A rapidly progressive dementia is the first symptom of Creutzfeldt–Jakob disease . A group of symptoms, clinically diagnostic, are: Rapidly progressive dementia, myoclonus, and characteristic electroencephographic changes . However, these signs are not seen in 25% of patients, making it difficult to make the diagnosis .
Damage to the central nervous system causes the symptoms of the disease and leads to memory loss, personality changes and hallucinations . Other psychological features, such as anxiety, depression, paranoia, obsessive-compulsive symptoms, and psychosis, occur in 1/3 of cases .
The condition may also be accompanied by physical symptoms such as seizures, speech impairment, myoclonus, and ataxia: Balance, coordination, gait, and posture dysfunction . Ataxia and visual abnormalities, perceptual abnormalities and hallucinations are also frequent signs of this disorder .
The duration of the disease can vary, but is usually fatal within months of diagnosis. In a small number of cases of sporadic Creutzfeldt Jakob disease, perhaps 15%, patients have survived 4 to 5 years. Most victims die of pneumonia due to impaired cough and swallow reflexes .
Approximately 10% of all European cases of Creutzfeldt Jakob disease are of the familial form . The clinical picture of familial Creutzfeldt Jakob disease varies according to the specific mutation. Usually it has an earlier onset and longer duration than sporadic Creutzfeldt Jakob disease .
In variant Creutzfeldt Jakob disease sufferers are younger and that its clinical presentation is often limited to psychiatric disturbances or sensory symptoms . The more classic physical signs do not develop until very late in the course of the disease  .
Entire Body System
- Progressive Dementia
Three weeks after the initial work-ups, the patient presented with typical neurological findings of CJD: rapidly progressive dementia, akinetic mutism, and myoclonus of the left arm. [ncbi.nlm.nih.gov]
Amy May Lin Quek and Andrew McKeon, Rapidly Progressive Dementia and its Mimics, Dementia, (15-34), (2013). [doi.org]
Pulmonologist 5 (2.2) Psychiatrist 5 (2.2) Otolaryngologist 3 (1.3) Geriatrician 2 (0.9) Optometrist 2 (0.9) Orthopedic surgeon 2 (0.9) Neuro-oncologist 1 (0.4) Gastroenterologist 1 (0.4) Rheumatologist 1 (0.4) Neuro-ophthalmologist 1 (0.4) Speech pathologist [ncbi.nlm.nih.gov]
Although CJD is not a formally notifiable disease in the United Kingdom, clinicians (and pathologists) have been asked to notify the National Creutzfeldt-Jakob Disease Surveillance Unit and the National Prion Clinic of any suspected cases (see Appendix [academic.oup.com]
A primer for practicing pathologists. Arch Pathol Lab Med. 1993;117:132-144. Frisoni GB, Boccardi M, Barkhof F, et al. Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers. Lancet Neurol. 2017;16(8):661-676. [library.med.utah.edu]
Kovacs, Prion diseases: a primer for general pathologists, Diagnostic Histopathology, 17, 5, (217), (2011). [doi.org]
He had sleep problems and then lots of fatigue over a 2-yr. period, but we both thought that it was the inability to sleep soundly and age. Who knows if that was part of this disease. Maybe, maybe not. [globalgenes.org]
Early non-specific symptoms may include dizziness, headaches, fatigue, sleep disturbance and weight loss. Behavioural symptoms such as mood swings and loss of interest may also be seen. [prion.ucl.ac.uk]
The patient's mother had a sudden onset of memory problems and rapidly deteriorating mental faculties in her late 70s, which led to difficulties ambulating, progressive non-fluent aphasia, dysphagia and death within 1 y of symptom onset. [ncbi.nlm.nih.gov]
[…] more information about how some of the specific symptoms of CJD may be treated, see: treating ataxia (loss of physical co-ordination) treating urinary incontinence (loss of bladder control) treating bowel incontinence (loss of bowel control) treating dysphagia [nhs.uk]
