INTRODUCTION — Prion diseases are neurodegenerative diseases that have long incubation periods and progress inexorably to death once clinical symptoms appear. Three categories of human prion diseases are recognized:
●Sporadic – Sporadic Creutzfeldt-Jakob disease (sCJD), sporadic fatal insomnia, and variably protease-sensitive prionopathy
●Genetic – Genetic Creutzfeldt-Jakob disease, fatal familial insomnia, and Gerstmann-Sträussler-Scheinker syndrome
●Acquired – Kuru, iatrogenic Creutzfeldt-Jakob disease, and variant Creutzfeldt-Jakob disease (vCJD)
These human prion diseases share certain common neuropathologic features including neuronal loss, proliferation of glial cells, absence of an inflammatory response, the presence of small vacuoles within the neuropil that produces a spongiform appearance, and the presence of protease-resistant prion protein.
vCJD was first reported in the United Kingdom in 1996 and subsequently in several other countries, and was determined to have features that are distinct from typical sCJD (table 1). vCJD was subsequently linked to an outbreak of bovine spongiform encephalopathy (BSE), also in the United Kingdom. Following the decline of BSE and the introduction of dietary protective measures, vCJD has become extremely rare.
The clinical manifestations and diagnosis of vCJD will be reviewed here. Classic CJD (sporadic, iatrogenic, and familial forms of CJD) and other prion diseases are discussed separately.
●(See "Creutzfeldt-Jakob disease".)
●(See "Diseases of the central nervous system caused by prions".)
EPIDEMIOLOGY AND PATHOGENESIS — First reported in 1996, vCJD was found to have unique clinical and epidemiologic features (table 1) and a link to bovine spongiform encephalopathy (BSE), a prion disease of cattle [1,2]. It is believed that most cases of vCJD have been acquired by ingestion of contaminated beef; genetic susceptibility may play a role in disease manifestation. A few cases of transfusion-related vCJD have been reported. There is no evidence of vertical transmission (mother to child) of vCJD, although the potentially long incubation period for this mechanism makes it difficult to exclude this possibility definitively [3].
One of the many features that distinguishes vCJD from sporadic CJD (sCJD) and other prion diseases is its prominent tropism for lymphoid organs such as the tonsils and appendix [4-9]. It is speculated that the younger age of vCJD patients compared with sCJD patients may relate to the greater amount of gut-associated lymphoreticular tissue in young people, making them more susceptible to infection [10,11].
Incidence and prevalence
●Clinical vCJD – The first reported case of vCJD in a 16-year-old patient from the United Kingdom appeared in 1995 and was subsequently included in a series of 10 cases from the United Kingdom proposing that these cases represented a "new variant" of CJD, possibly due to exposure to BSE [12].
As of October 2021, there have been a total of 232 cases of confirmed or probable vCJD reported worldwide, with 178 from the United Kingdom; 28 from France; five in Spain; four each in Ireland and the United States; three each in the Netherlands and Italy; two each in Portugal and Canada; and one each in Japan, Taiwan, and Saudi Arabia [13-17]. Country attribution is determined by the patient's country of residence at the time of diagnosis, not the country of suspected BSE exposure [18].
All of the cases detected in the United States, Canada, and Japan are thought to have been exposed to BSE outside of their respective countries of residence (eg, United Kingdom, Saudi Arabia). Most of the remaining vCJD cases are believed to have been exposed to BSE in their resident country. All patients are believed to have been infected through food product contamination consumed within the United Kingdom or that was exported from the United Kingdom. Similarities between clinical phenotype and transmission properties of vCJD brain tissue reported from different countries suggest that a common strain of infectious agent is involved, and therefore a single source of infection [19,20].
