The Impact of Oral-Gut Inflammation in Cerebral Palsy.

Background: Oral-gut inflammation has an impact on overall health, placing subjects at risk to acquire chronic conditions and infections. Due to neuromotor disturbances, and medication intake, cerebral palsy (CP) subjects present intestinal constipation, impacting their quality of life (QOL). We aimed to investigate how oral inflammatory levels predicted gut phenotypes and response to therapy. Methods: A total of 93 subjects aging from 5 to 17 years were included in the study, and assigned into one of the 4 groups: CP with constipation (G1, n = 30), CP without constipation (G2, n = 33), and controls without CP with constipation (G3, n = 07) and without CP and without constipation (G4, n = 23). In addition to characterizing subjects' clinical demographics, medication intake, disease severity levels, salivary cytokine levels [TNF-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10], and Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Statistical significance was evaluated by Shapiro-Wilks, Student's T-Test, ANOVA, and ANCOVA analysis. Results: Salivary proinflammatory cytokines were highly correlated with the severe form of gut constipation in G1 (P < 0.001), and out of all cytokines IL-1ß levels demonstrated highest correlation with all gut constipation (P < 0.05). A significant relationship was found between the type of medication, in which subjects taking Gamma-Aminobutyric Acid (GABA) and GABA+ (GABA in association with other medication) were more likely to be constipated than the other groups (P < 0.01). Cleary salivary inflammatory levels and gut constipation were correlated, and impacted QOL of CP subjects. G1 presented a lower QOL mean score of CPCHILD (49.0 ± 13.1) compared to G2 (71.5 ± 16.7), when compared to G3 (88.9 ± 7.5), and G4 (95.5 ± 5.0) (P < 0.01). We accounted for gingival bleeding as a cofounder of oral inflammation, and here were no differences among groups regarding gender (P = 0.332) and age (P = 0.292). Conclusions: Collectively, the results suggest that saliva inflammatory levels were linked to gut constipation, and that the clinical impact of medications that controlled gut was reliably monitored via oral cytokine levels, providing reliable and non-invasive information in precision diagnostics.

A systematic review of neurogenesis in animal models of early brain damage: Implications for cerebral palsy.

Brain damage during early life is the main factor in the development of cerebral palsy (CP), which is one of the leading neurodevelopmental disorders in childhood. Few studies, however, have focused on the mechanisms of cell proliferation, migration, and differentiation in the brain of individuals with CP. We thus conducted a systematic review of preclinical evidence of structural neurogenesis in early brain damage and the underlying mechanisms involved in the pathogenesis of CP. Studies were obtained from Embase, Pubmed, Scopus, and Web of Science. After screening 2329 studies, 29 studies, covering a total of 751 animals, were included. Prenatal models based on oxygen deprivation, inflammatory response and infection, postnatal models based on oxygen deprivation or hypoxic-ischemia, and intraventricular hemorrhage models showed varying neurogenesis responses according to the nature of the brain damage, the time period during which the brain injury occurred, proliferative capacity, pattern of migration, and differentiation profile in neurogenic niches. Results mainly from rodent studies suggest that prenatal brain damage impacts neurogenesis and curbs generation of neural stem cells, while postnatal models show increased proliferation of neural precursor cells, improper migration, and reduced survival of new neurons.

Inflammatory biomarkers in children with cerebral palsy: A systematic review.

BACKGROUND: An exacerbated systemic inflammatory response has been associated with the occurrence of central nervous system injuries that may determine, in long term, motor, sensorial and cognitive disabilities. Persistence of this exacerbated inflammatory response seems to be involved in the pathophysiology of cerebral palsy (CP). METHODS: A systematic search was conducted in Bireme, Embase, PubMed and Scopus including studies that were published until August 2019. The key words used were "cerebral palsy", "brain injury", "inflammation", "oxidative stress", "cytokines", "chemokines", "neuropsychomotor development", "neurodevelopment outcomes" and "child". The quality of the eligible studies was determined according to the criteria suggested by the Newcastle-Ottawa Scale (NOS). RESULTS: Fourteen eligible studies aimed to investigate the association between peripheral inflammatory molecules and neurodevelopment in infants. The studies differed regarding CP-related risk factors and its classification. Inflammatory proteins were measured in blood, plasma, serum, cerebrospinal fluid or urine. In ten studies, higher circulating levels of cytokines, including IL-1ß, IL-6, TNF and CXCL8/IL-8, were associated with abnormal neurological findings. CONCLUSION: The investigation of the potential association between inflammatory molecules and neurological development in children with CP requires further original studies in order to clarify the influence of prenatal and perinatal inflammation on neurological outcomes.