Case 1 2 3 4 5 Age/Sex 61 M 65 F 51 F 61 F 80 M Cognitive symptoms Psychosis, schizophrenia, cognitive decline Dysphasia, depression, psychosis Vertigo, progressive encephalopathy Memory loss, aphasia Aphasia, dysarthria, dysphagia Motor symptoms Impaired [idsa.confex.com]
- Muscle Rigidity
The main clinical features of this disease, in contrast to sCJD, are slowly progressive dysarthria, bradykinesia manifesting predominantly as gait disturbance, and muscle rigidity as well as diadochokinesis. [doi.org]
None of our cases had known history of any surgical procedure, head trauma, hypertension, intake of lithium or any hormone replacement therapy. No history suggestive of exposure to toxins like bismuth was noted in any of the cases. [neurologyindia.com]
Dementia resulting from dural arteriovenous fistulas: the pathologic findings of venous hypertensive encephalopathy. AJNR 1998; 19:1267 –1273 [Google Scholar] 27. Schwaninger M, Winter R, Hacke W, et al. [doi.org]
The signs include insomnia and oneiric or stuporous episodes with hallucinations and confusion, autonomic dysfunction (systemic hypertension, irregular breathing, diaphoresis, pyrexia and impotence), and often myoclonus, spasticity and seizures. [bmb.oxfordjournals.org]
- Visual Impairment
We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months [ncbi.nlm.nih.gov]
The most common form presents a number of symptoms including progressive dementia, abnormal eye movements or visual impairment, confusion, and lack of movement coordination. [news-medical.net]
Ocular disturbances (eg, visual field defects, diplopia, dimness or blurring of vision, visual agnosia) are common in sCJD. [merckmanuals.com]
Creutzfeldt-Jakob disease presenting with visual blurring, diplopia and visual loss: Heidenhain's variant. Ann Acad Med Singapore 1998; 27:854 –856 [Google Scholar] 11. Na DL, Suh CK, Choi SH, et al. [doi.org]
- Visual Hallucination
Features thought to support this diagnosis included psychiatric symptoms (anxiety and depression), visual hallucinations and a visual field defect. However, the finding of papilloedema broadened the differential diagnosis. [ncbi.nlm.nih.gov]
Further reading Low mood, visual hallucinations, and falls – heralding the onset of rapidly progressive probable sporadic Creutzfeldt–Jakob disease in a 73-year old: a case report Daniel Martin Klotz & Rose Sarah Penfold Journal of Medical Case Reports [nature.com]
hallucinations and aggression occasionally occur during the initial phase of the disease in sporadic CJD, suggesting a primary psychiatric diagnosis of psychosis or depression. 11 Very rare presentations include those that mimic a stroke ( 2%) or corticobasal [doi.org]
- Mood Swings
Agitation, apathy and mood swings. Rapidly worsening confusion, disorientation, and problems with memory, thinking, planning and judgment. Difficulty walking. Muscle stiffness, twitches and involuntary jerky movements. [alz.org]
Symptoms may include memory loss, poor judgment, confusion, mood swings, difficulty with coordination, and trouble learning new things. [dementiacarecentral.com]
Behavioural symptoms such as mood swings and loss of interest may also be seen. Because of these initial symptoms the person may at first be thought to be suffering from depression or other psychiatric disease. [prion.ucl.ac.uk]
- Abnormal Behavior
A 62-year-old man presented with abnormal behavior and cognitive impairment. Diffusion-weighted images (DWI) obtained on MRI showed extensive hyperintense regions in the cerebral cortex and striatum. [ncbi.nlm.nih.gov]
Shortly after, his family noted an ataxic gait and behavioral changes, for example, paranoid delusions. [ncbi.nlm.nih.gov]
Three weeks after the initial work-ups, the patient presented with typical neurological findings of CJD: rapidly progressive dementia, akinetic mutism, and myoclonus of the left arm. [ncbi.nlm.nih.gov]
