Clinical and genetic features of human prion diseases in Catalonia: 1993–2002

We describe the clinical and genetic characteristics of the 85 definite or probable human prion diseases cases died between January 1993 and December 2002 in Catalonia (an autonomous community of Spain, 6 million population). Seventy-three (86%) cases were sporadic Creutzfeld-Jakob diseases (sCJD) (49 definite, 24 probable), with a median age at onset of 66 years. The clinical presentation was dementia in 29 cases, ataxia in 14 and visual symptoms in five. The median survival was 3 months. The 14-3-3 assay was positive in 93% cases, 62% presented periodic sharp wave complexes (PSWC) in EEG but only 18% the typical signs on MRI. Forty-eight sCJD were studied for codon 129 PRNP polymorphism: 69% were methionine/methionine (M/M), 14.5% valine/valine (V/V) and 16.5% M/V. Six out of seven V/V cases did not present PSWC and in two survival was longer than 20 months. Eleven cases (13%) were genetic: five familial fatal insomnia and six familial CJD (fCJD). Up to four (67%) fCJD lacked family history of disease, two presented seizures early at onset and one neurosensorial deafness. The only iatrogenic case was related to a dura mater graft. No case of variant CJD was registered. The study confirms in our population the consistent pattern reported worldwide on human prion diseases. Atypical features were seen more frequently in sporadic 129 V/V CJD and fCJD cases.     

MRI characteristics of sporadic CJD with valine homozygosity at codon 129 of the prion protein gene and PrPSc type 2 in Japan

Two Japanese sporadic Creutzfeld-Jakob disease (sCJD) patients with valine homozygosity at codon 129 of the prion protein gene and protease-resistant prion protein (PrP(Sc)) type 2 (VV2) are described. In contrast with Western countries, this type of sCJD is very rare in Japan. In 123 sCJD cases, only two were recognised as VV2 by the Japanese CJD surveillance committee. The clinical symptoms and pathological findings of the patients were similar to those of European and US patients. The noteworthy finding of diffusion weighted MRI (DWI) was that an abnormal high intensity covered a wide range of the thalamus including the dorsomedial nucleus, the pulvinar, and the ventral anterior, lateral, and posterolateral nuclei. This thalamic pattern has not been recognised in sCJD with methionine homozygosity and PrP(Sc) type 1 (MM1) or methionine/valine heterozygosity and PrP(Sc) type 1 (MV1) which comprises the vast majority of sCJD. This finding may be characteristic to VV2 and may distinguish it from MM1, MV1, and variant CJD. DWI can provide a very important clue for the antemortem diagnosis of VV2 subjects.     

Early evolution and incidence of electroencephalographic abnormalities in Creutzfeldt-Jakob disease

The clinical and EEG findings in patients in the literature with Creutzfeldt-Jakob disease (CJD) were reviewed and compared with findings in 36 patients with CJD at the Massachusetts General Hospital (MGH). Twenty-one of the 36 MGH cases had histopathology, all with findings consistent with CJD. EEGs in 18 patients studied pathologically and in 10 without pathological investigation (28 of the 36) had periodic sharp wave complexes (PSWC) at some time during the clinical course. Of the other eight patients, two had only a single EEG early in the course of the illness, four experienced unusually long clinical courses, and two never showed PSWC despite numerous EEGs. PSWC made their appearance within 12 weeks of onset of clinical symptoms in 25 of 27 in whom EEGs were done during that period. In the early stages, EEGs in 14 of 28 showed focal PSWC or amplitude asymmetries of PSWC that corresponded well with focal myoclonus or other focal neurological abnormalities. In the literature, PSWC occurred within 12 weeks of the onset of the illness in 66 of 75 patients (88%) with CJD who had comparable clinical and neuropathological findings and adequate EEG data during the first 3 months of the illness. In the approximately 10% of patients who experienced unusually long courses, PSWC occurred in only about 55%. The presence of PSWC in association with the appropriate clinical, biochemical, cerebrospinal fluid, and neuroradiological findings is diagnostic of CJD. Brain biopsy is, therefore, unnecessary even when clinical therapeutic trials are undertaken and certainty of diagnosis is required. The absence of PSWC in the EEG after 12 weeks' duration of illness is a point strongly against the diagnosis of CJD unless it is a rare subtype of long duration. Only those patients without PSWC need to be biopsied.     