Morphofunctional characteristics of skeletal muscle in rats with cerebral palsy.

Knowledge of skeletal muscle adaptations is important to understand the functional deficits in cerebral palsy (CP). This study aimed to investigate the morphofunctional characteristics of skeletal muscle in a CP animal model. Initially, pregnant Wistar rats were injected intraperitoneally with saline or lipopolysaccharide over the last five days of pregnancy. The control group (n = 8) consisted of male pups born to females injected with saline. The CP group (n = 8) consisted of male pups born to females injected with lipopolysaccharide, which were submitted to perinatal anoxia [day of birth, postnatal day 0 (P0)] and sensorimotor restriction (P1-P30). The open-field test was undertaken on P29 and P45. On P48, the animals were weighed, and the plantaris muscle was collected and its weight and length were measured. Transverse sections were stained with haematoxylin-eosin, NADH-TR, Masson's trichrome and non-specific esterase reaction for analysis. and transmission electron microscopy was performed. In the CP group, reductions were observed in mobility time, number of crossings and rearing frequency, body weight, muscle weight and length, and nucleus-to-fibre and capillary-to-fibre ratios. There was a statistically significant increase in the percentage area of the muscle section occupied by collagen; reduction in the area and increase in the number of type I muscle fibres; increase in myofibrillar disorganization and Z-line disorganization and dissolution; and reduction in the area and largest and smallest diameters of neuromuscular junctions. Thus this animal model of CP produced morphofunctional alterations in skeletal muscle, that were associated with evidence of motor deficits as demonstrated by the open-field test.

Day/night melatonin content in cerebral palsy.

Changes in the sleep-wake cycle are frequent and may impair quality of life in individuals with cerebral palsy (CP). To investigate if a lack of a day/night variation of melatonin content could be related with sleep disorders (SD), the SD were evaluated with a Sleep Questionnaire and the melatonin content using ELISA in 33 individuals with CP and 24 controls. The indicative of SD were present in 47% of CP group, and the most frequent was the indicative of sleep breathing disorder. The CP group showed higher diurnal and lower nocturnal melatonin content than controls. Individuals with CP that had indicative of SD showed lower nocturnal content of melatonin than those without SD. These results showed that the lack of the day/night variation of melatonin was related to SD in individuals with CP.

Bone mineral density and nutritional status in children with quadriplegic cerebral palsy.

This study demonstrated the relationship of low bone mineral density (BMD) with the degree of motor impairment, method of feeding, anthropometric indicators, and malnutrition in children with quadriplegic cerebral palsy (CP). The control of these factors could optimize adequate bone mineralization, avoid the risk of osteoporosis, and would improve the quality of life. PURPOSE: The purpose of the study is to explore the relationship between low BMD and nutritional status in children with quadriplegic CP. METHODOLOGY: A cross-sectional analytical study included 59 participants aged 6 to 18 years with quadriplegic CP. Weight and height were obtained with alternative measurements, and weight/age, height/age, and BMI/age indexes were estimated. The BMD measurement obtained from the lumbar spine was expressed in grams per square centimeter and Z score (Z). Unpaired Student's t tests, chi-square tests, odds ratios, Pearson's correlations, and linear regressions were performed. RESULTS: The mean of BMD Z score was lower in adolescents than in school-aged children (p = 0.002). Patients with low BMD were at the most affected levels of the Gross Motor Function Classification System (GMFCS). Participants at level V of the GMFCS were more likely to have low BMD than levels III and IV [odds ratio (OR) = 5.8 (confidence interval [CI] 95% 1.4, 24.8), p = 0.010]. There was a higher probability of low BMD in tube-feeding patients [OR = 8.6 (CI 95% 1.0, 73.4), p = 0.023]. The probability of low BMD was higher in malnourished children with weight/age and BMI indices [OR = 11.4 (1.3, 94), p = 0.009] and [OR = 9.4 (CI 95% 1.1, 79.7), p = 0.017], respectively. CONCLUSION: There was a significant relationship between low BMD, degree of motor impairment, method of feeding, and malnutrition. Optimizing these factors could reduce the risk of osteopenia and osteoporosis and attain a significant improvement of quality of life in children with quadriplegic CP.