Myoclonus and periodic sharp‐wave complexes on the electroencephalogram were observed in the early disease stage. The clinical diagnosis was typical sCJD. [www3.interscience.wiley.com]
Neurological examination revealed progressive dementia, frontal signs, insomnia, speech disturbance, gait disturbance and bilaterally exaggerated tendon reflexes. [ncbi.nlm.nih.gov]
Fatal Familial Insomnia (FFI) Fatal familial insomnia (FFI) is a very rare autosomal dominant inherited disease of the brain. [memory.ucsf.edu]
Insomnia has not been reported in CJD D178N–129V. [bmb.oxfordjournals.org]
Clinical presentation of the MV2K C subtype includes predominant cerebral cortical involvement signs with ataxia and DWI hyperintensity of the cerebral cortex on MRI. [ncbi.nlm.nih.gov]
A 73-year-old British Caucasian woman presented with acute confusion of 2 weeks' duration on a background of low mood following a recent bereavement. Her symptoms included behavioral change, visual hallucinations, vertigo, and recent falls. [ncbi.nlm.nih.gov]
Seizures are known to occur in Creutzfeldt-Jakob disease (CJD). [ncbi.nlm.nih.gov]
Creutzfeldt Jakob disease is suspected through its clinical symptoms . Further testing to support the diagnosis includes:
- Electroencephalograph changes with characteristic triphasic spikes  , occurs in 2/3 of patients.
- Cerebrospinal fluid analysis shows 14-3-3 protein and neuron-specific enolase (NSE)   in 84-94% of patients with sporadic Creutzfeldt Jakob disease. A positive finding indicates a positive diagnosis for the disease . They are found less often in variant Creutzfeldt Jakob disease .
- Magnetic resonance imaging of the brain often shows high intensity signals in the caudate nucleus and putamen bilaterally in sporadic Creutzfeldt Jakob disease . Cortical and subcortical abnormalities are found in variant Creutzfeldt Jakob disease .
Normal findings in imaging studies do not rule out the diagnosis, however, because they are normal in as many as 20% of patients .
The only definitive diagnostic test for all forms of Creutzfeldt Jakob disease is the biopsy of brain tissue . However, a negative biopsy does not rule out the disease. Because of the invasive nature and possible complications of the procedure, and the fact that it will not alter the outcome, it is not often used for diagnosis .
Research is in the process of developing a possible blood test for Creutzfeldt Jakob disease that may be able to identify the prion responsible for the disease. It has not yet proven to be able to detect them in the early stages of the disease  .
Differential diagnoses for Creutzfeldt Jakob disease include Alzheimer’s disease and Lewy body dementia, in younger patients chronic inflammatory disorders of the central nervous system have to be ruled out .
The diagnosis of Creutzfeldt Jakob disease is ultimately made through a combination of clinical features, an electroencephalogram and magnetic resonance imaging with characteristic findings, and elevated levels of neuronal proteins in the cerebrospinal fluid .
Extensive spongiform changes were observed in the cerebral neocortex, striatum, thalamus and cerebellar cortex, but gliosis was mild or absent. Neuropil rarefaction and neuron loss were not apparent. [ncbi.nlm.nih.gov]
CONCLUSION: Although approximately 20% of the patients did not have MR imaging abnormalities, MR imaging did show signal intensity alterations due to gliosis and spongiform changes early in the course of CJD in the remaining 80%. [doi.org]
- Amyloid Plaque
Since cases lacking amyloid plaques may also manifest a prolonged (i.e. than one year) disease course, unidentified, host-specific factors likely play a significant role, in addition to disease duration, in generating white matter PrP-amyloid plaques [ncbi.nlm.nih.gov]
Moreover, misfolded prion protein aggregates, sometimes forming large amyloid plaques. [news-medical.net]
Currently there is no treatment for Creutzfeldt Jakob disease. The disease is always fatal, usually within a year of diagnosis.
