ABSTRACT
Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.
Subject(s)
Autism Spectrum Disorder/etiology , Autistic Disorder/etiology , Adult , Female , Fever/complications , Genetic Linkage , Gestational Age , Humans , Immunity, Innate/immunology , Infant , Infant, Newborn , Infections/complications , Male , Maternal Exposure , Mothers , Norway , Odds Ratio , Pregnancy , Pregnancy Trimester, Second/physiology , Prenatal Exposure Delayed Effects , Prospective Studies , Registries , Risk Factors , Surveys and QuestionnairesABSTRACT
OBJECTIVE: To assess the efficacy and safety of adding propranolol to topiramate in chronic migraine subjects inadequately controlled with topiramate alone. METHODS: This was a double-blind, placebo-controlled, randomized clinical trial conducted through the National Institute of Neurological Disorders and Stroke Clinical Research Collaboration, expected to randomize 250 chronic migraine subjects inadequately controlled (≥10 headaches/month) with topiramate (50-100 mg/day) to either propranolol LA (long acting) (240 mg/day) or placebo. Primary outcome was 28-day moderate to severe headache rate reduction at 6 months (weeks 16 to 24) compared with baseline (weeks -4 to 0). RESULTS: A planned interim analysis was performed after 48 sites randomized 171 subjects. The data and safety monitoring board recommended ending the trial after determining that it would be highly unlikely for the combination to result in a significant reduction in 28-day headache rate compared with topiramate alone if all 250 subjects were randomized. No safety concerns were identified. At study closure, 191 subjects were randomized. The 6-month reduction in moderate to severe 28-day headache rate and total 28-day headache rate for combination therapy vs topiramate alone was not significantly different: 4.0 vs 4.5 days (moderate to severe 28-day headache rate; p = 0.57) and 6.2 vs 6.1 days (total 28-day headache rate; p = 0.91). CONCLUSIONS: This study does not provide evidence that the addition of propranolol LA to topiramate adds benefit when chronic migraine is inadequately controlled with topiramate alone. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that propranolol LA, added to topiramate, is ineffective in chronic migraine patients who fail topiramate monotherapy.
Subject(s)
Fructose/analogs & derivatives , Migraine Disorders/drug therapy , Migraine Disorders/pathology , Propranolol/administration & dosage , Adolescent , Adult , Aged , Chronic Disease , Double-Blind Method , Drug Therapy, Combination , Female , Follow-Up Studies , Fructose/administration & dosage , Humans , Male , Middle Aged , Topiramate , Treatment Outcome , Young AdultABSTRACT
The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a 'nested case-control' design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.
Subject(s)
Autistic Disorder/etiology , Child Development Disorders, Pervasive/etiology , Genomics/methods , Population Surveillance/methods , Adult , Autistic Disorder/genetics , Autistic Disorder/metabolism , Case-Control Studies , Child , Child Development Disorders, Pervasive/diagnosis , Child Development Disorders, Pervasive/genetics , Cohort Studies , Early Diagnosis , Female , Humans , Male , Risk FactorsABSTRACT
OBJECTIVE: To evaluate published evidence of efficacy and safety of pharmacologic treatments for childhood spasticity due to cerebral palsy. METHODS: A multidisciplinary panel systematically reviewed relevant literature from 1966 to July 2008. RESULTS: For localized/segmental spasticity, botulinum toxin type A is established as an effective treatment to reduce spasticity in the upper and lower extremities. There is conflicting evidence regarding functional improvement. Botulinum toxin type A was found to be generally safe in children with cerebral palsy; however, the Food and Drug Administration is presently investigating isolated cases of generalized weakness resulting in poor outcomes. No studies that met criteria are available on the use of phenol, alcohol, or botulinum toxin type B injections. For generalized spasticity, diazepam is probably effective in reducing spasticity, but there are insufficient data on its effect on motor function and its side-effect profile. Tizanidine is possibly effective, but there are insufficient data on its effect on function and its side-effect profile. There were insufficient data on the use of dantrolene, oral baclofen, and intrathecal baclofen, and toxicity was frequently reported. RECOMMENDATIONS: For localized/segmental spasticity that warrants treatment, botulinum toxin type A should be offered as an effective and generally safe treatment (Level A). There are insufficient data to support or refute the use of phenol, alcohol, or botulinum toxin type B (Level U). For generalized spasticity that warrants treatment, diazepam should be considered for short-term treatment, with caution regarding toxicity (Level B), and tizanidine may be considered (Level C). There are insufficient data to support or refute use of dantrolene, oral baclofen, or continuous intrathecal baclofen (Level U).
Subject(s)
Botulinum Toxins, Type A/therapeutic use , Cerebral Palsy/drug therapy , Clonidine/analogs & derivatives , Diazepam/therapeutic use , Adolescent , Child , Clonidine/therapeutic use , Humans , Muscle Relaxants, Central/therapeutic use , Muscle Spasticity/drug therapy , Neuromuscular Agents/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities. AIM: To identify factors that contribute to brain damage in ELGANs. STUDY DESIGN: Multi-center cohort study. SUBJECTS: We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots. OUTCOME MEASURES: Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders. RESULTS: ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery; greater neonatal illness severity; severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis. CONCLUSIONS: In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma.
Subject(s)
Brain Diseases/etiology , Infant, Extremely Low Birth Weight , Infant, Premature, Diseases/etiology , Infant, Premature , Adult , Brain Diseases/complications , Brain Diseases/congenital , Brain Diseases/diagnosis , Bronchopulmonary Dysplasia/complications , Bronchopulmonary Dysplasia/epidemiology , Child Development/physiology , Cohort Studies , Female , Gestational Age , Humans , Infant, Extremely Low Birth Weight/growth & development , Infant, Extremely Low Birth Weight/physiology , Infant, Newborn , Infant, Premature/growth & development , Infant, Premature/physiology , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/epidemiology , Perinatal Care , Placenta Diseases/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Risk Factors , Young AdultABSTRACT
OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. METHODS: Systematic review of relevant articles published between January 1985 and June 2007. RESULTS: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. RECOMMENDATIONS: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).
Subject(s)
Abnormalities, Drug-Induced/etiology , Anticonvulsants/adverse effects , Cognition Disorders/chemically induced , Epilepsy/drug therapy , Pregnancy Complications/drug therapy , Anticonvulsants/therapeutic use , Birth Weight/drug effects , Contraindications , Drug Therapy, Combination , Female , Humans , Infant, Newborn , Pregnancy , Prenatal Exposure Delayed Effects , Risk , Valproic Acid/adverse effects , Valproic Acid/therapeutic useABSTRACT
OBJECTIVE: To estimate the current incidence and prevalence in the United States of 12 neurologic disorders. METHODS: We summarize the strongest evidence available, using data from the United States or from other developed countries when US data were insufficient. RESULTS: For some disorders, prevalence is a better descriptor of impact; for others, incidence is preferable. Per 1,000 children, estimated prevalence was 5.8 for autism spectrum disorder and 2.4 for cerebral palsy; for Tourette syndrome, the data were insufficient. In the general population, per 1,000, the 1-year prevalence for migraine was 121, 7.1 for epilepsy, and 0.9 for multiple sclerosis. Among the elderly, the prevalence of Alzheimer disease was 67 and that of Parkinson disease was 9.5. For diseases best described by annual incidence per 100,000, the rate for stroke was 183, 101 for major traumatic brain injury, 4.5 for spinal cord injury, and 1.6 for ALS. CONCLUSIONS: Using the best available data, our survey of a limited number of disorders shows that the burden of neurologic illness affects many millions of people in the United States.
Subject(s)
Nervous System Diseases/epidemiology , Proportional Hazards Models , Risk Assessment/methods , Bias , Data Interpretation, Statistical , Developed Countries/statistics & numerical data , Humans , Incidence , Prevalence , Reproducibility of Results , Risk Factors , Sample Size , United States/epidemiologyABSTRACT
OBJECTIVE: To review evidence on the assessment of the child with status epilepticus (SE). METHODS: Relevant literature were reviewed, abstracted, and classified. When data were missing, a minimum diagnostic yield was calculated. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: Laboratory studies (Na(++) or other electrolytes, Ca(++), glucose) were abnormal in approximately 6% and are generally ordered as routine practice. When blood or spinal fluid cultures were done on these children, blood cultures were abnormal in at least 2.5% and a CNS infection was found in at least 12.8%. When antiepileptic drug (AED) levels were ordered in known epileptic children already taking AEDs, the levels were low in 32%. A total of 3.6% of children had evidence of ingestion. When studies for inborn errors of metabolism were done, an abnormality was found in 4.2%. Epileptiform abnormalities occurred in 43% of EEGs of children with SE and helped determine the nature and location of precipitating electroconvulsive events (8% generalized, 16% focal, and 19% both). Abnormalities on neuroimaging studies that may explain the etiology of SE were found in at least 8% of children. RECOMMENDATIONS: Although common clinical practice is that blood cultures and lumbar puncture are obtained if there is a clinical suspicion of a systemic or CNS infection, there are insufficient data to support or refute recommendations as to whether blood cultures or lumbar puncture should be done on a routine basis in children in whom there is no clinical suspicion of a systemic or CNS infection (Level U). AED levels should be considered when a child with treated epilepsy develops SE (Level B). Toxicology studies and metabolic studies for inborn errors of metabolism may be considered in children with SE when there are clinical indicators for concern or when the initial evaluation reveals no etiology (Level C). An EEG may be considered in a child with SE as it may be helpful in determining whether there are focal or generalized epileptiform abnormalities that may guide further testing for the etiology of SE, when there is a suspicion of pseudostatus epilepticus (nonepileptic SE), or nonconvulsive SE, and may guide treatment (Level C). Neuroimaging may be considered after the child with SE has been stabilized if there are clinical indications or if the etiology is unknown (Level C). There is insufficient evidence to support or refute routine neuroimaging in a child presenting with SE (Level U).
Subject(s)
Anticonvulsants/therapeutic use , Clinical Laboratory Techniques/standards , Neurology/standards , Status Epilepticus/diagnosis , Anticonvulsants/analysis , Anticonvulsants/metabolism , Blood Chemical Analysis/standards , Brain Diseases, Metabolic, Inborn/diagnosis , Brain Diseases, Metabolic, Inborn/genetics , Child , Communicable Diseases/complications , Communicable Diseases/diagnosis , Diagnostic Imaging/standards , Drug-Related Side Effects and Adverse Reactions/diagnosis , Electroencephalography/standards , Evidence-Based Medicine , Genetic Testing/standards , Humans , Spinal Puncture/standards , Status Epilepticus/drug therapy , Status Epilepticus/etiology , Toxicology/standardsABSTRACT
Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of infancy. SMA type I is the most severe and mortality is usually due to respiratory failure. In type II the disability is of later onset and less severe, and prognosis has improved primarily due to supportive care. Type III is the mildest form with onset usually of weakness in adolescence or young adulthood. SMA is an autosomal recessive disorder with deletions or mutations of the gene at the 5 q11 locus. There is no specific prevention or treatment, but current progress toward potential therapies has been substantial and several candidates including histone deacetylase (HDAC) inhibitors are under consideration for further evaluation. The authors sought to address the challenges and opportunities for testing new therapies for SMA.
Subject(s)
Clinical Protocols/standards , Muscular Atrophy, Spinal/therapy , Child , Child, Preschool , Clinical Trials as Topic/standards , Cyclic AMP Response Element-Binding Protein/agonists , Cyclic AMP Response Element-Binding Protein/metabolism , Drug Design , Enzyme Inhibitors/therapeutic use , Histone Deacetylase Inhibitors , Humans , Infant , Infant, Newborn , International Cooperation , Motor Neurons/metabolism , Multicenter Studies as Topic/standards , Muscular Atrophy, Spinal/genetics , Muscular Atrophy, Spinal/physiopathology , Nerve Tissue Proteins/agonists , Nerve Tissue Proteins/metabolism , RNA-Binding Proteins/agonists , RNA-Binding Proteins/metabolism , Registries/standards , SMN Complex ProteinsABSTRACT
OBJECTIVE: To review evidence on the pharmacologic treatment of the child with migraine headache. METHODS: The authors reviewed, abstracted, and classified relevant literature. Recommendations were based on a four-tiered scheme of evidence classification. Treatment options were separated into medications for acute headache and preventive medications. RESULTS: The authors identified and reviewed 166 articles. For acute treatment, five agents were reviewed. Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs placebo. Acetaminophen is probably effective and is well tolerated vs placebo. Rizatriptan and zolmitriptan were safe and well tolerated but were not superior to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is probably effective. The data concerning cyproheptadine, amitriptyline, divalproex sodium, topiramate, and levetiracetam were insufficient. Conflicting data were found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine did not show efficacy. CONCLUSIONS: For children (>age 6 years), ibuprofen is effective and acetaminophen is probably effective and either can be considered for the acute treatment of migraine. For adolescents (>12 years of age), sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine. For preventive therapy, flunarizine is probably effective and can be considered, but is not available in the United States. There are conflicting or insufficient data to make any other recommendations for the preventive therapy of migraine in children and adolescents. For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials.
Subject(s)
Analgesics/therapeutic use , Migraine Disorders/drug therapy , Adolescent , Analgesics/classification , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticonvulsants/therapeutic use , Antidepressive Agents/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Child , Child, Preschool , Cross-Over Studies , Double-Blind Method , Evidence-Based Medicine , Female , Forecasting , Humans , Male , Migraine Disorders/prevention & control , Randomized Controlled Trials as Topic , Retrospective Studies , Serotonin Receptor Agonists/therapeutic useABSTRACT
OBJECTIVE: To determine the current best practice for treatment of infantile spasms in children. METHODS: Database searches of MEDLINE from 1966 and EMBASE from 1980 and searches of reference lists of retrieved articles were performed. Inclusion criteria were the documented presence of infantile spasms and hypsarrhythmia. Outcome measures included complete cessation of spasms, resolution of hypsarrhythmia, relapse rate, developmental outcome, and presence or absence of epilepsy or an epileptiform EEG. One hundred fifty-nine articles were selected for detailed review. Recommendations were based on a four-tiered classification scheme. RESULTS: Adrenocorticotropic hormone (ACTH) is probably effective for the short-term treatment of infantile spasms, but there is insufficient evidence to recommend the optimum dosage and duration of treatment. There is insufficient evidence to determine whether oral corticosteroids are effective. Vigabatrin is possibly effective for the short-term treatment of infantile spasm and is possibly also effective for children with tuberous sclerosis. Concerns about retinal toxicity suggest that serial ophthalmologic screening is required in patients on vigabatrin; however, the data are insufficient to make recommendations regarding the frequency or type of screening. There is insufficient evidence to recommend any other treatment of infantile spasms. There is insufficient evidence to conclude that successful treatment of infantile spasms improves the long-term prognosis. CONCLUSIONS: ACTH is probably an effective agent in the short-term treatment of infantile spasms. Vigabatrin is possibly effective.
Subject(s)
Anticonvulsants/therapeutic use , Spasms, Infantile/drug therapy , Administration, Oral , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adrenocorticotropic Hormone/administration & dosage , Adrenocorticotropic Hormone/therapeutic use , Child, Preschool , Drug Therapy, Combination , Evidence-Based Medicine , Female , Follow-Up Studies , Forecasting , Humans , Infant , Male , Nitrazepam/therapeutic use , Prospective Studies , Pyridoxine/therapeutic use , Randomized Controlled Trials as Topic , Retrospective Studies , Treatment Outcome , Valproic Acid/therapeutic use , Vigabatrin/therapeutic useABSTRACT
OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.
Subject(s)
Amines , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Cyclohexanecarboxylic Acids , Epilepsy/drug therapy , Fructose/analogs & derivatives , gamma-Aminobutyric Acid , Acetates/adverse effects , Acetates/pharmacokinetics , Acetates/therapeutic use , Acute Disease , Adolescent , Adult , Anticonvulsants/pharmacokinetics , Carbamazepine/adverse effects , Carbamazepine/analogs & derivatives , Carbamazepine/pharmacokinetics , Carbamazepine/therapeutic use , Child , Controlled Clinical Trials as Topic/statistics & numerical data , Drug Interactions , Evidence-Based Medicine/statistics & numerical data , Fructose/adverse effects , Fructose/pharmacokinetics , Fructose/therapeutic use , Gabapentin , Humans , Lamotrigine , Oxcarbazepine , Topiramate , Treatment Outcome , Triazines/adverse effects , Triazines/pharmacokinetics , Triazines/therapeutic useABSTRACT
OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.