Mechanisms contributing to gait speed and metabolic cost in children with unilateral cerebral palsy.

BACKGROUND: Gait speed and metabolic cost are indicators of functional capacity in children with cerebral palsy. Uncovering their mechanisms helps guide therapeutic actions. OBJECTIVES: To investigate the contributions of energy-generating and energy-conserving mechanisms to gait speed and metabolic cost of children with unilateral cerebral palsy. METHODS: Data on eccentric and concentric muscle work, co-contraction, elastic torque and vertical stiffness of the affected-limb, forcing torque of the non-affected limb, gait speed and metabolic cost were collected from 14 children with unilateral cerebral palsy, aged 6-12 years. Analyses included two groups of multiple regression models. The first group of models tested the association between each dependent variable (i.e., speed and metabolic cost) and the independent variables that met the input criteria. The second group verified the contribution of the non-selected biomechanical variables on the predictors of the first model. RESULTS: Gait speed (R2=0.80) was predicted by elastic torque (ß=0.62; 95%CI: 0.60, 0.63), vertical stiffness (ß=-0.477; 95%CI: -0.479, -0.474) and knee co-contraction (ß=0.27; 95%CI: -1.96, 2.49). The production of eccentric work by the affected limb proved relevant in adjusting the vertical stiffness (R2=0.42; ß=-0.64; 95%CI: 0.86, -0.42); elastic torque of the affected-leg was associated with impulsive torque of the non-affected leg (R2=0.31; ß=0.55; 95%CI: 0.46, 0.64). Metabolic cost of gait (R2=0.48) was partially predicted by knee co-contraction (ß=0.69; 95%CI: 0.685, 0.694). CONCLUSIONS: The chain of associations revealed by the two steps models helped uncover the mechanisms involved in the locomotion of children with unilateral cerebral palsy. Intervention that changes specific energy conserving and generating mechanisms may improve gait of these children.

Food pattern and nutritional status of children with cerebral palsy.

OBJECTIVES To assess the food intake pattern and the nutritional status of children with cerebral palsy. METHODS Cross-sectional study with 90 children from two to 12.8 years with cerebral palsy in the following forms: hemiplegia, diplegia, and tetraplegia. Nutritional status was assessed by weight, height, and age data. Food intake was verified by the 24-hour recall and food frequency questionnaire. The ability to chew and/or swallowing, intestinal habits, and physical activity were also evaluated. RESULTS For 2-3 year-old age group, the mean energy intake followed the recommended range; in 4-6 year-old age group with hemiplegia and tetraplegia, energy intake was below the recommended limits. All children presented low intake of carbohydrates, adequate intake of proteins and high intake of lipids. The tetraplegia group had a higher prevalence of chewing (41%) and swallowing (12.8%) difficulties compared to 14.5 and 6.6% of children with hemiplegia, respectively. Most children of all groups had a daily intestinal habit. All children presented mild physical activity, while moderate activity was not practiced by any child of the tetraplegia group, which had a significantly lower height/age Z score than those with hemiplegia (-2.14 versus -1.05; p=0.003). CONCLUSIONS The children with cerebral palsy presented inadequate dietary pattern and impaired nutritional status, with special compromise of height. Tetraplegia imposes difficulties regarding chewing/swallowing and moderate physical activity practice.

