Aspectos motores da Paralisia Cerebral Espástica diparética : o Nintendo WII 'MARCA REGISTRADA' como atividade motora complementar = Motor aspects of Spastic Cerebral Palsy : the Nintendo WII 'TRADEMARK' as a supplementary motor activity

Universidade Estadual de Campinas . Faculdade de Educação Física

A pilot study of delayed versus immediate serial casting after botulinum toxin injection for partially reducible spastic equinus.

BACKGROUND: Serial casting is often prescribed after botulinum toxin injections to improve joint ranges of motion and to potentiate the decrease in hypertonia. The aim of this study was to compare delayed versus immediate serial casting as an adjunct to botulinum toxin therapy for partially reducible spastic equinus. METHODS: Twelve children who presented spastic equinus associated with mild gastrosoleus contracture took part. Five of them had a diagnosis of spastic diplegia, whereas 7 had a diagnosis of congenital hemiplegia. Children were randomized to immediate serial casting (same day) or delayed serial casting (4 weeks later) after botulinum toxin injection to their gastrosolei. Casts were replaced weekly for 3 weeks. RESULTS: Three children complained of pain that required recasting in the immediate casting group versus none in the delayed casting group (P = 0.08). At 3 months, there was a 27-degree improvement in the fast dorsiflexion angle (Tardieu R1) in the delayed casting group versus 17 degrees in the immediate casting group (P = 0.029). At 6 months, a 19-degree improvement persisted in the delayed group compared with 11 degrees in the immediate group (P = 0.010). CONCLUSIONS: There is a clear benefit in delaying serial casting after the injection of botulinum toxin in the recurrence of spasticity at the gastrosoleus that may also offer an advantage regarding the incidence of painful episodes associated with casting. Most importantly, reducing the recurrence of spasticity by delayed serial casting may offer the possibility of decreasing the frequency of botulinum toxin reinjections.

Development and mechanical testing of a short intramedullary nail for fixation of femoral rotational osteotomy in cerebral palsy patients

Background: Rotational osteotomy is frequently indicated to correct excessive femoral anteversion in cerebral palsy patients. Angled blade plate is the standard fixation device used when performed in the proximal femur, but extensile exposure is required for plate accommodation. The authors developed a short locked intramedullary nail to be applied percutaneously in the fixation of femoral rotational osteotomies in children with cerebral palsy and evaluated its mechanical properties. Methods: The study was divided into three stages. In the first part, a prototype was designed and made based on radiographic measurements of the femoral medullary canal of ten-year-old patients. In the second, synthetic femoral models based on rapid-prototyping of 3D reconstructed images of patients with cerebral palsy were obtained and were employed to adjust the nail prototype to the morphological changes observed in this disease. In the third, rotational osteotomies were simulated using synthetic femoral models stabilized by the nail and by the AO-ASIF fixed-angle blade plate. Mechanical testing was done comparing both devices in bending-compression and torsion. Results: The authors observed proper adaptation of the nail to normal and morphologically altered femoral models, and during the simulated osteotomies. Stiffness in bending-compression was significantly higher in the group fixed by the plate (388.97 +/- 57.25 N/mm) than in that fixed by the nail (268.26 +/- 38.51 N/mm) as torsional relative stiffness was significantly higher in the group fixed by the plate (1.07 +/- 0.36 Nm/degrees) than by the nail (0.35 +/- 0.13 Nm/degrees). Conclusions: Although the device presented adequate design and dimension to fit into the pediatric femur, mechanical tests indicated that the nail was less stable than the blade plate in bending-compression and torsion. This may be a beneficial property, and it can be attributed to the more flexible fixation found in intramedullary devices.