●Asymptomatic infections – The true number of vCJD infections is unknown as the incubation period is long, several years, and infected individuals may be asymptomatic. Studies that have surveyed a large number of lymphoreticular tissue samples, including tonsils and appendices, have variably estimated the prevalence in the United Kingdom [16,21-24]. Two studies, one screening tonsillar tissue and one screening both tonsils and appendices, found no vCJD-positive samples out of a total of over 5000 specimens screened [23,24]. Another much larger study identified one case out of 63,007 tonsils screened that was positive via immunohistochemistry but negative by enzyme immunoassay [25]. Other studies have detected higher prevalences of 120 to 493 per million inhabitants (roughly 1 in 2000 to 4000) [16,21,22]. This last statistic was reported in a large-scale survey of 32,441 appendix samples that identified 16 that were positive for vCJD [16].
Another large study (Appendix-III) examined appendices from two groups of individuals that were believed not to have been exposed to BSE: individuals who underwent appendectomy prior to 1980 (prior to the BSE epidemic) and individuals born after January 1, 1996 (after infected meat had been removed from the food chain) [26]. Unexpectedly, positive cases were detected in both groups (2 of 14,692 and 5 of 14,824, respectively) and the estimated prevalence of infection in both groups, while lower than prior studies in the exposed population, was not statistically significantly different from that reported in those studies. Possible explanations of these findings include a low background prevalence of vCJD staining that is unrelated to intensity and duration of BSE exposure or a small increased prevalence in high-exposure time periods that is not statistically significant [27].
The much lower and declining number of clinically recognized vCJD cases in the United Kingdom may support a lower overall prevalence of vCJD or may be due to differences in clinical onset as determined by codon 129 prion protein (PRNP) polymorphism. The latter explanation is supported by high proportion of valine homozygosity at codon 129 in positive appendectomy samples compared with confirmed clinical cases of vCJD, which are virtually all methionine homozygous [16]. (See 'Genetic risk factors' below.)
Bovine spongiform encephalopathy — Several lines of epidemiologic and experimental evidence have demonstrated that vCJD represents bovine-to-human transmission of BSE, a prion disease in cattle [28].
●BSE epidemic – The source of BSE remains unclear. The first cases were reported in 1986 in the United Kingdom. Theories of its origination include the transmission of either sheep scrapie or another prion disease to cattle via contaminated feed [29]; it has even been speculated that the original source was human CJD [30]. An intrinsic genetic event in cattle seems less likely.
The BSE epidemic in the United Kingdom was perpetuated via the refeeding of contaminated material to cattle, particularly in the form of meat and bone meal. Approximately 50,000 infected cattle are estimated to have entered the human food chain [28]. A ruminant feed ban aimed at preventing further dissemination of disease was instituted in 1989 in the United Kingdom and enforced in other European countries in 2000. The feed bans have dramatically reduced the cases of BSE, though isolated cases continue to be detected.
BSE was first reported in North America in 2003 in Alberta, Canada. The first BSE case in the United States, confirmed in December 2003, was found in a Washington state dairy cow that had been slaughtered with meat sent to market [31]. As of 2016, 21 cases of Canadian-born cattle BSE cases have been identified. As of November 2019, Canada is listed as a "controlled BSE risk" country by the World Organisation for Animal Health (Office International des Epizooties [OIE]).
There have been six cases of BSE detected in the United States [32]. The first reported case in 2003 was imported from Canada. The first endemic BSE case was detected in Texas in 2005. Four cases were atypical BSE, which occur in older cattle and may be due to a spontaneous form of prion disease in cattle. One case of BSE had a mutation of the PRNP gene. As of November 2019, the OIE lists the United States as a "negligible BSE risk" country.
The United States Department of Agriculture (USDA) has several safety measures to prevent the transmission of BSE to other cattle and to humans. These measures include prohibiting the inclusion of mammalian meat and bone meal in animal feed, prohibiting the use of specified risk materials (eg, brain and spinal cord), and destroying cattle demonstrating symptoms of BSE or those that are at risk of developing it. Updated USDA information regarding BSE testing is available online.
Updated information on the number of BSE cases reported throughout the world in imported or indigenous cattle is available online from the OIE website.
●Link to vCJD – The temporal association between the BSE epidemic in 1986 and the outbreak of vCJD in 1995 is consistent with the known incubation periods for prion disease.
Other evidence that supports the connection between vCJD and BSE includes near-exclusive occurrence of vCJD in the United Kingdom where BSE originated. In addition, the prions derived from BSE and vCJD are similar [28].
