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Creutzfeldt–Jakob disease (CJD) is an incurable, always fatal
neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...
belonging to the transmissible spongiform encephalopathy (TSE) group. Early symptoms include memory problems, behavioral changes, poor coordination, visual disturbances and auditory disturbances. Later symptoms include
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
, involuntary movements, blindness, deafness, weakness, and
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
. About 70% of sufferers die within a year of diagnosis. The name "Creutzfeldt–Jakob disease" was introduced by Walther Spielmeyer in 1922, after the German neurologists
Hans Gerhard Creutzfeldt Hans Gerhard Creutzfeldt (June 2, 1885 – December 30, 1964) was a German neurologist and neuropathologist. Although he is typically credited as the physician to first describe the Creutzfeldt–Jakob disease, this has been disputed. He was bo ...
and Alfons Maria Jakob. CJD is caused by abnormal folding of a protein known as a
prion A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...
. Infectious prions are misfolded proteins that can cause normally folded proteins to also become misfolded. About 85% of cases of CJD occur for unknown reasons, while about 7.5% of cases are inherited in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
manner. Exposure to brain or spinal tissue from an infected person may also result in spread. There is no evidence that sporadic CJD can spread among people via normal contact or blood transfusions, although this is possible in variant Creutzfeldt–Jakob disease. Diagnosis involves ruling out other potential causes. An electroencephalogram, spinal tap, or
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
may support the diagnosis. Another diagnosis technique is the real-time quaking-induced conversion assay which can detect the disease in early stages. There is no specific treatment for CJD. Opioids may be used to help with pain, while clonazepam or sodium valproate may help with involuntary movements. CJD affects about one person per million people per year. Onset is typically around 60 years of age. The condition was first described in 1920. It is classified as a type of transmissible spongiform encephalopathy. Inherited CJD accounts for about 10% of prion disease cases. Sporadic CJD is different from bovine spongiform encephalopathy (mad cow disease) and variant Creutzfeldt–Jakob disease (vCJD).


Signs and symptoms

The first symptom of CJD is usually rapidly progressive
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
, leading to memory loss, personality changes, and
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s. Myoclonus (jerky movements) typically occurs in 90% of cases, but may be absent at initial onset. Other frequently occurring features include
anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
, depression,
paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety, suspicion, or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of co ...
, obsessive-compulsive symptoms, and
psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...
. This is accompanied by physical problems such as
speech Speech is the use of the human voice as a medium for language. Spoken language combines vowel and consonant sounds to form units of meaning like words, which belong to a language's lexicon. There are many different intentional speech acts, suc ...
impairment, balance and coordination dysfunction (
ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
), changes in
gait Gait is the pattern of Motion (physics), movement of the limb (anatomy), limbs of animals, including Gait (human), humans, during Animal locomotion, locomotion over a solid substrate. Most animals use a variety of gaits, selecting gait based on s ...
, and rigid posture. In most people with CJD, these symptoms are accompanied by involuntary movements. Rarely, unusual symptoms like the alien limb phenomenon have been observed. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks. Most affected people die six months after initial symptoms appear, often of
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
due to impaired coughing reflexes. About 15% of people with CJD survive for two or more years. The symptoms of CJD are caused by the progressive death of the brain's nerve cells, which are associated with the build-up of abnormal prion proteins forming in the brain. When brain tissue from a person with CJD is examined under a microscope, many tiny holes can be seen where the nerve cells have died. Parts of the brain may resemble a sponge where the prions were infecting the areas of the brain.


