Growth patterns in children and adolescents with cerebral palsy from Argentina and Germany.

To analyze growth patterns of children with CP between countries; to examine differences in growth; and to assess the fit of growth charts. Cross-sectional study in children with CP from 2 to 19 years old, 399 from Argentina and 400 from Germany. Growth measures were converted into z-scores and compared to WHO reference and US CP growth charts. Generalized Linear Model was used to analyze the growth expressed as mean z-scores. 799 children. Mean age 9 years (± 4). Compared to the WHO reference, the decrease in Height z-scores (HAZ) with age in Argentina (- 0.144/year) was double that in Germany (- 0.073/year). For children in GMFCS IV-V, BMI z-scores (BMIZ) decreased with age (- 0.102/year). Using the US CP charts, both countries showed decreasing HAZ with age, in Argentina (- 0.066/year) and in Germany (- 0.032/year). BMIZ increased more among children with feeding tubes (0.062/year), similar in both countries. Argentinian children with oral feeding decrease their Weight z-score (WAZ) by - 0.553 compared to their peers. With WHO charts BMIZ presented an excellent fit for GMFCS I-III. HAZ presents a poor fit to growth references. BMIZ and WAZ presented a good fit to US CP Charts. Growth differences due to ethnicity also act in children with CP, and are related to motor impairment, age and feeding modality, possibly reflecting differences in environment or health care.

Neurodevelopmental disorder with dystonia due to SOX6 mutations.

BACKGROUND: Mutations in SOX6 have recently been recognized as a new molecular cause of neurodevelopmental disorders characterized by intellectual disability, behavioral changes, and nonspecific facial and digital skeletal abnormalities. To date, <25 cases have been reported in the literature. METHODS AND FINDINGS: Here we report a new case of SOX6-associated neurodegeneration and expand the phenotype to include ceratoconus. The clinical picture consisted of early onset mildly reduced intellectual function, facial asymmetry, and dystonic tremor of hands and neck, substantially improved by levodopa. Skeletal abnormalities included scoliosis and hypertrophy of the mandibular coronoid process. A heterozygous de novo loss-of-function variant in SOX6 (c.277 C>T. p.Arg93*) was molecularly confirmed which leads to truncation of the SOX6 protein in its N-terminus, upstream of any known functional domain. CONCLUSION: SOX6-associated neurodevelopmental delayis ultrarare with less than 25 cases described in the literature. We report a new case who presented with early-onset mildly reduced intellectual function, facial asymmetry, skeletal abnormalities and dystonic tremor of hands and neck, substantially improved by levodopa. Given the therapeutic implications, SOX6 mutations should be considered in patients with complex dystonia parkinsonism.

Growth in infants, children and adolescents with unilateral and bilateral cerebral palsy.

To compare growth patterns during infancy, childhood and adolescence in children with unilateral and bilateral cerebral palsy (CP) phenotype and to assess the association with gross motor impairment, dysphagia and gestational age. We retrospectively studied 389 children with CP from a single center population in Munich, Germany. 1536 measurements of height and weight were tabulated and z-scored from 6 to 180 months of age. Generalized linear mixed model were used to examine the association between growth, GMFCS, dysphagia and gestational age by CP phenotype. Children with unilateral CP tend to grow similarly to their typically developed peers. In the main effect model, bilateral CP phenotype was significantly associated with decreased mean z-scores for height (ß [95% CI] - 0.953 [- 1.145, - 0.761], p < 0.001), weight (- 0.999 [- 1.176, - 0.807], p < 0.001) and BMI (ß [95% CI] - 0.437 [- 0.799, - 0.075]), compared with unilateral CP phenotype. This association remained significant in the interaction models. The height-for-age z-scores, weight-for-age decreased z-scores and BMI-for-age z-scores of children with bilateral CP and GMFCS III-V or dysphagia decreased more significantly than those of children with unilateral CP. Preterm birth was not significantly associated with decreased growth in height, weight and BMI. Reduced growth in children with bilateral CP was strongly associated with moderate to severe impairment in gross motor function (GMFCS III-V) and dysphagia.