Other factors supporting the link between BSE and vCJD include neuropathologic similarities between macaques intracerebrally inoculated with BSE and vCJD and identical lesion profiles in wild-type mice inoculated with BSE and vCJD [33,34].
Despite the apparent link between vCJD and BSE, the number of cases of vCJD has remained small. Possible reasons for this include low levels of the pathological prion protein (PrPSc) in milk and meat, which are the main bovine products consumed; inefficiency of the oral route of infection; restriction of spread based upon a species barrier; and host genetic factors, especially codon 129 polymorphism [28,35-40]. (See 'Genetic risk factors' below.)
Transfusion-related vCJD
Reported cases — Unlike other forms of CJD, vCJD prions are detected in lymphoreticular tissues, raising the concern of possible transmission via blood and/or blood products.
Four cases of transfusion-related vCJD have been reported in the United Kingdom. One case involved the onset of vCJD in a patient 6.5 years after a transfusion of red blood cells; the donor had developed symptoms of vCJD 3.5 years after donation [41]. Although this association raised the possibility of transfusion-associated transmission of vCJD, dietary exposure to BSE in the recipient could not be excluded.
The second case involved a recipient with no evidence of a neurologic disorder, who died (not from vCJD) five years after receiving a blood transfusion. The donor developed symptoms of vCJD 18 months after donation, and vCJD was confirmed in the donor at autopsy. The recipient was found to have protease-resistant prion protein in splenic but not brain tissue at autopsy [42]. The recipient was heterozygous at codon 129 of PRNP, which may have limited the prion load or distribution in tissues as well as the clinical expression of disease [43]. (See 'Genetic risk factors' below.)
The third patient was diagnosed with vCJD premortem and had postmortem pathologic confirmation of disease 15 months after presentation in 2005 [44]. He had received a transfusion in 1997 (7.5 years earlier) after a complicated surgical procedure. One of the blood donors had developed vCJD 20 months after donating the blood and had pathologic confirmation of the disease at postmortem 11 months later. Both donor and recipient were homozygous for methionine at PRNP codon 129. The same blood donor in the third case was implicated in the fourth patient with probably transfusion-related vCJD, who developed symptoms of vCJD 8.5 years after receiving a blood transfusion [15,45].
A fifth case may have had asymptomatic vCJD infection due to factor VIII treatment for hemophilia [46]. The factor VIII was manufactured from plasma of United Kingdom donors. This patient, also heterozygous at codon 129, was identified through a surveillance program; PrPSc was detected in a single spleen sample only (other samples were negative); he died of unrelated causes [18,47,48].
Prevention — In the absence of a reliable blood test to detect preclinical or asymptomatic vCJD, efforts to prevent transfusion-related vCJD have focused on restriction of blood donation from high-risk individuals [49]. Reports of cases of confirmed vCJD who have little to no detectable prion protein in peripheral lymphoreticular tissue suggest that blood testing may have an inherently low sensitivity for disease detection [50]. One prototype blood-based vCJD assay has been developed that appears to have sufficient sensitivity and specificity and is being investigated for screening population samples and at-risk groups [51].
New restrictions were instituted in the United Kingdom in 2004 because of the demonstration of probable blood-borne vCJD transmission [52]. Recipients of blood, plasma, or tissue since 1980 were excluded as blood donors. In addition, recipients of vCJD-implicated plasma products and their physicians were contacted and asked to inform other practitioners of their status in advance of any future medical, surgical, or dental treatment. Beginning in November 1999, leukocyte depletion of all blood components was mandated in the United Kingdom in order to reduce the concentration of transmissible agents [53]. All four documented cases of transfusion-related vCJD received transfusions of nonleukocyte depleted red blood cells between 1996 and 1999 [15]. Other risk-reduction measures, including a blood-based assay to detect vCJD, are in development [54-59].
The US Food and Drug Administration (FDA) adopted a policy that a prospective blood donor be indefinitely deferred if they had lived for more than six months in the United Kingdom during the peak years of BSE (1981 through 1996) [60]. This policy went into effect in April 2000, to attempt to balance increased safety against decreased blood availability.
