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Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single-gene disorders is under-characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP.We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non-cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline.We included 50 probands in this analysis (20 females, 30 males). Twenty-four had cryptogenic CP, 20 had non-cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic-ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty-six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST-related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non-cryptogenic CP (n = 3/20) had a Mendelian disorder on WES.WES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors.

Despite extensive literature showing damages in the sensorimotor projection fibers of children with hemiplegic cerebral palsy (HCP), little is known about how these damages affect the global brain network. In this study, we assess the relationship between the structural integrity of sensorimotor projection fibers and the integrity of intergyral association white matter connections in children with HCP. Diffusion tensor imaging was performed in 10 children with HCP and 16 typically developing children. We estimated the regional and global white-matter connectivity using a region-of-interest (ROI)-based approach and a whole-brain gyrus-based parcellation method. Using the ROI-based approach, we tracked the spinothalamic (STh), thalamocortical (ThC), corticospinal (CST), and sensorimotor U- (SMU) fibers. Using the whole-brain parcellation method, we tracked the short-, middle-, and long-range association fibers. We observed for the more affected hemisphere of children with HCP: (i) an increase in axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) for the STh and ThC fibers; (ii) a decrease in fractional anisotropy (FA) and an increase in MD and RD for the CST and SMU fibers; in (iii) a decrease in FA and an increase in AD, MD, and RD for the middle- and long-range association fibers; and (iv) an association between the integrity of sensorimotor projection and intergyral association fibers. Our findings indicate that altered structural integrity of the sensorimotor projection fibers disorganizes the intergyral association white matter connections among local and distant regions in children with HCP.

Niemann-Pick disease type C is a rare progressive genetic disorder that leads to the abnormal accumulation of lipids within various tissues of the body, including brain tissue and liver. There is a rapid progression of the disease, resulting in severe disability in only a few years after the first symptoms, and survival is not much longer. Spasticity, dystonia, and chronic pain are common findings that severely impact quality of life in these patients. Analgesic management with traditional pain medications is not always effective, and the risk for secondary effects in medically complex patients is high. Liver function is also a limiting factor in these patients. This is a case report of a boy with advanced Niemann-Pick disease type C with developmental regression, cataplexia, and seizures. His severe spasticity made positioning and care difficult, and intense pain required multiple hospitalizations. He had unsuccessfully trialed multiple drugs. An intrathecal baclofen pump was placed without surgical complications and resulted in positive clinical effects. Baclofen pumps have classically been used for spasticity management in adults and children with nonprogressive diseases such as cerebral palsy or spinal cord injury with relatively long life expectancies. In adults, they have been used in patients with multiple sclerosis; however, use in pediatric neurodegenerative diseases has scarcely been reported. The use of intrathecal baclofen in palliative settings might provide an additional resource to provide comfort and quality of life for children with neurodegenerative diseases not only at end-of-life stages but also earlier on.

Functional neuroimaging studies argue that sensory deficits in hemiplegic cerebral palsy (HCP) are related to deviant somatosensory processing in the ipsilesional primary somatosensory cortex (S1). A separate body of structural neuroimaging literature argues that these deficits are due to structural damage of the ascending sensory tracts (AST). The relationship between the functional and structural integrity of the somatosensory system and the sensory performance is largely unknown in HCP. To address this relationship, we combined findings from magnetoencephalography (MEG) and probabilistic diffusion tractography (PDT) in 10 children with HCP and 13 typically developing (TD) children. With MEG, we mapped the functionally active regions in the contralateral S1 during tactile stimulation of the thumb, middle, and little fingers of both hands. Using these MEG-defined functional active regions as regions of interest for PDT, we estimated the diffusion parameters of the AST. Somatosensory function was assessed via two-point discrimination tests. Our MEG data showed: (i) an abnormal somatotopic organization in all children with HCP in either one or both of their hemispheres; (ii) longer Euclidean distances between the digit maps in the S1 of children with HCP compared to TD children; (iii) suppressed gamma responses at early latencies for both hemispheres of children with HCP; and (iv) a positive correlation between the Euclidean distances and the sensory tests for the more affected hemisphere of children with HCP. Our MEG-guided PDT data showed: (i) higher mean and radian diffusivity of the AST in children with HCP; (ii) a positive correlation between the axial diffusivity of the AST with the sensory tests for the more affected hemisphere; and (iii) a negative correlation between the gamma power change and the AD of the AST for the MA hemisphere. Our findings associate for the first time bilateral cortical functional reorganization in the S1 of HCP children with abnormalities in the structural integrity of the AST, and correlate these abnormalities with behaviorally-assessed sensory deficits., Graphical abstract Image 1, Highlights • Hemiplegic CP exhibits abnormal somatotopy in one or both hemispheres. • Hemiplegic CP shows longer distances between digit somatosensory representations. • Suppressed gamma somatosensory responses are seen in hemiplegic CP. • Altered somatosensory organization is associated with deficient sensory fibers. • Injury of sensory fibers correlates with the severity of sensory deficits.

