain tissue, often through a biopsy or autopsy. However, several clinical diagnostic methods can support a probable diagnosis before death. These include magnetic resonance imaging (MRI) scans, which can reveal characteristic changes in the brain, and electroencephalography (EEG), which measures brain electrical activity. Cerebrospinal fluid (CSF) analysis, particularly the Real-Time Quaking-Induced Conversion (RT-QuIC) test, is also highly specific and sensitive for detecting the abnormal prion proteins.
There is no cure for CJD, nor are there treatments that can slow its progression. Management focuses on supportive and palliative care to alleviate symptoms and improve the patient’s comfort and quality of life. This may involve medications to manage psychological symptoms like anxiety and depression, or to control muscle jerks and pain. Hospice services and comprehensive nursing care become important as the disease advances, providing assistance with daily functions such as feeding, washing, and mobility.
Prevention efforts are primarily aimed at limiting the transmission of acquired forms of CJD. Strict sterilization protocols for surgical instruments are in place, as prions are resistant to conventional sterilization methods. Screening of blood donors is conducted to reduce the risk of variant CJD transmission through blood transfusions, with individuals who have received transfusions in the UK since 1980 often deferred from donating. Regulations on animal feed, such as the ban on feeding meat-and-bone mix to farm animals, continue to be implemented to prevent BSE and, consequently, variant CJD.