Clinical changes and EEG patterns preceding the onset of periodic sharp complexes in Creutzfeldt — Jakob disease

The conversion of EEG findings and the evolution of clinical signs was investigated in 7 CJD patients who underwent serial EEG recordings along the course. At the onset of PSWC (mean 8.7 weeks), 5 patients had already progressed to akinetic mutism (characterized by loss of verbal contact and directed responses); and a CJD-typical-movement disorder (myoclonia, exaggerated startle reaction or focal dyskinesia) had started in 5 patients. When akinetic mutism commenced (on average at 7.5 weeks), runs of frontal intermittent non-peaked rhythmical delta activity (FIRDA) were found in all cases. These were later replaced by PSWC in 6 patients (interval 1 to 3 weeks). Occurrence of PSWC was often negatively related to external stimuli (2 of 6 cases), and sedative medication (all patients tested). We conclude that the selection of EEG recording dates to detect PSWC in CJD-candidates should be guided by detailed information about movement disorders and conscious level. Regarding the short survival time after their onset (average 8 weeks), PSWC usually mark the terminal stage of CJD. To detect PSWC, especially, EEG registrations in advanced stages are often necessary. In earlier disease stages, FIRDA-like EEG activities should be regarded as compatible with this diagnosis, and encourage further EEG studies for the demonstration of PSWC in a more advanced stage of CJD.     

Spatial distribution of abnormal EEG activity in Creutzfeldt-Jakob disease

ObjectivesElectroencephalogram (EEG) pattern in Creutzfeldt-Jakob disease (CJD) is characterized by diffuse abnormal activity, although lateralization to one hemisphere has been described in the first stages of the disease. This study aimed to determine whether abnormal EEG activity predominantly occurs in anterior versus posterior brain regions.MethodsAs part of a prospective study, the demographics, clinical features and MRI findings of genetic E200K CJD patients were collected. EEG was performed and the recordings reviewed for the typical periodic sharp wave complex (PSWC) and non-specific slow activity. Data were analyzed using the qEEG tool, and the activity in anterior and posterior regions of the brain compared.ResultsEleven genetic E200K CJD patients were included in the study (67% women). The average age was 59.1 ± 8.4 SD years and the average disease duration was 2.4 ± 2.1 months. EEG showed the classic PSWC pattern in 5/11 (45%) of the patients, and slow activity was seen in 9/11 (82%). EEG was normal in 2 patients. PSWC activity was diffuse in 2/5 patients and unilateral in 3/5 patients; slow activity was diffuse in 9 patients. Quantitative analysis of PSWC and slow activity showed no significant difference between anterior and posterior distribution.ConclusionThe abnormal EEG activity in CJD is diffuse with no clear spatial predominance in anterior or posterior brain regions.     

散发性克-雅病PrP基因129密码子基因型与临床表型14例研究

目的：探讨散发性克－雅病（Creutzfeldt-Jakob disease,CJD)PrP基因129位点密码子基因型与临床表型的关系。方法：对14例散发性CJD患者进行PrP基因129例密码子的检测，并与临床表现进行了分析。结果：（1）根据诊断标准，14例散发性CJD中8例诊断为肯定CJD，6例诊断为很可能CJD。（2）8例诊断肯定CJD组中，PrP基因129例位点密码子为甲硫氨酸纯合型6例，甲充氨酸／缬氨酸2例，6例诊断很可能CJD组的PrP基因129密码子均为甲硫氨酸纯合型。（3）12例PrP基因129位点为甲硫氨酸纯合型的患者以认知障碍起病8例，共济失调1例；视觉障碍2例；肌阵挛1例，病程最长20个月，最短2．5个月，病程中有癫痫5例，肌阵挛6周，视觉障碍6例。7例有典型周期性同步放电（PSD）脑电改变。（4）2例甲硫氨酸／缬氨型患者均以共济失调起病。2个月后才出现痴呆，病理程分析为16个月和20个月，均无典型的PSD。（2）本组散发性CJDPrP基因129位点密码子甲硫氨酸／甲硫氨酸，甲硫氨酸／缬氨酸，分布比例与日本相同，但与西方不同，而且没有缬氨酸纯合型。     

Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.

Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.     