Anticipatory and compensatory postural adjustments in sitting in children with cerebral palsy

The aim of this study was to examine postural control in children with cerebral palsy performing a bilateral shoulder flexion to grasp a ball from a sitting posture. The participants were 12 typically developing children (control) without cerebral palsy and 12 children with cerebral palsy (CP). We analyzed the effect of ball mass (1 kg and 0.18 kg), postural adjustment (anticipatory, APA, and compensatory, CPA), and groups (control and CP) on the electrical activity of shoulder and trunk muscles with surface electromyography (EMG). Greater mean iEMG was seen in CPA, with heavy ball, and for posterior trunk muscles (p < .05). The children with CP presented the highest EMG and level of co-activation (p < .05). Linear regression indicated a positive relationship between EMG and aging for the control group, whereas that relationship was negative for participants with CP. We suggest that the main postural control strategy in children is based on corrections after the beginning of the movement. The linear relationship between EMG and aging suggests that postural control development is affected by central nervous disease which may lead to an increase in muscle co-activation. (C) 2011 Elsevier B.V. All rights reserved.

The relation of triceps surae surgical lengthening and crouch gait in patients with cerebral palsy

To investigate the effect of earlier triceps surae (TS) surgical lengthening at knee kinematics in the stance phase in patients with cerebral palsy (CP). One thousand and thirty-nine participants from an eligible total of 1750 children with CP were referred to gait analysis laboratory from January 2000 to April 2007. Inclusion criteria were the diagnosis of diparetic spastic CP levels I to III (GMFCS) and complete kinematics documentation. Patients with an asymmetrical knee pattern at kinematics and with different types of TS management among sides were excluded. The patients were divided into two groups according to the mean minimum knee flexion (MMKF) in stance phase: group A (n = 253) MMKF >= 30 degrees and group B (n = 786) MMKF less than 30 degrees. For each group, the occurrence of following procedures for TS in the past: (i) earlier surgery, (ii) gastrocnemius lengthening (zone I), (iii) gastrocnemius and soleus lengthening (zone II), and (iv) calcaneous tendon lengthening (zone III), was investigated. A chi(2) test was applied to check if the number of procedures performed was different between groups. The level of significance was defined as P value of less than 0.05. The number of patients with no earlier surgeries at TS was higher in group B (51.8%) than in group A (39.1%), and this difference was significant (P<0.01). In addition, the number of procedures at the calcaneous tendon was more elevated in group A (36.8%) than in group B (27%), and this finding was statistically significant as well (P<0.02). The percentage of surgical lengthening at zones I and II was very similar between the groups A and B. This study has shown that patients without earlier surgical procedures at TS are more susceptible to reach better extension of the knees in the stance phase. Patients in a crouch gait had a higher number of calcaneous tendon lengthening performed in the past than patients with a more normal knee extension in the stance phase. J Pediatr Orthop B 19:226-230 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Idiopathic Toe Walking A Kinematic and Kinetic Profile

Purpose: The differential diagnosis in children who walk on their toes includes mild spastic diplegia and idiopathic toe walking (ITW). A diagnosis of ITW is often one of exclusion. To better characterize the diagnosis of ITW, quantitative gait analysis was utilized in a series of patients with an established diagnosis of ITW. Study Design: Patients with an established diagnosis of ITW were analyzed by quantitative gait analysis. Data were recorded as each subject walked in a self-selected toe-walking pattern. The subject was then asked to ambulate making every effort to walk in a normal heel-toe reciprocating fashion. Data were collected to determine if this group of idiopathic toe walkers was able to normalize their gait. Data sets were compared with each other and with historical normal controls. Results: Fifty-one neurologically normal children ( 102 extremities) with ITW were studied in the Motion Analysis Laboratory at a mean age of 9.3 years. In the self-selected trials, significant deviations in both kinematics and kinetics at the level of the ankle were identified. Disruption of all 3 ankle rockers and a plantar flexion bias of the ankle throughout the gait cycle were most commonly seen. When asked to attempt a normal heel-toe gait, 17% of the children were able to normalize both stance and swing variables. In addition, 70% were able to normalize some but not all of the stance and swing variables. Conclusion: Quantitative gait analysis is an effective tool for differentiating mild cerebral palsy from ITW. Kinematic and kinetic distinctions between the diagnoses are evident at the knee and ankle. The ability to normalize on demand at least some of the kinematic and kinetic variables associated with toe walking is seen in most children with ITW.

