A feasibility randomized controlled trial of a NICU rehabilitation program for very low birth weight infants.

Motor disability is common in children born preterm. Interventions focusing on environmental enrichment and emotional connection can positively impact outcomes. The NICU-based rehabilitation (NeoRehab) program consists of evidence-based interventions provided by a parent in addition to usual care. The program combines positive sensory experiences (vocal soothing, scent exchange, comforting touch, skin-to-skin care) as well as motor training (massage and physical therapy) in a gestational age (GA) appropriate fashion. To investigate the acceptability, feasibility and fidelity of the NeoRehab program in very low birthweight (VLBW) infants. All interventions were provided by parents in addition to usual care. Infants (≤ 32 weeks' GA and/or ≤ 1500 g birthweight) were enrolled in a randomized controlled trial comparing NeoRehab to usual care (03/2019-10/2020). The a priori dosing goal was for interventions to be performed 5 days/week. The primary outcomes were the acceptability, feasibility and fidelity of the NeoRehab program. 36 participants were randomized to the intervention group and 34 allocated to usual care. The recruitment rate was 71% and retention rate 98%. None of the interventions met the 5 days per week pre-established goal. 97% of participants documented performing a combination of interventions at least 3 times per week. The NeoRehab program was well received and acceptable to parents of VLBW infants. Programs that place a high demand on parents (5 days per week) are not feasible and goals of intervention at least 3 times per week appear to be feasible in the context of the United States. Parent-provided motor interventions were most challenging to parents and alternative strategies should be considered in future studies. Further studies are needed to evaluate the relationship between intervention dosing on long term motor outcomes.

Handwritten Geometrical Patterns in the Evaluation of Motor Symptoms in Psychotic Disorders.

The analysis of handwriting has been used in several contexts. For example, handwriting has shown to be of value in the study of motor symptoms in neurological and mental disorders. In the present work, the geometric analysis of handwriting patterns is proposed as a tool to evaluate motor symptoms in psychotic disorders. Specifically, we have employed the lacunarity, a measure of the heterogeneity of a spatial structure. Forty-two patients with a psychotic disorder and 35 matched healthy controls participated in the study. Participants were asked to copy some patterns with a pen on a white paper. The results showed that lacunarity was significantly higher in handwritten patterns from patients than from controls. In addition, we found higher values of lacunarity in handwritten patterns from patients with severe motor symptoms in comparison with patients with mild or absent motor symptoms. Lacunarity of handwritten patterns was significantly correlated with clinical scores of rigidity. In conclusion we argue that the heterogeneity of handwritten patterns could be used as a simple and objective measure of motor symptoms.

Characteristics of patients with motor functional neurological disorder in a large UK mental health service: a case-control study.

BACKGROUND: Functional neurological disorder (FND), previously known as conversion disorder, is common and often results in substantial distress and disability. Previous research lacks large sample sizes and clinical surveys are most commonly derived from neurological settings, limiting our understanding of the disorder and its associations in other contexts. We sought to address this by analysing a large anonymised electronic psychiatric health record dataset. METHODS: Data were obtained from 322 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who had an ICD-10 diagnosis of motor FND (mFND) (limb weakness or disorders of movement or gait) between 1 January 2006 and 31 December 2016. Data were collected on a range of socio-demographic and clinical factors and compared to 644 psychiatric control patients from the same register. RESULTS: Weakness was the most commonly occurring functional symptom. mFND patients were more likely to be female, British, married, employed pre-morbidly, to have a carer and a physical health condition, but less likely to have had an inpatient psychiatric admission or to receive benefits. No differences in self-reported sexual or physical abuse rates were observed between groups, although mFND patients were more likely to experience life events linked to inter-personal difficulties. CONCLUSIONS: mFND patients have distinct demographic characteristics compared with psychiatric controls. Experiences of abuse appear to be equally prevalent across psychiatric patient groups. This study establishes the socio-demographic and life experience profile of this understudied patient group and may be used to guide future therapeutic interventions designed specifically for mFND.

A qualitative study of the experiences and perceptions of patients with functional motor disorder.

