Video Rating in Neurodegenerative Disease Clinical Trials: The Experience of PRION-1.

Background/aims: Large clinical trials including patients with uncommon diseases involve assessors in different geographical locations, resulting in considerable inter-rater variability in assessment scores. As video recordings of examinations, which can be individually rated, may eliminate such variability, we measured the agreement between a single video rater and multiple examining physicians in the context of PRION-1, a clinical trial of the antimalarial drug quinacrine in human prion diseases.

Methods: We analysed a 43-component neurocognitive assessment battery, on 101 patients with Creutzfeldt-Jakob disease, focusing on the correlation and agreement between examining physicians and a single video rater.

Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial.

Background: The propagation of prions, the causative agents of Creutzfeldt-Jakob disease and other human prion diseases, requires post-translational conversion of normal cellular prion protein to disease-associated forms. The antimalarial drug quinacrine (mepacrine) prevents this conversion in vitro, and was given to patients with various prion diseases to assess its safety and efficacy in changing the course of these invariably fatal and untreatable diseases.

Methods: Patients with prion disease were recruited via the UK national referral system and were offered a choice between quinacrine (300 mg daily), no quinacrine, or randomisation to immediate quinacrine or deferred quinacrine in an open-label, patient-preference trial.

Imaging cadavers: cold FLAIR and noninvasive brain thermometry using CSF diffusion.

There is increasing interest in imaging cadavers for noninvasive autopsies for research purposes. However, the temperature is well below that of in vivo imaging, and a variety of interesting 'cold brain' effects are observed. At lower temperatures conventional FLAIR sequences no longer produce dark cerebrospinal fluid (CSF); T(1) is reduced from about 4.