Maternal antecedents for cerebral palsy in extremely preterm babies: A case-controlled study

The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks' gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids.

Comportamento da tibiotársica na sequência de movimento de sentar para de pé em crianças prematuras

Introdução: A prematuridade constitui um fator de risco para a ocorrência de lesões ao nível do sistema nervoso central, sendo que uma idade gestacional inferior a 36 semanas potencia esse mesmo risco, nomeadamente para a paralisia cerebral (PC) do tipo diplegia espástica. A sequência de movimento de sentado para de pé (SPP), sendo uma das aprendizagens motoras que exige um controlo postural (CP) ao nível da tibiotársica, parece ser uma tarefa funcional frequentemente comprometida em crianças prematuras com e sem PC. Objetivo(s): Descrever o comportamento dos músculos da tibiotársica, tibial anterior (TA) e solear (SOL), no que diz respeito ao timing de ativação, magnitude e co-ativação muscular durante a fase I e início da fase II na sequência de movimento de SPP realizada por cinco crianças prematuras com PC do tipo diplegia espástica e cinco crianças prematuras sem diagnóstico de alteração neuromotoras, sendo as primeiras sujeitas a um programa de intervenção baseado nos princípios do conceito de Bobath – Tratamento do Neurodesenvolvimento (TND). Métodos: Foram avaliadas 10 crianças prematuras, cinco com PC e cinco sem diagnóstico de alterações neuromotoras, tendo-se recorrido à eletromiografia de superfície para registar parâmetros musculares, nomeadamente timings, magnitudes e valores de co-ativação dos músculos TA e SOL, associados à fase I e inico da fase II da sequência de movimento de SPP. Procedeu-se ao registo de imagem de modo a facilitar a avaliação dos componentes de movimento associados a esta tarefa. Estes procedimentos foram realizados num único momento, no caso das crianças sem diagnóstico de alterações neuromotoras e em dois momentos, antes e após a aplicação de um programa de intervenção segundo o Conceito de Bobath – TND no caso das crianças com PC. A estas foi ainda aplicado o Teste da Medida das Funções Motoras (TMFM–88) e a Classificação Internacional da Funcionalidade Incapacidade e Saúde – crianças e jovens (CIF-CJ). Resultados: Através da eletromiografia constatou-se que ambos os grupos apresentaram timings de ativação afastados da janela temporal considerada como ajustes posturais antecipatórios (APAs), níveis elevados de co-ativação, em alguns casos com inversão na ordem de recrutamento muscular o que foi possível modificar nas crianças com PC após o período de intervenção. Nestas, verificou-se ainda que, a sequência de movimento de SPP foi realizada com menor número de compensações e com melhor relação entre estruturas proximais e distais compatível com o aumento do score final do TMFM-88 e modificação positiva nos itens de atividade e participação da CIF-CJ. Conclusão: As crianças prematuras com e sem PC apresentaram alterações no CP da tibiotársica e níveis elevados de co-ativação muscular. Após o período de intervenção as crianças com PC apresentaram modificações positivas no timing e co-ativação muscular, com impacto funcional evidenciado no aumento do score final da TMFM-88 e modificações positivas na CIF-CJ.

Sleep disorders in children with cerebral palsy.