Experimentally a medication, pentosan polysulphate (cystitis), infused directly into the lateral ventricle of the brain has shown promise. This treatment does not stop the disease but seems to slow its progression and may result in a longer survival time  .
Other drugs such as amphotericin B and doxorubicin have been suggested in the treatment of the condition. As yet no evidence exists that they are effective curing or slowing the disease .
Drug trials using quinacrine, a malaria drug, and astemizole are currently under way. It is hoped that these drugs will clear abnormal prion proteins from cells. Currently trial results have been inconclusive  .
There are, however, drugs available currently to treat and reduce the symptoms of the disease. Valproate can be used to prevent seizures. Clonazepam and benzodiazepine may be helpful to reduce muscle spasms and jerks  .
Because of the long incubation period for variant Creutzfeldt Jakob disease, it is not known how many people have been infected but are still asymptomatic . This is a continuing public health concern because of the risk of iatrogenic transmission through blood, transplantation, and surgical instruments  .
Creutzfeldt Jakob disease is defined as a transmissible spongiform encephalopathy or human prion disease . It is the most common of these disorders, yet is exceptionally rare. It was named after two German neuropathologists, Creutzfeld and Jakob in the 1920s . They identified its specific features in certain families in France .
Creutzfeldt Jakob disease is always fatal. The disease duration in 85% of cases is less than 1 year from the onset of symptoms, with a median of 4 months .
Creutzfeldt Jakob disease may have any of three different origins. Sporadic and familial Creutzfeldt Jakob disease are due to mutations in the prion gene. Infectious forms of the disease are due to exposure to infected human or animal material .
There are four forms of the disease  :
- Sporadic Creutzfeldt Jakob disease is the most common form accounting for 85% of all cases   . Its cause is unknown; however, it is thought to be associated with gene mutations related to the aging process .
- Familial Creutzfeldt Jakob disease is an autosomal dominant inherited disorder and accounts for 10% of cases of the disease   .
- Iatrogenic Creutzfeldt Jakob disease is caused by contamination with tissue from an infected person through a medical procedure . This accidentally transmitted disease has been associated with corneal graft transplantation, contaminated human pituitary-derived growth hormone or gonadotropin and dura mater grafts .
- Variant Creutzfeldt Jakob disease is thought to be caused by the consumption of contaminated animal products (sheep or beef). It was identified in the United Kingdom in1996 when 10 atypical cases of Creutzfeldt Jakob disease were diagnosed .
The symptoms of Creutzfeldt Jakob disease are caused by the death of nerve cells of the brain caused by the accumulation of abnormal prion proteins that form amyloid plaques . Microscopically the brain tissue of a patient with Creutzfeldt Jakob disease has a sponge-like appearance with many small holes where areas of nerve cells have died . This is where the term spongiform encephalopathy, sponge-like, originated.
The incidence of Creutzfeldt Jakob disease worldwide is about 1 case per million population . In individuals under the age of 30 the rate is even lower, less than 5 deaths per billion . Creutzfeldt Jakob disease generally affects individuals aged 45 to 75, with a mean age of 65 years   with a rate of approximately 3-4 per million in that population group  . Only the variant form occurs in younger individuals
There have been 173 cases of variant Creutzfeldt Jakob disease (vCJD) in the United Kingdom since 2010 due to the bovine spongiform encephalopathy epidemic  . Although seen primarily in the United Kingdom and France, there have been scattered cases worldwide of this form .
There are no gender or racial differences in the prevalence of the disease .
The etiology of Creutzfeldt Jakob disease is the production or introduction of abnormal prion proteins into the body . Stanley Prusiner proposed the prion hypothesis in 1982, suggesting the existence of a pathogen, smaller than a virus, with no nucleic acid  . The abnormal proteins, although containing the same amino-acid sequencing are non-functional . The normal prion protein is water-soluble and presents in healthy cells. Its function is thought to be transmembrane transport or signaling in nerve cells. The abnormal prion protein is not water soluble and readily forms protein aggregates  . Their propagation is due to an autocatalytic prion protein conversion process .