Background: Patients with functional motor disorder are perceived as difficult by health care professionals, but we know very little about the patients' perspective. Understanding the experiences and perceptions of patients could help to improve clinical services and patient outcomes.Purpose: To explore the experiences and perspectives of patients with functional motor disorder using qualitative research methods.Methods: This qualitative study was embedded within a feasibility study of specialist physiotherapy. Eleven patients with functional motor disorder participated in semi-structured qualitative interviews prior to receiving treatment. The interview transcripts were subjected to an inductive thematic analysis.Results: The data were arranged into six themes: (1) the burden of living with functional motor disorder; (2) nobody knew what was wrong; (3) dissatisfaction with psychological explanations; (4) patients feel abandoned; (5) iatrogenic harm; and (6) powerlessness.Discussion and Conclusion: The study participants experienced substantial physical and emotional burdens associated with functional motor disorder. They were generally dissatisfied with psychological explanations for their symptoms and commonly felt misunderstood and abandoned by health care professionals, which appeared to leave them vulnerable to iatrogenic harm. A lack of understanding of functional motor disorder left participants feeling unable to help themselves. This research highlights a number of inadequacies within current clinical services for patients with functional motor disorder.Implications for rehabilitationCareful communication is required to help patients understand and accept the diagnosis of functional motor disorder.It is important to listen to the patient's narrative in order to help them make sense of their illness experience.A nuanced biopsychosocial explanatory model is needed to help patients understand how psychological factors can be relevant to physical symptoms and symptoms that are often perceived to be precipitated by a physical event.A lack of understanding and acceptance of the diagnosis may leave patients vulnerable to iatrogenic harm and powerless to help themselves.

Basic smartphone-aided communication and leisure for people with extensive neuro-motor impairment and absence of speech.

BACKGROUND: Individuals with extensive neuro-motor impairment and lack of speech tend to remain passive and isolated, and to rely on others for communication and leisure. While their problems are known, only limited evidence is available about intervention tools that could help them curb those problems. OBJECTIVE: This study was aimed at upgrading and assessing a smartphone-based technology package, which was recently developed to help those individuals to independently engage in basic communication and leisure. METHODS: The study included 11 non-ambulatory participants who had no speech or functional active communication. They were provided with (a) a Samsung A3 smartphone with Android 6.0 Operating System, which was fitted with WhatsApp Messenger and programmed via MacroDroid, and (b) cards fitted with radio frequency identification (RFID) tags. By bringing those cards in contact with the back of the smartphone, the participant could start a communication event (e.g., sending a message to a friend) or activate a leisure event (e.g., a song). The smartphone would automatically read to the participant any incoming messages. RESULTS: During the baseline (i.e., when a standard smartphone was available), the participants were unable to engage in communication or leisure. Once the aforementioned technology package was introduced, the participants spent between about 65 and 85% of their session time engaging in communication and leisure. CONCLUSIONS: The smartphone-based technology package seems to be a useful tool to support basic communication and leisure in individuals like those involved in this study.

Emotional Intelligence Profiles of University Students with Motor Disabilities: Differential Analysis of Self-Concept Dimensions.

Background: This study compares the self-concept of students that have motor disabilities with that of students in the normative group. It also considers whether there are EI (emotional intelligence) profiles based on combinations of EI components (attention, clarity, and mood repair). Finally, it analyzes whether there are statistically significant differences in self-concept based on the EI profiles found. Method: 102 university students with motor disabilities participated. The age range was 19-33 (M = 20.22, SD = 4.36). The Escala de Autoconcepto Forma 5 (Self-Concept Scale Form 5, AF5) and the Trait Meta-Mood Scale-24 (TMMS-24) were administered. Results: The scores for self-concept were lower in the sample of students with reduced mobility. The cluster analysis also identified three different EI profiles: one group of young people with high general EI scores, one group with high scores for clarity and mood repair, and a last group of students with low EI scores. Finally, the ANOVA showed better self-concept in the group with high scores in the three EI dimensions. The results suggest that better self-concept is associated with a high EI profile. Conclusions: It would be interesting to provide programs that consider EI in more depth to strengthen these students' self-concept.

Life story of university students and the adjustment of living with motor deficiency.

OBJECTIVE: To understand the life story of university students and the adjustment of living with motor deficiency. METHOD: A qualitative research, developed with eight university students with motor deficiency. Data collect was performed between October 2016 and March 2017. Thematic data analysis was used. RESULTS: Two categories emerged: family as safe harbor and extra-family relationships: weaknesses and strengths. Family and friends were fundamental for facing disability, standing out for their support and affection. Friends have been encouraged to overcome the limitations and difficulties. Extra-family life was exposed to prejudice that resulted in fears and traumas. CONCLUSION: The impact of motor deficiency on daily life is the result of life experiences. Healthy family relationships, along with strong bonds of friendship, made the difficulties found in the daily life of these students smoother.

