RESUMO
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.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Síndrome Pós-Concussão , Adulto , Adolescente , Criança , Humanos , Síndrome Pós-Concussão/diagnóstico , Síndrome Pós-Concussão/epidemiologia , Concussão Encefálica/diagnóstico , Inquéritos e Questionários , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/epidemiologia , Questionário de Saúde do PacienteRESUMO
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.
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Paralisia Cerebral , Masculino , Humanos , Criança , Paralisia Cerebral/terapia , Estudos de Viabilidade , Músculo Esquelético , Caminhada , Terapia por Exercício/métodos , Espasticidade Muscular/terapia , Fenômenos MagnéticosRESUMO
The Gait Outcome Assessment List (GOAL) is a patient or caregiver-reported assessment of gait-related function across different domains of the International Classification of Functioning, Disability, and Health (ICF) developed for ambulant children with cerebral palsy (CP). So far, the questionnaire is only available in English. The aim of this study was to translate the GOAL into German and to evaluate its reliability and validity by studying the association between GOAL scores and gross motor function as categorized by the gross motor function classification system (GMFCS) in children with cerebral palsy (CP). The GOAL was administered to primary caregivers of n = 91 children and adolescents with CP (n = 32, GMFCS levels I; n = 27, GMFCS level II; and n = 32, GMFCS level III) and n = 15 patients were capable of independently completing the whole questionnaire (GMFCS level I). For assessing test-retest reliability, the questionnaire was completed for a second time 2 weeks after the first by the caregivers of n = 36 patients. Mean total GOAL scores decreased significantly with increasing GMFCS levels with scores of 71 (95% confidence interval [CI]: 66.90-74.77) for GMFCS level I, 56 (95% CI: 50.98-61.86) for GMFCS level II, and 45 (95% CI: 40.58-48.48) for GMFCS level III, respectively. In three out of seven domains, caregivers rated their children significantly lower than children rated themselves. The test-retest reliability was excellent as was internal consistency given the GOAL total score. The German GOAL may serve as a much needed patient-reported outcome measure of gait-related function in ambulant children and adolescents with CP.
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Paralisia Cerebral , Adolescente , Paralisia Cerebral/diagnóstico , Criança , Marcha , Objetivos , Humanos , Avaliação de Resultados em Cuidados de Saúde , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
The most important salivary glands are the paired parotid and submandibular glands. Adults produce 1 to 1.5 liters of saliva which are then regularly swallowed. When the act of swallowing is disturbed, salivation occurs. More rarely, the cause can be found in increased saliva production, for example, when caused through medication. Sialorrhea impairs the quality of life substantially and is frequently often socially stigmatizing. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, as well as, in selected cases, radiation and surgical measures. Over the last 20 years, local injection of botulinum toxin has been successfully applied in the treatment of this condition. With approval of incobotulinumtoxinA toxin for children and adults, this procedure will become the therapy of choice for chronic sialorrhea. The results of the phase III registration trials have demonstrated high efficacy and good safety of the injection treatment in both children and adults.
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Toxinas Botulínicas Tipo A , Sialorreia , Adulto , Toxinas Botulínicas Tipo A/uso terapêutico , Criança , Humanos , Qualidade de Vida , Glândulas Salivares , Salivação , Sialorreia/tratamento farmacológico , Sialorreia/etiologia , Glândula Submandibular , Resultado do TratamentoRESUMO
Sialorrhea, uncontrolled, excessive drooling, accompanies different, mostly neurological disorders from childhood to adulthood. With incobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH), an approved medication for the treatment of sialorrhea has been available since 2019. Patient selection, possible therapy goals, treatment and the management of specific treatment situations build the focus of this interdisciplinary expert consensus recommendations with the intent to facilitate access to treatment and to contribute to qualified botulinum toxin therapy.