When the Creutzfeldt Jakob prion comes into contact with a normal protein it causes the restructuring of the natural proteins into the abnormal form . The number of abnormal protein molecules increases exponentially. This majority of abnormal proteins disrupts cell function and causes cell death  .
The physicochemical biology of the protein prion is unknown. The function of the normal prion protein is not clear . The reasons for the various forms of the disorder and their differing presentations and characteristics are not understood  . It is thought that host genetics and the properties of the different prion strains are factors .
Creutzfeldt Jakob disease causes a spongiform change in the gray matter . There is the presence of diffuse small round vacuoles and plaques of amyloid-like material .
Creutzfeldt Jakob disease is a transmissible disease indicating that the prion is an infective agent. However, it does not elicit an immune response in the host  . In certain groups of people, the frequency is higher, emphasizing the role of a genetic predisposition . In addition, there are certain familial inherited forms of the disease that also point to a genetic component .
Familial cases are due to inherited mutations in the gene responsible for the production of the protein  . Sporadic Creutzfeldt Jakob disease is caused by mutations occurring spontaneously in susceptible individuals  .
Variant Creutzfeldt Jakob disease (vCJD) arose from the ingestion of animal products contaminated with bovine spongiform encephalopathy (Mad cow disease)   . The neuropathology of variant Creutzfeldt Jakob disease is distinct from that of bovine spongiform encephalitis . The transmission of the disease from one species to another results in changes in the neuropathology due to different agent/host interactions .
Unlike other forms of the disease variant Creutzfeldt Jakob disease has shown abnormal prion in the lymphoid tissues. This raises concerns about the possibility that the prion may be present in blood  and suggests that the disease may be transmissible through transfusion of blood or blood products .
No evidence exists that there is an increased risk of transmission to medical personnel, not even to those handling tissue from patients with known or suspected Creutzfeldt Jakob disease .
The risk of new exposure to bovine spongiform encephalitis through the diet is remote today. The United Kingdom and other nations have instituted excellent screening procedures for cattle and sheep .
Screening tests are being researched in order to identify asymptomatic infected patients. This screening will help to eliminate these individuals as blood or organ donors . None are as yet available.
Creutzfeldt Jakob disease is an incurable, fatal degenerative neurological disease  caused by an abnormal protein called a prion  . Prions are abnormally structured proteins that replicate by converting normal proteins, within their host, to the abnormal structure  . Creutzfeldt Jakob disease leads to rapid neurodegeneration causing brain tissue to develop holes and take on a sponge-like appearance   .
Creutzfeldt Jakob disease is not one disorder, but includes four subtypes : Sporadic, familial , iatrogenic, and variant forms. Variant Creutzfeldt Jakob disease has been associated with bovine spongiform encephalopathy, mad cow disease  .
Creutzfeldt Jakob disease is a very rare disorder, affecting less than 1 person per million population worldwide . It is always fatal and there is no known treatment at this time.
What is Creutzfeldt Jakob disease?
Creutzfeldt Jakob disease is a rapidly progressing neurodegenerative disease which is always fatal. It is a human prion disorder, a spongiform encephalitis, in which proliferation of abnormal proteins, prions, in the brain cause destruction of brain cells. The death of brain tissue results in the formation of holes making the brain sponge-like in appearance. There are three forms of the disease: sporadic (classic), familial, iatrogenic (as a result of a medical procedure), and variant (associated with mad cow disease).
What are the symptoms of Creutzfeldt Jakob disease?
Creutzfeldt Jakob disease is characterized by dementia, motor dysfunction, twitches, seizures, psychosis, and hallucinations.
The duration of the disease is generally less than 1 year and death may occur within weeks or months.