Cause

CJD is a type of transmissible spongiform encephalopathy (TSE), which are caused by prions. Prions are misfolded proteins that occur in the neurons of the central nervous system (CNS). Current research suggests that small, oligomeric aggregates of PrP^Sc (rather than large
fibril Fibrils () are structural biological materials found in nearly all living organisms. Not to be confused with fibers or protein filament, filaments, fibrils tend to have diameters ranging from 10 to 100 nanometers (whereas fibers are micro to ...
s) are the most neurotoxic species, interacting with cell surfaces to disrupt neuronal function . The binding of prion oligomers to normal prion protein on neurons may trigger toxic signals similar to how oligomeric β-amyloid causes synaptic damage in Alzheimer’s disease . Different conformations of PrP^Sc (often termed prion “strains”) are thought to cause the distinct subtypes of prion disease, explaining variations in clinical features and progression. They are thought to affect signaling processes, damaging neurons and resulting in degeneration that causes the spongiform appearance in the affected brain. Other forms of TSEs that are found in humans are Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, and kuru, as well as the variably protease-sensitive prionopathy and familial spongiform encephalopathy transmissible spongiform encephalopathy. Susceptibility and disease phenotype are influenced by a common polymorphism at codon 129 of the PRNP gene (methionine/valine). Notably, individuals homozygous at codon 129 are over-represented in sporadic CJD cases and tend to have shorter incubation periods. The CJD prion is dangerous because it promotes refolding of the cellular prion protein into the diseased state. The number of misfolded protein molecules will increase exponentially and the process leads to a large quantity of insoluble protein in affected cells. This mass of misfolded proteins disrupts neuronal cell function and causes cell death. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and induce other prion protein molecules to misfold in a self-sustaining
feedback loop Feedback occurs when outputs of a system are routed back as inputs as part of a chain of cause and effect that forms a circuit or loop. The system can then be said to ''feed back'' into itself. The notion of cause-and-effect has to be handle ...
. These neurodegenerative diseases are commonly called '' prion diseases''.


Transmission

The defective protein can be transmitted by contaminated harvested human brain products,
cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...
l grafts, dural grafts, or
electrode An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit (e.g. a semiconductor, an electrolyte, a vacuum or a gas). In electrochemical cells, electrodes are essential parts that can consist of a varie ...
implants and pituitary human growth hormone, which has been replaced by recombinant human growth hormone that poses no such risk. It can be familial (fCJD) or it may appear without clear risk factors (sporadic form: sCJD). In the familial form, a
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
has occurred in the
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
for PrP, '' PRNP'', in that family. All types of CJD are transmissible irrespective of how they occur in the person. It is thought that humans can contract the variant form of the disease by eating food from animals infected with bovine spongiform encephalopathy (BSE), the bovine form of TSE, also known as ''mad cow disease''. However, it can also cause sCJD in some cases. Cannibalism has also been implicated as a transmission mechanism for abnormal prions, causing the disease known as kuru, once found primarily among women and children of the Fore people in
Papua New Guinea Papua New Guinea, officially the Independent State of Papua New Guinea, is an island country in Oceania that comprises the eastern half of the island of New Guinea and offshore islands in Melanesia, a region of the southwestern Pacific Ocean n ...
, who previously engaged in funerary cannibalism. While the men of the tribe ate the muscle tissue of the deceased, women and children consumed other parts, such as the brain, and were more likely than men to contract kuru from infected tissue. Prions, the infectious agent of CJD, may not be inactivated by means of routine
surgical instrument A surgical instrument is a medical device for performing specific actions or carrying out desired effects during a surgery or operation, such as modifying biological tissue, or to provide access for viewing it. Over time, many different kinds of ...
sterilization procedures. The
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
and the US
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
recommend that instrumentation used in such cases be immediately destroyed after use; short of destruction, it is recommended that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. Thermal depolymerization also destroys prions in infected organic and inorganic matter, since the process chemically attacks protein at the molecular level, although more effective and practical methods involve destruction by combinations of detergents and enzymes similar to biological washing powders.


Genetics

People can also develop CJD because they carry a mutation of the gene that codes for the prion protein (PRNP), located on chromosome 202p12-pter. This occurs in only 10–15% of all CJD cases. In sporadic cases, the misfolding of the prion protein is a process that is hypothesized to occur as a result of the effects of aging on cellular machinery, explaining why the disease often appears later in life. An EU study determined that "87% of cases were sporadic, 8% genetic, 5% iatrogenic and less than 1% variant."