The American Red Cross has adopted more stringent deferral criteria. These include deferral of anyone receiving a blood transfusion in the United Kingdom, anyone residing in or visiting the United Kingdom for three or more months since 1980, and anyone visiting or residing in another European country, Turkey, or Oman for six or more months since 1980. (See "Blood donor screening: Medical history".)
While several countries have started to restrict persons who have received a blood transfusion from donating blood, such a policy would not have prevented the first two cases of transfusion-related vCJD discussed above. Furthermore, a mathematical model based on epidemiologic data suggests that such a policy would prevent less than 1 percent of future vCJD cases [61].
Genetic risk factors — PRNP gene mutations are not present in vCJD, but nearly all patients with symptomatic vCJD have been homozygous for methionine at the polymorphic codon 129, which appears to confer susceptibility to the disease as it is estimated that only 40 percent of the population in the United Kingdom is homozygous for methionine at codon 129 [52]. One case of a methionine/valine (MV) heterozygote with vCJD was reported in 2016 [62]. However, all codon 129 polymorphisms (MM, MV, VV) have been represented in asymptomatic cases. It is speculated that individuals with these other polymorphisms may have longer asymptomatic incubation rather than protection from disease.
At least one of the transfusion-related cases was MV heterozygous. In addition, studies in mice infected with vCJD have demonstrated that secondary infection can occur in MV and VV as well as in MM lines [47,48]. In this study, MM and MV lines were the most susceptible to transmission. These findings, with a long preclinical phase predicted in these models, suggest that transfusion-related vCJD may represent a persistent health risk. Further cause for concern comes from case reports of kuru after more than 50 years of incubation [63]. (See "Diseases of the central nervous system caused by prions", section on 'Kuru'.)
In addition, other candidate loci that may confer susceptibility have also been identified [64,65]. (See "Diseases of the central nervous system caused by prions", section on 'Genetics of human prion diseases'.)
Accidentally acquired vCJD — A 33-year-old prion disease researcher died from vCJD nine years after an accidental percutaneous exposure to transgenic mice that overexpressed the prion protein and were inoculated with a sheep-adapted form of BSE [66].
CLINICAL AND DEMOGRAPHIC FEATURES — The mean age at onset of vCJD in the initial report was 29 years (range 16 to 48 years), a finding that contrasts with a mean age of 65 years for sporadic CJD (sCJD) [67]. However, patients presenting with vCJD at ages 11 and 74 years have been reported [68-70]. There is no sex predilection.
The clinical syndrome of vCJD overlaps with classic sCJD but has some distinctive features (table 1). Patients with vCJD have frequently displayed prominent sensory disturbances and psychiatric symptoms [68-70].
●Psychiatric symptoms are among the presenting manifestations in most (more than 90 percent) patients [70-72]. Depression is the most common psychiatric disorder; in addition to depressed mood, patients may manifest apathy, anxiety, irritability, social withdrawal, agitation, and insomnia [70-72]. A minority present with psychotic features of delusions and/or hallucinations.
●Sensory symptoms are seen early on in 64 percent of patients [73,74]. These include dysesthesias, paresthesias, and numbness; involve the face, hands, feet, and/or legs; and are often lateralized (in one-third of patients). In most patients with sensory symptoms, sensory signs are absent.
●Neurologic signs are absent initially in most patients, but develop in all patients as the disease progresses, typically in four to six months after the initial symptoms appear. A smaller proportion of patients present with neurologic symptoms as the initial manifestations of disease [72].
Characteristic neurologic features include cerebellar ataxia with gait disturbance, impaired coordination and dysarthria, involuntary movements (myoclonus, tremor, chorea, and dystonia are all described), and progressive cognitive impairment and dementia [67,70-72,75]. Late stages of disease are characterized by immobility, unresponsiveness, and mutism. Seizures are relatively uncommon [72,73].