Amyotrophic lateral sclerosis type 8 is not a pure motor disease: evidence from a neuropsychological and behavioural study.

OBJECTIVE: Amyotrophic lateral sclerosis type 8 (ALS8) is a familial form of motor neuron disease, with predominance of lower motor neuron degeneration, and is caused by mutation of the vesicle-associated membrane protein-associated protein B (VAPB). We aimed to compare the cognitive profile of patients with ALS8 and healthy controls (HC), and to screen for behavioural features in ALS8 patients. METHODS: The sample was composed of ALS8 patients (n = 22; 14 men; median age 48 years old; median disease duration 6.5 years) and HC (n = 33; 19 men; median age 48 years old). Patients and HC were matched for sex, age and educational level. Participants underwent behavioural, psychiatric (Hospital Anxiety and Depression Scale and Cambridge Behavioural Inventory-Revised) and neuropsychological assessments, focused on executive functions, visual memory, and facial emotion recognition. RESULTS: ALS8 patients exhibited subtle deficits in executive functions. Compared to controls, ALS8 patients were significantly impaired in measures of flexibility and inhibitory control. ALS8 patients and HC did not differ in scores of facial emotion recognition. There was clinically relevant anxiety and depression in 36% and 27% of ALS8 patients, respectively. Behavioural disorders such as stereotypic and motor behaviours were present in more than 30% of patients. CONCLUSIONS: ALS8 patients present mild executive dysfunction and behavioural changes such as mood disorders, apathy and stereotypic behaviour. Our findings suggest that ALS8 is not a pure motor disorder and it is associated with subtle cognitive and behavioural impairments.

Medication prescriptions in 322 motor functional neurological disorder patients in a large UK mental health service: A case control study.

OBJECTIVE: This study describes medication prescribing patterns in patients with motor functional neurological disorder (mFND) treated in South London and Maudsley NHS Foundation Trust (SLaM), comparing outcomes to a control group of psychiatric patients from the same hospital trust. METHOD: This is a retrospective case-control study using a psychiatric case register. Cross-sectional data were obtained from 322 mFND patients and 644 psychiatry controls who had had contact with SLaM between 1st January 2006 and 31st December 2016. RESULTS: A slightly lower proportion of mFND patients received medication compared to controls (76.6% v. 83.4%, OR: 0.59, CI: 0.39-0.89, p < 0.05). Of medication recipients, mFND patients were prescribed a higher number of agents (mean: 4.7 v 2.9, p = 0.001) and had higher prescription rates of antidepressants, anti-epileptics, analgesics, and certain non-psychotropic medications. Higher numbers of prescriptions were associated with co-morbid physical conditions, and previous psychiatric admissions. CONCLUSIONS: This is the first study to describe medication prescriptions in a large cohort of mFND patients. Patients were prescribed a wide range of psychiatric and physical health medications, with higher rates of polypharmacy than controls. Psychotropic medication prescription is not necessarily the first line treatment for mFND, where physiotherapy and psychotherapy may be offered initially. There is limited, early-phase evidence for pharmacological therapies for mFND, and as such, the benefit-to-risk ratio of prescribing in this complex and poorly understood disorder should be carefully assessed.

Paliperidone Long-Acting Injections in Huntington's Disease for Motor and Behavioural Disturbances.

Oral antipsychotics are used to treat motor and behavioural disturbances in Huntington's disease (HD). However, patients with behavioural disturbances are often non-compliant, thus the oral route is inappropriate. The effects of antipsychotic long-acting injections (LAI) in HD are significantly underrepresented in literature. Paliperidone LAI (P-LAI), an atypical antipsychotic, has benefits over other antipsychotics LAI with its long dosing interval and no initial oral overlap, but has no documented cases for this indication. This case of a 45-year-old female highlights the use of P-LAI for severe aggression and chorea secondary to HD causing failed placement in assisted-care accommodation and mobility via an electronic-wheelchair. Three weeks after commencing treatment, she could walk unassisted, and displayed no aggression. After 10 months, she still had significant improvements and resided in the same accommodation for 6 months without any concern. Thus, this case suggests that P-LAI may be a treatment option for non-compliant HD patients.

Parent-reported sleep disorders in children with motor disabilities: a comparison with the Sleep Disturbance Scale for Children's new norms.

