Applicability and clinical utility of the German rivermead post-concussion symptoms questionnaire in proxies of children after traumatic brain injury: an instrument validation study.

BACKGROUND: The German Rivermead Post-Concussion Symptoms Questionnaire (RPQ) can be used to assess post-concussion symptoms (PCS) after traumatic brain injury (TBI) in adults, adolescents, and children. METHODS: In this study, we examined the psychometric properties of the German RPQ proxy version (N = 146) for children (8-12 years) after TBI at the item, total and scale score level. Construct validity was analyzed using rank correlations with the proxy-assessed Post-Concussion Symptoms Inventory (PCSI-P), the Patient Health Questionnaire 9 (PHQ-9), and the Generalized Anxiety Disorder Scale 7 (GAD-7). Furthermore, sensitivity testing was performed concerning subjects' sociodemographic and injury-related characteristics. Differential item functioning (DIF) was analyzed to assess the comparability of RPQ proxy ratings for children with those for adolescents. RESULTS: Good internal consistency was demonstrated regarding Cronbach's α (0.81-0.90) and McDonald's ω (0.84-0.92). The factorial validity of a three-factor model was superior to the original one-factor model. Proxy ratings of the RPQ total and scale scores were strongly correlated with the PCSI-P (ϱ = 0.50-0.69), as well as moderately to strongly correlated with the PHQ-9 (ϱ = 0.49-0.65) and the GAD-7 (ϱ = 0.44-0.64). The DIF analysis revealed no relevant differences between the child and adolescent proxy versions. CONCLUSIONS: The German RPQ proxy is a psychometrically reliable and valid instrument for assessing PCS in children after TBI. Therefore, RPQ self- and proxy-ratings can be used to assess PCS in childhood as well as along the lifespan of an individual after TBI.

Final Validation of the Quality of Life after Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) Questionnaire.

Until recently, no disease-specific health-related quality of life (HRQoL) questionnaire existed for pediatric traumatic brain injuries (TBIs). In this revalidation study, the psychometric properties and the validity of the 35-item QOLIBRI-KID/ADO questionnaire in its final German version were examined in 300 children and adolescents. It is the first self-reported TBI-specific tool for measuring pediatric HRQoL in individuals aged between 8 and 17 years. The six-factor model fits the data adequately. The questionnaire's internal consistency was excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability, and the measure's construct validity was supported by the overlap between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. The discriminant validity tests showed that older children and girls reported a significantly lower HRQoL than comparison groups, and this was also true of children who were anxious or depressed, or who suffered from post-concussion symptoms, replicating the results of the questionnaire's first developmental study. Our results suggest that the QOLIBRI-KID/ADO is a reliable and valid multidimensional tool that can be used together with the adult version in clinical contexts and research to measure disease-specific HRQoL after pediatric TBI throughout a person's life. This may help improve care, treatment, daily functioning, and HRQoL after TBI.

Perfusion imaging by arterial spin labeling in migraine: A literature review.

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022. Out of 236 initial articles, 20 remained after filtering, encompassing data from 1155 subjects in total. Cross-sectional studies in adults showed inconsistent results, while longitudinal studies demonstrated that cerebral perfusion changes over the migraine cycle can be tracked using ASL. The most consistent findings were observed in ictal states among pediatric migraine patients, where studies showed hypoperfusion matching aura symptoms during early imaging followed by hyperperfusion. Overall, ASL is a useful but currently underutilized modality for evaluating cerebral perfusion in patients with migraine. The generalizability of results is currently limited by heterogeneities regarding study design and documentation of clinical variables (e.g., relation of attacks to scanning timepoint, migraine subtypes). Future MRI studies should consider augmenting imaging protocols with ASL to further elucidate perfusion dynamics in migraine.

Instrumented Balance Error Scoring System in Children and Adolescents-A Cross Sectional Study.