Diagnosis

Testing for CJD has historically been problematic, due to nonspecific nature of early symptoms and difficulty in safely obtaining brain tissue for confirmation. The diagnosis may initially be suspected in a person with rapidly progressing dementia, particularly when it is also found with the characteristic medical signs and symptoms such as involuntary muscle jerking, difficulty with coordination/balance and walking, and visual disturbances. Further testing can support the diagnosis and may include: *
Electroencephalography Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignal, bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in ...
– may have characteristic generalized periodic sharp wave pattern. Periodic sharp wave complexes develop in half of the people with sporadic CJD, particularly in the later stages. * Cerebrospinal fluid (CSF) analysis for elevated levels of 14-3-3 protein and tau protein could be supportive in the diagnosis of sCJD. The two proteins are released into the CSF by damaged nerve cells. Increased levels of tau or 14-3-3 proteins are seen in 90% of prion diseases. The markers have a specificity of 95% in clinical symptoms suggestive of CJD, but specificity is 70% in other less characteristic cases. 14-3-3 and tau proteins may also be elevated in the CSF after ischemic strokes, inflammatory brain diseases, or seizures. The protein markers are also less specific in early CJD, genetic CJD or the bovine variant. However, a positive result should not be regarded as sufficient for the diagnosis. The real-time quaking-induced conversion (RT-QuIC) assay, which amplifies misfolded PrP^Sc, now plays a central role in CJD diagnosis. Second-generation RT-QuIC on cerebrospinal fluid has sensitivity in the 90–97% range and ~100% specificity in sporadic CJD, far superior to earlier CSF tests. A positive RT-QuIC (on CSF or other tissues) is now included as a criterion for probable CJD in many national surveillance center. Studies have shown RT-QuIC can also be done on olfactory mucosa swabs obtained via nasal brushing and on skin biopsies, with high diagnostic accuracy (reported sensitivities ~90–100%) * MRI with diffusion weighted inversion (DWI) and fluid-attenuated inversion recovery (FLAIR) shows a high signal intensity in certain parts of the
cortex Cortex or cortical may refer to: Biology * Cortex (anatomy), the outermost layer of an organ ** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain'' *** Motor cortex, the regions of the cerebral cortex i ...
(a cortical ribboning appearance), the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
, and the thalami. The most common presenting patterns are simultaneous involvement of the cortex and
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
(60% of cases), cortical involvement without the striatum (30%), thalamus (21%),
cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
(8%) and striatum without cortical involvement (7%). In populations with a rapidly progressive dementia (early in the disease process), MRI has a sensitivity of 91% and specificity of 97% for diagnosing CJD. The MRI changes characteristic of CJD may also be seen in the immediate aftermath (hours after the event) of autoimmune encephalitis or focal seizures. In recent years, studies have shown that the tumour marker neuron-specific enolase (NSE) is often elevated in CJD cases; however, its diagnostic utility is seen primarily when combined with a test for the 14-3-3 protein. , screening tests to identify infected
asymptomatic Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). P ...
individuals, such as blood donors, are not yet available, though methods have been proposed and evaluated.


Imaging

Imaging of the brain may be performed during medical evaluation, both to rule out other causes and to obtain supportive evidence for diagnosis. Imaging findings are variable in their appearance, and also variable in sensitivity and specificity. While imaging plays a lesser role in diagnosis of CJD, characteristic findings on brain MRI in some cases may precede onset of clinical manifestations. Brain MRI is the most useful imaging modality for changes related to CJD. Of the MRI sequences, diffuse-weighted imaging sequences are most sensitive. Characteristic findings are as follows: *Focal or diffuse diffusion-restriction involving the cerebral cortex or basal ganglia. The most characteristic and striking cortical abnormality has been called "cortical ribboning" or "cortical ribbon sign" due to hyperintensities resembling ribbons appearing in the cortex on MRI. The involvement of the thalamus can be found in sCJD, is even stronger and constant in vCJD. *Varying degree of symmetric T2 hyperintense signal changes in the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
(i.e., caudate and putamen), and to a lesser extent
globus pallidus The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a major component of the Cerebral cortex, subcortical basal ganglia in the brain. It consists of two adjacent segments, one external (or lateral), known in rodents simpl ...
and occipital cortex. Brain FDG PET-CT tends to be markedly abnormal, and is increasingly used in the investigation of dementias. *Patients with CJD will normally have hypometabolism on FDG PET.