OBJECTIVE: Children with motor disabilities such as cerebral palsy or neuromuscular diseases present more sleep disorders than their typically developing (TD) peers. However, research on these populations has always been performed using historical normative datasets or controls such as siblings. Therefore, we assessed the sleep quality of children with motor disabilities in comparison with a large, contemporary, general population sample. METHODS: Demographic, medical, and the Sleep Disturbance Scale for Children (SDSC) questionnaires were sent to parents of children aged 4-18 years and followed by our tertiary pediatric neurorehabilitation clinic, and to those of school-aged children in regional primary and secondary schools. TD participant data allowed us to set pathological sleep score thresholds (T score ≥70). RESULTS: We collected 245 responses for children with motor disabilities and 2891 for those from the general population (37% and 26% response rates, respectively). Cerebral palsy was the most frequent diagnosis (N = 109, 44.5%). Children with motor disabilities had significantly more frequent pathological sleep reported in their total SDSC score (7% vs 1.9%, odds ratio (OR) 3.98, 95% confidence interval (CI) 2.17-7.27, p < 0.001) and in five subscores. Single-parent households and drug-resistant epilepsy showed significant positive associations with pathological sleep among children with motor disabilities. For TD peers, parental unemployment and parental nationality were positively associated with pathological sleep. CONCLUSION: This population-based study robustly estimated the prevalence of sleep disorders in children with motor disabilities. Sleep disorders were significantly more frequent in children with motor disabilities, but at a lower frequency than previously reported.

An Open-Label Uncontrolled Trial of the Efficacy and Safety of a Hug with Singing and Rocking for Promotion of Relaxation in Pediatric Patients with Severe Motor and Intellectual Disabilities: Study Protocol.

Children with severe motor and intellectual disabilities (SMID) are continually exposed to stress due to their need to receive daily care. In particular, chronic physical and acute mental stress derived from daily medical care due to unstable health status are issues specific to SMID children. Therefore, it is important to approach these issues for the maintenance of their lives and quality of life. Seventeen children with a SMIDmedical care dependent group (SMID-MCDG) score of 25 or more will be enrolled in this study. Intervention by a hug while singing and rocking will be performed once a week for 24 weeks. The practitioner will sing, and slowly rock the child back and forth. Primary endpoint is high-frequency component of heart rate variability by frequency analysis. Secondary endpoints are low-frequency/high-frequency components of heart rate variability by frequency analysis, activity of salivary amylase, the incidence of adverse events, and changes in appearance. Frequency analysis of heart beat changes and salivary amylase activity are used as physiological indexes for assessing response to being held while singing and rocking. In this study, we will examine the efficacy and safety of hugging while singing and rocking as a practice of Ryouiku to promote relaxation in SMID-MCDG children.

Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances social adjustment.

BACKGROUND: Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with ε-sarcoglycan (DYT11)-positive myoclonus-dystonia. METHODS: Consecutive myoclonus-dystonia patients with ε-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. RESULTS: Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. CONCLUSIONS: GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.

Life story of university students and the adjustment of living with motor deficiency / Historia de vida de estudiantes universitarios y la (con)vivencia con la discapacidad motriz / A história de vida de estudantes universitários e a (con)vivência com a deficiência motora

Abstract Objective: To understand the life story of university students and the adjustment of living with motor deficiency. Method: A qualitative research, developed with eight university students with motor deficiency. Data collect was performed between October 2016 and March 2017. Thematic data analysis was used. Results: Two categories emerged: family as safe harbor and extra-family relationships: weaknesses and strengths. Family and friends were fundamental for facing disability, standing out for their support and affection. Friends have been encouraged to overcome the limitations and difficulties. Extra-family life was exposed to prejudice that resulted in fears and traumas. Conclusion: The impact of motor deficiency on daily life is the result of life experiences. Healthy family relationships, along with strong bonds of friendship, made the difficulties found in the daily life of these students smoother.

