Deep Brain Stimulation in childhood-onset dystonia due to brain pathology. A long-term study.

BACKGROUND: Pallidal Deep Brain Stimulation (DBS) is an established treatment option for isolated, inherited or idiopathic dystonia, however data on its safety and efficacy in other forms of dystonia are more limited. OBJECTIVES: Retrospective analysis of motor and non-motor outcomes in pediatric onset refractory dystonia due to static or progressive brain disorders in a cohort of patients with a DBS treatment duration ≥12 months. METHODS: Multidisciplinary assessments including standardised scales/tests of motor function, pain, quality of life, cognition and language were carried out before implantation and longitudinally afterwards. RESULTS: 9 patients were included, 7 had cerebral palsy. Mean age at implantation was 209 months ± 156, mean treatment duration 84 ± 37 months. DBS was well tolerated and positively affected both motor and non-motor functions. In particular, statistically significant improvements were documented in Burke-Fahn-Marsden Scale scores (- 19.9% p 0.01031) at 12 months and in long-term quality of life (+28.6%, p 0.0292). CONCLUSIONS: DBS may be a useful treatment option in generalized dystonia associated with brain pathology. Even when the motor benefits are limited, improvements in quality of life and non-motor functions, or the possible prevention of serious dystonia-related complications, may have a significant impact on overall clinical status.

Functional and Structural Brain Damage in Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder caused by a GAA repeat expansion in the FXN gene. There is still no cure or quantitative biomarkers reliaby correlating with the progression rate and disease severity. Investigation of functional and structural alterations characterizing white (WM) and gray matter (GM) in FRDA are needed prerequisite to monitor progression and response to treatment. Here we report the results of a multimodal cross-sectional MRI study of FRDA including Voxel-Based Morphometry (VBM), diffusion-tensor imaging (DTI), functional MRI (fMRI), and a correlation analysis with clinical severity scores. Twenty-one early-onset FRDA patients and 18 age-matched healthy controls (HCs) were imaged at 3T. All patients underwent a complete cognitive and clinical assessment with ataxia scales. VBM analysis showed GM volume reduction in FRDA compared to HCs bilaterally in lobules V, VI, VIII (L>R), as well as in the crus of cerebellum, posterior lobe of the vermis, in the flocculi and in the left tonsil. Voxel-wise DTI analysis showed a diffuse fractional anisotropy reduction and mean, radial, axial (AD) diffusivity increase in both infratentorial and supratentorial WM. ROI-based analysis confirmed the results showing differences of the same DTI metrics in cortico-spinal-tracts, forceps major, corpus callosum, posterior thalamic radiations, cerebellar penduncles. Additionally, we observed increased AD in superior (SCP) and middle cerebellar peduncles. The WM findings correlated with age at onset (AAO), short-allelle GAA, and disease severity. The intragroup analysis of fMRI data from right-handed 14 FRDA and 15 HCs showed similar findings in both groups, including activation in M1, insula and superior cerebellar hemisphere (lobules V-VIII). Significant differences emerged only during the non-dominant hand movement, with HCs showing a stronger activation in the left superior cerebellar hemisphere compared to FRDA. Significant correlations were found between AAO and the fMRI activation in cerebellar anterior and posterior lobes, insula and temporal lobe. Our multimodal neuroimaging protocol suggests that MRI is a useful tool to document the extension of the neurological impairment in FRDA.

Electrical status epilepticus during sleep in Mowat-Wilson syndrome.

AIM: Mowat-Wilson Syndrome (MWS) is a genetic rare disease. Epilepsy is present in 70-75% of Patients and an age-dependent electroclinical pattern has been described. Up to date, there are studies with overnight sleep EEGs, probably because of the severe intellectual disability (ID) and hyperactivity of these Patients. Our purpose was to verify the hypothesis that MWS Patients might have electrical status epilepticus in slow wave sleep (ESES pattern). METHODS: A retrospective analysis of anamnestic and electrographic data was performed on 7 consecutive MWS Patients followed between 2007 and 2016. Only Patients with at least one overnight sleep EEG were included in the study. RESULTS: Five out of 7 Patients had overnight sleep EEG studies and were included in this study. All of them had an anterior ESES pattern with spike-and-wave index>85%. The architecture of sleep was abnormal. An ESES related regression of cognitive and motor functions with impact on daily activities (ESES-related syndrome) was demonstrated in 3 out of 5 (60%) Patients. In two Patients marked improvement of cognitive and motor performances was observed when the epileptiform activity during sleep was successfully controlled or it was spontaneously reduced. CONCLUSIONS: The clinical significance of the ESES pattern is hard to assess in MWS Patients due to severe ID, but changing in behaviour or in motor and cognitive functions should mandate sleep EEG investigation and, if ESES is present, an appropriate treatment should be tried. Furthermore, overnight sleep EEG recordings, if regularly performed in the follow up, might help to understand if ESES pattern hampers the cognitive and communicative profile in MWS.

Implementation of an ICF-based project/program in a pediatric neuro-rehabiltation hospital: follow-up evaluation by stakeholders.

PURPOSE: We follow-up on the experience started 3 years ago with the introduction in a pediatric neurorehabilitation hospital of an ICF-CY based form for rehabilitation projecting/programming, by probing the impact that this process had on stakeholders to establish its long term cost/benefit ratio. METHODS: Two hundred and two rehabilitation projects/programs forms for children with various health conditions admitted for intensive rehabilitation were completed in 36 months. Assessment was carried out by (i) evaluating the compliance with the new process design, (ii) assessing the resource consumption and (iii) appraising the perceived change in terms of added quality. A structured questionnaire built by clustering statements about added quality determinants in rehabilitation expressed by team members and families, explored the perceived change in the rehabilitation process associated with the introduced form with a 0-5 Likert-type scaling. RESULTS: (i) Most projects/programs forms were filled appropriately, allowing the link of functional problems, objectives, rehabilitation activities, and outcome indicators. (ii) No additional resources were needed to implement the process. (iii) Questionnaire scores were 3.25 SD 0.2 for team members and 4.05 SD 0.2 for families, showing moderate to relevant appreciation in particular by families. CONCLUSIONS: The results confirmed the feasibility of ICF implementation in the clinical setting. ICF based project/program was appreciated by both team members and caregivers as adding quality to the rehabilitation process. These results further encourage the implementation of ICF based tools in the clinical sector.