Improved treatments and rehabilitation for cerebral palsy (CP) have led to an increased number of children with CP surviving into adulthood. Adults with CP show an increased prevalence of pain, fatigue, and musculoskeletal dysfunction, leading to a decrease in ambulatory function. Recent work has demonstrated the potential benefits of intensive task-specific gait training, including the use of robotic-driven gait orthoses, on motor recovery in children with CP. In contrast, reports of interventions aimed at improving motor function in adults with CP are lacking. This case study reports on the outcomes of a 6-week intervention of robotic-assisted gait training administered to a 52-year-old woman with right hemiplegia attributable to CP. Improvements were noted in balance, walking speed, and time to negotiate stairs at posttraining and follow-up. Gait analysis showed an increase in step length and a reduction in the period of double support. In conclusion, robotic-assisted gait training may be beneficial in enhancing locomotor function in adults with CP.

Purpose Therapist-assisted videotaped sessions have been used to augment physical examinations in the evaluation of hand and arm function in patients with spastic hemiplegia. The purpose of this study was to assess the interobserver and intraobserver reliability of standardized videotaped examinations in the evaluation and functional classification of these patients. Methods Three examiners reviewed standardized videotaped examinations of 10 adolescents with spastic hemiplegia on 2 separate occasions. All 10 patients were under consideration for surgical intervention for their upper-extremity dysfunction. Videotapes were used to assess upper-extremity range of motion, finger and thumb deformity, and reach, pinch, and grip function. Upper-extremity function was graded according to the House and Mowery classification systems. Interobserver and intraobserver reliabilities were measured with the kappa coefficient. Results Range of motion, deformity, and upper-extremity functional strategy assessment showed slight to excellent interobserver reliability and good to almost perfect intraobserver reliability. Interobserver and intraobserver reliability of the consolidated House classification system was more reliable than the Mowery or standard House classification systems. Conclusions Evaluations of standardized videotaped examinations in patients with hemiplegia were reliable between and among observers. Such therapist-assisted videotaped evaluations may provide useful data for clinical decision-making and multicenter outcomes studies in patients with upper-extremity involvement with spastic hemiplegia.

The clinical management of children with Cerebral Palsy (CP) relies upon periodic assessments of changes in the severity of gait deviations in response to clinical interventions. Current clinical practice is limited to sporadic assessments in a clinical environment and hence it is limited in its ability to estimate the impact of CP-related gait deviations in real-life conditions. Frequent home-based quantitative assessments of the severity of gait deviations would be extremely useful in scheduling clinical visits and gathering feedback about the effectiveness of intervention strategies. The use of a wearable system would allow clinicians to gather information about the severity of gait deviations in the home setting. In this paper, we present ActiveGait, a novel sensorized shoe-based system for monitoring gait deviations. The ActiveGait system was used to gather data, under supervised and unsupervised conditions, from a group of 11 children with various levels of CP-related gait deviation severities. We present a methodology to derive severity measures based on features extracted from Center of Pressure (CoP) trajectories. Results show that a Random Forest classifier is able to estimate severity scores based on the Edinburgh Visual Scale with a level of accuracy >80% adequate for clinical use.

Recent work has examined the feasibility of robotic-assisted gait training in pediatric patients, including children with cerebral palsy (CP). Herein we present a case series describing clinical outcomes in four children with CP who underwent gait training using a robotic driven gait orthosis (DGO) (Pediatric Lokomat©). Children had a diagnosis of spastic diplegia due to CP. They were paired based on functional abilities and observed gait characteristics. Two children had a GMFCS of III and showed excessive ankle plantarflexion during stance. The other two children had a GMFCS of II and displayed a crouch gait pattern. Each subject participated in a 6-week intervention of robotic-assisted gait training that involved three 30-minute sessions per week. Pre-and post-training evaluations were performed including clinical tests of standing and walking function, walking speed, and walking endurance. Clinical gait analysis was also performed using a motion capture system to assess changes in gait mechanics. All subjects showed an improvement in locomotor function. For lower functioning children, this may be mediated by improved trunk control. The use of augmented feedback was associated with larger. However, these results have to be considered with caution because of the limited sample size of the study.