EVALUATION — In most cases, the evaluation for vCJD is delayed, as the disease is rare and the presentation is more suggestive of a primary psychiatric disorder. When neurologic symptoms emerge, an evaluation for rapidly progressive dementia or other symptoms is initiated that often starts with neuroimaging and eventually includes lumbar puncture and other testing as outlined below.
Neuroimaging — A noncontrast magnetic resonance imaging (MRI) study is typically indicated in patients with progressive central nervous system signs, including a rapidly progressive dementia.
In vCJD, brain MRI typically shows signal hyperintensity in the pulvinar (pulvinar sign) or in both pulvinar and dorsomedial thalamus (hockey stick sign) [76]. The pulvinar sign is defined as having greater hyperintensity in the thalamus compared with the caudate and putamen. In one series, 28 of 36 cases of vCJD and none of 57 controls demonstrated prominent bilateral pulvinar high signal, for a sensitivity and specificity of 78 and 100 percent, respectively [77]. The pulvinar sign may disappear in follow-up MRIs [78,79]. This finding is not seen in patients with classic sporadic CJD (sCJD) (image 1). (See "Creutzfeldt-Jakob disease", section on 'Brain MRI'.)
Fluid-attenuated inversion recovery (FLAIR) images appear to be the most sensitive sequence for identifying this sign; T2-weighted, proton density-weighted, and diffusion-weighted imaging (DWI) may also show these abnormalities [78].
Head computed tomography (CT) is usually normal. Single-photon emission computed tomography (SPECT) has demonstrated decreased perfusion in four patients [80], but the clinical utility of SPECT for this condition has not been demonstrated in large studies.
Lumbar puncture — Cerebrospinal fluid (CSF) studies may be performed to exclude infections and other possible causes of the patient's symptoms, but is otherwise not helpful in the diagnosis of vCJD.
In the original series of 14 patients with vCJD, the CSF had no cells in any of the patients and a mildly elevated protein in four [67].
While detection of 14-3-3 protein in CSF is a useful clinical marker in sCJD, it is not a sensitive marker for vCJD; the protein has been detected in CSF of fewer than half of the patients tested. CSF tau may be more sensitive than 14-3-3 but is not specific for vCJD. It has been suggested that the combination of a CSF 14-3-3 protein assay and measurement of CSF tau protein may be useful in the identification of patients with vCJD, but additional studies are required to determine the sensitivity and specificity of combining these CSF markers [81,82].
Although highly sensitive for sCJD, CSF real-time quaking-induced conversion (RT-QuIC) lacks sensitivity in vCJD, which was 25 percent in one study [83].
Electroencephalography — The periodic sharp wave complexes (PSWCs) characteristic of sCJD are generally not seen in vCJD, except rarely in the later stages of disease [79,84,85]. The electroencephalogram (EEG) was abnormal in 70 percent of the initial patients with vCJD, but usually only displayed a nonspecific slow wave pattern [67]. (See "Creutzfeldt-Jakob disease", section on 'Electroencephalogram'.)
PrPSc detection — The pathological prion protein (PrPSc) associated with vCJD appears to be remarkably stereotyped, unlike the heterogeneity that exists for the PrPSc associated with sCJD [40]. In vCJD, the PrPSc type detected on Western blot is classified as type 4 (Collinge) or type 2B (Parchi and Gambetti). (See "Creutzfeldt-Jakob disease", section on 'Subtypes of sCJD'.)
Tonsillar tissue — Examination of tonsillar tissue for PrPSc is a highly useful test for vCJD. Tissue demonstration of PrPSc requires limited protease digestion of tissue samples followed by Western blotting [86]. Analysis of PrPSc extracted from tonsil biopsy tissue using this technique appears to provide a sensitive and specific method for the diagnosis of vCJD in the appropriate clinical context [4,5,87]. The use of streptomycin precipitation holds promise for rapidly and reliably diagnosing CJD with relatively small tissue samples [88].
In a study of 20 patients with suspected vCJD, tonsillar tissue was positive for PrPSc by Western blot or immunohistochemistry in all eight patients whose subsequent course either confirmed or was highly consistent with vCJD [4]. In addition, tonsillar tissue was negative for PrPSc in all patients subsequently confirmed to have non-vCJD diagnoses. Thus, this test appeared to correlate highly with the diagnosis of vCJD and not with other forms of prion disease.