Resumen Objetivo: Comprender la historia de vida de los estudiantes universitarios y la convivencia con la discapacidad motriz. Método: Investigación de enfoque cualitativo, desarrollada con ocho estudiantes universitarios con discapacidad motriz. Recolección de datos realizada entre octubre de 2016 y marzo de 2017. Se utilizó el análisis temático de los datos. Resultados: Emergieron dos categorías: familia como puerto seguro y relaciones extrafamiliares: debilidades y fortalezas. La familia y los amigos fueron fundamentales para enfrentar la discapacidad, destacándose por el apoyo y el afecto. Los amigos se presentan como alentadores para superar las limitaciones y dificultades. La vida extrafamiliar fue expuesta a preconceptos que resultan en miedos y traumas. Conclusión: El impacto de la discapacidad motriz en el cotidiano es el resultado de las experiencias de vida. Las convivencias familiares sanas, junto a lazos fuertes de amistad, hacen que las dificultades encontradas en el cotidiano de estos estudiantes sean amenizadas.

Resumo Objetivo: Compreender a história de vida de estudantes universitários e a convivência com a deficiência motora. Método: Pesquisa de abordagem qualitativa, desenvolvida com oito estudantes universitários com deficiência motora. Coleta de dados realizada entre outubro de 2016 e março de 2017. Foi utilizada a análise temática dos dados. Resultados: Emergiram duas categorias: família como porto seguro e relacionamentos extrafamiliares: fraquezas e fortalezas. A família e os amigos foram fundamentais para o enfrentamento da deficiência, destacando-se pelo apoio e afeto. Os amigos apresentaram-se encorajadores para superar as limitações e dificuldades. A vida extrafamiliar foi exposta a preconceitos que resultaram em medos e traumas. Conclusão: O impacto da deficiência motora no cotidiano é resultante das experiências de vida. As convivências familiares saudáveis, junto com laços fortes de amizade, fizeram com que as dificuldades encontradas no cotidiano desses estudantes fossem amenizadas.

Multicenter, Open-Label, Randomized Controlled Trial of Warfarin and Edoxaban Tosilate Hydrate for the Treatment of Deep Vein Thrombosis in Persons with Severe Motor Intellectual Disabilities.

Sudden death in patients with severe motor and intellectual disabilities (SMID) is sometimes caused in part by pulmonary thromboembolism (PTE), and deep venous thrombosis (DVT) has drawn attention as a possible embolic source. Warfarin, which is a conventional therapeutic agent, is not easy to control appropriately, and daily management can be especially difficult in SMID patients. On the other hand, edoxaban tosilate hydrate, which has been newly approved for insurance coverage for the treatment of DVT, is not listed in the Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism and Deep Vein Thrombosis (DVT-PTE guidelines). The aim of this study is to evaluate the efficacy and safety of anticoagulation therapy (warfarin vs. edoxaban) in DVT treatment in SMID patients by means of an open-label, randomized controlled trial. The primary endpoint is the incidence of hemorrhagic events during 12 months of follow up.

Body Structure, Function, Activity, and Participation in 3- to 6-Year-Old Children Born Very Preterm: An ICF-Based Systematic Review and Meta-Analysis.

Background: The World Health Organization's International Classification of Functioning, Disability, and Health framework, Children and Youth Version (ICF-CY), provides a valuable method of conceptualizing the multidomain difficulties experienced by children born very preterm (VP). Reviews investigating motor outcomes at preschool age across ICF-CY domains are lacking. Purpose: The purpose of this review is to identify and compare motor outcomes of 3- to 6-year-old children born VP and children born full-term (FT) within the ICF-CY framework. Data Sources: Four electronic databases and reference lists of included and key articles were searched. Study Selection: Studies comparing motor outcomes of 3- to 6-year-old children born VP (<32 weeks' gestation or birth weight <1500 g) with peers born FT were included. Data Extraction: Two independent authors extracted data and completed quality assessments. Data Synthesis: Thirty-six studies were included. Activity motor performance of children born VP was consistently poorer compared with peers born FT: standardized mean difference (SMD) was -0.71 (95% CI = -0.80 to -0.61; 14 studies, 2056 participants). Furthermore, children born VP had higher relative risk (RR) of motor impairment (RR = 3.39; 95% CI = 2.68 to 4.27; 9 studies, 3466 participants). Body structure and function outcomes were largely unable to be pooled because assessment tools varied too widely. However, children born VP had higher RR of any neurological dysfunction (Touwen Neurological Examination) (RR = 4.55; 95% CI = 1.20 to 17.17; 3 studies, 1363 participants). There were no participation outcome data. Limitations: Limitations include the lack of consistent assessment tools used in VP follow-up at preschool age and the quality of the evidence. Conclusions: Children born VP experience significant motor impairment across ICF-CY activity and body structure and function domains at preschool age compared with peers born FT. Evidence investigating participation in VP preschool-age populations relative to children born at term is sparse, requiring further research.