Food pattern and nutritional status of children with cerebral palsy / Estandar alimentar y estado nutricional de ninos con paralisis cerebral / Padrao alimentar e estado nutricional de criancas com paralisia cerebral

OBJECTIVES To assess the food intake pattern and the nutritional status of children with cerebral palsy. METHODS Cross-sectional study with 90 children from two to 12.8 years with cerebral palsy in the following forms: hemiplegia, diplegia, and tetraplegia. Nutritional status was assessed by weight, height, and age data. Food intake was verified by the 24-hour recall and food frequency questionnaire. The ability to chew and/or swallowing, intestinal habits, and physical activity were also evaluated. RESULTS For 2-3 year-old age group, the mean energy intake followed the recommended range; in 4-6 year-old age group with hemiplegia and tetraplegia, energy intake was below the recommended limits. All children presented low intake of carbohydrates, adequate intake of proteins and high intake of lipids. The tetraplegia group had a higher prevalence of chewing (41%) and swallowing (12.8%) difficulties compared to 14.5 and 6.6% of children with hemiplegia, respectively. Most children of all groups had a daily intestinal habit. All children presented mild physical activity, while moderate activity was not practiced by any child of the tetraplegia group, which had a significantly lower height/age Z score than those with hemiplegia (-2.14 versus -1.05; p=0.003). CONCLUSIONS The children with cerebral palsy presented inadequate dietary pattern and impaired nutritional status, with special compromise of height. Tetraplegia imposes difficulties regarding chewing/swallowing and moderate physical activity practice. .

OBJETIVO Evaluar el estándar alimentar y estado nutricional de niños con parálisis cerebral. MÉTODOS Estudio transversal con 90 niños de 2 a 12,8 años de edad, con parálisis cerebral de tipo hemiplejía, diplejía y tetraplejía. Se evaluaron el estado nutricional por medio de los datos de peso, altura y edad, el consumo alimentar por el Recordatorio de 24 horas y por el Cuestionario de Frecuencia Alimentar, la capacidad de masticar y/o deglutir, el hábito intestinal y la práctica de actividad física. RESULTADOS En el grupo de 2 a 3 años, el promedio de ingestión energética estaba conforme a la recomendación; en la franja de 4 a 6 años, los grupos con hemiplejía y con tetraplejía presentaban promedios inferiores al límite inferior de recomendación. El grupo como un todo presentó estándar dietético bajo en carbohidratos, adecuado en proteínas y alto en lípidos. El grupo con tetraplejía presentó mayor prevalencia de dificultad para masticación (41%) y deglución (12,8%), versus, respectivamente, 14,5 y 6,6% de los niños con hemiplejía. Se observó que la mayoría de los niños con cada tipo de parálisis cerebral presentaba hábito intestinal diario. Todos los niños estudiados tenían actividad física liviana, mientras que la actividad moderada no era practicada por ningún niño del grupo tetraplejía, que también presentó escore Z de -2,14 de la relación estatura/edad, significantemente menor respecto al grupo con hemiplejía (escore Z de -1,05; p=0,003). CONCLUSIONES Los niños presentaron estándar alimentar inadecuado, estado nutricional comprometido, principalmente la estatura. La tetraplejía impone dificultades de masticación/deglución y práctica de actividad física ...

OBJETIVO Avaliar o padrão alimentar e o estado nutricional de crianças com paralisia cerebral. MÉTODOS Estudo transversal com 90 crianças de dois a 12,8 anos de idade, com paralisia cerebral do tipo hemiplegia, diplegia e tetraplegia. Avaliaram-se o estado nutricional por meio dos dados de peso, altura e idade, o consumo alimentar pelo Recordatório de 24 horas e pelo Questionário de Frequência Alimentar, a capacidade de mastigar e/ou deglutir, o hábito intestinal e a prática de atividade física. RESULTADOS No grupo de dois a três anos, a média de ingestão energética estava de acordo com a recomendação; na faixa de quatro a seis anos, os grupos com hemiplegia e com tetraplegia apresentaram médias abaixo do limite inferior da recomendação. O grupo como um todo apresentou padrão dietético baixo em carboidratos, adequado em proteína e alto em lipídios. O grupo com tetraplegia apresentou maior prevalência de dificuldade para mastigação (41%) e para deglutição (12,8%) versus, respectivamente, 14,5 e 6,6% das crianças com hemiplegia. Observou-se que a maioria das crianças com cada tipo de paralisia cerebral apresentava hábito intestinal diário. Todas as crianças estudadas tinham atividade física leve, enquanto a atividade moderada não era praticada por nenhuma criança do grupo com tetraplegia, que também apresentou escore Z de -2,14 da relação estatura/idade, significantemente menor em relação ao grupo com hemiplegia (escore Z de -1,05; p=0,003). CONCLUSÕES As crianças apresentaram padrão alimentar inadequado, estado nutricional comprometido, o que afetou principalmente a estatura. A tetraplegia impõe dificuldade de mastigação/deglutição e da prática de atividade física moderada. .