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Toxinas Botulínicas Tipo A , Doenças do Sistema Nervoso , Sialorreia , Adolescente , Adulto , Toxinas Botulínicas Tipo A/uso terapêutico , Criança , Consenso , Humanos , Sialorreia/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
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Distonia , Distúrbios Distônicos , Doença de Parkinson , Algoritmos , Distonia/diagnóstico , Distonia/genética , Distúrbios Distônicos/genética , Testes Genéticos , HumanosRESUMO
BACKGROUND: Childhood stroke is rare and can predispose to post-stroke epilepsy. The purpose of this study was to evaluate long-term quality of life (QoL) in patients with childhood stroke, focusing on epileptic aspects. METHOD: This involves a retrospective study of 98 patients with childhood stroke (pre- and neonatal strokes excluded), who had been inpatients between 1986 and 2003 for early rehabilitation. Data were obtained via interviews using a standardized questionnaire: QoL evaluation with KINDL, functional outcome with Barthel Index, and motor handicaps-assessment with modified Rankin Score. RESULTS: Forty-nine of 98 patients (31 males, mean follow-up 16 years, range 8-25 years) were included. Six patients passed away (three of sudden unexpected death in epilepsy). At least one epileptic seizure occurred in 27/49 patients (occurrence: 2 days-13 years.; mean 3.3 years.). Epilepsy manifested in 19/49 patients. No correlation was found between the development of epilepsy and the location or etiology of the stroke. The presence of functional independence was significantly higher in seizure-free patients and in patients without epilepsy. For the external assessment (filled in for the patient by the parent/caregiver), there was no significant difference in QoL in patients with and without epilepsy; however, in the in-person KINDL questionnaire a significantly lower QoL was noted in epilepsy patients compared with patients without epilepsy. CONCLUSION: One important finding in our study is that in the long-term course 39% of patients developed epilepsy after a childhood stroke. It occurred as late as 13 years after the acute episode and affected the QoL especially in cognitively less handicapped patients.
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Epilepsia , Acidente Vascular Cerebral , Criança , Epilepsia/etiologia , Humanos , Recém-Nascido , Masculino , Qualidade de Vida , Estudos Retrospectivos , Convulsões/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
Nicolaides-Baraitser syndrome (NCBRS), caused by a mutation in the SMARCA2 gene, which goes along with intellectual disability, congenital malformations, especially of face and limbs, and often difficult-to-treat epilepsy, is surveyed focusing on epilepsy and its treatment. Patients were recruited via "Network Therapy of Rare Epilepsies (NETRE)" and an international NCBRS parent support group. Inclusion criterion is NCBRS-defining SMARCA2 mutation. Clinical findings including epilepsy classification, anticonvulsive treatment, electroencephalogram (EEG) findings, and neurodevelopmental outcome were collected with an electronic questionnaire. Inclusion of 25 NCBRS patients with epilepsy in 23 of 25. Overall, 85% of the participants (17/20) reported generalized seizures, the semiology varied widely. EEG showed generalized epileptogenic abnormalities in 53% (9/17), cranial magnetic resonance imaging (cMRI) was mainly inconspicuous. The five most frequently used anticonvulsive drugs were valproic acid (VPA [12/20]), levetiracetam (LEV [12/20]), phenobarbital (PB [8/20]), topiramate (TPM [5/20]), and carbamazepine (CBZ [5/20]). LEV (9/12), PB (6/8), TPM (4/5), and VPA (9/12) reduced the seizures' frequency in more than 50%. Temporary freedom of seizures (>6 months) was reached with LEV (4/12), PB (3/8), TPM (1/5, only combined with PB and nitrazepam [NZP]), and VPA (4/12). Seizures aggravation was observed under lamotrigine (LTG [2/4]), LEV (1/12), PB (1/8), and VPA (1/12). Ketogenic diet (KD) and vagal nerve stimulation (VNS) reduced seizures' frequency in one of two each. This first worldwide retrospective analysis of anticonvulsive therapy in NCBRS helps to treat epilepsy in NCBRS that mostly shows only initial response to anticonvulsive therapy, especially with LEV and VPA, but very rarely shows complete freedom of seizures in this, rather genetic than structural epilepsy.