Background: The Balance Error Scoring System (BESS) is a commonly used method for clinically evaluating balance after traumatic brain injury. The utilization of force plates, characterized by their cost-effectiveness and portability, facilitates the integration of instrumentation into the BESS protocol. Despite the enhanced precision associated with instrumented measures, there remains a need to determine the clinical significance and feasibility of such measures within pediatric cohorts. Objective: To report a comprehensive set of posturographic measures obtained during instrumented BESS and to examine the concurrent validity, reliability, and feasibility of instrumented BESS in the pediatric point of care setting. Methods: Thirty-seven participants (18 female; aged 13.32 ± 3.31 years) performed BESS while standing on a force plate to simultaneously compute stabilometric measures (instrumented BESS). Ellipse area (EA), path length (PL), and sway velocity (VM) were obtained for each of the six BESS positions and compared with the respective BESS scores. Additionally, the effects of sex and age were explored. A second BESS repetition was performed to evaluate the test-retest reliability. Feedback questionnaires were handed out after testing to evaluate the feasibility of the proposed protocol. Results: The BESS total score was 20.81 ± 6.28. While there was no statistically significant age or sex dependency in the BESS results, instrumented posturography demonstrated an age dependency in EA, VM, and PL. The one-leg stance on a soft surface resulted in the highest BESS score (8.38 ± 1.76), EA (218.78 cm2 ± 168.65), PL (4386.91 mm ± 1859.00), and VM (21.93 mm/s ± 9.29). The Spearman's coefficient displayed moderate to high correlations between the EA (rs = 0.429-0.770, p = 0.001-0.009), PL (rs = 0.451-0.809, p = 0.001-0.006), and VM (rs = 0.451-0.809, p = 0.001-0.006) when compared with the BESS scores for all testing positions, except for the one-leg stance on a soft surface. The BESS total score significantly correlated during the first and second repetition (rs = 0.734, p ≤ 0.001), as did errors during the different testing positions (rs = 0.489-0.799, p ≤ 0.001-0.002), except during the two-legged stance on a soft surface. VM and PL correlated significantly in all testing positions (rs = 0.465-0.675, p ≤ 0.001-0.004; (rs = 0.465-0.675, p ≤ 0.001-0.004), as did EA for all positions except for the two-legged stance on a soft surface (rs = 0.392-0.581, p ≤ 0.001-0.016). A total of 92% of participants stated that the instructions for the testing procedure were very well-explained, while 78% of participants enjoyed the balance testing, and 61% of participants could not decide whether the testing was easy or hard to perform. Conclusions: Instrumented posturography may complement clinical assessment in investigating postural control in children and adolescents. While the BESS score only allows for the consideration of a total score approximating postural control, instrumented posturography offers several parameters representing the responsiveness and magnitude of body sway as well as a more differentiated analysis of movement trajectory. Concise instrumented posturography protocols should be developed to augment neuropediatric assessments in cases where a deficiency in postural control is suspected, potentially stemming from disruptions in the processing of visual, proprioceptive, and/or vestibular information.

Neuromodulation in Pediatric Migraine using Repetitive Neuromuscular Magnetic Stimulation: A Feasibility Study.

Migraine has a relevant impact on pediatric health. Non-pharmacological modalities for its management are urgently needed. This study assessed the safety, feasibility, acceptance, and efficacy of repetitive neuromuscular magnetic stimulation (rNMS) in pediatric migraine. A total of 13 patients with migraine, ≥6 headache days during baseline, and ≥1 myofascial trigger point in the upper trapezius muscles (UTM) received six rNMS sessions within 3 weeks. Headache frequency, intensity, and medication intake were monitored using headache calendars; headache-related impairment and quality of life were measured using PedMIDAS and KINDL questionnaires. Muscular involvement was assessed using pressure pain thresholds (PPT). Adherence yielded 100%. In 82% of all rNMS sessions, no side effects occurred. All participants would recommend rNMS and would repeat it. Headache frequency, medication intake, and PedMIDAS scores decreased from baseline to follow-up (FU), trending towards statistical significance (p = 0.089; p = 0.081, p = 0.055). A total of 7 patients were classified as responders, with a ≥25% relative reduction in headache frequency. PPT above the UTM significantly increased from pre- to post-assessment, which sustained until FU (p = 0.015 and 0.026, respectively). rNMS was safe, feasible, well-accepted, and beneficial on the muscular level. The potential to reduce headache-related symptoms together with PPT changes of the targeted UTM may underscore the interplay of peripheral and central mechanisms conceptualized within the trigemino-cervical complex.

