Accurately predicting functional outcomes for unresponsive patients with acute brain injury is a medical, scientific and ethical challenge. This prospective study assesses how a multimodal approach combining various numbers of behavioral, neuroimaging and electrophysiological markers affects the performance of outcome predictions. We analyzed data from 349 patients admitted to a tertiary neurointensive care unit between 2009 and 2021, categorizing prognoses as good, uncertain or poor, and compared these predictions with observed outcomes using the Glasgow Outcome Scale–Extended (GOS-E, levels ranging from 1 to 8, with higher levels indicating better outcomes). After excluding cases with life-sustaining therapy withdrawal to mitigate the self-fulfilling prophecy bias, our findings reveal that a good prognosis, compared with a poor or uncertain one, is associated with better one-year functional outcomes (common odds ratio (95% CI) for higher GOS-E: OR = 14.57 (5.70–40.32), P < 0.001; and 2.9 (1.56–5.45), P < 0.001, respectively). Moreover, increasing the number of assessment modalities decreased uncertainty (OR = 0.35 (0.21–0.59), P < 0.001) and improved prognostic accuracy (OR = 2.72 (1.18–6.47), P = 0.011). Our results underscore the value of multimodal assessment in refining neuroprognostic precision, thereby offering a robust foundation for clinical decision-making processes for acutely brain-injured patients. ClinicalTrials.gov registration: NCT04534777.

Background: The locus coeruleus/subcoeruleus complex (LC/LsC) is a structure comprising melanized noradrenergic neurons.Objective: To study the LC/LsC damage across Parkinson's disease (PD) and atypical parkinsonism in a large group of subjects.Methods: We studied 98 healthy control subjects, 47 patients with isolated rapid eye movement sleep behavior disorder (RBD), 75 patients with PD plus RBD, 142 patients with PD without RBD, 19 patients with progressive supranuclear palsy (PSP), and 19 patients with multiple system atrophy (MSA). Twelve patients with MSA had proven RBD. LC/LsC signal intensity was derived from neuromelanin magnetic resonance imaging using automated software.Results: The signal intensity was reduced in all parkinsonian syndromes compared with healthy control subjects, except in PD without RBD. The signal intensity decreased as age increased. Moreover, the signal intensity was lower in MSA than in isolated RBD and PD without RBD groups. In PD, the signal intensity correlated negatively with the percentage of REM sleep without atonia. There were no differences in signal intensity between PD plus RBD, PSP, and MSA.Conclusions: Neuromelanin signal intensity was reduced in all parkinsonian disorders, except in PD without RBD. The presence of RBD in parkinsonian disorders appears to be associated with lower neuromelanin signal intensity. Furthermore, lower LC/LsC signal changes in PSP could be partly caused by the effect of age. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: International clinical criteria are the reference for the diagnosis of degenerative parkinsonism in clinical research, but they may lack sensitivity and specificity in the early stages.Objectives: To determine whether magnetic resonance imaging (MRI) analysis, through visual reading or machine‐learning approaches, improves diagnostic accuracy compared with clinical diagnosis at an early stage in patients referred for suspected degenerative parkinsonism.Materials: Patients with initial diagnostic uncertainty between Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multisystem atrophy (MSA), with brain MRI performed at the initial visit (V1) and available 2‐year follow‐up (V2), were included. We evaluated the accuracy of the diagnosis established based on: (1) the international clinical diagnostic criteria for PD, PSP, and MSA at V1 (“Clin1”); (2) MRI visual reading blinded to the clinical diagnosis (“MRI”); (3) both MRI visual reading and clinical criteria at V1 (“MRI and Clin1”), and (4) a machine‐learning algorithm (“Algorithm”). The gold standard diagnosis was established by expert consensus after a 2‐year follow‐up.Results: We recruited 113 patients (53 with PD, 31 with PSP, and 29 with MSA). Considering the whole population, compared with clinical criteria at the initial visit (“Clin1”: balanced accuracy, 66.2%), MRI visual reading showed a diagnostic gain of 14.3% (“MRI”: 80.5%; P = 0.01), increasing to 19.2% when combined with the clinical diagnosis at the initial visit (“MRI and Clin1”: 85.4%; P < 0.0001). The algorithm achieved a diagnostic gain of 9.9% (“Algorithm”: 76.1%; P = 0.08).Conclusion: Our study shows the use of MRI analysis, whether by visual reading or machine‐learning methods, for early differentiation of parkinsonism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Healthcare professionals’ statistical illiteracy can impair medical decision quality and compromise patient safety. Previous studies have documented clinicians’ insufficient proficiency in statistics and a tendency in overconfidence. However, an underexplored aspect is clinicians’ awareness of their lack of statistical knowledge that precludes any corrective intervention attempt. Here, we investigated physicians’, residents’ and medical students’ alignment between subjective confidence judgments and objective accuracy in basic medical statistics. We also examined how gender, profile of experience and practice of research activity affect this alignment, and the influence of problem framing (conditional probabilities, CP vs. natural frequencies, NF). Eight hundred ninety-eight clinicians completed an online survey assessing skill and confidence on three topics: vaccine efficacy, p value and diagnostic test results interpretation. Results evidenced an overall consistent poor proficiency in statistics often combined with high confidence, even in incorrect answers. We also demonstrate that despite overconfidence bias, clinicians show a degree of metacognitive sensitivity, as their confidence judgments discriminate between their correct and incorrect answers. Finally, we confirm the positive impact of the more intuitive NF framing on accuracy. Together, our results pave the way for the development of teaching recommendations and pedagogical interventions such as promoting metacognition on basic knowledge and statistical reasoning as well as the use of NF to tackle statistical illiteracy in the medical context.

Background: Carriers of small cytosine‐adenine‐guanine (CAG) repeats below 39 in the HTT gene are traditionally associated with milder Huntington's disease, but their clinical profile has not been extensively studied.Objective: To study the phenotype of CAG_36‐38 repeat carriers.Methods: We included 35 patients and premanifest carriers of CAG_36‐38 repeats. We compared clinical and neuropsychological profiles of 11 CAG_36‐38 patients with 11 matched CAG_40‐42 patients. In addition, we analyzed 243 CAG_36‐38 individuals from the ENROLL study to complete the phenotype description.Results: Global cognitive efficiency and performance in different cognitive subdomains were similar in small CAG_36‐38 and typically CAG_40‐42 expanded individuals. Chorea as the first symptom was significantly less frequent for CAG_36‐38 patients (P = 0.04) despite similar total motor scores at first visit. Total motor score at last visit was significantly lower in CAG_36‐38 carriers (P = 0.003). The similar cognitive and different motor profile of CAG_36‐38 (n = 243) and CAG_40‐42 (n = 4675) carriers was confirmed in the ENROLL database. Additionally, clinicians were significantly less confident in diagnosing Huntington's disease (P = 2.4e−8) and diagnosis happened significantly later in CAG_36‐38 (P = 2.2e−6) despite a similar age at symptom onset (P = 0.29).Conclusions: We showed that small CAG_36‐38 expansion carriers had a similar cognitive profile to those with the more common CAG_40‐42 expansions. These individuals may evade molecular diagnosis because of the absence of chorea rather than because of a low penetrance of symptoms. This finding should encourage neurologists to consider Huntington's disease in cognitively impaired elderly patients without typical chorea and anticipate consequences for genetic counseling in their offspring. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.