Histopathology

Testing of tissue remains the most definitive way of confirming the diagnosis of CJD, although even biopsy is not always conclusive. In one-third of people with sporadic CJD, deposits of "prion protein (scrapie)", PrPSc, can be found in the
skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...
or the
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
. Diagnosis of vCJD can be supported by biopsy of the tonsils, which harbor significant amounts of PrPSc; however,
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...
of brain tissue is the definitive diagnostic test for all other forms of prion disease. Due to its invasiveness, biopsy will not be done if clinical suspicion is sufficiently high or low. A negative biopsy does not rule out CJD, since it may predominate in a specific part of the brain.Sternberg's Diagnostic Surgical Pathology, 5th edition. The classic histologic appearance is spongiform change in the gray matter: the presence of many round vacuoles from one to 50 micrometers in the neuropil, in all six cortical layers in the cerebral cortex or with diffuse involvement of the cerebellar molecular layer. These vacuoles appear glassy or eosinophilic and may coalesce. Neuronal loss and
gliosis Gliosis is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes ...
are also seen. Plaques of
amyloid Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human ...
-like material can be seen in the
neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, ...
in some cases of CJD. However, extra-neuronal vacuolization can also be seen in other disease states. Diffuse cortical vacuolization occurs in
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
, and superficial cortical vacuolization occurs in
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
and
frontotemporal dementia Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal lobe, frontal and tempor ...
. These vacuoles appear clear and punched-out. Larger vacuoles encircling neurons, vessels, and glia are a possible processing artifact.


Classification

Types of CJD include: *Sporadic (sCJD), caused by the spontaneous misfolding of prion-protein in an individual. This accounts for 85% of cases of CJD. Sporadic CJD is can be further sub-classified by molecular profile into subtypes (MM1, MV2, etc.), which correlate with certain clinical-pathologic features. **MM1 / MV1 Subtype: ***Clinical Features: Accounts for approximately 75% of sCJD cases. Characterized by rapidly progressive dementia, myoclonus, and typical EEG findings. ***Neuropathology: Synaptic-type PrP^Sc deposition predominantly in the cerebral cortex. Spongiform changes are widespread, with significant neuronal loss and gliosis. **MM2 Subtype: ***MM2C (Cortical): Presents with a more prolonged disease course and prominent cortical involvement. Neuropathology reveals PrP^Sc deposits in the cortex with less spongiform change compared to MM1. ***MM2T (Thalamic): Rare; characterized by predominant thalamic involvement, leading to sleep disturbances and autonomic dysfunction. Neuropathology shows significant PrP^Sc deposition and neuronal loss in the thalamus. **VV1 Subtype: ***Clinical Features: Rare; presents at a younger age with a slower disease progression. ***Neuropathology: Predominant cortical involvement with synaptic-type PrP^Sc deposition. **VV2 Subtype: ***Clinical Features: Second most common subtype. Patients often present with ataxia and other cerebellar signs. ***Neuropathology: Significant PrP^Sc deposition in the cerebellum and basal ganglia, with prominent spongiform changes and neuronal loss. *Familial (fCJD), caused by an inherited mutation in the prion-protein gene. This accounts for the majority of the other 15% of cases of CJD. *Acquired CJD, caused by contamination with tissue from an infected person, usually as the result of a medical procedure ( iatrogenic CJD). Medical procedures that are associated with the spread of this form of CJD include
blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
from the infected person, use of human-derived pituitary growth hormones, gonadotropin hormone therapy, and corneal and meningeal transplants. Variant Creutzfeldt–Jakob disease (vCJD) is a type of acquired CJD potentially acquired from bovine spongiform encephalopathy or caused by consuming food contaminated with prions. Sporadic CJD, while transmissible through tissue transplants, may not be transmitted through blood transfusion.


