Prediction of Upper Limb Motor Recovery by the PREP2 Algorithm in a Nonselected Population: External Validation and Influence of Cognitive Syndromes.

BACKGROUND: Early prediction of poststroke motor recovery is challenging in clinical settings. The Prediction recovery potential (PREP2) algorithm is the most accurate approach for prediction of Upper Limb function available to date but lacks external validation. OBJECTIVES: (i) To externally validate the PREP2 algorithm in a prospective cohort, (ii) to study the characteristics of patients misclassified by the algorithm, and (iii) to compare the performance according to the presence of cognitive syndromes (aphasia, neglect, cognitive disorders). METHODS: We enrolled 143 patients with stroke and upper extremity weakness persistent at Day 3. Evaluation to predict the recovery status according to the PREP2 algorithm included age, SAFE and NIHSS scores at Day 3 and transcranial magnetic stimulation to determine the presence of the motor-evoked potential before day seven. Actual recovery (excellent, good, limited, or poor) was defined based on the Action Research Arm test score at 3 months. Accuracy was computed by comparing the predictions of the PREP2 and the actual category of the patient. Additionally, to investigate misclassifications and the impact of cognitive syndromes, we recorded SAFE and NIHSS scores at Day 7, the Montreal Cognitive Assessment (MoCA) score, the presence of aphasia and neglect and Magnetic Resonance Imaging was used to evaluate the corticospinal tract lesion load. RESULTS: The PREP2 algorithm showed a very good predictive value with 78% accuracy [95% CI: 71.2%-86.1%], especially for the extreme categories of recovery (EXCELLENT 87.5% [95% CI: 78.9%-96.2%] and POOR 94.9% [95% CI: 87.9%-100%]), and only 46.5% [95% CI: 19.05%-73.25%] for the GOOD category and even worse than chance for the LIMITED category 0%. Pessimistic predictions (false-negative cases) had a drastic improvement in the SAFE score acutely compared to that of well-predicted patients with unfavorable recovery (P < 001). The predictive value of PREP2 decreased significantly when patients had cognitive disorders (MoCA score <24) versus not (69.4% [95% CI: 52.8%-86.1%] vs 93.1% [95% CI: 83.9%-100%], P = .01). CONCLUSION: Our study provides an external validation of the PREP2 algorithm in a prospective population and underlines the importance of taking into account cognitive syndromes in motor recovery prediction.

Projected pooling loss for red nucleus segmentation with soft topology constraints.

Purpose: Deep learning is the standard for medical image segmentation. However, it may encounter difficulties when the training set is small. Also, it may generate anatomically aberrant segmentations. Anatomical knowledge can be potentially useful as a constraint in deep learning segmentation methods. We propose a loss function based on projected pooling to introduce soft topological constraints. Our main application is the segmentation of the red nucleus from quantitative susceptibility mapping (QSM) which is of interest in parkinsonian syndromes. Approach: This new loss function introduces soft constraints on the topology by magnifying small parts of the structure to segment to avoid that they are discarded in the segmentation process. To that purpose, we use projection of the structure onto the three planes and then use a series of MaxPooling operations with increasing kernel sizes. These operations are performed both for the ground truth and the prediction and the difference is computed to obtain the loss function. As a result, it can reduce topological errors as well as defects in the structure boundary. The approach is easy to implement and computationally efficient. Results: When applied to the segmentation of the red nucleus from QSM data, the approach led to a very high accuracy (Dice 89.9%) and no topological errors. Moreover, the proposed loss function improved the Dice accuracy over the baseline when the training set was small. We also studied three tasks from the medical segmentation decathlon challenge (MSD) (heart, spleen, and hippocampus). For the MSD tasks, the Dice accuracies were similar for both approaches but the topological errors were reduced. Conclusions: We propose an effective method to automatically segment the red nucleus which is based on a new loss for introducing topology constraints in deep learning segmentation.

Sensitivity of Advanced Magnetic Resonance Imaging to Progression over Six Months in Early Spinocerebellar Ataxia.

BACKGROUND: Clinical trials for upcoming disease-modifying therapies of spinocerebellar ataxias (SCA), a group of rare movement disorders, lack endpoints sensitive to early disease progression, when therapeutics will be most effective. In addition, regulatory agencies emphasize the importance of biological outcomes. OBJECTIVES: READISCA, a transatlantic clinical trial readiness consortium, investigated whether advanced multimodal magnetic resonance imaging (MRI) detects pathology progression over 6 months in preataxic and early ataxic carriers of SCA mutations. METHODS: A total of 44 participants (10 SCA1, 25 SCA3, and 9 controls) prospectively underwent 3-T MR scanning at baseline and a median [interquartile range] follow-up of 6.2 [5.9-6.7] months; 44% of SCA participants were preataxic. Blinded analyses of annual changes in structural, diffusion MRI, MR spectroscopy, and the Scale for Assessment and Rating of Ataxia (SARA) were compared between groups using nonparametric testing. Sample sizes were estimated for 6-month interventional trials with 50% to 100% treatment effect size, leveraging existing large cohort data (186 SCA1, 272 SCA3) for the SARA estimate. RESULTS: Rate of change in microstructural integrity (decrease in fractional anisotropy, increase in diffusivities) in the middle cerebellar peduncle, corona radiata, and superior longitudinal fasciculus significantly differed in SCAs from controls (P < 0.005), with high effect sizes (Cohen's d = 1-2) and moderate-to-high responsiveness (|standardized response mean| = 0.6-0.9) in SCAs. SARA scores did not change, and their rate of change did not differ between groups. CONCLUSIONS: Diffusion MRI is sensitive to disease progression at very early-stage SCA1 and SCA3 and may provide a >5-fold reduction in sample sizes relative to SARA as endpoint for 6-month-long trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Combined in vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in amnestic Alzheimer's disease, suspected-LATE and frontotemporal dementia.

BACKGROUND: The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls. METHODS: Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy. RESULTS: We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients. CONCLUSIONS: The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.

Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia.

Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of SGCE (DYT-SGCE) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT-SGCE and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder.