RESUMO
OBJECTIVE: In stiff person syndrome (SPS), an antibody-mediated impaired γ-aminobutyric acidergic (GABAergic) neurotransmission is believed to cause muscle stiffness and spasms. Most patients improve with GABA-enhancing drugs and intravenous immunoglobulin, but some respond poorly and remain disabled. The need for more effective therapy prompted a trial with the anti-CD20 monoclonal antibody rituximab. METHODS: This was a placebo-controlled randomized trial of rituximab (2 biweekly infusions of 1g each). The primary outcome was a change in stiffness scores at 6 months. Secondary outcomes were changes in heightened-sensitivity and quality of life scores. Enrolling 24 patients was calculated to detect 50% change in stiffness scores. RESULTS: Randomization was balanced for age, sex, disease duration, and glutamic acid decarboxylase autoantibody titers. No significant changes were noted at 6 months after treatment in all outcomes. Specifically, no differences were noted in the stiffness index, the primary outcome, or sensitivity scores, the secondary outcome, at 3 or 6 months. Quality of life scores improved significantly (p < 0.01) at 3 months in both groups, but not at 6 months, denoting an early placebo effect. Blinded self-assessment rating of the overall stiffness for individual patients revealed improvement in 4 patients in each group. At 6 months, improvement persisted in 1 patient in the placebo group versus 3 of 4 in the rituximab group, where these meaningful improvements were also captured by video recordings. INTERPRETATION: This is the largest controlled trial conducted in SPS patients and demonstrates no statistically significant difference in the efficacy measures between rituximab and placebo. Rituximab's lack of efficacy could be due to a considerable placebo effect; insensitivity of scales to quantify stiffness, especially in the less severely affected patients; or drug effectiveness in only a small patient subset. Ann Neurol 2017;82:271-277.
Assuntos
Rituximab/uso terapêutico , Rigidez Muscular Espasmódica/tratamento farmacológico , Autoanticorpos/sangue , Método Duplo-Cego , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rigidez Muscular Espasmódica/sangue , Resultado do TratamentoRESUMO
OBJECTIVE: Report a double-blind, placebo-controlled study of rituximab in patients with anti-MAG demyelinating polyneuropathy (A-MAG-DP). METHODS: Twenty-six patients were randomized to four weekly infusions of 375 mg/m(2) rituximab or placebo. Sample size was calculated to detect changes of > or = 1 Inflammatory Neuropathy Course and Treatment (INCAT) leg disability scores at month 8. IgM levels, anti-MAG titers, B cells, antigen-presenting cells, and immunoregulatory T cells were monitored every 2 months. RESULTS: Thirteen A-MAG-DP patients were randomized to rituximab and 13 to placebo. Randomization was balanced for age, electrophysiology, disease duration, disability scores, and baseline B cells. After 8 months, by intention to treat, 4 of 13 rituximab-treated patients improved by > or = 1 INCAT score compared with 0 of 13 patients taking placebo (p = 0.096). Excluding one rituximab-randomized patient who had normal INCAT score at entry, and thus could not improve, the results were significant (p = 0.036). The time to 10m walk was significantly reduced in the rituximab group (p = 0.042) (intention to treat). Clinically, walking improved in 7 of 13 rituximab-treated patients. At month 8, IgM was reduced by 34% and anti-MAG titers by 50%. CD25+CD4+Foxp3+ regulatory cells significantly increased by month 8. The most improved patients were those with high anti-MAG titers and most severe sensory deficits at baseline. INTERPRETATION: Rituximab is the first drug that improves some patients with A-MAG-DP in a controlled study. The benefit may be exerted by reducing the putative pathogenic antibodies or by inducing immunoregulatory T cells. The results warrant confirmation with a larger trial.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Desmielinizantes/imunologia , Imunoglobulina M/sangue , Fatores Imunológicos/uso terapêutico , Glicoproteína Associada a Mielina/imunologia , Polineuropatias/imunologia , Idoso , Anticorpos Monoclonais Murinos , Linfócitos B/efeitos dos fármacos , Doenças Desmielinizantes/complicações , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/complicações , Rituximab , Vazamento Acidental em Seveso , Linfócitos T/efeitos dos fármacos , Resultado do TratamentoRESUMO
OBJECTIVE: To examine whether selected genetic polymorphisms in the infant are associated with spontaneous preterm birth (less than 37 weeks) among children with or without later-diagnosed cerebral palsy. METHODS: Exploratory case-control study investigating the relationship of gestational age at delivery to 31 single nucleotide polymorphisms measured in newborn screening bloodspots. Among all 443 children with later-diagnosed cerebral palsy born to white women in South Australia in 1986-1999, 234 were born after spontaneous onset of labor, and 108 of these were preterm (gestational age less than 37 weeks). The comparison group was 549 infants born after spontaneous onset of labor, of whom 147 were preterm. Distributions of genotypic frequencies were examined in preterm compared with term infants with and without cerebral palsy. Genotyping was performed using a Taqman assay. RESULTS: In children without cerebral palsy, preterm birth after spontaneous onset of labor was more frequent in association with a variant of the beta2 adrenergic receptor gene (ADRB2 Q27E, P=.003), inducible nitric oxide synthase (iNOS or NOS2A, P=.042), or thrombomodulin (G127A, P=.006). Among children with cerebral palsy, preterm birth was associated with polymorphisms in genes for endothelial nitric oxide synthase (eNOS -922, P=.012), plasminogen activator inhibitor-2 (P=.015 and .019), and alpha adducin (ADD1, P=.047). CONCLUSION: We confirm previous observations that variants of the beta adrenergic receptor and of nitric oxide synthase are associated with prematurity, and suggest that genetic variants of the placental antifibrinolytic plasminogen activator inhibitor-2, and thrombomodulin and alpha adducin may be contributors to risk of spontaneous preterm birth. LEVEL OF EVIDENCE: II.
Assuntos
Paralisia Cerebral/genética , Doenças do Prematuro/genética , Polimorfismo de Nucleotídeo Único/genética , Nascimento Prematuro/genética , População Branca/genética , Estudos de Casos e Controles , Paralisia Cerebral/etnologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etnologia , Masculino , Gravidez , Austrália do Sul/epidemiologiaRESUMO
Using a double-antibody immunoaffinity assay (Luminex) and ELISA technology, we measured concentrations of certain neurotrophins, neuropeptides, and cytokines in pooled samples (one to three subjects per sample) eluted from archived neonatal blood of children with later-diagnosed autism, Down syndrome, very preterm birth, or term control infants. We also measured analytes in blood from healthy adult controls. Case or control status for infant subjects was ascertained by retrospective review of service agency medical records. We observed inhibitory substances in eluates from archived bloodspots, especially marked for measurement of BDNF. Concentrations in control subjects differed by age: BDNF rose markedly with age, while NT-3 and NT-4/5 concentrations were lower in adults than in newborn infants. IL-8 concentrations were higher in newborn infants, preterm and term, than in adults. Considered by diagnostic group, total protein was higher in Down syndrome than in either autism or control subjects. In infants with Down syndrome, concentrations of IL-8 levels were higher than in controls, whether or not corrected for total protein; NT-3 and CGRP were lower and VIP higher. In samples from autistic subjects, NT-3 levels were significantly lower than controls and an increase in VIP approached statistical significance. Concentrations of NT-4/5 and CGRP were correlated in infants with autism but not in Down syndrome or controls. Some of these results differ from earlier findings using a single-antibody recycling immunoaffinity chromatography (RIC) system. We discuss interrelationships of VIP, NT-3 and IL-8 and their potential relevance to features of the neuropathology of autism or Down syndrome.
Assuntos
Transtorno Autístico/sangue , Síndrome de Down/sangue , Interleucina-8/sangue , Neurotrofina 3/sangue , Peptídeo Intestinal Vasoativo/sangue , Adulto , Fatores Etários , Animais , Fator Neurotrófico Derivado do Encéfalo/sangue , Peptídeo Relacionado com Gene de Calcitonina/sangue , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Fatores de Crescimento Neural/sangue , Gravidez , Estudos RetrospectivosRESUMO
The Guide for the Care and Use of Laboratory Animals (Guide) recommends minimum floor space per mouse based on weight, with no other factors considered. We conducted a randomized experiment to evaluate the effect of housing density on reproductive indices and corticosterone levels in lactating mice. Female mice matched for age, strain, and date-of-pregnancy were housed individually. At parturition the dams were randomly allocated to have litters culled or remain intact. The experimental group had litters culled to meet the Guide's space density requirement. Litters of the second group were maintained as the numbers born to each dam. Fecal corticosterone levels (first-generation mice only), growth, and weaning weights were measured for mice in all cages; in addition, the reproductive behavior of progeny generated under both housing conditions was assessed to determine whether a space x litter size interaction affected subsequent reproduction. The growth rates for pups from culled litters were significantly greater than those from intact litters. The first-generation pups showed no statistically significant differences in fecal corticosterone or reproductive parameters. The second-generation pups showed no statistically significant differences in growth rates. The results of the study suggest that a strict interpretation of space requirements as listed in Table 2.1 of the Guide is not warranted for lactating dams with litters.
Assuntos
Corticosterona/sangue , Abrigo para Animais , Lactação/sangue , Reprodução/fisiologia , Animais , Peso Corporal/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Controle da População , Densidade Demográfica , Distribuição Aleatória , Isolamento Social , DesmameRESUMO
In the present study, we examine whether selected genetic polymorphisms contribute to the development of cerebral palsy (CP) in very preterm infants. Subjects were 96 singleton infants with later-diagnosed CP and 119 control children, white non-Hispanic (n for CP=74, controls=88) or white Hispanic (CP=22, controls=31), born <32 wk gestation. Presence of CP was identified through state service agencies, with review of medical records. DNA extracted from archived neonatal blood was genotyped using multi-locus polymerase chain reaction amplification and immobilized sequence-specific oligonucleotide probes. Single nucleotide polymorphisms (SNPs) showing evidence of association with development of CP were endothelial nitric oxide synthase (eNOS) A(-922)G, factor 7 (F7) arg353gln and del(-323)10bp-ins, and lymphotoxin A (LTA) thr26asn. In white non-Hispanic children, beta-2 adrenergic receptor gln27glu was associated with CP risk; in Hispanic children, plasminogen activator inhibitor-1 (PAI-1) 4G(-675)5G and G11053T were associated with risk of CP. In a logistic regression considering these SNPs simultaneously in non-Hispanics, an association with CP was observed for heterozygotes of eNOS -922 (OR 3.0, CI 1.4-6.4), F7 (OR 2.7, CI 1.1-6.5), LTA (OR 2.1, CI 1.0-4.6), and PAI-1 (OR 3.2, CI 1.2-8.7). Factor 5, Factor 2, methylene tetrahydrofolate reductase, tumor necrosis factor-alpha, and other SNPs tested were not significantly associated with CP risk. We conclude that further study of genetic factors that may influence susceptibility to CP in very preterm infants is warranted.
Assuntos
Paralisia Cerebral/genética , Recém-Nascido Prematuro , Polimorfismo Genético , Estudos de Casos e Controles , Paralisia Cerebral/diagnóstico , Pré-Escolar , Citocinas/genética , Feminino , Genótipo , Idade Gestacional , Humanos , Hipertensão/genética , Lactente , Recém-Nascido , Óxido Nítrico/genética , Gravidez , Trombose/genéticaRESUMO
Focal hand dystonia may arise as a result of aberrant plasticity from excessive repetitive use. Improvement might be possible with appropriate motor training. Focusing on trying to decrease abnormal overflow of movement to fingers not involved in a task, we developed a motor training program for individualized finger movements. Ten patients with writer's cramp participated in the motor training program. Evaluation was done with the Fahn dystonia scale, kinematic analysis of handwriting, transcranial magnetic stimulation (TMS), and electroencephalography (EEG). Clinical improvement of dystonia was significant using the Fahn dystonia scale, and 6 patients reported an improvement in writing. The handwriting analysis showed a trend for improvement after training in simple exercises. There were no changes in cortical excitability measured by TMS and EEG. Whereas this method of motor training for 4 weeks led to mild subjective improvement and some improvement in handwriting, it is not sufficient to reverse motor cortex abnormalities measured by TMS and EEG.
Assuntos
Distonia/fisiopatologia , Distonia/terapia , Mãos/fisiopatologia , Magnetismo/instrumentação , Ensino/métodos , Córtex Cerebral/fisiologia , Distonia/diagnóstico , Distúrbios Distônicos/fisiopatologia , Distúrbios Distônicos/terapia , Eletroencefalografia , Eletromiografia/instrumentação , Potencial Evocado Motor/fisiologia , Dedos/fisiologia , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Punho/fisiologiaRESUMO
BACKGROUND: Fabry disease is an underdiagnosed, treatable, X-linked, multisystem disorder. OBJECTIVES: To test the hypothesis that quality of life and sweating are decreased among pediatric patients with Fabry disease, compared with control subjects, and to provide quantitative natural history data and novel clinical end points for therapeutic trials. DESIGN: Prospective, cross-sectional, observational study. SETTING: Referral to the National Institutes of Health. PARTICIPANTS: Twenty-five male children with Fabry disease (mean age: 12.3 +/- 3.5 years) and 21 age-matched control subjects. MAIN OUTCOME MEASURES: Quality of life (measured with the Child Health Questionnaire) and sweating (assessed with the quantitative sudomotor axon reflex test). RESULTS: Quality of life scores for pediatric patients <10 years of age with Fabry disease, compared with published normative values, were 55 +/- 17 vs 83 +/- 19 for bodily pain and 62 +/- 19 vs 80 +/- 13 for mental health. Bodily pain scores for patients > or =10 years of age were 54 +/- 22 vs 74 +/- 23. Sweat volume in the Fabry disease group was 0.41 +/- 0.46 microL/mm2, compared with 0.65 +/- 0.44 microL/mm2 in the control group. Renal function, urinary protein excretion, and cardiac function and structure were normal for the majority of patients. The 3 patients with residual alpha-galactosidase A activity > or =1.5% of normal values were free of cornea verticillata and had normal serum and urinary globotriaosylceramide levels. All other children had glycolipid levels comparable to those of adult patients with Fabry disease. Acroparesthesia and cardiac abnormalities were generally present before anhidrosis and proteinuria. Mapping of the missense mutations on the crystallographic structure of alpha-galactosidase A revealed that the mutations were partially surface-exposed and distal to the active site among individuals with residual enzyme activity. Mutations associated with left ventricular hypertrophy (defined as left ventricular mass index of >51 g/m2.7) were localized near the catalytic site of the enzyme. CONCLUSIONS: Despite the absence of major organ dysfunction, Fabry disease demonstrates significant morbidity already in childhood. We have identified important, potentially correctable or preventable, outcome measures for future therapeutic trials. Prevention of complications involving major organs should be the goal for long-term specific therapy.
Assuntos
Doença de Fabry/complicações , Saúde Mental/estatística & dados numéricos , Dor/epidemiologia , Qualidade de Vida , Adolescente , Contagem de Células Sanguíneas , Tamanho Corporal , Estudos de Casos e Controles , Criança , Estudos Transversais , Doença de Fabry/fisiopatologia , Doença de Fabry/psicologia , Taxa de Filtração Glomerular , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Mutação , Dor/etiologia , Sudorese , Triexosilceramidas/sangue , alfa-Galactosidase/genéticaRESUMO
The pathologic substrate of essential tremor (ET) remains unknown. The authors studied 10 patients with ET and 10 volunteers using a multislice MR spectroscopy imaging sequence. Left and right cerebellar hemisphere NAA/CR and NAA/Cho ratios were significantly smaller in the ET patients than healthy subjects. The authors' data suggest that the decreased NAA/Cr and NAA/Cho ratios within the cerebellum may represent an abnormality in neuronal function.
Assuntos
Ácido Aspártico/análogos & derivados , Cerebelo/fisiopatologia , Tremor Essencial/fisiopatologia , Espectroscopia de Ressonância Magnética , Adulto , Idoso , Ácido Aspártico/análise , Química Encefálica , Estudos de Casos e Controles , Cerebelo/química , Colina/análise , Creatina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Some patients with focal hand dystonia have impaired sensory perception. Abnormal sensory processing may lead to problems with fine motor control. For patients with focal hand dystonia who demonstrate sensory dysfunction, sensory training may reverse sensory impairment and dystonic symptoms. We studied the efficacy of learning to read braille as a method of sensory training for patients with focal hand dystonia. Sensory spatial discrimination was evaluated in 10 patients who had focal hand dystonia and 10 age- and gender-matched controls with a spatial acuity test (JVP domes were used in this test). Clinical dystonia evaluation included the Fahn dystonia scale and time needed to write a standard paragraph. Each individual was trained in braille reading at the grade 1 level for 8 weeks, between 30 and 60 minutes daily, and was monitored closely to ensure that reading was done regularly. Both controls and patients demonstrated improvement on the spatial acuity test. Patients showed a significant mean difference from baseline to 8 weeks on the Fahn dystonia scale. Sixty percent of the patients shortened the time they needed to write a standard paragraph. Improved sensory perception correlated positively with improvement on the Fahn dystonia scale. We conclude that training in braille reading improves deficits in spatial discrimination and decreases disability in patients with focal hand dystonia.
Assuntos
Distúrbios Distônicos/reabilitação , Mãos/fisiopatologia , Desempenho Psicomotor/fisiologia , Adulto , Aprendizagem por Discriminação/fisiologia , Distúrbios Distônicos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção/fisiologia , Limiar Sensorial/fisiologia , Estatísticas não ParamétricasRESUMO
Fabry disease is an X-linked disorder caused by a deficiency of lysosomal alpha-galactosidase A resulting in accumulation of alpha-D-galatosyl conjugated glycosphingolipids. Clinical manifestations include a small-fiber neuropathy associated with debilitating pain and hypohidrosis. We report the effect of a 3-year open-label extension of a previously reported 6-month placebo-controlled enzyme replacement therapy (ERT) trial in which 26 hemizygous patients with Fabry disease received 0.2 mg/kg of alpha-galactosidase A every 2 weeks. The effect of ERT on neuropathic pain scores while off pain medications, quantitative sensory testing, quantitative sudomotor axon reflex test (QSART), and thermoregulatory sweat test (TST) is reported. In the patients who crossed-over from placebo to ERT (n = 10), mean pain-at-its-worst scores on a 0-10 scale decreased (from 6.9 to 4.5). There was a significant reduction in the threshold for cold and warm sensation in the foot. At the 3-year time-point, pre-ERT sweat excretion in 17 Fabry patients was 0.24 +/- 0.33 microl/mm(2) vs. 1.05 +/- 0.81 in concurrent controls (n = 38). Sweat function improved 24-72 h post-enzyme infusion (0.57 +/- 0.71 microl/mm(2)) and normalized in four anhidrotic patients. TST confirmed the QSART results. We conclude that prolonged ERT in Fabry disease leads to a modest but significant improvement in the clinical manifestations of the small-fiber neuropathy associated with this disorder. QSART may be useful to further optimize the dose and frequency of ERT.
Assuntos
Doença de Fabry/terapia , Nervos Periféricos/fisiopatologia , Sudorese/fisiologia , alfa-Galactosidase/uso terapêutico , Adulto , Axônios/fisiologia , Regulação da Temperatura Corporal/fisiologia , Método Duplo-Cego , Doença de Fabry/fisiopatologia , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Exame Neurológico , Dor/etiologia , Dor/fisiopatologia , Medição da Dor , Reflexo/fisiologia , Sensação , VibraçãoRESUMO
Little is known about the effect of enzyme replacement therapy (ERT) on the bone abnormalities in Gaucher disease. Splenectomized Gaucher patients tend to suffer the most severe skeletal complications. We hypothesized that vitamin D supplementation would act synergistically with glucocerebrosidase infusions to increase bone density in splenectomized Gaucher patients. In a 24-month study, 29 splenectomized Gaucher patients were randomized to three groups: Group 1, calcitriol (1,25-dihydroxyvitamin D3; 0.25-3.0 microg/day) alone for the first 6 months with the addition of ceredase/cerezyme at 60 IU/kg every 2 weeks during months 7-12; Group 2, calcitriol together with ceredase/cerezyme at 60 IU/kg every 2 weeks during months 1-6; and Group 3, enzyme only at 60 IU/kg body wt every 2 weeks. In all three groups, enzyme dose was halved after the first 6 months of therapy. The primary outcome measure was bone mineral density of the lumbar spine measured by single-energy quantitative CT. Bone density by single-energy CT (P = 0.001) and by dual-energy CT (P = 0.06) declined overall, but there was no significant difference between the groups. Calcitriol had no significant effect on bone density. Fat fraction in lumbar spine increased (P = 0.000) and skeletal MRI scores improved. Bone-specific alkaline phosphatase (P = 0.002) and serum osteocalcin increased (P = 0.008), while blood cyclic AMP and urinary deoxypyridinoline did not change appreciably. Hemoglobin, platelet counts, and liver volume significantly improved. We conclude that ERT alone, or in combination with calcitriol, cannot repair the bone composition in splenectomized adult Gaucher patients. Alternatively, measuring trabecular bone density may be an inadequate marker of clinical efficacy for treating skeletal involvement in Gaucher disease.