What causes Creutzfeldt Jakob disease?
Creutzfeldt Jakob disease is cause by an abnormally formed protein called a prion. Prions carry the same amino acid sequences as normal proteins, but are structurally different and non-functional. They causes the damage to the central nervous system and the resulting neurobiological symptoms and ultimately death. Sporadic Creutzfeldt Jakob disease is due to a spontaneous mutation of the gene producing the prion protein and appears to increase with age. Familial Creutzfeldt Jakob disease is an autosomal dominant inherited disorder in which the abnormal gene is passed on through families. Iatrogenic Creutzfeldt Jakob disease is caused by the transplantation or transfusion of infected blood or tissue. Variant Creutzfeldt Jakob disease is caused by consumption of infected animal products.
Who gets Creutzfeldt Jakob disease?
Creutzfeldt Jakob disease is most common in individuals age 55 to 65 years. Variant Creutzfeldt Jakob disease occurs in younger people who have eaten contaminated animal protein.
How is it diagnosed?
There are no specific tests. It is suspected using the clinical symptoms. Diagnosis is supported by electroencephalograph, cerebrospinal fluid analysis, or magnetic resonance imaging.
A definitive diagnosis can only be made by brain tissue biopsy. Research is underway to develop a means of testing for the presence of the abnormal prion proteins early in the disease.
How is Creutzfeldt Jakob disease treated?
Creutzfeldt Jakob disease does not have any effective treatment at this time. Current research is searching for a way to remove the abnormal prion proteins from the body, but no medications are available today. There are medications that are effective in treating some of the symptoms of the disease: seizures, muscle twitches, depression, and psychosis.
How can it be prevented?
The risk of new exposure to bovine spongiform encephalitis through the diet is remote today. The United Kingdom and other nations have instituted excellent screening procedures for cattle and sheep. Prevention of iatrogenic Creutzfeldt Jakob disease may be achieved by routine surgical instrument sterilization procedures. Screening tests are being researched in order to identify asymptomatic infected patients. This screening will help to eliminate these individuals as blood or organ donors. None are as yet available.
- Norrby E. Prions and protein-folding diseases. Journal of InternalMedicine. 2011; 270: 1–14.
- DeArmond SJ, Prusiner SB. The Neurochemistry of Pion Diseases. Journal of’Neitrochemistry. 1993;61(5):1589-1602.
- Gençerag, Pelin Z, Küçükali C, Topçuog˘lu Öb, Yilmaz N. Creutzfeldt–Jakob disease. Psychogeriatrics. 2011; 11: 119–124.
- Ironsid JW. Variant Creutzfeldt–Jakob disease EHaemophilia. 2010; 16 (Suppl. 5): 175–180.
- Haik S, Brandel, J-P. Biochemical and strain properties of CJD prions: complexity versus simplicity. Journal Of Neurochemistry. 2011; 119:251–261.
- Wadsworth JDF, Dalmau-Mena I, Joiner S, Linehan JM, O’Malley C,
- Powell C, Brandner S, et al. Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study. J Pathol. 2011; 223: 511–518.
- Sorbia S, Hortb J, Erkinjunttic T, Fladbye T, Gainottig G, Gurvith H, Nacmiasa B, et al. EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia. European Journal of Neurology. 2012; 19: 1159–1179.
- Pedersen NS, Smith E. Prion diseases: Epidemiology in man. APMIS.2002; 110: 14–22.
- de Marco MF, Linehan J, Gill ON, Clewley JP, Brandner S. Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain. J Pathol. 2010; 222: 380–387.
- Aguzzi A. Prion diseases of humans and farm animals: epidemiology, genetics, and pathogenesis. Journal of Neurochemistry. 2006, 97, 1726–1739.
- Ironside JW, Mccardle L, Horsburgh A, Lim Z, Head MW. Pathological diagnosis of variant Creutzfeldt-Jakob disease. APMIS. 2002; 110: 79–87.