To determine the frequency and predictors of sleep disorders in children with cerebral palsy (CP) we analyzed the responses of 173 parents who had completed the Sleep Disturbance Scale for Children. The study population included 100 males (57.8%) and 73 females (42.2%; mean age 8y 10mo [SD 1y 11mo]; range 6y-11y 11mo). Eighty-three children (48.0%) had spastic diplegia, 59 (34.1%) congenital hemiplegia, 18 (10.4%) spastic quadriplegia, and 13 (7.5%) dystonic/dyskinetic CP. Seventy-three children (42.2%) were in Gross Motor Function Classification System Level I, 33 (19.1%) in Level II, 30 (17.3%) in Level III, 23 (13.3%) in Level IV, and 14 (8.1%) in Level V. Thirty children (17.3%) had epilepsy. A total sleep problem score and six factors indicative of the most common areas of sleep disorder in childhood were obtained. Of the children in our study, 23% had a pathological total sleep score, in comparison with 5% of children in the general population. Difficulty in initiating and maintaining sleep, sleep-wake transition, and sleep breathing disorders were the most frequently identified problems. Active epilepsy was associated with the presence of a sleep disorder (odds ratio [OR]=17.1, 95% confidence interval [CI] 2.5-115.3), as was being the child of a single-parent family (OR=3.9, 95% CI 1.3-11.6). Disorders of initiation and maintenance of sleep were more frequent in children with spastic quadriplegia (OR=12.9, 95% CI 1.9-88.0), those with dyskinetic CP (OR=20.6, 95% CI 3.1-135.0), and those with severe visual impairment (OR=12.5, 95% CI 2.5-63.1). Both medical and environmental factors seem to contribute to the increased frequency of chronic sleep disorders in children with CP.

Use of a dynamic foot pressure index to monitor the effects of treatment for equinus gait in children with cerebral palsy.

The purpose of this study is to introduce and describe a newly developed index using foot pressure analysis to quantify the degree of equinus gait in children with cerebral palsy before and after injection with botulinum toxin. Data were captured preinjection and 12 weeks postinjection. Ten children aged 2(1/2) to 6(1/2) years took part (5 boys and 5 girls). Three of them had a diagnosis of spastic diplegia and 7 of congenital hemiplegia. In total, 13 limbs were analyzed. After orientation and segmentation of raw pedobarographic data, we determined a dynamic foot pressure index graded 0 to 100 that quantified the relative degree of heel and forefoot contact during stance. These data were correlated (Pearson correlation) with clinical measurements of dorsiflexion at the ankle (on a slow and fast stretch) and video observation (using the Observational Gait Scale). Pedobarograph data were strongly correlated with both the Observational Gait Scale scores (R = 0.79, P < 0.005) and clinical measurements of dorsiflexion on a fast stretch, which is reflective of spasticity (R = 0.70, P < 0.005). We demonstrated the index's sensitivity in detecting changes in spasticity and good correlation with video observations seems to indicate this technique's potential validity. When manipulated and segmented appropriately, and with the development of a simple ordinal index, we found that foot pressure data provided a useful tool in tracking changes in patients with spastic equinus.

CRISPR/Cas9-Mediated Gene Editing of ARG1 in Cell Lines and Primary Cells

Arginase 1 deficiency, a urea cycle disorder resulting from an inability of the body to convert arginine into urea, results in hyperargininemia and sporadic episodes of hyperammonemia. Arginase 1 deficiency can lead to a range of developmental disorders and progressive spastic diplegia in children, and current therapeutic options are limited. Clustered regularly interspaced short palindromic repeat (CRISPR) /CRISPR associated protein (Cas) 9 gene editing systems serve as a novel means of treating genetic disorders such as Arginase 1 (ARG1) deficiency, and must be thoroughly examined to determine their curative capabilities. In these experiments numerous guide RNAs and CRISPR/Cas9 systems targeting the ARG1 gene were designed and observed by heteroduplex assay for their targeting capabilities and cleavage efficiencies in multiple cell lines. The CRISPR/Cas9 system utilized in these experiments, along with a panel of guide RNAs targeting various locations in the arginase 1 gene, successfully produced targeted cleavage in HEK293, MCF7, A549, K562, HeLa, and HepG2 cells; however, targeted cleavage in human dermal fibroblasts, blood outgrowth endothelial cells, and induced pluripotent stem cells was not observed. Additionally, a CRISPR/Cas system involving partially inactivated Cas9 was capable of producing targeted DNA cleavage in intron 1 of ARG1, while a Cas protein termed Cpf1 was incapable of producing targeted cleavage. These results indicate a complex set of variables determining the CRISPR/Cas9 systems’ capabilities in the cell lines and primary cells tested. By examining epigenetic factors and alternative CRISPR/Cas9 gene targeting systems, the CRISPR/Cas9 system can be more thoroughly considered in its ability to act as a means towards editing the genome of arginase 1-deficient individuals.