Treatment

As of 2025, there is no cure or effective treatment for CJD. Some of the symptoms like twitching can be managed, but otherwise treatment is palliative care. Psychiatric symptoms like anxiety and depression can be treated with sedatives and
antidepressants Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexu ...
. Myoclonic jerks can be handled with clonazepam or sodium valproate. Opiates can help in pain.
Seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
are very uncommon but can nevertheless be treated with antiepileptic drugs. In 2022, results of an early-stage trial of PRN100, a monoclonal antibody against PrP, were reported: the drug appeared safe and reached the brain, but treated patients did not show clearly improved survival compared to historical controls. While not curative, this trial demonstrated the feasibility of immunotherapy for prion disease.


Prognosis

Life expectancy is greatly reduced for people with Creutzfeldt–Jakob disease and the average is less than 6 months. As of 1981, no one was known to have lived longer than 2.5 years after the onset of CJD symptoms. One of the world's longest survivors of vCJD was Jonathan Simms, a Northern Irish man who lived for 10 years after his diagnosis and received experimental treatment with pentosan polysulphate. Simms died in 2011.


Epidemiology

The CDC monitors the occurrence of CJD in the United States through periodic reviews of national mortality data. According to the CDC: *CJD occurs worldwide at roughly 1–1.5 cases per million people per year. Recent surveillance reports indicate a slight increase in recorded incidence in many countries over time. For example, a study made in 2020 noted that sporadic CJD incidence in the U.K. rose from 1990 to 2018, and several other countries also reported increases in CJD cases in the 2000s. *On the basis of mortality surveillance from 1979 to 1994, the annual incidence of CJD remained stable at approximately 1 case per million people in the United States. *In the United States, CJD deaths among people younger than 30 years of age are extremely rare (fewer than five deaths per billion per year). *The disease is found most frequently in people 55–65 years of age, but cases can occur in people older than 90 years and younger than 55 years of age. *In more than 85% of cases, the duration of CJD is less than one year (median: four months) after the onset of symptoms. Further information from the CDC: *Risk of developing CJD increases with age. *CJD incidence was 3.5 cases per million among those over 50 years of age between 1979 and 2017. *Approximately 85% of CJD cases are sporadic and 10–15% of CJD cases are due to inherited mutations of the prion protein gene. *CJD deaths and age-adjusted death rate in the United States indicate an increasing trend in the number of deaths between 1979 and 2017. Although not fully understood, additional information suggests that CJD rates in nonwhite groups are lower than in whites. While the mean onset is approximately 67 years of age, cases of sCJD have been reported as young as 17 years and over 80 years of age. Mental capabilities rapidly deteriorate and the average amount of time from onset of symptoms to death is 7 to 9 months. According to a 2020 systematic review on the international epidemiology of CJD: *Surveillance studies from 2005 and later show the estimated global incidence is 1–2 cases per million population per year. *Sporadic CJD (sCJD) incidence increased from the years 1990–2018 in the UK. *Probable or definite sCJD deaths also increased from the years 1996–2018 in twelve additional countries. *CJD incidence is greatest in those over the age of 55 years old, with an average age of 67 years old. The intensity of CJD surveillance increases the number of reported cases, often in countries where CJD epidemics have occurred in the past and where surveillance resources are greatest. An increase in surveillance and reporting of CJD is most likely in response to BSE and vCJD. Possible factors contributing to an increase of CJD incidence are an aging population, population increase, clinician awareness, and more accurate diagnostic methods. Since CJD symptoms are similar to other neurological conditions, it is also possible that CJD is mistaken for
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
, acute nephropathy, general dementia, and hyperparathyroidism.