Quantitative Motion Measurements Based on Markerless 3D Full-Body Tracking in Children with SMA Highly Correlate with Standardized Motor Assessments.

BACKGROUND: Spinal Muscular Atrophy (SMA) is the most common neurodegenerative disease in childhood. New therapeutic interventions have been developed to interrupt rapid motor deterioration. The current standard of clinical evaluation for severely weak infants is the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), originally developed for SMA type 1. This test however, remains subjective and requires extensive training to be performed reliably. OBJECTIVE: Proof of principle of the motion tracking method for capturing complex movement patterns in ten children with SMA. METHODS: We have developed a system for tracking full-body motion in infants (KineMAT) using a commercially available, low-cost RGB-depth sensor. Ten patients with SMA (2-46 months of age; CHOP INTEND score 10-50) were recorded for 2 minutes during unperturbed spontaneous whole-body activity. Five predefined motion parameters representing 56 degrees of freedom of upper, lower extremities and trunk joints were correlated with CHOP INTEND scores using Pearson product momentum correlation (r). Test-retest analysis in two patients used descriptive statistics. RESULTS: 4/5 preselected motion parameters highly correlated with CHOP INTEND: 1. Standard deviation of joint angles (r = 0.959, test-retest range 1.3-1.9%), 2. Standard deviation of joint position (r = 0.933, test-retest range 2.9%), 3. Absolute distance of hand/foot travelled (r = 0.937, test-retest range 6-10.5%), 4. Absolute distance of hand/foot travelled against gravity (r = 0.923; test-retest range 4.8-8.5%). CONCLUSIONS: Markerless whole-body motion capture using the KineMAT proved to objectively capture motor performance in infants and children with SMA across different severity and ages.

Estado nutricional de niños y niñas con parálisis cerebral que asisten a centros de rehabilitación.

OBJETIVO: Describir el estado nutricional de niños con parálisis cerebral (PC) en centros de rehabilitación y terapéuticos de Argentina, y analizar el riesgo de desnutrición en relación su nivel según el sistema de la clasificación de la función motora gruesa (GMFCS). MÉTODO: Este fue un estudio transversal con datos recolectados de 321 niños (196 varones, 125 mujeres) con PC de 2 a 19 años (edad media 9 años 3 meses, DE 4 años) de 17 centros de rehabilitación y terapéuticos en cinco provincias argentinas. El estado nutricional se definió con puntajes z según peso, talla e índice de masa corporal para la edad utilizando patrones de crecimiento de la Organización Mundial de la Salud. Se utilizó Odds ratio para evaluar la asociación entre el nivel GMFCS y el estado nutricional. RESULTADOS: De los niños con PC estudiados, 52.4% tenían nivel IV y V de GMFCS. En cuanto al estado nutricional, 41,7% eran normales, 19,0% tenían desnutrición moderada, 33,9% desnutrición severa, 2,5 % sobrepeso, y 2,8% obesidad. En comparación con los niños con niveles I-III de GMFCS, los niños con niveles IV y V de GMFCS presentaron 4 veces más probabilidades de presentar desnutrición moderada y 14 veces más probabilidades de tener desnutrición severa. INTERPRETACIÓN: Existe una alta prevalencia de desnutrición asociada a la PC (niveles IV y V de GMFCS) entre niños de centros de rehabilitación y terapéuticos en Argentina. El riesgo de desnutrición severa aumenta cuando aumenta el compromiso motor.

Childhood Arterial Ischaemic Stroke: Clinical Presentation, Risk Factors and Management.