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Anticonvulsivantes/farmacologia , Epilepsia/terapia , Deformidades Congênitas do Pé/terapia , Hipotricose/terapia , Deficiência Intelectual/terapia , Adolescente , Criança , Pré-Escolar , Dieta Cetogênica , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/etiologia , Epilepsia/fisiopatologia , Fácies , Feminino , Deformidades Congênitas do Pé/complicações , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas do Pé/fisiopatologia , Humanos , Hipotricose/complicações , Hipotricose/diagnóstico , Hipotricose/fisiopatologia , Lactente , Deficiência Intelectual/complicações , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Transcrição/genética , Estimulação do Nervo VagoRESUMO
Nicolaides-Baraitser syndrome (NCBRS) is a rare disease caused by a mutation in the SMARCA2 gene. Clinical features include craniofacial dysmorphia and abnormalities of the limbs, as well as intellectual disorder and often epilepsy. Hepatotoxicity is a rare complication of the therapy with valproic acid (VPA) and a mutation of the polymerase γ (POLG) might lead to a higher sensitivity for liver hepatotoxicity. We present a patient with the coincidence of two rare diseases, the NCBRS and additionally a POLG1 mutation in combination with a liver hepatotoxicity. The co-occurrence in children for two different genetic diseases is discussed with the help of literature review.
Assuntos
Anticonvulsivantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , DNA Polimerase gama/genética , Fácies , Deformidades Congênitas do Pé , Hipotricose , Deficiência Intelectual , Fatores de Transcrição/genética , Ácido Valproico/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Criança , Feminino , Deformidades Congênitas do Pé/tratamento farmacológico , Deformidades Congênitas do Pé/genética , Humanos , Hipotricose/tratamento farmacológico , Hipotricose/genética , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/genéticaRESUMO
Among 131 children admitted to our institution for early phase rehabilitation after freshwater near-drowning (ND) between the year 1986 and 2000, 87 were in unresponsive wakefulness syndrome (UWS) for at least 4 weeks after the accidents. An anonymous questionnaire was sent to the families after 0.5 to 15.0 years (median: 4.6) and 48 mothers and 51 fathers of 55 of these 87 children were interviewed after 6.6 to 23.8 years (median: 13.8) of ND. At the time of the interviews, 8/55 children were able to perform daily living activities independently, 36/55 children were not able to do so (many of them suffered from chronic medical conditions like spasticity or disorders of swallowing), and 11/55 children had died. Health-related quality of life (HRQoL) was, however, similar to the normal population for mothers, and even higher for fathers. Furthermore, the ND accident had apparently not lead to a higher rate of separations of parents but had increased their likelihood to have further children. Feelings of guilt were highly prevalent (23/47 mothers, 20/47 fathers), and correlated with lower HRQoL of the respective parent. We found correlations between duty of supervision and feelings of guilt and between outcome and HRQoL for only the fathers. In conclusion, we found that after 4 weeks in UWS, the long-term neurological outcome of pediatric ND victims is often but not always poor. Despite often severe disabilities or death of the child during long-term care, parents surprisingly report little impact on their HRQoL, on the stability of their partnership or on their wish to have further children. Our findings may help parents and physicians to choose the best treatment for a child in UWS due to different etiologies striking the balance between rehabilitation and palliative care.
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Afogamento Iminente/psicologia , Pais/psicologia , Estado Vegetativo Persistente/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Vigília , Criança , Pré-Escolar , Feminino , Culpa , Humanos , Lactente , Masculino , Afogamento Iminente/diagnóstico , Estado Vegetativo Persistente/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The application of rehabilitation robots has grown during the last decade. While meta-analyses have shown beneficial effects of robotic interventions for some patient groups, the evidence is less in others. We established the Advanced Robotic Therapy Integrated Centers (ARTIC) network with the goal of advancing the science and clinical practice of rehabilitation robotics. The investigators hope to exploit variations in practice to learn about current clinical application and outcomes. The aim of this paper is to introduce the ARTIC network to the clinical and research community, present the initial data set and its characteristics and compare the outcome data collected so far with data from prior studies. METHODS: ARTIC is a pragmatic observational study of clinical care. The database includes patients with various neurological and gait deficits who used the driven gait orthosis Lokomat® as part of their treatment. Patient characteristics, diagnosis-specific information, and indicators of impairment severity are collected. Core clinical assessments include the 10-Meter Walk Test and the Goal Attainment Scaling. Data from each Lokomat® training session are automatically collected. RESULTS: At time of analysis, the database contained data collected from 595 patients (cerebral palsy: n = 208; stroke: n = 129; spinal cord injury: n = 93; traumatic brain injury: n = 39; and various other diagnoses: n = 126). At onset, average walking speeds were slow. The training intensity increased from the first to the final therapy session and most patients achieved their goals. CONCLUSIONS: The characteristics of the patients matched epidemiological data for the target populations. When patient characteristics differed from epidemiological data, this was mainly due to the selection criteria used to assess eligibility for Lokomat® training. While patients included in randomized controlled interventional trials have to fulfill many inclusion and exclusion criteria, the only selection criteria applying to patients in the ARTIC database are those required for use of the Lokomat®. We suggest that the ARTIC network offers an opportunity to investigate the clinical application and effectiveness of rehabilitation technologies for various diagnoses. Due to the standardization of assessments and the use of a common technology, this network could serve as a basis for researchers interested in specific interventional studies expanding beyond the Lokomat®.
