Prodromal Cognitive Changes as a Prognostic Indicator of Forthcoming Huntington's Disease Severity: A Retrospective Longitudinal Study.

BACKGROUND: Cognitive changes in Huntington's disease (HD) precede motor manifestations. ENROLL-HD platform includes four cognitive measures of information processing speed (IPS). Our group is eager to seek clinical markers in the life stage that is as close as possible to the age of onset (ie, the so called prodromal HD phase) because this is the best time for therapeutic interventions. OBJECTIVES: Our study aimed to test whether cognitive scores in prodromal ENROLL-HD mutation carriers show the potential to predict the severity of motor and behavioral changes once HD became fully manifested. METHODS: From the global ENROLL-HD cohort of 21,343 participants, we first selected a premanifest Cohort#1 (ie, subjects with Total Motor Score (TMS) <10 and Diagnostic Confidence Level (DCL) <4, N = 1.222). From this cohort, we then focused on a prodromal Cohort#2 of subjects who were ascertained to phenoconvert into manifest HD at follow-up visits (ie, subjects from 6 ≤ TMS≤9 and DCL <4 to TMS≥10 and DCL = 4, n = 206). RESULTS: The main results of our study showed that low IPS before phenoconversion in Cohort#2 predicted the severity of motor and behavioral manifestations. By combining the four IPS cognitive measures (eg, the Categorical Verbal Fluency Test; Stroop Color Naming Test; Stroop Word Reading; Symbol Digit Modalities Test), we generated a Composite Cognition Score (CCS). The lower the CCS score the higher the TMS and the apathy scores in the same longitudinally followed-up patients after phenoconversion. CONCLUSIONS: CCS might represent a clinical instrument to predict the prognosis of mutation carriers who are close to manifesting HD.

"Spazio Huntington": Tracing the Early Motor, Cognitive and Behavioral Profiles of Kids with Proven Pediatric Huntington Disease and Expanded Mutations > 80 CAG Repeats.

The "Spazio Huntington-A Place for Children" program was launched in 2019. The aim was to contact at risk kids within Huntington disease (HD) families, to provide counseling to their parents and to start a prospective follow-up of kids suspicious to manifest pediatric HD (PHD). We met 25 at risk kids in two years, four of whom with PHD and highly expanded (HE) mutations beyond 80 CAG repeats. We rated motor, neuropsychological and behavioral changes in all PHD kids by the Unified HD Rating Scale (UHDRS)-total motor score (TMS) and additional measures of (1) cognitive level (Leiter International Performance Scale), (2) adaptive functioning (Adaptive Behavior Assessment Systems), (3) receptive language (Peabody Picture Vocabulary Test) and (4) behavioral abnormalities (Child Behavior Check List and Children's Yale-Brown Obsessive Compulsive Scale). All PHD kids showed a severe progression of neurological and psychiatric manifestations including motor, cognitive and behavioral changes. The magnetic resonance imaging contributed to confirm the suspicious clinical observation by highlighting very initial striatum abnormalities in PHD. Spazio Huntington is a program to prospectively study PHD, the most atypical face of HD, and may represent the basis to recruit PHD patients in future clinical trials.