Childhood arterial ischaemic stroke (AIS) is a rare, but potentially life-threatening event which requires early diagnosis and adequate treatment. The reported significant time delay to childhood AIS diagnosis may be associated with low awareness, the more nonspecific clinical presentation as well as difficult clinical differentiation to more common "stroke mimics" and a less established "acute care structure" with delayed access to proper neuroimaging. Compared with adult stroke care, experiences with acute reperfusion therapies like thrombolysis and mechanical thrombectomy are promising but limited and not based on clinical trials. The etiological work-up is absolutely essential, as the child's individual risk profile determines acute management, secondary prevention, risk of recurrence and outcome. Follow-up care should be organized in a multidisciplinary setting covering all bio-psycho-social aspects to achieve the best integration of the child into its educational, later professional and social environments.

Successful mechanical thrombectomy in a three-year-old boy with cardioembolic occlusion of both the basilar artery and the left middle cerebral artery.

BACKGROUND: Paediatric stroke is a potentially life-threatening emergency and requires immediate treatment to improve clinical outcome. In contrast to adult treatment recommendations, little is known about safety and efficacy of thrombolysis and mechanical thrombectomy in children. CASE DESCRIPTION AND CONCLUSION: We report on a three-year-old boy with a cardioembolic intracranial two-vessel occlusion and successful therapy with thrombolysis and mechanical thrombectomy. Furthermore, this case emphasizes the need of standardized protocols for acute management of paediatric stroke.

Patient-specific determinants of responsiveness to robot-enhanced treadmill therapy in children and adolescents with cerebral palsy.

AIM: The aim of the study was to evaluate patient-specific determinants of responsiveness to robot-enhanced repetitive treadmill therapy (ROBERT) in patients with early-developed movement disorders. METHOD: Patients were treated over 12 sessions during a 3-week period. Gross Motor Function Measure-66 (GMFM-66) scores 1 day before ROBERT were compared with scores recorded 1 day after ROBERT. The association of GMFM-66 baseline score, age, sex, aetiology, and add-on botulinum toxin therapy to response to treatment was assessed. RESULTS: Eighty-three patients aged between 4 and 18 years (48 males, 35 females; mean age 10y 8mo, SD 6y 1mo; Gross Motor Function Classification System level I [n=12], II [n=21], III [n=35], IV [n=10], and V [n=1]) were each treated for a total of 7.2 (SD 1.9) treadmill walking hours. Aetiology was bilateral spastic cerebral palsy (BS-CP; n=69), unilateral CP (n=3), ataxic CP (n=3), hereditary spastic paraparesis (n=6), and genetic syndrome including spasticity (n=2). Meaningful improvements were observed in GMFM-66 (+2.5; 95% CI 2.0-3.0), GMFM-D (+5.2; 95% CI 3.6-6.8), and GMFM-E (+4.0; 95% CI 2.8-5.3). There was a high inter-individual variability in treatment response. After multivariable adjustment, the improvements in GMFM-66 and GMFM-E scores were positively associated with the GMFM-66 baseline score. The effect on GMFM-D improvement was inversely associated with age. INTERPRETATION: Gross motor abilities at baseline and age were identified as relevant determinants for the high degree of interpersonal variability in response to ROBERT.

Self-reported neck pain is associated with migraine but not with tension-type headache in adolescents.

AIM: The aim of the present analysis is to confirm or refute the association of neck pain to migraine or tension-type headache and to assess whether this association is independent of other risk factors for headache. METHODS: Secondary school students were invited to complete a questionnaire on headache and lifestyle factors in a cross-sectional study. Neck pain was assessed via (a) a screening question concerning neck pain and (b) denoting affected areas in schematic drawings of the human body. RESULTS: Absolute increment in prevalence of headache with pain in the shoulder-neck region was between 7.5% and 9.6%. Gender, grade, stress and lifestyle factors were assessed as potential confounding factors. Nearly all factors were associated with shoulder-neck pain and most with headache. After adjustment for confounders, the association of neck pain with headache was almost completely confined to migraine (OR 2.39; 95% CI 1.48-3.85) and migraine + tension-type headache (OR 2.12; 95% CI 1.50-2.99), whereas the association with isolated tension-type headache was negligible (OR 1.22, 95% CI 0.87-1.69). CONCLUSION: Neck pain is associated with migraine but not with tension-type headache. A possible link between migraine and neck pain may be the cervico-trigeminal convergence of neck and meningeal sensory afferents or a disturbed descending inhibition in migraine.