History

The disease was first described by German neurologist
Hans Gerhard Creutzfeldt Hans Gerhard Creutzfeldt (June 2, 1885 – December 30, 1964) was a German neurologist and neuropathologist. Although he is typically credited as the physician to first describe the Creutzfeldt–Jakob disease, this has been disputed. He was bo ...
in 1920 and shortly afterward by Alfons Maria Jakob, giving it the name Creutzfeldt–Jakob disease. Some of the clinical findings described in their first papers do not match current criteria for Creutzfeldt–Jakob disease, and it has been speculated that at least two of the people in initial studies had a different ailment. An early description of familial CJD stems from the German psychiatrist and neurologist Friedrich Meggendorfer (1880–1953). A study published in 1997 counted more than 100 cases worldwide of transmissible CJD and new cases continued to appear at the time. The first report of suspected iatrogenic CJD was published in 1974. Animal experiments showed that corneas of infected animals could transmit CJD, and the causative agent spreads along visual pathways. A second case of CJD associated with a corneal transplant was reported without details. In 1977, CJD transmission caused by silver electrodes previously used in the brain of a person with CJD was first reported. Transmission occurred despite the decontamination of the electrodes with
ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
and formaldehyde. Retrospective studies identified four other cases likely of similar cause. The rate of transmission from a single contaminated instrument is unknown, although it is not 100%. In some cases, the exposure occurred weeks after the instruments were used on a person with CJD. In the 1980s it was discovered that Lyodura, a dura mater transplant product, was shown to transmit CJD from the donor to the recipient. This led to the product being banned in Canada but it was used in other countries such as
Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...
until 1993. A review article published in 1979 indicated that 25 dura mater cases had occurred by that date in Australia, Canada, Germany, Italy, Japan, New Zealand, Spain, the United Kingdom, and the United States. By 1985, a series of case reports in the United States showed that when injected,
cadaver A cadaver, often known as a corpse, is a Death, dead human body. Cadavers are used by medical students, physicians and other scientists to study anatomy, identify disease sites, determine causes of death, and provide tissue (biology), tissue to ...
-extracted pituitary human growth hormone could transmit CJD to humans. In 1992, it was recognized that human gonadotropin administered by injection could also transmit CJD from person to person. Stanley B. Prusiner of the
University of California, San Francisco The University of California, San Francisco (UCSF) is a Public university, public Land-grant university, land-grant research university in San Francisco, California, United States. It is part of the University of California system and is dedic ...
(UCSF) was awarded the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
in 1997 "for his discovery of Prions—a new biological principle of infection".
Yale University Yale University is a Private university, private Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the List of Colonial Colleges, third-oldest institution of higher education in the United Stat ...
neuropathologist Laura Manuelidis has challenged the prion protein (PrP) explanation for the disease. In January 2007, she and her colleagues reported that they had found a
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
-like particle in naturally and experimentally infected animals. "The high infectivity of comparable, isolated virus-like particles that show no intrinsic PrP by antibody labeling, combined with their loss of infectivity when nucleic acid–protein complexes are disrupted, make it likely that these 25-nm particles are the causal TSE virions".


Australia

Australia has documented 10 cases of healthcare-acquired CJD (iatrogenic or ICJD). Five of the deaths resulted after the patients, who were in treatment either for
infertility In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...
or short stature, were treated using contaminated pituitary extract hormone but no new cases have been noted since 1991. The other five deaths occurred due to dura grafting procedures that were performed during brain surgery, in which the covering of the brain is repaired. There have been no other ICJD deaths documented in Australia due to transmission during healthcare procedures.


New Zealand

A case was reported in 1989 in a 25-year-old man from New Zealand, who also received dura mater transplant. Five New Zealanders have been confirmed to have died of the sporadic form of Creutzfeldt–Jakob disease (CJD) in 2012.