Safety and Feasibility of Functional Repetitive Neuromuscular Magnetic Stimulation of the Gluteal Muscles in Children and Adolescents with Bilateral Spastic Cerebral Palsy.

Background: For children and adolescents affected by bilateral spastic cerebral palsy (BSCP), non-invasive neurostimulation with repetitive neuromuscular magnetic stimulation (rNMS) combined with physical exercises, conceptualized as functional rNMS (frNMS), represents a novel treatment approach. Methods: In this open-label study, six children and two adolescents (10.4 ± 2.5 years) with BSCP received a frNMS intervention targeting the gluteal muscles (12 sessions within 3 weeks). Results: In 77.1% of the sessions, no side effects were reported. In 16.7%, 6.3% and 5.2% of the sessions, a tingling sensation, feelings of pressure/warmth/cold or very shortly lasting pain appeared, respectively. frNMS was highly accepted by families (100% adherence) and highly feasible (97.9% of treatment per training protocol). A total of 100% of participants would repeat frNMS, and 87.5% would recommend it. The Canadian Occupational Performance Measure demonstrated clinically important benefits for performance in 28% and satisfaction in 42% of mobility-related tasks evaluated by caregivers for at least one follow-up time point (6 days and 6 weeks post intervention). Two patients accomplished goal attainment for one mobility-related goal each. One patient experienced improvement for both predefined goals, and another participant experienced improvement in one and outreach of the other goal as assessed with the goal attainment scale. Conclusions: frNMS is a safe and well-accepted neuromodulatory approach that could improve the quality of life, especially in regard to activity and participation, of children and adolescents with BSCP. Larger-scaled studies are needed to further explore the effects of frNMS in this setting.

Functional Repetitive Neuromuscular Magnetic Stimulation (frNMS) Targeting the Tibialis Anterior Muscle in Children with Upper Motor Neuron Syndrome: A Feasibility Study.

Non-invasive neurostimulation as an adjunctive intervention to task-specific motor training is an approach to foster motor performance in patients affected by upper motor neuron syndrome (UMNS). Here, we present first-line data of repetitive neuromuscular magnetic stimulation (rNMS) in combination with personalized task-specific physical exercises targeting the tibialis anterior muscle to improve ankle dorsiflexion (functional rNMS (frNMS)). The main objective of this pilot study was to assess the feasibility in terms of adherence to frNMS, safety and practicability of frNMS, and satisfaction with frNMS. First, during 10 training sessions, only physical exercises were performed (study period (SP) A). After a 1 week break, frNMS was delivered during 10 sessions (SPC). Twelve children affected by UMNS (mean age 8.9 ± 1.6 years) adhered to 93% (SPA) and 94% (SPC) of the sessions, and omittance was not related to the intervention itself in any case. frNMS was safe (no AEs reported in 88% of sessions, no AE-related discontinuation). The practicability of and satisfaction with frNMS were high. Patient/caregiver-reported outcomes revealed meaningful benefits on the individual level. The strength of the ankle dorsiflexors (MRC score) clinically meaningfully increased in four participants as spasticity of ankle plantar flexors (Tardieu scores) decreased in four participants after SPC. frNMS was experienced as a feasible intervention for children affected by UMNS. Together with the beneficial effects achieved on the individual level in some participants, this first study supports further real-world, large-scale, sham-controlled investigations to investigate the specific effects and distinct mechanisms of action of frNMS.

Addressing gross motor function by functional repetitive neuromuscular magnetic stimulation targeting to the gluteal muscles in children with bilateral spastic cerebral palsy: benefits of functional repetitive neuromuscular magnetic stimulation targeting the gluteal muscles.