Reliability of EEG in the diagnosis of Creutzfeldt-Jakob disease

Although EEG is generally considered a useful tool for the diagnosis of Creutzfeldt-Jakob disease (CJD), some cases have been reported where the EEG was non-specific.We reviewed a series of 15 CJD patients, observed in our institute in the period 1975–1991. In 12 cases the diagnosis was confirmed on post-mortem examination.The prominent aspect of the present series was the homogeneity of clinical, neurophysiological and neuropathological data. All patients showed the presence of periodic sharp wave complexes (PSWC) and EEG reactivity to external stimuli or drugs was uniform.The EEG can give essential information for the diagnosis of CJD if 2 basic conditions are satisfied: (1)serial recordings are performed in relation to the different stages of the disease, and (2) not only the presence of PSWC is considered, but also the reactivity of EEG to dynamic events such as the response to external stimuli and drugs,aand the level of consciousness.     

The EEG in E200K familial CJD: relation to MRI patterns

The aim of the study was to examine the relationship between EEG abnormalities and the pattern of MRI changes in familial Creutzfeldt–Jakob Disease (fCJD) patients with E200K mutation. As part of a controlled, prospective study, 13 E200K fCJD patients underwent comprehensive evaluations, with EEG and an extensive MRI protocol that included one of the most prion-disease sensitive sequences, diffusion-weighted imaging (DWI). The relationship between EEG abnormalities and the pattern of DWI hyperintensities was examined. EEG demonstrated the classical CJD finding of PSWC (periodic sharp wave complexes) in five patients (38%) while in eight patients (62%) the EEG showed only slow activity. Six patients showed the typical cortical changes on MRI, and in five of them (83%) concordance between the MRI and the EEG was found. Five patients had isolated basal ganglia involvement per MRI, and in two of them (40%) concordance between the MRI and the EEG laterality was found. In the remaining two patients MRI did not show any changes suggesting CJD and EEG showed focal slow activity. The EEG of our E200K fCJD patients appears similar to that of the largest prion disease patient group, sporadic CJD (sCJD). EEG abnormalities in E200K fCJD appear to correlate mainly with cortical pathology, as revealed by DWI, rather than basal ganglia pathology. The observation that PSWC abnormalities reflect cortical rather than basal ganglia pathology is significant with respect to theories of the origins of EEG abnormalities in prion disease.     

Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution

Objective To describe the clinical features of Creutzfeldt-Jakob disease with a substitution of arginine for methionine (M232R substitution) at codon 232 (CJD232) of the prion protein gene (PRNP). Patients and methods We evaluated the clinical and laboratory features of 20 CJD232 patients: age of onset, initial symptoms, duration until becoming akinetic and mute, duration until occurrence of periodic sharp and wave complexes on EEG (PSWC), MRI findings, and the presence of CSF 14-3-3 protein. Immunohistochemically, prion protein (PrP) deposition was studied. Results None of the patients had a family history of CJD. We recognized two clinical phenotypes: a rapidly progressive type (rapidtype) and a slowly progressive type (slow-type). Out of 20 patients, 15 became akinetic and mute, demonstrated myoclonus, and showed PSWC within a mean duration of 3.1, 2.4, and 2.8 months, respectively (rapid-type). Five showed slowly progressive clinical courses (slow-type). Five became akinetic and mute and four demonstrated myoclonus within a mean duration of 20.6 and 15.3 months, respectively, which were significantly longer than those in the rapid-type. Only one demonstrated PSWC 13 months after the onset. Diffuse synaptic-type deposition was demonstrated in four rapidtype patients, and perivacuolar and diffuse synaptic-type deposition in two, and diffuse synaptic-type deposition in one slow-type patient. Three of 50 suspected but non-CJD patients had the M232R substitution. Conclusions Patients with CJD232 had no family history like patients with sCJD, and showed two different clinical phenotypes in spite of having the same PRNP genotype. More studies are needed to determine whether M232R substitution causes the disease and influences the disease progression. * The Creutzfeldt-Jakob Disease Surveillance Committee, Japan.     

