periodic sharp waves on electroencephalogram often presentoften absent signal hyperintensity in the caudate nucleus and putamen on diffusion-weighted and flair mri often presentoften absent pulvinar sign-bilateral high signal intensities on axial flair mri. also posterior thalamic involvement on sagittal t2 sequencesnot reported present in >75% of cases immunohistochemical analysis of brain tissue variable accumulation. marked accumulation of protease-resistant prion protein presence of agent in lymphoid tissue not readily detectedreadily detected increased glycoform ratio on immunoblot analysis of protease-resistant prion protein not reported marked accumulation of protease-resistant prion protein presence of amyloid plaques in brain tissue may be presentmay be present treatment as of 2023, 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. myoclonic jerks can be handled with clonazepam or sodium valproate. opiates can help in pain. seizures are very uncommon but can nevertheless be treated with antiepileptic drugs. prognosis the condition is universally fatal. as of 1981, no one is known to have lived longer than 2.5 years after the onset of cjd symptoms. the longest recorded survivor of variant creutzfeldt–jakob disease (vcjd) was jonathan simms, a northern irish man who lived 10 years after his diagnosis. epidemiology 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 a rate of about 1 case per million population per year. 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 african american and 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, acute nephropathy, general dementia, and hyperparathyroidism. history the disease was first described by german neurologists hans gerhard creutzfeldt in 1920 and shortly afterward by alfons maria jakob, giving it the name creutzfeldt–jakob. 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 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 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-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 (ucsf) was awarded the nobel prize in physiology or medicine in 1997 "for his discovery of prions—a new biological principle of infection". yale university 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-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 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 manchester, new hampshire. 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 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's 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, 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. research diagnosis in 2010, a team from 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 polysulphate (pps) was thought to 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 polysulphate 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, anticonvulsants and 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.