Background: Impaired selective motor control, weakness and spasticity represent the key characteristics of motor disability in the context of bilateral spastic cerebral palsy. Independent walking ability is an important goal and training of the gluteal muscles can improve endurance and gait stability. Combining conventional physical excercises with a neuromodulatory, non-invasive technique like repetitive neuromuscular magnetic stimulation probably enhances effects of the treatment. This prospective study aimed to assess the clinical effects of repetitive neuromuscular magnetic stimulation in combination with a personalized functional physical training offered to children and adolescents with bilateral spastic cerebral palsy. Methods: Eight participants Gross Motor Function Classification System level II and III (10.4 ± 2y5m; 50% Gross Motor Function Classification System level II) received a personalized intervention applying functional repetitive neuromuscular magnetic stimulation (12 sessions within 3 weeks; 12,600 total stimuli during each session). At baseline and follow up the following assessments were performed: 10-m-walking-test, 6-min-walking-test, GMFM-66. Six weeks after the end of treatment the patient-reported outcome measure Gait Outcome Assessment List was completed. Results: GMFM-66 total score improved by 1.4% (p = 0.002), as did scoring in domain D for standing (1.9%, p = 0.109) and domain E for walking, jumping and running (2.6%, p = 0.021). Gait speed or distance walked during 6 min did not improve from baseline to follow up. Patient-reported outcome showed improvement in 4 patients in altogether 14 ratings. Caregiver-reported outcome reported benefits in 3 participants in altogether 10 ratings. Conclusion: Repetitive neuromuscular magnetic stimulation promises to be a meaningful, non-invasive treatment approach for children and adolescents with bilateral spastic cerebral palsy that could be offered in a resource-efficient manner to a broad number of patients. To further investigate the promising effects of repetitive neuromuscular magnetic stimulation and its mechanisms of action, larger-scaled, controlled trials are needed as well as comprehensive neurophysiological investigations.

Headache frequency and neck pain are associated with trapezius muscle T2 in tension-type headache among young adults.

BACKGROUND: Tension-type headache (TTH) is the most prevalent primary headache disorder. Neck pain is commonly associated with primary headaches and the trigemino-cervical complex (TCC) refers to the convergence of trigeminal and cervical afferents onto neurons of the brainstem, thus conceptualizes the emergence of headache in relation to neck pain. However, no objective biomarkers exist for the myofascial involvement in primary headaches. This study aimed to investigate the involvement of the trapezius muscles in primary headache disorders by quantitative magnetic resonance imaging (MRI), and to explore associations between muscle T2 values and headache frequency and neck pain. METHODS: This cohort study prospectively enrolled fifty participants (41 females, age range 20-31 years): 16 subjects with TTH only (TTH-), 12 with mixed-type TTH plus migraine (TTH+), and 22 healthy controls (HC). The participants completed fat-suppressed T2-prepared three-dimensional turbo spin-echo MRI, a headache diary (over 30 days prior to MRI), manual palpation (two weeks before MRI), and evaluation of neck pain (on the day of MRI). The bilateral trapezius muscles were manually segmented, followed by muscle T2 extraction. Associations between muscle T2 and the presence of neck pain as well as the number of days with headache (considering the 30 days prior to imaging using the headache calendar) were analyzed using regression models (adjusting for age, sex, and body mass index). RESULTS: The TTH+ group demonstrated the highest muscle T2 values (right side: 31.4 ± 1.2 ms, left side: 31.4 ± 0.8 ms) as compared to the TTH- group or HC group (p < 0.001). Muscle T2 was significantly associated with the number of headache days (ß-coefficient: 2.04, p = 0.04) and the presence of neck pain (odds ratio: 2.26, p = 0.04). With muscle T2 as the predictor, the area under the curve for differentiating between HC and the TTH+ group was 0.82. CONCLUSIONS: Increased T2 of trapezius muscles may represent an objective imaging biomarker for myofascial involvement in primary headache disorders, which could help to improve patient phenotyping and therapy evaluation. Pathophysiologically, the increased muscle T2 values could be interpreted as a surrogate of neurogenic inflammation and peripheral sensitization within myofascial tissues.

Trends in Pediatric Mild Traumatic Brain Injury During COVID-19-Related Lockdown-A Single-Center Study.