Clinicopathological phenotype of codon 129 valine homozygote sporadic Creutzfeldt-Jakob disease

The naturally occurring polymorphism at codon 129 of the human prion protein gene (PRNP) influences susceptibility to sporadic Creutzfeldt-Jakob Disease (CJD); the majority of the patients are methionine homozygotes at this locus, while valine homozygotes represent only 10% of cases. The aim was to study the clinical and neuropathological phenotype of sporadic CJD in valine homozygotes, to estimate the reliability of current clinical diagnostic criteria, and to identify any consistent and distinct features. Twelve cases of sporadic CJD with a codon 129 valine homozygote genotype were identified at the National CJD Surveillance Unit in Edinburgh. In addition to a retrospective clinical analysis, tissue blocks were stained by conventional techniques and by immunocytochemistry for prion protein. Frozen brain tissue was available from five cases for Western blot analysis of PrPRES, which in all cases showed a type 2 mobility. The cases included four males and eight females, average age 63.6 years, with a mean duration of illness of 6 months. Eleven patients presented with ataxia, and none had the characteristic EEG changes found in sporadic CJD. The neuropathological phenotype comprised spongiform change and prion protein immunopositivity most marked in the subcortical grey matter and cerebellum, prion protein positive plaque-like deposits in all regions, laminar deposition of prion protein in the cerebral cortex, and hippocampal involvement (which is seldom reported in sporadic CJD). In conclusion, these cases exhibited a fairly uniform phenotype, which is relatively distinct from sporadic CJD in methionine homozygotes, and thus diagnosis may be difficult using existing clinical criteria.     

Serial EEG findings in sporadic and iatrogenic Creutzfeldt-Jakob disease.

OBJECTIVE: To study temporal and spatial development of EEG patterns in sporadic and iatrogenic Creutzfeldt-Jakob disease patients. METHODS: Temporal and spatial development of EEG patterns in 4 patients with sporadic Creutzfeldt-Jakob disease and 2 patients with iatrogenic Creutzfeldt-Jakob disease due to implantation of contaminated brain depth electrodes were investigated. A total of 56 EEGs were analyzed, over time spans ranging from 1272 to 3 days prior to death. RESULTS: Frontal intermittent rhythmical delta activity (FIRDA) was seen at early timepoints in 4/6 patients and might represent an early EEG pattern that is associated, with human prion diseases. EEG patterns associated with CJD are sensitive to midazolam. Initial EEG changes were seen at the site of prion exposure in iatrogenic Creutzfeldt-Jakob disease patients, before they could be observed at distant sites, suggesting that prion disease was initiated at the site of prion exposure. CONCLUSIONS: Serial EEG recordings are a valuable tool not only in the early diagnosis of sporadic CJD, but also in the determination of prion exposure in iatrogenic Creutzfeldt-Jakob disease. SIGNIFICANCE: FIRDA occur at an early stage of CJD and are progressively replaced by the classical PSWC. The EEG patterns of CJD are sensitive to midazolam. The initial EEG changes in iatrogenic CJD are seen at the site of prion exposure.     

Current clinical diagnosis in Creutzfeldt-Jakob disease: identification of uncommon variants

According to the recently established molecular basis for phenotypic heterogeneity of sporadic Creutzfeldt-Jakob disease (CJD), six different phenotypes are characterized by the size of the protease-resistant fragment of the pathological prion protein (types 1 and 2) and homozygosity or heterozygosity for methionine or valine at codon 129 of the prion protein gene (designated by MM1, MM2, MV1, MV2, W1, and W2). In the present investigation, we analyzed the value of commonly used clinical tests (electroencephalogram [EEG], detection of 14-3-3 protein in cerebrospinal fluid [CSF], and hyperintensity of the basal ganglia in magnetic resonance imaging) for the clinical diagnosis in each CJD phenotype. The detection of periodic sharp and slow wave complexes in the EEG is reliable in the clinical diagnosis of MM1 and MV1 patients only. The CSF analysis for 14-3-3 protein showed high sensitivity in all analyzed subgroups with the exception of MV2 patients. Valine-homozygous patients had a negative EEG, but most had detectable levels of neuronal proteins in the CSF. The sensitivity of the magnetic resonance imaging was 70%, irrespective of the subgroup, but was particularly reliable in the clinical diagnosis of MV2 patients. The widening spectrum of diagnostic techniques in CJD is not only useful in the increased accuracy of the clinical diagnosis but should also lead to the identification of more atypical cases of sporadic CJD.     