Subject(s)
Amines , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Cyclohexanecarboxylic Acids , Epilepsies, Partial/drug therapy , Epilepsy, Generalized/drug therapy , Fructose/analogs & derivatives , gamma-Aminobutyric Acid , Acetates/adverse effects , Acetates/therapeutic use , Adult , Carbamazepine/adverse effects , Carbamazepine/analogs & derivatives , Carbamazepine/therapeutic use , Child , Clinical Trials as Topic/statistics & numerical data , Drug Resistance , Evidence-Based Medicine/statistics & numerical data , Fructose/adverse effects , Fructose/therapeutic use , Gabapentin , Humans , Isoxazoles/adverse effects , Isoxazoles/therapeutic use , Lamotrigine , Levetiracetam , Nipecotic Acids/adverse effects , Nipecotic Acids/therapeutic use , Oxcarbazepine , Piracetam/adverse effects , Piracetam/analogs & derivatives , Piracetam/therapeutic use , Tiagabine , Topiramate , Treatment Outcome , Triazines/adverse effects , Triazines/therapeutic use , ZonisamideABSTRACT
OBJECTIVE: To make evidence-based recommendations concerning the evaluation of the child with a nonprogressive global developmental delay. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: Global developmental delay is common and affects 1% to 3% of children. Given yields of about 1%, routine metabolic screening is not indicated in the initial evaluation of a child with global developmental delay. Because of the higher yield (3.5% to 10%), even in the absence of dysmorphic features or features suggestive of a specific syndrome, routine cytogenetic studies and molecular testing for the fragile X mutation are recommended. The diagnosis of Rett syndrome should be considered in girls with unexplained moderate to severe developmental delay. Additional genetic studies (e.g., subtelomeric chromosomal rearrangements) may also be considered in selected children. Evaluation of serum lead levels should be restricted to those children with identifiable risk factors for excessive lead exposure. Thyroid studies need not be undertaken (unless clinically indicated) if the child underwent newborn screening. An EEG is not recommended as part of the initial evaluation unless there are historical features suggestive of epilepsy or a specific epileptic syndrome. Routine neuroimaging, with MRI preferred to CT, is recommended particularly if abnormalities are found on physical examination. Because of the increased incidence of visual and auditory impairments, children with global developmental delay may undergo appropriate visual and audiometric assessment at the time of diagnosis. CONCLUSIONS: A specific etiology can be determined in the majority of children with global developmental delay. Certain routine screening tests are indicated and depending on history and examination findings, additional specific testing may be performed.
Subject(s)
Developmental Disabilities/diagnosis , Algorithms , Child , Cytogenetic Analysis , Developmental Disabilities/etiology , Diagnosis, Differential , Electroencephalography , Evidence-Based Medicine , Female , Fragile X Syndrome/complications , Fragile X Syndrome/diagnosis , Hearing Disorders/diagnosis , Hearing Disorders/etiology , Humans , Lead Poisoning, Nervous System, Childhood/complications , Lead Poisoning, Nervous System, Childhood/diagnosis , Magnetic Resonance Imaging , Male , Metabolism, Inborn Errors/complications , Metabolism, Inborn Errors/diagnosis , Rett Syndrome/complications , Rett Syndrome/diagnosis , Thyroid Diseases/complications , Thyroid Diseases/diagnosis , Tomography, X-Ray Computed , Vision Disorders/diagnosis , Vision Disorders/etiologyABSTRACT
The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence regarding risks and benefits. This parameter reviews published literature relevant to the decision to begin treatment after a child or adolescent experiences a first unprovoked seizure and presents evidence-based practice recommendations. Reasons why treatment may be considered are discussed. Evidence is reviewed concerning risk of recurrence as well as effect of treatment on prevention of recurrence and development of chronic epilepsy. Studies of side effects of anticonvulsants commonly used to treat seizures in children are also reviewed. Relevant articles are classified according to the Quality Standards Subcommittee classification scheme. Treatment after a first unprovoked seizure appears to decrease the risk of a second seizure, but there are few data from studies involving only children. There appears to be no benefit of treatment with regard to the prognosis for long-term seizure remission. Antiepileptic drugs (AED) carry risks of side effects that are particularly important in children. The decision as to whether or not to treat children and adolescents who have experienced a first unprovoked seizure must be based on a risk-benefit assessment that weighs the risk of having another seizure against the risk of chronic AED therapy. The decision should be individualized and take into account both medical issues and patient and family preference.