BACKGROUND: A relevant number of visits to pediatric emergency departments (pED) are associated with mild traumatic brain injury (mTBI). On March 16, 2020, the Bavarian government declared a first full lockdown (LD) related to the coronavirus (COVID-19) pandemic. AIM: The aim of the study was to investigate the impact of LD on pediatric mTBI. METHODS: Retrospective chart review of presentations to a pED due to mTBI. Study periods covered LD (03/17/2020 through 05/05/2020) and the same time in 2017, 2018, and 2019 as reference period (RP). Comparative analyses were performed by Chi-square or Fisher's exact test. RESULTS: Numbers of mTBI cases decreased by half. Age distribution did not differ. A significantly higher proportion of mTBI were related to falls at home (p = 0.001). Further, a higher rate of hospital admissions (p = 0.03), a higher proportion of intensive care unit admissions (p = 0.001), a longer duration of hospital stay (p = 0.02), and a higher rate of intracranial pathologies on neuroimaging were observed during LD (p = 0.007). CONCLUSION: The decrease in mTBI presentations is likely due to an absolute decrease in numbers related to the LD measures, combined with a hesitation to present very minor mTBI to the hospital, because of fear of being infected or not to put additional strain on the healthcare system during this healthcare crisis. On the other hand, data of those that presented with mTBI tend to reflect the more severe spectrum of mTBI.

Feasibility of Functional Repetitive Neuromuscular Magnetic Stimulation (frNMS) Targeting the Gluteal Muscle in a Child with Cerebral Palsy: A Case Report.

BACKGROUND: Motor impairment due to spasticity, weakness, and insufficient selective motor control is a key feature of cerebral palsy (CP). For standing and walking, the gluteal muscles play an important role. Physical therapy represents an evidence-based treatment to promote strength and endurance but may be limited to address selective motor control. Treatment incorporating neurostimulating techniques may increase the therapeutic benefits in these situations. PURPOSE: The aim of this case report was to evaluate the feasibility, safety and clinical effects of a customized protocol of functional repetitive neuromuscular magnetic stimulation (frNMS). METHODS: This case report describes a frNMS protocol applied to the gluteal muscles in an 8-year old boy with bilateral spastic CP. The protocol combines 12 sessions of customized physiotherapeutic exercises with simultaneous electromagnetic stimulation. RESULTS: frNMS protocol was adhered to as planned, no relevant adverse events were observed. At day fourafter the intervention the patient reported clinical benefits and improvements of standing and walking assessed by Gross Motor Function Measure dimensions D (+5.1%) and E (+4.2%) were documented. Body sway as measured by center of pressure displacement during posturography decreased. CONCLUSION: Clinical studies are warranted to assess effects of frNMS and its mechanisms of action in a controlled setting.

Functional magnetic resonance imaging in migraine: A systematic review.

BACKGROUND: Migraine is a highly prevalent primary headache disorder. Despite a high burden of disease, key disease mechanisms are not entirely understood. Functional magnetic resonance imaging is an imaging method using the blood-oxygen-level-dependent signal, which has been increasingly used in migraine research over recent years. This systematic review summarizes recent findings employing functional magnetic resonance imaging for the investigation of migraine. METHODS: We conducted a systematic search and selection of functional magnetic resonance imaging applications in migraine from April 2014 to December 2021 (PubMed and references of identified articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). Methodological details and main findings were extracted and synthesized. RESULTS: Out of 224 articles identified, 114 were included after selection. Repeatedly emerging structures of interest included the insula, brainstem, limbic system, hypothalamus, thalamus, and functional networks. Assessment of functional brain changes in response to treatment is emerging, and machine learning has been used to investigate potential functional magnetic resonance imaging-based markers of migraine. CONCLUSIONS: A wide variety of functional magnetic resonance imaging-based metrics were found altered across the brain for heterogeneous migraine cohorts, partially correlating with clinical parameters and supporting the concept to conceive migraine as a brain state. However, a majority of findings from previous studies have not been replicated, and studies varied considerably regarding image acquisition and analyses techniques. Thus, while functional magnetic resonance imaging appears to have the potential to advance our understanding of migraine pathophysiology, replication of findings in large representative datasets and precise, standardized reporting of clinical data would likely benefit the field and further increase the value of observations.

Relationship between kinematic gait quality and caregiver-reported everyday mobility in children and youth with spastic Cerebral Palsy.