Sporadic Creutzfeldt–Jakob disease presenting as nonconvulsive status epilepticus case report and review of the literature

Creutzfeldt–Jakob disease (CJD) is the most common transmissible human spongiform encephalopathy. Seizures and status epilepticus (SE) are an uncommon finding in CJD. We report a 64-year-old woman with rapid cognitive decline who had electroencephalographic (EEG) changes suggestive of nonconvulsive status epilepticus (NCSE). She was later diagnosed with sporadic CJD (sCJD). We also reviewed the literature for published cases on this topic. MEDLINE was employed to identify all published reports of CJD and SE. We identified 8 references with a total of 12 cases with CJD and NCSE. sCJD should be considered in the differential diagnosis of any patient who presents with rapid cognitive decline and EEG changes consistent with status epilepticus.     

Sporadic Creutzfeldt–Jakob disease without dementia at onset: clinical features,laboratory tests and sequential diffusion MRI (in an autopsy–proven case)

Abstract. A rapidly progressing dementia, followed by focal neurological signs, and evidence of periodic sharp wave complexes (PSWC) in the EEG may lead to the clinical suspicion of Creutzfeldt–Jakob disease (CJD). Different clinical variants of CJD have been described in the past, with prominent extrapyramidal or occipital lobe involvement, all included in the sporadic form of CJD (sCJD). Familiar and iatrogenic forms of CJD are also known. More recently a new variant has been described, vCJD [1], casually linked to bovine spongiform encephalopathy (BSE) and it has attracted increasing attention toward each form of rapidly progressing dementia; likewise the differential diagnosis between sCJD vs. vCJD is not always easy. Magnetic resonance imaging (MRI) too seems to have a peculiar role in differentiating sCJD from vCJD, even if the role of MRI in the diagnosis of CJD is still debated. Diffusion MRI is expected to play an important role in the clinical setting of CJD, contributing to formulation of an early diagnosis, especially in cases with unusual clinical presentation. In fact, the sensitivity of diffusion MRI is superior to that of conventional MRI (T1, T2, FLAIR) in detecting specific basal ganglia and cortical abnormalities early in the course of CJD [2] and these abnormalities correlate well with areas of the most severe and characteristic neuropathological changes [3]. We describe a case of autopsy–proven sCJD, with an unusual clinical course without dementia as a presenting symptom and discuss the role of diffusion MRI and laboratory tests in making an early diagnosis.     

磁共振弥散加权对克-雅氏病早期诊断的意义

目的探讨克-雅氏病(Creutzfeldt-Jakob disease,CJD)早期的磁共振弥散加权成像(DWI)表现。方法回顾性分析和总结3例CJD患者的临床症状及体征、影像学、脑电图和脑脊液中14-3-3蛋白的改变等资料。结果 3例患者脑部MRI均表现为皮质不同程度的DWI"缎带样"高信号,脑电图均出现周期性尖慢波或三相波,脑脊液14-3-3蛋白2例(+),1例(-)。结论对于绝大部分CJD患者,无论脑电图和脑脊液中14-3-3蛋白是否改变,DWI即可先于前两者出现异常改变,对于临床上出现早期相应症状及体征的患者,若DWI有此特征性改变,应高度疑诊CJD,故应考虑将DWI的异常改变纳入CJD的临床诊断标准中。     

Autopsy-proven Creutzfeldt-Jakob disease in a patient with a negative 14-3-3 assay and nonspecific EEG and MRI

Abstract. Detection of 14-3-3 protein in cerebrospinal fluid (CSF), in combination with findings on electroencephalography (EEG) and magnetic resonance imaging (MRI), is a highly sensitive and specific diagnostic test for sporadic Creutzfeldt-Jakob disease (CJD) in patients premortem. We present a case of classic, sporadic CJD, confirmed on autopsy and by Western blot. However, all routine premorbid testing was negative, the CSF was negative for the 14-3-3 protein, EEG did not show periodic sharp wave complexes (PSWC), and MRI failed to show hyperintense signal in the basal ganglia. Thus, laboratory support for the diagnosis of CJD was not obtained premortem. The chances of all three diagnostic testing modalities to be negative in a single case of sporadic CJD are extremely remote. Autopsy with neuropathologic confirmation remains the only definitive way to make a diagnosis of CJD.     