Increased salivary immunoglobulin A and reduced α-amylase activity in whole saliva from spastic cerebral palsy individuals.

BACKGROUND: Salivary immunoglobulin A (SIgA) together with innate defenses such as α-amylase, provides the 'first line of defense' against pathogens present at mucosal surfaces. This study aimed to evaluate salivary α-amylase and immunoglobulin A (IgA) in whole saliva of spastic cerebral palsy (CP) individuals. METHODS: Whole saliva was collected from 22 CP and 24 sibling volunteers with no neurological damage control groups (CG) (aged 7-14 years). The salivary flow rate, total protein and SIgA concentrations, and α-amylase activity were determined. RESULTS: The CP group presented higher salivary flow rate (35%) and lower total protein concentration (18%) compared with the CG (P ≤ 0.05). CPG had higher absolute (68%, µg SIgA/ml) and relative (55%, µg SIgA/mg prot and 108%, µg SIgA/min) concentrations of IgA compared with the CG (P ≤ 0.05). CPG had lower relative α-amylase activity (15% mg malt/mg prot and 33%, mg malt/min) compared with the CG (P ≤ 0.05). CONCLUSION: This study concluded that CP individuals presented alterations in the profile of salivary proteins involved in the defense system of the oral cavity.

Salivary osmolality in individuals with cerebral palsy.

OBJECTIVE: To measure the salivary flow rate, osmolality, electrolyte and total protein concentrations in individuals with cerebral palsy (CP). DESIGN: Thirty-eight individuals with CP were divided according to the neuromotor abnormality type (total, spastic and dyskinectic) and compared to 22 nondisabled children (control group). Whole saliva was collected under slight suction. The salivary parameters studied were salivary flow rate, osmolality, sodium, potassium, chloride and total protein concentrations. RESULTS: CP individuals, with both neuromotor abnormality types (spastic and dyskinectic), presented an increase in salivary osmolality, total protein, potassium and chloride concentrations compared to the control group (p<0.05). Moreover, a reduction in salivary flow rate was verified in spastic individuals (p<0.05). CONCLUSION: The reduction in salivary flow rate and increase in osmolality, total protein and electrolyte concentrations of saliva from cerebral palsy individuals could be caused by hypohydration status.

Does the neuromotor abnormality type affect the salivary parameters in individuals with cerebral palsy?

BACKGROUND: Previous studies reported alterations in salivary flow rate and biochemical parameters of saliva in cerebral palsy (CP) individuals; however, none of these considered the type of neuromotor abnormality among CP individuals, thus it remains unclear whether the different anatomical and extended regions of the brain lesions responsible for the neurological damage in CP might include disruption of the regulatory mechanism of saliva secretion as part of the encephalopathy. The aim of this study was to evaluate salivary flow rate, pH and buffer capacity in saliva of individuals with CP, aged 3-16 years, with spastic neuromotor abnormality type and clinical patterns of involvement. METHODS: Sixty-seven individuals with CP spasticity movement disorder, were divided in two groups according to age (3-8- and 9-16-years-old) and compared with 35 sibling volunteers with no neurological damage, divided in two groups according to age (3-8- and 9-16-years-old). Whole saliva was collected under slight suction and pH and buffer capacity were determined using a digital pH meter. Buffer capacity was measured by titration using 0.01N HCL, and flow rate was calculated in ml/min. RESULTS: In both age groups studied, whole saliva flow rate, pH and buffer capacity were significantly lower in the spastic CP group (P<0.05). The clinical patterns of involvement did not influence the studied parameters. CONCLUSION: These findings show that individuals with spastic cerebral palsy present lower salivary flow rate, pH and buffer capacity that can increase the risk of oral disease in this population.

