Our algorithm demonstrates an individualized approach to stroke rehabilitation, wherein imaging and functional performance measures can be used to develop an optimized rehabilitation paradigm for rats, particularly those with severe impairments. Exploring this approach in human patients could lead to an increase in the proportion of individuals experiencing recovery of lost motor function poststroke.

Background: Studies on the clinical manifestation and course of disease in children suffering from Huntington’s disease (HD) are rare. Case reports of juvenile HD (onset ≤ 20 years) describe heterogeneous motoric and non-motoric symptoms, often accompanied with a delay in diagnosis. We aimed to describe this rare group of patients, especially with regard to socio-medical aspects and individual or common treatment strategies. In addition, we differentiated between juvenile and the recently defined pediatric HD population (onset < 18 years). Methods: Out of 2593 individual HD patients treated within the last 25 years in the Huntington Centre, North Rhine-Westphalia (NRW), 32 subjects were analyzed with an early onset younger than 21 years (1.23%, juvenile) and 18 of them younger than 18 years of age (0.69%, pediatric). Results: Beside a high degree of school problems, irritability or aggressive behavior (62.5% of pediatric and 31.2% of juvenile cases), serious problems concerning the social and family background were reported in 25% of the pediatric cohort. This includes an attempted rape and robbery at the age of 12, as problems caused by the affected children, but also alcohol-dependency in a two-year-old induced by a non-HD affected stepfather. A high degree of suicidal attempts and ideations (31.2% in pediatric and 33.3% in juvenile group) was reported, including drinking of solvents, swallowing razor blades or jumping from the fifth floor with following incomplete paraparesis. Beside dopaminergic drugs for treatment of bradykinesia, benzodiazepines and tetrabenazine for treatment of dystonia, cannabinoids, botulinum toxin injection and deep brain stimulation were used for the improvement of movement disorders, clozapine for the treatment of tremor, and dopa-induced hallucinations and zuclopenthixole for the treatment of severe aggressive behavior. Conclusions: Beside abnormalities in behavior from an early age due to HD pathology, children seem to have higher socio-medical problems related to additional burden caused by early affected parents, instable family backgrounds including drug abuse of a parent or multiple changes of partners. Treatment required individualized strategies in many cases.

Background: Reducing the progress of neurodegeneration is a key goal in Huntington´s disease (HD). A previously performed systematic screening for medications with neuroprotective features identified tricyclic antidepressants and neuroleptics as neuroprotective and mitochondrioprotective agents. Here, we analyzed the characteristics of disease manifestation, progression and potential beneficial effects in HD patients treated with afore-mentioned medications compared to un- and otherwise treated motor-manifest patients in a large real-world cohort over two years. Methods: We analyzed cross-sectional data of the largest cohort worldwide of motor-manifest HD patients using the ENROLL-HD database, including demographic, moleculargenetic, clinical-motoric, cognitive and functional data. Longitudinal data of up to two years were obtained to analyze potential effects on disease progression between groups with different medications used. Data were analyzed using repeated ANOVA-analyses while controlling for the co-variates age and CAG-repeat length. Results: We identified n = 7397 motor-manifest HD patients using no or different medication (HD-ctrl) and subgroups treated with clomipramine (n = 56), clozapine (n = 66), chlorpromazine (n = 17), doxepine (n = 34) and desi-, imi- or trimipramine (n = 19). Demographic parameters, disease onset and CAP-score did not differ. Total motor scores (TMS) at baseline were higher in patients treated with clozapine (p < 0.001), chlorpromazine and clomipramine (p < 0.05) compared to HD-ctrl with higher sub scores for bradykinesia (all p < 0.01) and dystonia in clozapine treated patients (p < 0.001). Functional and cognitive capacities were worse in medication groups in comparison to HD-ctrl at baseline (p < 0.001). Repeated measures analysis of variance documented no differences regarding motoric, functional and cognitive disease progressions between groups. Conclusions: We identified group differences, potentially caused by side effects or potential selection bias in terms of bradykinetic motoric symptoms, more dystonia and lower functional and cognitive performance in some treatment groups at baseline, which were not entirely explained because of underlying fundamental characteristics. Disease progression regarding clinical, functional and cognitive outcomes over two years was not affected by any of the treatment groups compared to HD-ctrl. Our data do not support our hypothesis of a potential neuroprotective effect of these drugs on disease progression.