Early infantile sensory-motor neuropathy with late onset respiratory distress.

Children with spinal muscular atrophy with respiratory distress (SMARD1) usually present within their first year of life, with respiratory failure due to diaphragmatic paralysis and progressive distal limb weakness. We present a child with a confirmed compound heterozygous IGHMBP2 mutation c.[676G>T];[2083A>T] in whom severe sensory-motor neuropathy preceded diaphragmatic paralysis by almost 3years. Autonomic system involvement with neurogenic bladder and urine retention were found at 3years. In summary, our patient highlights the broad spectrum of phenotypes observed in SMARD1. Currently, no prediction of phenotype according to genotype is possible, suggesting that yet unknown factors cause the observed phenotypic variation. Even in the absence of obvious diaphragmatic weakness, SMARD1 should be considered in severe infantile onset neuropathies. High throughput techniques, such as next generation sequencing, will possibly offer a useful approach in the heterogeneous group of inherited neuropathies.

Primary headache in children and adolescents: update on pharmacotherapy of migraine and tension-type headache.

Primary headache disorders are frequently encountered in the pediatric population. The therapeutic approach consists of a multimodal program, including lifestyle modification, psychotherapeutic intervention, pharmacotherapy, and complementary measures. This systematic review focuses on the pharmacotherapy of pediatric migraine and tension-type headache (TTH). In addition to the general treatment principles, the results of 33 clinical reports published on the topic since 2008 are outlined in detail. Furthermore, a tabular summary of previously investigated agents not studied since 2008 is given, as is an overview of promising pharmacologic approaches so far only evaluated in adults. A variety of pharmacologic options is available, but high-quality evidence is limited to single agents. At this time, approval is restricted to four triptans and flupirtine for the symptomatic treatment of pediatric acute migraine and TTH, respectively. No agent has been approved for the prevention of pediatric primary headaches. This review does not grade the drugs hierarchically because the complex profiles of many agents differ only slightly or even overlap. However, a detailed expert opinion is provided. On the basis of the outlined facts, the team of physician, patient, and parents has to decide on the most appropriate regimen for the individual situation in the sense of personalized medicine.

Mirror movements in healthy humans across the lifespan: effects of development and ageing.

AIM: mirror movements are a transient phenomenon during childhood, which decrease in intensity with motor development. An increasing inhibitory competence resulting in the ability of movement lateralization is thought to be the underlying mechanism. We aimed to quantify unintended mirror movements systematically across the lifespan and to investigate the influences of age, sex, handedness, and task frequency. METHOD: a total of 236 participants (127 females, 109 males; 216 right-handed, 20 left-handed; age range 3-96y, median 25y 8mo) first performed four clinical routine tests while mirror movements were rated by the observer. They were then asked to hold a force transducer in each hand between the thumb and index finger and to perform oscillatory grip force changes in one hand, while the other hand had to prevent the force transducer from dropping. RESULTS: age showed a strong nonlinear effect on the mirror-movement ratio (the amplitude ratio of the mirror and active hand, adjusted by the respective maximum grip force). Initially, there was a steep decline in the mirror-movement ratio during childhood and adolescence, followed by a gradual rise during adulthood. Males had lower mirror-movement ratios than females. The high-frequency condition triggered lower mirror-movement ratios. No significant differences of mirror movements between dominant and non-dominant hand, or left- and right-handed participants, were found. INTERPRETATION: this study provides, for the first time to our knowledge, normative values of mirror movements across the lifespan that can aid differentiation between physiological and pathological mirror movements.