BACKGROUND: 3D gait analysis (3DGA) is a common assessment in Cerebral Palsy (CP) to quantify the extent of movement abnormalities. Yet, 3DGA is performed in laboratories and may thus be of debatable significance to everyday life. AIM: The aim was to assess the relationship between kinematic gait abnormality and everyday mobility in ambulatory children and youth with spastic CP. METHODS: 73 paediatric and juvenile patients with uni- or bilateral spastic CP (N = 21 USCP, N = 52, BSCP, age: 4-20 y, GMFCS I-III) underwent a 3DGA, while the MobQues47 Questionnaire quantified caregiver-reported mobility. We calculated the Gait Profile Score (GPS), a metric that summarizes how far the lower limb joint angles during walking deviate from those of matched controls. RESULTS: The GPS correlated well with indoor and outdoor mobility (rho = -0.69 and -0.70, both p < 0.001) and the relationships were not significantly different for USCP and BSCP. Still, mobility was lower in BSCP (p < 0.001) and more compromised outdoors (p = 0.002). Indoor mobility could be predicted by walking speed, GPS and age (adj. R2 = 0.62). Outdoor mobility was best predicted by walking speed and GPS (adj. R2 = 0.60). The additive explained variance by the GPS was even higher outdoors than indoors (17.1% vs. 11.4%). CONCLUSIONS: Measuring movement deviations with 3DGA seems equally meaningful in uni- and bilaterally affected children and has considerable relevance for real-life ambulation, particurlarly outdoors, where children with spastic CP typically face greater difficulties. Therapeutic strategies that achieve faster walking and reduction of kinematic deviations may increase outdoor mobility.

Neurological soft signs are associated with reduced medial-lateral postural control in adolescent athletes.

INTRODUCTION: Neurological soft signs (NSS) are minor deviations from the norm in motor performance that are commonly assessed using neurological examinations. NSS may be of clinical relevance for evaluating the developmental status of adolescents. Here we investigate whether quantitative force plate measures may add relevant information to observer-based neurological examinations. METHODS: Male adolescent athletes (n = 141) aged 13-16 years from three European sites underwent a neurological examination including 28 tests grouped into six functional clusters. The performance of tests and functional clusters was rated as optimal/non-optimal resulting in NSS+/NSS- groups and a continuous total NSS score. Participants performed a postural control task on a Balance Tracking System measured as path length, root mean square and sway area. ANCOVAs were applied to test for group differences in postural control between the NSS+ and NSS- group, and between optimal/non-optimal performance on a cluster- and test-level. Moreover, we tested for correlations between the total NSS score and postural control variables. RESULTS: There was no significant overall difference between the NSS+ and NSS- group in postural control. However, non-optimal performing participants in the diadochokinesis test swayed significantly more in the medial-lateral direction than optimal performing participants. Moreover, a lower total NSS score was associated with reduced postural control in the medial-lateral direction. CONCLUSION: Our findings demonstrate that NSS are related to postural control in adolescent athletes. Thus, force plate measures may add a quantitative, objective measurement of postural control to observer-based qualitative assessments, and thus, may complement clinical testing.

Neurological soft signs in adolescents are associated with brain structure.

Neurological soft signs (NSS) are minor deviations in motor performance. During childhood and adolescence, NSS are examined for functional motor phenotyping to describe development, to screen for comorbidities, and to identify developmental vulnerabilities. Here, we investigate underlying brain structure alterations in association with NSS in physically trained adolescents. Male adolescent athletes (n = 136, 13-16 years) underwent a standardized neurological examination including 28 tests grouped into 6 functional clusters. Non-optimal performance in at least 1 cluster was rated as NSS (NSS+ group). Participants underwent T1- and diffusion-weighted magnetic resonance imaging. Cortical volume, thickness, and local gyrification were calculated using Freesurfer. Measures of white matter microstructure (Free-water (FW), FW-corrected fractional anisotropy (FAt), axial and radial diffusivity (ADt, RDt)) were calculated using tract-based spatial statistics. General linear models with age and handedness as covariates were applied to assess differences between NSS+ and NSS- group. We found higher gyrification in a large cluster spanning the left superior frontal and parietal areas, and widespread lower FAt and higher RDt compared with the NSS- group. This study shows that NSS in adolescents are associated with brain structure alterations. Underlying mechanisms may include alterations in synaptic pruning and axon myelination, which are hallmark processes of brain maturation.