Machado-Joseph disease versus hereditary spastic paraplegia: case report

Machado-Joseph disease (MJD) is the most common autosomal dominant spinocerebellar ataxia and presents great phenotypic variability. MJD presenting with spastic paraparesis was recently described in Japanese patients. We report the case of 41-year-old woman with the phenotype of complicated hereditary spastic paraplegia. Her father died at the age of 56 years due to an undiagnosed progressive neurological disease that presented parkinsonism. She had an expanded allele with 66 CAG repeats and a normal allele with 22 repeats in the gene of MJD. MJD should be considered in the differential diagnosis of autosomal dominant complicated HSP. A patient with the phenotype of complicated HSP and relatives with other clinical features of a neurodegenerative disease should raise the suspicion of MJD.

Motor and functional evaluation of patients with spastic paraplegia, optic atrophy, and neuropathy (SPOAN)

Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming.

The frequency of CD127(low) expressing CD4(+)CD25(high) T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

Background: CD4(+)CD25(high) regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg) cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg) cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-1 drives activation, spontaneous IFN gamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+) T(Reg) cells (CD4(+)CD25(high) T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+) T(Reg) cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low) T(Reg) cells in healthy control subjects. Finally, the proportion of CD127(low) T(Reg) cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that T(Reg) cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4(+) T cells, in particular those expressing the CD25(high)CD127(low) phenotype. T(Reg) cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice

The spastic (spa) and oscillator (ot) mouse have naturally occurring mutations in the inhibitory glycine receptor (GlyR) and exhibit severe motor disturbances when exposed to unexpected sensory stimuli. We examined the effects of the spa and ot mutations on GlyR- and GABA(A)R-mediated synaptic transmission in the superficial dorsal horn (SFDH), a spinal cord region where inhibition is important for nociceptive processing. Spontaneous mIPSCs were recorded from visually identified neurones in parasagittal spinal cord slices. Neurones received exclusively GABA(A)R-mediated mIPSCs, exclusively GlyR-mediated mIPSCs or both types of mIPSCs. In control mice (wild-type and spa/+) over 40 % of neurones received both types of mIPSCs, over 30 % received solely GABA(A)R-mediated mIPSCs and the remainder received solely GlyR-mediated mIPSCs. In spa/spa animals, 97 % of the neurones received exclusively GABA(A)ergic or both types of mIPSCs. In ot/ot animals, over 80 % of the neurones received exclusively GABA(A)R-mediated mIPSCs. GlyR-mediated mIPSC amplitude and charge were reduced in spa/spa and ot/ot animals. GABA,Rmediated mIPSC amplitude and charge were elevated in spa/spa but unaltered in ot/ot animals. GlyR- and GABA(A)R-mediated mIPSC decay times were similar for all genotypes, consistent with the mutations altering receptor numbers but not kinetics. These findings suggest the spastic and oscillator mutations, traditionally considered motor disturbances, also disrupt inhibition in a sensory region associated with nociceptive transmission. Furthermore, the spastic mutation results in a compensatory increase in GABA(A)ergic transmission in SFDH neurones, a form of inhibitory synaptic plasticity absent in the oscillator mouse.