Fatigue, not self-rated motor symptom severity, affects quality of life in functional motor disorders.

While fatigue is found to be an impairing symptom in functional motor disorders (FMD) in clinical practice, scientific evidence is lacking. We investigated fatigue severity and subtypes in FMD compared to organic neurological disease. Furthermore, the role of fatigue within FMD and its impact on quality of life and self-rated health were investigated. Data from 181 patients participating in the self-help on the internet for functional motor disorders, randomised Trial were included. Data from 217 neurological controls with neuromuscular disorders (NMD) originated from a historical cohort. Fatigue was measured using the checklist individual strength (CIS). Motor symptom severity, depression and anxiety were correlated to fatigue. For multivariable regression analyses, physical functioning and pain were additionally taken into account. Severe fatigue was, respectively, present in 78 and 53% of FMD and NMD patients (p < 0.001). FMD patients scored higher than NMD patients on all fatigue subdomains (p < 0.001). In the FMD group, fatigue subdomains were correlated to depression, anxiety and partly to motor symptom severity. Quality of life was negatively associated with fatigue [OR 0.93 (0.90-0.96), p < 0.001] and depression [OR 0.87 (0.81-0.93), p < 0.001], but not self-rated motor symptom severity. Self-rated health was negatively associated with fatigue [OR 0.92 (0.88-0.96), p < 0.001] and pain [OR 0.98 (0.97-0.99), p < 0.001]. Fatigue was found to be a prevalent problem in FMD, more so than in organic neurological disease. It significantly affected quality of life and self-rated health, while other factors such as motor symptom severity did not. Fatigue should be taken into account in clinical practice and treatment trials.

Medical Cannabis for Pediatric Moderate to Severe Complex Motor Disorders.

A complex motor disorder is a combination of various types of abnormal movements that are associated with impaired quality of life (QOL). Current therapeutic options are limited. We studied the efficacy, safety, and tolerability of medical cannabis in children with complex motor disorder. This pilot study was approved by the institutional ethics committee. Two products of cannabidiol (CBD) enriched 5% oil formulation of cannabis were compared: one with 0.25% δ-9-tetrahydrocannabinol (THC) 20:1 group, the other with 0.83% THC 6:1 group. Patients aged 1 to 17 years (n = 25) with complex motor disorder were enrolled. The assigned medication was administered for 5 months. Significant improvement in spasticity and dystonia, sleep difficulties, pain severity, and QOL was observed in the total study cohort, regardless of treatment assignment. Adverse effects were rare and included worsening of seizures in 2 patients, behavioral changes in 2 and somnolence in 1.

Early fine motor impairment and behavioral dysfunction in (Thy-1)-h[A30P] alpha-synuclein mice.

Introduction: Intraneuronal inclusions of alpha-synuclein are commonly found in the brain of patients with Parkinson's disease and other α-synucleinopathies. The correlation between alpha-synuclein pathology and symptoms has been studied in various animal models. In (Thy-1)-h[A30P] alpha-synuclein transgenic mice, behavioral and motor abnormalities were reported from 12 and 15 months, respectively. The aim of this study was to investigate whether these mice also display symptoms at earlier time points. Methods: We analyzed gait deficits, locomotion, and behavioral profiles in (Thy-1)-h[A30P] alpha-synuclein and control mice at 2, 8, and 11 months of age. In addition, inflammatory markers, levels of alpha-synuclein oligomers, and tyrosine hydroxylase reactivity were studied. Results: Already at 2 months of age, transgenic mice displayed fine motor impairments in the challenging beam test that progressively increased up to 11 months of age. At 8 months, transgenic mice showed a decreased general activity with increased risk-taking behavior in the multivariate concentric square field test. Neuropathological analyses of 8- and 11-month-old mice revealed accumulation of oligomeric alpha-synuclein in neuronal cell bodies. In addition, a decreased presence of tyrosine hydroxylase suggests a dysregulation of the dopaminergic system in the transgenic mice, which in turn may explain some of the motor impairments observed in this mouse model. Conclusions: Taken together, our results show that the (Thy-1)-h[A30P] alpha-synuclein transgenic mouse model displays early Parkinson's disease-related symptoms with a concomitant downregulation of the dopaminergic system. Thus, this should be an appropriate model to study early phenotypes of alpha-synucleinopathies.