Safety Profile and Lack of Immunogenicity of IncobotulinumtoxinA in Pediatric Spasticity and Sialorrhea: A Pooled Analysis.

IncobotulinumtoxinA, a pure botulinumtoxinA formulation, is free of accessory proteins. This analysis provides pooled safety data from phase 3 trials of children/adolescents (2-17 years), investigating incobotulinumtoxinA for the treatment of spasticity associated with cerebral palsy (at doses ≤20 U/kg (max. 500 U) per injection cycle (IC) for ≤6 ICs; three trials) or sialorrhea associated with neurologic disorders (at total doses of 20-75 U per IC for ≤4 ICs; one trial) for ≤96 weeks. Safety endpoints included the incidences of different types of treatment-emergent adverse events (TEAEs) and immunogenicity. IncobotulinumtoxinA dose groups were combined. Of 1159 patients (mean age 7.3 years, 60.4% males) treated with incobotulinumtoxinA, 3.9% experienced treatment-related TEAEs, with the most common being injection site reactions (1.3%) (both indications), muscular weakness (0.7%) (spasticity), and dysphagia (0.2%) (sialorrhea). Two patients (0.2%) experienced a treatment-related treatment-emergent serious adverse event, and 0.3% discontinued the study due to treatment-related TEAEs. No botulinumtoxinA-naïve patients developed neutralizing antibodies (NAbs) after incobotulinumtoxinA. All children/adolescents with known pre-treatment status and testing positive for Nabs at final visit (n = 7) were previously treated with a botulinumtoxinA other than incobotulinumtoxinA. IncobotulinumtoxinA was shown to be safe, with very few treatment-related TEAEs in a large, diverse cohort of children/adolescents with chronic conditions requiring long-term treatment and was without new NAb formation in treatment-naïve patients.

Response Predictors of Repetitive Neuromuscular Magnetic Stimulation in the Preventive Treatment of Episodic Migraine.

Background: Repetitive neuromuscular magnetic stimulation (rNMS) of the trapezius muscles showed beneficial effects in preventing episodic migraine. However, clinical characteristics that predict a favorable response to rNMS are unknown. The objective of this analysis is to identify such predictors. Methods: Thirty participants with a diagnosis of episodic migraine (mean age: 24.8 ± 4.0 years, 29 females), who were prospectively enrolled in two non-sham-controlled studies evaluating the effects of rNMS were analyzed. In these studies, the interventional stimulation of the bilateral trapezius muscles was applied in six sessions and distributed over two consecutive weeks. Baseline and follow-up assessments included the continuous documentation of a headache calendar over 30 days before and after the stimulation period, the Migraine Disability Assessment Score (MIDAS) questionnaire (before stimulation and 90 days after stimulation), and measurements of pain pressure thresholds (PPTs) above the trapezius muscles by algometry (before and after each stimulation session). Participants were classified as responders based on a ≥25% reduction in the variable of interest (headache frequency, headache intensity, days with analgesic intake, MIDAS score, left-sided PPTs, right-sided PPTs). Post-hoc univariate and multivariate binary logistic regression analyses were performed. Results: Lower headache frequency (P = 0.016) and intensity at baseline (P = 0.015) and a migraine diagnosis without a concurrent tension-type headache component (P = 0.011) were significantly related to a ≥25% reduction in headache frequency. Higher headache frequency (P = 0.052) and intensity at baseline (P = 0.014) were significantly associated with a ≥25% reduction in monthly days with analgesic intake. Lower right-sided PPTs at baseline were significantly related to a ≥25% increase in right-sided PPTs (P = 0.015) and left-sided PPTs (P =0.030). Performance of rNMS with higher stimulation intensities was significantly associated with a ≥25% reduction in headache intensity (P = 0.046). Conclusions: Clinical headache characteristics at baseline, the level of muscular hyperalgesia, and stimulation intensity may inform about how well an individual patient responds to rNMS. These factors may allow an early identification of patients that would most likely benefit from rNMS.

Repetitive Neuromuscular Magnetic Stimulation for Pediatric Headache Disorders: Muscular Effects and Factors Affecting Level of Response.