Assuntos
Densidade Óssea/efeitos dos fármacos , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/fisiopatologia , Glucosilceramidase/administração & dosagem , Adulto , Biomarcadores/análise , Densidade Óssea/fisiologia , Calcitriol/administração & dosagem , Quimioterapia Combinada , Enzimas/administração & dosagem , Feminino , Doença de Gaucher/complicações , Humanos , Região Lombossacral/fisiopatologia , Masculino , Pessoa de Meia-Idade , Esplenectomia , Resultado do TratamentoRESUMO
Fabry's disease is commonly associated with a painful, debilitating neuropathy. Characterization of the physiological abnormalities is an important step in evaluating response to specific therapies. Twenty-two patients with Fabry's disease, and with relatively preserved renal function, underwent conventional and near-nerve conduction studies, electromyography, sympathetic skin responses, and quantitative sensory testing (QST). Nerve conduction studies were mostly normal except for an increased frequency of median nerve entrapment at the wrist in 6 (27%) patients. Sympathetic skin responses were preserved in 19 of 20 (95%) of the patients. The QST showed increased or immeasurable cold and warm detection thresholds in patients, significantly different from controls (n = 28) in the hand (P < 0.001, P = 0.04, respectively) and foot (P < 0.001 for both). Cold thresholds were more often abnormal than were warm thresholds. Vibration thresholds were normal in the feet and, in some patients, elevated in the hand only, probably due to frequent median nerve entrapment at the wrist. Our findings suggest that the neuropathy of Fabry's disease is characterized by an increased prevalence of median nerve entrapment at the wrist and by thermal afferent fiber dysfunction in a length-dependent fashion, with greater impairment of cold than warm sensation.
Assuntos
Doença de Fabry/fisiopatologia , Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adulto , Doença de Fabry/patologia , Feminino , Humanos , Masculino , Mecanorreceptores/fisiologia , Pessoa de Meia-Idade , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/patologia , Fibras Nervosas Amielínicas/fisiologia , Condução Nervosa/fisiologia , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/patologia , Limiar Sensorial/fisiologia , Fibras Simpáticas Pós-Ganglionares/patologia , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Sensação Térmica/fisiologiaRESUMO
To examine the relationship of cytokines in blood of very preterm neonates with later diagnosis of spastic cerebral palsy (CP) compared with infants of similar gestational age without CP, we measured concentrations of inflammatory cytokines and other substances in archived neonatal blood by recycling immunoaffinity chromatography. Subjects were surviving children born before 32 wk gestational age (GA) to women without preeclampsia, 64 with later diagnoses of CP and 107 control children. The initial analyses were augmented by measurement of 11 cytokines by a bead-based flow analytic system (Luminex) in an additional 37 children with CP and 34 control children from the same cohort. Concentrations of examined substances did not differ by presence of indicators of infection in mother, infant, or placenta. On ANOVA, concentrations of a number of cytokines were significantly related to neonatal ultrasound abnormalities (periventricular leukomalacia, ventricular enlargement, or moderate or severe germinal matrix hemorrhage). None of the substances measured either by immunoaffinity chromatography or flow analytic methods, including IL-1, -6, and -8 and tumor necrosis factor-alpha, was related to later diagnosis of CP or its subtypes. Inflammatory cytokines in neonatal blood of very premature infants did not distinguish those with later diagnoses of CP from control children.