La alimentación del niño con parálisis cerebral un reto para el nutricionista dietista: perspectivas desde una revisión / Nutrition for children having cerebral paralysis is challenging for dietitians: review

Antecedentes: la parálisis cerebral es un término usado para describir el síndrome producido por lesión o daño del sistema nervioso central durante períodos críticos del desarrollo. Los niños con parálisis cerebral presentan diferentes manifestaciones clínicas, pero todos presentan deterioro de la función neurológica. Esta enfermedad, considerada altamente incapacitante, presenta una incidencia de 2,5 por cada mil nacidos vivos en países en desarrollo y de 2,0 en países desarrollados. Objetivo: identificar características alimentarias y nutricionales de los niños con parálisis cerebral para orientar a los profesionales de la salud con recomendaciones que contribuyan a la intervención efectiva de este grupo. Materiales y métodos: se realizó una búsqueda sistemática de artículos publicados en los últimos 10 años en bases de datos nacionales e internacionales. Resultados: la parálisis cerebral afecta el desarrollo de los diferentes sistemas reguladores de las funciones vitales del organismo: succión, masticación, deglución y respiración, que comprometen los procesos de alimentación y el estado nutricional de los niños que la padecen.Conclusiones: la atención alimentaria y nutricional de niños con parálisis cerebral, requiere que el nutricionista dietista, de forma interdisciplinaria, desarrolle modificaciones dietéticas acordes a las características del paciente para favorecer el consumo de alimentos y mejorar su estado nutricional.

Cerebral paralysis defined the syndrome for damage of nervous system, it could happen during critical periods of child development. Children having cerebral paralysis present different clinical manifestations, but all present damage of neurological function. Cerebral paralysis is an extremely disable disease, the world incidence is 2,5 per 1000 newborns in developing countries and 2,0 per 1000 newborns in developed nations. Objective: to identify feeding and nutritional characteristics in children having cerebral paralysis in order to develop guidelines for health professionals working with these children. Methods: a systematic search of articles published the last 10 years related to the topic was done, looking in scientific national and international data base. Results: cerebral paralysis affects physiological functions like suction, mastication, swallowing and breading system, that affect feeding process and nutritional status of children. Conclusion: the main purpose of this review was to understand the impact of cerebral paralysis on nutritional status in children having this syndrome, also this review provides information about recommendations that health professionals should apply to improve the quality of life for this population.

Comparison of electrolyte concentrations in whole saliva of individuals with and without cerebral palsy.

OBJECTIVE: To analyze sodium, potassium, calcium, phosphorus, and magnesium concentrations in whole saliva of adolescents with cerebral palsy (CP) and compare them with those of normal individuals. METHOD AND MATERIALS: Thirty-six adolescents with CP aged 12.0 +/- 1.8 years were compared with 36 healthy age-matched individuals. Saliva was collected under slight suction. Electrolyte concentrations were determined by inductively coupled argon plasma with atomic emission spectrometry. RESULTS: Significant differences were observed with matched and unmatched flow rates. Sodium concentrations were significantly decreased, whereas potassium levels were significantly increased in the CP group. No statistically significant differences were observed regarding phosphorus, magnesium, and calcium concentrations between adolescents with CP and controls. CONCLUSION: Our results suggest that there is an alteration in the sodium and potassium concentration in whole saliva of individuals with CP.

Daily physical activity of schoolchildren with spastic diplegia and of healthy control subjects.

OBJECTIVE: To assess the differences in daily physical activity between children with spastic diplegia and healthy schoolchildren, to determine whether special physical activity programs are needed in the population with cerebral palsy. DESIGN: Cross-sectional design. SETTING: Children's rehabilitation center Franciscusoord (day care center) and elementary schools. SUBJECTS: Children with spastic diplegia (5 boys; mean (+/- SD) age 8.0 +/- 1.4 years; 9 ambulant, 1 wheelchair use) and healthy children (5 boys; mean (+/- SD) age 8.4 +/- 1.0 years). MEASUREMENTS: Total daily energy expenditure (TEE) and sleeping metabolic rate (SMR) were measured by the doubly labeled water technique and a respiration chamber. The TEE/SMR ratio was used as an index for the level of daily physical activity. RESULTS: The TEE/SMR ratio under normal daily conditions in the children with cerebral palsy (mean +/- SD): 1.56 +/- 0.19) was significantly lower (p < 0.05) than in their healthy peers (mean +/- SD: 1.83 +/- 0.23) and was similar to the TEE/SMR ratio in a room-sized chamber. CONCLUSION: Children with spastic diplegia are considerably less active than their healthy peers. We recommend special physical activity programs for these children.