Repetitive neuromuscular magnetic stimulation (rNMS) for pediatric headache disorders is feasible, safe, and alleviates headache symptoms. This study assesses muscular effects and factors affecting response to rNMS. A retrospective chart review included children with headaches receiving six rNMS sessions targeting the upper trapezius muscles. Pressure pain thresholds (PPT) were measured before and after rNMS, and at 3-month follow-up (FU). Mean headache frequency, duration, and intensity within the last 3 months were documented. In 20 patients (14.1 ± 2.7 years), PPT significantly increased from pre- to post-treatment (p < 0.001) sustaining until FU. PPT changes significantly differed between primary headache and post-traumatic headache (PTH) (p = 0.019−0.026). Change in headache frequency was significantly higher in patients with than without neck pain (p = 0.032). A total of 60% of patients with neck pain responded to rNMS (≥25%), while 20% of patients without neck pain responded (p = 0.048). 60% of patients receiving rNMS twice a week were responders, while 33% of patients receiving rNMS less or more frequently responded to treatment, respectively. Alleviation of muscular hyperalgesia was demonstrated sustaining for 3 months, which was emphasized in PTH. The rNMS sessions may positively modulate headache symptoms regardless of headache diagnosis. Patients with neck pain profit explicitly well. Two rNMS sessions per week led to the highest reduction in headache frequency.

Repetitive neuromuscular magnetic stimulation in children with headache.

INTRODUCTION: Repetitive neuromuscular magnetic stimulation (rNMS) was previously applied in adult patients with episodic migraine, showing beneficial effects on headache characteristics, high safety, and convincing satisfaction. This study aims to assess rNMS as a personalized intervention in pediatric headache. METHODS: Retrospective chart review including patients with migraine, TTH, mixed type headache, or PTH, who had received at least one test rNMS session targeting the upper trapezius muscles (UTM). RESULTS: 33 patients (13.9 ± 2.5 years; 61% females) were included in the primary analysis, resulting in a total of 182 rNMS sessions. 43 adverse events were documented for 40 of those sessions (22%). Most common side effects were tingling (32.6%), muscle sore (25.5%), shoulder (9.3%) and back pain (9.3%). Secondly, in patients (n = 20) undergoing the intervention, headache frequency (p = 0.017) and minimum and maximum intensities (p = 0.017; p = 0.023) significantly decreased from baseline to 3-month after intervention. 11 patients (44%) were classified as ≥25% responders, with 7 patients (28%) experiencing a ≥75% reduction of headache days. After 73% of interventions, patients reported rNMS helped very well or well. A majority of patients would repeat (88.5%) and recommend rNMS (96.2%) to other patients. CONCLUSION: rNMS seems to meet the criteria of safety, feasibility, and acceptance among children and adolescents with three age-typical headache disorders. A significant reduction in headache frequency and intensity during a 3 months follow-up was documented. Larger, prospective, randomized, sham-controlled studies are urgently needed to confirm if rNMS may become a new valuable non-invasive, non-pharmacological treatment option for pediatric headache disorders.

Burden of disease and lifestyle habits in adolescents and young adults prone to frequent episodic migraine: A secondary comparative analysis.

The objective of this study was to assess the burden of disease and prevalence of lifestyle factors for adolescents and young adults with frequent episodic migraine. We conducted a secondary comparative analysis of data collected during two previous studies. Inclusion criteria for this analysis were age 15-35 years, 15 to 44 migraine episodes within 12 weeks, and completeness of Migraine Disability Assessment and lifestyle questionnaire data. Datasets of 37 adults (median age [interquartile range]: 25 [6]) and 27 adolescents (median age [interquartile range]: 15 [1]) were analyzed. 81% (n = 30) of adults reported severe disability (16% [n = 3] of adolescents; p < 0.001). Headache frequency (24 vs. 17 days; p = 0.005) and prevalence of regular analgesic use (60% [n = 22] vs. 18% [n = 5]; p = 0.002) were significantly higher in adults. In adults, sleep duration on weekdays was significantly lower (8.5 vs. 10 h; p < 0.001). Any consumption of caffeine tended to be higher in adolescents and alcohol consumption tended to be higher in adults (p > 0.05). This study underlines the importance of educating adolescents and young adults with migraine about lifestyle habits that are likely to interfere with the condition.