Blood and urine — Using protein misfolding cyclic amplification (PMCA) technique, minute quantities of PrPSc have been detected in the urine and blood of patients with vCJD [89-91]. In one study, PrPSc was detected in 13 of 14 urine samples obtained from patients with vCJD and in none of 224 samples obtained from patients with other neurologic diseases and from healthy controls [89]. However, these tests are not available for clinical use. (See "Diseases of the central nervous system caused by prions", section on 'Detection of abnormal prion protein'.)
Neuropathology — While neuropathology provides a definitive diagnosis of vCJD, a brain biopsy is undertaken primarily with the purpose of excluding an alternative treatable etiology if that is suspected. However, autopsy should be performed for definitive diagnosis and for the purpose of surveillance.
The following confirmatory features should be present [92]:
●Numerous widespread kuru-type amyloid plaques surrounded by vacuoles in both the cerebellum and cerebrum. These so-called florid plaques have an eosinophilic center and pale periphery with surrounding spongiform changes giving the appearance of a flower with petals; they stain intensely for PrPSc and are distributed throughout the cerebrum and cerebellum and, to a lesser degree, the basal ganglia and thalamus [1,93].
●Spongiform change and extensive prion protein deposition shown by immunohistochemistry throughout the cerebellum and cerebrum [1,93].
As noted above, PrPSc extracted from the brains of vCJD cases also has the distinct type 4/2B pattern, determined by electrophoretic mobility and glycosylation pattern [37].
DIAGNOSIS — Diagnostic criteria for vCJD based upon clinical features and diagnostic test results have been developed and validated [70,73,85,92]. While a definite diagnosis requires neuropathological confirmation, it is reasonable to make the diagnosis in life using the probable criteria as outlined below, as these appear to be highly sensitive and specific. However, an autopsy should be performed for definitive diagnosis.
●Definite vCJD requires the neuropathological confirmation of vCJD in the setting of a progressive neuropsychiatric syndrome. (See 'Neuropathology' above.)
●Probable vCJD can be diagnosed in the presence of a progressive neuropsychiatric disorder and a positive tonsil biopsy.
In the absence of a tonsil biopsy, a diagnosis of probable vCJD requires:
•A progressive neuropsychiatric disorder; and
•A duration of illness >6 months; and
•Routine investigations that do not suggest an alternative diagnosis; and
•No history of a potential iatrogenic exposure; and
•No family history of transmissible spongiform encephalopathy; and
•Four of five of the following clinical features: early psychiatric features, persistent painful sensory symptoms, ataxia, movement disorder (myoclonus or chorea or dystonia), dementia; and
•Bilateral pulvinar signal on magnetic resonance imaging (MRI); and
•Absent periodic sharp wave complexes (PSWCs) on electroencephalography (EEG)
●Possible vCJD requires all of the features of probable vCJD with the exception that MRI findings are not required.
In one case series of confirmed and suspected cases of vCJD, 83 percent of confirmed cases were classified as probable in life; no cases ultimately disproven to be vCJD met criteria for probable vCJD in life [73].
An important caveat is that the case of vCJD in at least one methionine/valine (MV) heterozygous patient did not resemble typical vCJD; the clinical phenotype and MRI findings were suggestive of sporadic CJD (sCJD) [62], while another heterozygous patient did have more typical features of vCJD [94]. Hence, the above criteria may be less sensitive for vCJD cases that are not homozygous for methionine at codon 129.
The Centers for Disease Control and Prevention (CDC) list similar criteria for definite and suspected vCJD; however, these have not been validated [92].
DIFFERENTIAL DIAGNOSIS — The early symptoms of vCJD are nonspecific; depression and other psychiatric disease are commonly considered as the initial diagnosis [70].