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Bases de Dados como Assunto/organização & administração , Exoesqueleto Energizado , Transtornos Neurológicos da Marcha/reabilitação , Feminino , Humanos , MasculinoRESUMO
PURPOSE: The aim of the article is to investigate whether motor competence and cognitive abilities influence the quality of performance of activities of daily living (ADL) in children with hemiparesis. Patients and METHODS: A total of 20 children with hemiparesis (age, 6-12 years; 11 congenital, 9 acquired during childhood) were studied. Motor competence was assessed with the Assisting Hand Assessment, cognitive abilities with the German version of the Wechsler Intelligence Scale for Children IV, and the quality of ADL performance with the Assessment of Motor and Process Skills (AMPS). RESULTS: The motor skills scale of the AMPS correlated with motor competence, and the process skills scale of the AMPS correlated with cognitive abilities. CONCLUSION: The quality of ADL performance is influenced not only by motor competence but also by the cognitive abilities of a hemiparetic child. This suggests that, in addition to motor-oriented training programs, an optimal therapy for hemiparetic children should also consider cognitive approaches.
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Atividades Cotidianas , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/psicologia , Paresia/fisiopatologia , Paresia/psicologia , Paralisia Cerebral/complicações , Criança , Cognição , Feminino , Humanos , Masculino , Destreza Motora , Paresia/complicaçõesRESUMO
We aimed to translate the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire into German and to evaluate its reliability and validity by studying the association between CPCHILD scores and gross motor function as measured by the gross motor function classification system (GMFCS) in children with cerebral palsy (CP). The original CPCHILD questionnaire and manual were translated and back translated. It was administered to primary caregivers of persons with CP (GMFCS levels III-V) and was completed a second time 2 weeks after the first to measure test-retest reliability (n = 17). Primary caregivers of 68 children with CP; GMFCS level III (n = 14), level IV (n = 28), and level V (n = 26) completed the questionnaire. Mean total CPCHILD scores across GMFCS levels were 67.1 ± 14.9 for GMFCS level III, 56.6 ± 11.8 for level IV, and 44.3 ± 12.9 for level V. Good correlation (r = - 0.56) was observed between GMFCS and total scores test-retest reliability showed intraclass correlation coefficients between 0.4 and 0.9. The German CPCHILD yielded similar test-retest reliability and score distributions across the GMFCS level as the original version. The best correlations were observed for domains that are close to the functional deficits.
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Atividades Cotidianas/psicologia , Cuidadores/psicologia , Paralisia Cerebral , Deficiências do Desenvolvimento/etiologia , Inquéritos e Questionários , Traduções , Adolescente , Adulto , Paralisia Cerebral/complicações , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/enfermagem , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Adulto JovemRESUMO
In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.
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Baclofeno/uso terapêutico , Distúrbios Distônicos/tratamento farmacológico , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Índice de Gravidade de Doença , Adolescente , Criança , Consenso , Feminino , Seguimentos , Humanos , Injeções Espinhais , MasculinoRESUMO
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.
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Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/reabilitação , Terapia por Exercício/métodos , Robótica/métodos , Adolescente , Criança , Avaliação da Deficiência , Teste de Esforço , Feminino , Humanos , Masculino , Análise de Regressão , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
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.
RESUMO
BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin. METHODS: In NF1 patients (n = 11; 19-44 years) and healthy controls (HC; n = 11; 19-31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed. RESULTS: In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness. CONCLUSIONS: This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option.