Type 1 protease resistant prion protein and valine homozygosity at codon 129 of PRNP identify a subtype of sporadic Creutzfeldt-Jakob disease

A man was studied with sporadic Creutzfeldt-Jakob disease (sCJD) who had serial cortical syndromes evolving over 15 months without significant ataxia, prominent myoclonus, or periodic complexes on EEG examinations. This clinical phenotype correlated with a predominantly cortical and striatal distribution of lesions and accumulation of protease resistant prion protein with relative sparing of the brainstem or cerebellum. No amyloid plaques were seen and prion protein (PrP) immunohistochemistry only demonstrated very faint granular deposits in the cerebral cortex. Molecular analysis showed homozygosity for valine at codon 129 in the prion protein gene (PRNP) and protease resistant prion protein type 1 deposition. The comparison of molecular and clinicopathological features of the present case with those previously reported in sCJD, indicates that valine homozygosity at codon 129 and type 1 protease resistant prion protein are associated with a distinct phenotypic variant of sCJD. The data also support the view that the PRNP codon 129 polymorphism and the physicochemical properties of the protease resistant prion protein are major determinants of phenotypic variability in sCJD.     

散发性Creutzfeldt-Jakob病23例临床分析

目的为提高散发性Creutzfeldt-Jakob病(Creutzfeldt-Jakob Disease,CJD)的临床诊断水平,对目前应用的诊断指标进行评价。方法对23例CJD的临床表现、脑电图、影像学、脑脊液、组织病理、基因、免疫组化、14-3-3蛋白等临床资料进行回顾性分析。结果(1)23例中10例为确定CJD,10例很可能CJD,3例为可能CJD。(2)83%为亚急性发病,首发症状按出现频率依次为认知障碍,走路不稳,视力障碍及精神症状。所有病人晚期均发展为去皮层状态。(3)22例脑电图均有中到重度广泛异常EEG改变,11例出现典型的周期性尖慢复合波(PSWCs)。(4)检测19例脑脊液14-3-3蛋白,16例阳性,3例阴性。(5)PrP基因129位点密码子检测,14例中有12例为甲硫氨酸/甲硫氨酸(Met/Met)纯合子,2例为甲硫氨酸/缬氨酸(Met/Val)杂合子。(6)8例头颅MRI显示双基底节区异常信号。(7)10例病理检查发现,有不同程度的海绵状变性和神经细胞脱失。可见异常PrP沉积。结论(1)国人EEG典型改变-PSWCs诊断CJD的灵敏度及特异度均低于西方。(2)14-3-3蛋白对诊断sCJD敏感度和特异度均高。在没有脑活检的前提下,是确诊CJD的指标之一。(3)病理检查证实,在人脑组织中有prpSc沉积仍是确诊CJD的不可替代的指标。     

The risk of iatrogenic Creutzfeldt‐Jakob disease through medical and surgical procedures

There have been more than 400 patients who contracted Creutzfeldt‐Jakob disease (CJD) via a medical procedure, that is, through the use of neurosurgical instruments, intracerebral electroencephalographic electrodes (EEG), human pituitary hormone, dura mater grafts, corneal transplant, and blood transfusion. The number of new patients with iatrogenic CJD has decreased; however, cases of variant CJD that was transmitted via blood transfusion have been reported since 2004. Clearly, iatrogenic transmission of CJD remains a serious problem. Recently, we investigated medical procedures (any surgery, neurosurgery, ophthalmic surgery, and blood transfusion) performed on patients registered by the CJD Surveillance Committee in Japan during a recent 9‐year period. In a case‐control study comprising 753 sporadic CJD (sCJD) patients and 210 control subjects, we found no evidence that prion disease was transmitted via the investigated medical procedures before onset of sCJD. In a review of previously reported case‐control studies, blood transfusion was never shown to be a significant risk factor for CJD; our study yielded the same result. Some case‐control studies reported that surgery was a significant risk factor for sCJD. However, when surgical procedures were categorized by type of surgery, the results were conflicting, which suggests that there is little possibility of prion transmission via surgical procedures. In our study, 4.5% of sCJD patients underwent surgery after onset of sCJD, including neurosurgeries in 0.8% and ophthalmic surgeries in 1.9%. The fact that some patients underwent surgery, including neurosurgery, even after the onset of sCJD indicates that we cannot exclude the possibility of prion transmission via medical procedures. We must remain vigilant against prion diseases to reduce the risk of iatrogenesis.