United States

In 1988 there was a confirmed death from CJD of a person from
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. Massachusetts General Hospital believed the person acquired the disease from a surgical instrument at a podiatrist's office. In 2007 Michael Homer, former Vice President of Netscape, had been experiencing consistent memory problems which led to his diagnosis. In August 2013 the British journalist Graham Usher (journalist), Graham Usher died in New York of CJD. In September 2013, another person in Manchester was posthumously determined to have died of the disease. The person had undergone brain surgery at Catholic Medical Center three months before his death, and a surgical probe used in the procedure was subsequently reused in other operations. Public health officials identified thirteen people at three hospitals who may have been exposed to the disease through the contaminated probe but said the risk of anyone contracting CJD is "extremely low". In January 2015, former speaker of the Utah House of Representatives Rebecca D. Lockhart died of the disease within a few weeks of diagnosis. John Carroll (journalist), John Carroll, former editor of ''The Baltimore Sun'' and ''Los Angeles Times'', died of CJD in Kentucky in June 2015, after having been diagnosed in January. American actress Barbara Tarbuck (''General Hospital'', ''American Horror Story'') died of the disease on December 26, 2016. José Baselga, clinical oncologist having headed the AstraZeneca oncology division, died in Cerdanya, March 21, 2021, from CJD. In April 2024, a report was published regarding two hunters from the same lodge who, in 2022, were found to be afflicted with sporadic CJD after eating Venison, deer meat infected with chronic wasting disease (CWD), suggesting a potential link between CWD and CJD.


Research


Diagnosis

*In 2010, a team from New York (state), New York described detection of PrPSc in sheep's blood, even when initially present at only one part in one hundred billion (10−11) in sheep's brain tissue. The method combines amplification with a novel technology called surround optical fiber immunoassay (SOFIA) and some specific antibodies against PrPSc. The technique allowed improved detection and testing time for PrPSc. *In 2014, a human study showed a nasal brushing method that can accurately detect PrP in the olfactory epithelial cells of people with CJD.


Treatment

*Pentosan polysulfate (PPS) may slow the progression of the disease, and may have contributed to the longer than expected survival of the seven people studied. The CJD Therapy Advisory Group to the UK Health Departments advises that data are not sufficient to support claims that pentosan polysulfate is an effective treatment and suggests that further research in animal models is appropriate. A 2007 review of the treatment of 26 people with PPS finds no proof of efficacy because of the lack of accepted objective criteria, but it was unclear to the authors whether that was caused by PPS itself. In 2012 it was claimed that the lack of significant benefits has likely been caused because of the drug being administered very late in the disease in many patients. *Use of RNA interference to slow the progression of scrapie has been studied in mice. The RNA blocks production of the protein that the CJD process transforms into prions. *Both amphotericin B and doxorubicin have been investigated as treatments for CJD, but as yet there is no strong evidence that either drug is effective in stopping the disease. Further study has been taken with other medical drugs, but none are effective. However, Anticonvulsant, anticonvulsants and Anxiolytic, anxiolytic agents, such as valproate or a benzodiazepine, may be administered to relieve associated symptoms. *Quinacrine, a medicine originally created for malaria, has been evaluated as a treatment for CJD. The efficacy of quinacrine was assessed in a rigorous clinical trial in the UK and the results were published in ''Lancet Neurology'', and concluded that quinacrine had no measurable effect on the clinical course of CJD. *Astemizole, a medication approved for human use, has been found to have anti-prion activity and may lead to a treatment for Creutzfeldt–Jakob disease. *A monoclonal antibody (code name PRN100) targeting the prion protein (PrP) was given to six people with Creutzfeldt–Jakob disease in an early-stage clinical trial conducted from 2018 to 2022. The treatment appeared to be well-tolerated and was able to access the brain, where it might have helped to clear PrPC. While the treated patients still showed progressive neurological decline, and while none of them survived longer than expected from the normal course of the disease, the scientists at University College London who conducted the study see these early-stage results as encouraging and suggest to conduct a larger study, ideally at the earliest possible intervention.


See also

*Transmissible spongiform encephalopathy *Chronic wasting disease *Kuru (disease), Kuru


References


External links

{{Authority control Transmissible spongiform encephalopathies Neurodegenerative disorders Dementia Rare infectious diseases Wikipedia medicine articles ready to translate Wikipedia neurology articles ready to translate Rare diseases 1920 in biology