Putaminal diffusion tensor imaging measures predict disease severity across human prion diseases.

Therapeutic trials of disease-modifying agents in neurodegenerative disease typically require several hundred participants and long durations for clinical endpoints. Trials of this size are not feasible for prion diseases, rare dementia disorders associated with misfolding of prion protein. In this situation, biomarkers are particularly helpful.

Neuroanatomical correlates of prion disease progression - a 3T longitudinal voxel-based morphometry study.

Purpose: MRI has become an essential tool for prion disease diagnosis. However there exist only a few serial MRI studies of prion patients, and these mostly used whole brain summary measures or region of interest based approaches. We present here the first longitudinal voxel-based morphometry (VBM) study in prion disease.

Quantitative EEG parameters correlate with the progression of human prion diseases.

Background: Prion diseases are universally fatal and often rapidly progressive neurodegenerative diseases. EEG has long been used in the diagnosis of sporadic Creutzfeldt-Jakob disease; however, the characteristic waveforms do not occur in all types of prion diseases. Here, we re-evaluate the utility of EEG by focusing on the development of biomarkers.

Clinical Trial Simulations Based on Genetic Stratification and the Natural History of a Functional Outcome Measure in Creutzfeldt-Jakob Disease.

Importance: A major challenge for drug development in neurodegenerative diseases is that adequately powered efficacy studies with meaningful end points typically require several hundred participants and long durations. Prion diseases represent the archetype of brain diseases caused by protein misfolding, the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. There is no well-established trial method in prion disease.

Evolution of Diffusion-Weighted Magnetic Resonance Imaging Signal Abnormality in Sporadic Creutzfeldt-Jakob Disease, With Histopathological Correlation.

Importance: Prion diseases represent the archetype of brain diseases caused by protein misfolding, with the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion-weighted imaging (DWI) has emerged as the most sensitive magnetic resonance imaging (MRI) sequence for the diagnosis of sCJD, but few studies have assessed the evolution of MRI signal as the disease progresses.

Objectives: To assess the natural history of the MRI signal abnormalities on DWI in sCJD to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation.

The cognitive profile of prion disease: a prospective clinical and imaging study.

Objectives: Prion diseases are dementing illnesses with poorly defined neuropsychological features. This is probably because the most common form, sporadic Creutzfeldt-Jakob disease, is often rapidly progressive with pervasive cognitive decline making detailed neuropsychological investigation difficult. This study, which includes patients with inherited, acquired (iatrogenic and variant) and sporadic forms of the disease, is the only large-scale neuropsychological investigation of this patient group ever undertaken and aimed to define a neuropsychological profile of human prion diseases.

Behavioral and psychiatric symptoms in prion disease.

The prion diseases are rare neurodegenerative conditions that cause complex and highly variable neuropsychiatric syndromes, often with remarkably rapid progression. Prominent behavioral and psychiatric symptoms have been recognized since these diseases were first described. While research on such symptoms in common dementias has led to major changes in the way these symptoms are managed, evidence to guide the care of patients with prion disease is scarce.

Variant Creutzfeldt-Jakob disease with extremely low lymphoreticular deposition of prion protein.

Importance: Human transmission of bovine spongiform encephalopathy causes the fatal neurodegenerative condition variant Creutzfeldt-Jakob disease (vCJD) and, based on recent human prevalence studies, significant subclinical prion infection of the UK population. To date, all clinical cases have been fatal, totaling 228 mostly young adults residing in the United Kingdom.

Observations: Here we describe the investigation and case history of a patient recently diagnosed as having vCJD in the United Kingdom.

The Medical Research Council prion disease rating scale: a new outcome measure for prion disease therapeutic trials developed and validated using systematic observational studies.

Progress in therapeutics for rare disorders like prion disease is impeded by the lack of validated outcome measures and a paucity of natural history data derived from prospective observational studies. The first analysis of the U.K.