Prospective 25-year surveillance of prion diseases in France, 1992 to 2016: a slow waning of epidemics and an increase in observed sporadic forms.

BackgroundPrion diseases are rare, fatal disorders that have repeatedly raised public health concerns since the early 1990s. An active prion disease surveillance network providing national level data was implemented in France in 1992.AimWe aimed to describe the epidemiology of sporadic, genetic and infectious forms of prion diseases in France since surveillance implementation.

Validation of the Medical Research Council prion disease rating scale in France.

The development of assessment tools other than survival time is necessary to conduct therapeutic trials in prion diseases (also known as subacute transmissible encephalopathies). The Medical Research Council Prion Disease Rating Scale published by Thompson . (The Medical Research Council prion disease rating scale: A new outcome measure for prion disease therapeutic trials developed and validated using systematic observational studies.

The role of environmental factors on sporadic Creutzfeldt-Jakob disease mortality: evidence from an age-period-cohort analysis.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of prion diseases. The causes of sCJD are still unknown and exogenous factors may play a role. Worldwide, the number of patients with sCJD has progressively increased over time.

Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease.

Importance: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly lethal disease. Rapid, accurate diagnosis is imperative for epidemiological surveillance and public health activities to exclude treatable differentials and facilitate supportive care. In 2017, the International CJD Surveillance Network diagnostic criteria were revised to incorporate cortical ribboning on magnetic resonance imaging and the real-time quaking-induced conversion (RT-QuIC) assay, developments that require multicenter evaluation.

Subcutaneous apomorphine in the treatment of progressive supranuclear palsy and corticobasal syndrome: A preliminary study of 7 cases.

Background: Treatment of tauopathies such as Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) remains a major challenge. These neurodegenerative extrapyramidal movement disorders share phenotypic overlap and are usually painful. Continuous subcutaneous apomorphine infusion (CSAI) is commonly used in patients with advanced Parkinson's disease (PD) to alleviate motor and non-motor fluctuations.

[Prion diseases or transmissible spongiform encephalopathies].

Prion diseases or transmissible spongiform encephalopathies (TSEs) are human and animal diseases naturally or experimentally transmissible with a long incubation period and a fatal course without remission. The nature of the transmissible agent remains debated but the absence of a structure evoking a conventional microorganism led Stanley B. Prusiner to hypothesize that it could be an infectious protein (proteinaceous infectious particle or prion).

The importance of ongoing international surveillance for Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance.

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrP). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG.

Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.

Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms.

Autoantibodies against the prion protein in individuals with mutations.

Objective: To determine whether naturally occurring autoantibodies against the prion protein are present in individuals with genetic prion disease mutations and controls, and if so, whether they are protective against prion disease.

Methods: In this case-control study, we collected 124 blood samples from individuals with a variety of pathogenic mutations and 78 control individuals with a positive family history of genetic prion disease but lacking disease-associated mutations. Antibody reactivity was measured using an indirect ELISA for the detection of human immunoglobulin G antibodies against wild-type human prion protein.

Examining the Reserve Hypothesis in Parkinson's Disease: A Longitudinal Study.

Background: Whether reserve plays a role in Parkinson's disease (PD) patients has received less attention than in dementia and has been mainly examined in relation with cognitive function.

Objective: To investigate whether reserve plays a role in the severity and progression of motor, cognitive, and nonmotor PD symptoms by examining whether education level (proxy of reserve) is associated with baseline performance and rate of progression.

Methods: We used data from a longitudinal cohort of PD patients (≤5-year disease duration at baseline) annually followed up to 5 years (n = 393; 41% women; mean age = 62.

Factors Influencing the Incubation of an Infectious Form of Creutzfeldt-Jakob Disease.

The French epidemics of iatrogenic Creutzfeldt-Jakob disease after growth hormone (GH) treatment provide an opportunity to understand factors governing the inter-human transmission of prions. The present analysis relying on truncated Weibull distribution supports a relationship between host genetics, dose of the at-risk GH, age at treatment onset, and duration of the incubation period.

Amplification techniques and diagnosis of prion diseases.

Protein misfolding cyclic amplification assay (PMCA) and real-time quaking-induced conversion (RT-QuIC) are two amplification techniques based on the ability of PrPsc to induce a conformational change in PrP allowing the detection of minute amounts of PrPsc in body fluids or tissues. PMCA and RT-QuIC have different ability to amplify PrPsc from sporadic, variant and genetic forms of Creutzfeldt-Jakob disease (CJD). PMCA readily amplifies PrPsc from variant CJD (vCJD) tissue while RT-QuIC easily amplifies PrPsc from sporadic CJD (sCJD) patient tissues.

Age at onset in genetic prion disease and the design of preventive clinical trials.

Objective: To determine whether preventive trials in genetic prion disease could be designed to follow presymptomatic mutation carriers to onset of disease.

Methods: We assembled age at onset or death data from 1,094 individuals with high penetrance mutations in the prion protein gene () in order to generate survival and hazard curves and test for genetic modifiers of age at onset. We used formulae and simulations to estimate statistical power for clinical trials.

Tonic spinal cord stimulation as therapeutic option in Parkinson disease with axial symptoms: Effects on walking and quality of life.

Spinal cord stimulation (SCS) is an effective surgical therapy used for the treatment of chronic neuropathic pain. Tonic SCS is safe and improve not only gait disorders, motor symptoms, but also quality of life in Parkinson patients even with dopa-resistant symptoms with or without associated deep brain stimulation.

Susceptibility to Creutzfeldt-Jakob disease after human growth hormone treatment in France.

Objective: To identify, among the available data concerning host characteristics and exposure, risk factors influencing the susceptibility for developing iatrogenic Creutzfeldt-Jakob disease (iCJD) in a cohort of patients treated with human cadaver-sourced growth hormone (hGH) in France.

Methods: This study included all 1,443 individuals treated in France with hGH from January 1982 to December 1985, out of which 119 cases of hGH-iCJD have been identified so far. We applied a 3 sequential step Cox analysis involving univariable, stepwise, and nonstepwise multivariable procedures.

Longitudinal analysis of impulse control disorders in Parkinson disease.

Objective: To investigate the longitudinal dose-effect relationship between dopamine replacement therapy and impulse control disorders (ICDs) in Parkinson disease (PD).

Methods: We used data from a multicenter longitudinal cohort of consecutive patients with PD with ≤5 years' disease duration at baseline followed up annually up to 5 years. ICDs were evaluated during face-to-face semistructured interviews with movement disorder specialists.

Variant Creutzfeldt-Jakob disease.

Variant CJD (vCJD) was described first in the United Kingdom in 1996. It is a zoonotic form of human prion disease, originating from dietary contamination of human food with material from bovine spongiform encephalopathy (BSE)-affected cattle. It has important epidemiologic, clinical, and neuropathogic differences from other forms of human prion disease.