The dystonic child treated with deep brain stimulation: ICF reading of a high-tech approach.

PURPOSE: The available tools used to describe childhood dystonia tend to offer a monodimensional view of the person functioning, which may overlook significant changes induced by treatment. We applied the International Classification of Functioning, Disability and Health (ICF) perspective to the description of the clinical picture of a dystonic child treated with deep brain stimulation (DBS) to get a more global representation of the treatment effect. METHOD: An 8-year-old child with secondary dystonia was selected within the institutional program for advanced treatment of pediatric dystonia as a candidate for bilateral implantation of electrodes into globus pallidus and chronic stimulation. The International Classification of Functioning, Disability and Health -children and youth (ICF-CY) based project and program format was used by the rehabilitation team to define the clinical picture, rehabilitation objectives, and to verify the outcome. RESULTS: The rehabilitation project and program included 39 ICF categories: 14 body functions, two body structures, 18 activities and participation, and five environment. On such basis we defined the individualized specific rehabilitation objectives and we checked for clinical changes after DBS. CONCLUSION: The ICF-CY format provides a complete and balanced profile of functioning in secondary dystonia treated with DBS and it could offer a novel perspective for outcome evaluation.

Projecting and programming rehabilitation based on ICF-CY format in a neuropediatric hospital unit.

OBJECTIVE: To follow-up the impact of a format based upon the International Classification of Functioning Disability and Health, version for children and youth (ICF-CY) as a roadmap for in-hospital pediatric neuro-rehabilitation. DESIGN: Longitudinal study in a single Centre testing with impact assessment. SUBJECTS/PATIENTS: The team members of a tertiary care pediatric neuro-rehabilitation unit approaching 88 consecutive patients with various physical and/or neurological conditions. METHODS: A revised version of the protocol ICF-CY based format for rehabilitation projecting and programming was applied for 24 months. Impact on the rehabilitation team was assessed with an ad hoc questionnaire. RESULTS: Fifteen questionnaires were returned, all of them reporting strongly positive judgements. Time constraint was no longer considered the main problem, probably because of a learning effect. Ongoing utilization reduced the time needed and the problems perceived in completing the task. CONCLUSION: This application confirmed that ICF contribute to improve the quality of interdisciplinary work and to share the rehabilitation process between team members and family. Indeed ICF-CY works efficiently as a roadmap for in-hospital pediatric neuro-rehabilitation. Its implementation results in perceived improvements in the process, ongoing utilization reduces the time needed and the problems encountered in completing the task.

Scale for evaluation of movement disorders in the first three years of life.

Most rating scales to assess movement disorders in children were mainly designed for adult patients, and are limited to a single type of disorder. A new scale for developmental age, the Movement Disorder-Childhood Rating Scale, was recently designed and validated for children and adolescents aged 4-18 years. We introduce a new version of this scale, the Movement Disorder-Childhood Rating Scale 0-3, suitable for application in children aged <4 years. The scale was tested for reliability and consistency in 40 children (aged 0.3-3.6 years) with different types of movement disorders. The results indicate high interrater agreement on each item, and a high degree of internal consistency on several proposed items. The scale can be used to assess and monitor young children with movement disorders during specific treatments.

Movement disorder-childhood rating scale: reliability and validity.

A new scale for children and adolescents aged 4-18 years, called the Movement Disorder Childhood Rating Scale, was designed to: (1) describe clinical features of different types of movement disorders; (2) evaluate the intensity of movement disorders in different body regions at rest and during specific tasks; and (3) assess the influence of movement disorders on motor function and daily living activities. The scale is divided into 2 parts: Part I for general assessment, and Part II for movement-disorder severity. It includes a 20-minute standardized video protocol of all items. The scale was applied to 61 patients with different types of movement disorder, and was independently scored by 3 observers. Reliability, construct validity, and consistency indexes are reported. High interrater agreement on each item, and a high degree of internal consistency on several proposed items, were evident.

Brain representation of active and passive hand movements in children.

Several functional neuroimaging studies have been performed exploring the sensorimotor function in children with neurologic disorders. However, little is known about normal activation patterns of the sensorimotor system at a young age. We explored brain representation of active and passive hand movements in school-age children and young adults. Nine healthy children (7-15 y) and six adults were studied. Functional magnetic resonance imaging (fMRI) data were acquired on a 1.5-T scanner in block designs. Active movement consisted of repetitive opening and closing of the hand; passive movement consisted of the same movement performed by the examiner. Both hands were assessed separately. The pattern of brain activation (contralateral primary sensorimotor cortex (SMC), ipsilateral cerebellum, supplementary motor area (SMA), and lateral premotor cortex (PMC) was generally more widespread in the adult group, suggesting a developmental course in the organization of both motor and sensory cortex. Surprisingly, no difference was generally detected when contrasting active versus passive tasks. Our results suggest that active and passive hand movements can be used for the exploration of the sensorimotor system in children. Passive and active tasks confirmed to be tightly coupled, thus supporting the idea of the former as a helpful performance-independent paradigm in the study of brain reorganization and presurgical assessment.