Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (CALD) is an X-linked rapidly progressive demyelinating disease leading to death usually within a few years. The standard of care is hematopoietic stem cell transplantation (HSCT), but many men are not eligible due to age, absence of a matched donor, or lesions of the corticospinal tracts (CST). Based on the ADVANCE study showing that leriglitazone decreases the occurrence of CALD, we treated 13 adult CALD patients (19-67 years of age) either not eligible to HSCT (n= 8) or awaiting HSCT (n= 5). Patients were monitored every 3 months with standardized neurological scores, plasma biomarkers and brain MRI comprising lesion volumetrics and diffusion tensor imaging. The disease stabilized clinically and radiologically in 10 patients with up to 2 years of follow-up. Five patients presented with gadolinium enhancing CST lesions that all turned gadolinium negative and, remarkably, regressed in four patients. Plasma neurofilament light chain levels stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were over 60 years of age with prominent cognitive impairment. One patient rapidly died from Covid19. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT.

Body-Worn Sensors for Parkinson's disease: A qualitative approach with patients and healthcare professionals.

Body-Worn Sensors (BWS) provide reliable objective and continuous assessment of Parkinson's disease (PD) motor symptoms, but their implementation in clinical routine has not yet become widespread. Users' perceptions of BWS have not been explored. This study intended to evaluate the usability, user experience (UX), patients' perceptions of BWS, and health professionals' (HP) opinions on BWS monitoring. A qualitative analysis was performed from semi-structured interviews conducted with 22 patients and 9 HP experts in PD. Patients completed two interviews before and after the BWS one-week experiment, and they answered two questionnaires assessing the usability and UX. Patients rated the three BWS usability with high scores (SUS median [range]: 87.5 [72.5-100]). The UX across all dimensions of their interaction with the BWS was positive. During interviews, all patients and HP expressed interest in BWS monitoring. Patients' hopes and expectations increased the more they learned about BWS. They manifested enthusiasm to wear BWS, which they imagined could improve their PD symptoms. HP highlighted needs for logistical support in the implementation of BWS in their practice. Both patients and HP suggested possible uses of BWS monitoring in clinical practice, for treatment adjustments for example, or for research purposes. Patients and HP shared ideas about the use of BWS monitoring, although patients may be more likely to integrate BWS into their disease follow-up compared to HP in their practice. This study highlights gaps that need to be fulfilled to facilitate BWS adoption and promote their potential.

First European case of Creutzfeldt-Jakob disease with a PRNP G114V mutation.

Genetic Creutzfeldt-Jakob disease is due to mutations in the PRNP gene. Only two families with a PRNP G114V mutation have been described around the world. We report the first European case, who had no family history and initially presented with isolated deficit in hippocampus-dependent memory. Initial investigations were normal except for elevated total tau protein in the cerebrospinal fluid. He died 4 years after disease onset. This case highlights the diagnostic difficulties posed by genetic Creutzfeldt-Jakob disease, and shows that genetic analyses should be considered even in sporadic cases.