Once neurologic symptoms appear, the differential diagnosis usually broadens to include sporadic CJD (sCJD), Alzheimer disease, paraneoplastic disease or malignancy, viral encephalitis, frontotemporal dementia, demyelination, vasculitis, subacute sclerosing panencephalitis, cerebrovascular disease, multisystem atrophy, Huntington disease, Wilson disease, and autoimmune limbic encephalitis [70,73]. Magnetic resonance imaging (MRI) findings, laboratory studies, and lumbar puncture typically help exclude many of these diagnoses and provide evidence of vCJD.
PROGNOSIS AND TREATMENT — The mean duration of illness for vCJD is longer than for sporadic CJD (sCJD), 14 versus 4 to 5 months [67,70]. Both diseases are progressive and uniformly fatal.
There is no known effective treatment for vCJD. Experience with the use of intraventricular pentosan polysulfate (iPPS) as a treatment for vCJD has been published for five patients [95-98]. Apparent extension of survival (37 to 114 months) was seen in four patients. In one 20-year-old man, treatment was also associated with some initial improvement in his neurologic status [95]. In a 22-year-old man, survival time was also prolonged (51 months), but institution of treatment did not clearly correlate with a change in the rate of neurologic deterioration [96]. This patient had a prolonged course (19 months) even before treatment. Postmortem neuropathologic examination of a 19-year-old girl who survived for 105 months in association with iPPS treatment revealed expected neuropathological changes of vCJD [98].
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Creutzfeldt-Jakob disease (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Variant Creutzfeldt-Jakob disease (vCJD) is a prion disease, first reported in 1996; many of its clinical, pathological, diagnostic, and other features are distinct from classic sporadic CJD (sCJD) (table 1). As of November 2019, there have been a total of 232 cases of probable vCJD reported worldwide. Following the decline of bovine spongiform encephalopathy (BSE) and the introduction of dietary protective measures, vCJD has become extremely rare. (See 'Incidence and prevalence' above.)
●The available evidence indicates that vCJD represents bovine-to-human transmission of BSE, with most patients acquiring the disorder through ingestion of infected meat products. Genetic factors may influence susceptibility and/or the clinical manifestations of the disease. (See 'Bovine spongiform encephalopathy' above and 'Genetic risk factors' above.)
●A few cases of transmission of vCJD via blood transfusion have been reported. Efforts to reduce the spread of vCJD via transfusions include leukocyte depletion of all blood components, now mandated in the United Kingdom, and restricting at-risk individuals from donating blood. (See 'Transfusion-related vCJD' above.)
●vCJD presents with prominent psychiatric features often accompanied by sensory symptoms; in many patients the presence of neurologic signs (dementia, ataxia, involuntary movements) does not appear for a few to several months. vCJD presents at a younger age than sCJD and has a more protracted although still rapidly evolving course. (See 'Clinical and demographic features' above.)
●An evaluation for patients presenting with an acute to subacute neuropsychiatric disorder will typically have neuroimaging, lumbar puncture, and electroencephalography (EEG) as part of their evaluation. Most of such testing is valuable chiefly to exclude other conditions; however, the presence of the pulvinar sign on brain magnetic resonance imaging (MRI) is very suggestive of vCJD in the appropriate clinical setting. (See 'Evaluation' above and 'Neuroimaging' above.)
Tonsillar biopsy with evaluation for the pathological prion protein (PrPSc) is a highly useful confirmatory test for vCJD and allows for a diagnosis of probable vCJD in the appropriate clinical setting. In the absence of tonsillar tissue, a diagnosis of probable vCJD can be made on the basis of clinical and laboratory findings as discussed above. (See 'Tonsillar tissue' above and 'Diagnosis' above.)
●Brain biopsy is not always required, unless to exclude another treatable condition. The diagnosis of probable vCJD made antemortem should be confirmed by autopsy, which should reveal the diagnostic neuropathologic features. (See 'Neuropathology' above.)
●vCJD is uniformly fatal. The mean duration of illness for vCJD is longer than for sCJD (14 versus 4 to 5 months). There is no known effective treatment for vCJD. (See 'Prognosis and treatment' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Henry G Brown, MD, PhD, and John M Lee, MD, PhD, who contributed to an earlier version of this topic review.