Subject(s)
Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Seizures/drug therapy , Adolescent , Adult , Behavior/drug effects , Child , Child, Preschool , Clinical Trials as Topic/statistics & numerical data , Cognition/drug effects , Cohort Studies , Drug Eruptions , Follow-Up Studies , Humans , Prognosis , Remission Induction , Risk Assessment , Secondary Prevention , Seizures/classification , Seizures/diagnosis , Sleep Stages/drug effects , Treatment Outcome , United StatesABSTRACT
OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter, the authors reviewed available evidence on the evaluation of the child with recurrent headaches and made recommendations based on this evidence. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: There is inadequate documentation in the literature to support any recommendation as to the appropriateness of routine laboratory studies or performance of lumbar puncture. EEG is not recommended in the routine evaluation, as it is unlikely to define or determine an etiology or distinguish migraine from other types of headaches. In those children undergoing evaluation for recurrent headache found to have a paroxysmal EEG, the risk for future seizures is negligible; therefore, further investigation for epilepsy or treatments aimed at preventing future seizures is not indicated. Obtaining a neuroimaging study on a routine basis is not indicated in children with recurrent headaches and a normal neurologic examination. Neuroimaging should be considered in children with an abnormal neurologic examination or other physical findings that suggest CNS disease. Variables that predicted the presence of a space-occupying lesion included 1) headache of less than 1-month duration; 2) absence of family history of migraine; 3) abnormal neurologic findings on examination; 4) gait abnormalities; and 5) occurrence of seizures. CONCLUSIONS: Recurrent headaches occur commonly in children and are diagnosed on a clinical basis rather than by any testing. The routine use of any diagnostic studies is not indicated when the clinical history has no associated risk factors and the child's examination is normal.
Subject(s)
Headache/diagnosis , Headache/etiology , Neurologic Examination/standards , Adolescent , Child , Child, Preschool , Electroencephalography , Female , Humans , Magnetic Resonance Imaging , Male , Migraine Disorders/diagnosis , Predictive Value of Tests , Recurrence , Risk Factors , Spinal Puncture , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: The authors reviewed available evidence on neonatal neuroimaging strategies for evaluating both very low birth weight preterm infants and encephalopathic term neonates. IMAGING FOR THE PRETERM NEONATE: Routine screening cranial ultrasonography (US) should be performed on all infants of <30 weeks' gestation once between 7 and 14 days of age and should be optimally repeated between 36 and 40 weeks' postmenstrual age. This strategy detects lesions such as intraventricular hemorrhage, which influences clinical care, and those such as periventricular leukomalacia and low-pressure ventriculomegaly, which provide information about long-term neurodevelopmental outcome. There is insufficient evidence for routine MRI of all very low birth weight preterm infants with abnormal results of cranial US. IMAGING FOR THE TERM INFANT: Noncontrast CT should be performed to detect hemorrhagic lesions in the encephalopathic term infant with a history of birth trauma, low hematocrit, or coagulopathy. If CT findings are inconclusive, MRI should be performed between days 2 and 8 to assess the location and extent of injury. The pattern of injury identified with conventional MRI may provide diagnostic and prognostic information for term infants with evidence of encephalopathy. In particular, basal ganglia and thalamic lesions detected by conventional MRI are associated with poor neurodevelopmental outcome. Diffusion-weighted imaging may allow earlier detection of these cerebral injuries. RECOMMENDATIONS: US plays an established role in the management of preterm neonates of <30 weeks' gestation. US also provides valuable prognostic information when the infant reaches 40 weeks' postmenstrual age. For encephalopathic term infants, early CT should be used to exclude hemorrhage; MRI should be performed later in the first postnatal week to establish the pattern of injury and predict neurologic outcome.
Subject(s)
Brain Injuries/diagnosis , Infant, Newborn , Neonatal Screening/standards , Academies and Institutes/standards , Brain Injuries/diagnostic imaging , Humans , Infant, Premature , Magnetic Resonance Imaging/methods , Neonatal Screening/methods , Neurology/standards , Radiography , UltrasonographyABSTRACT
OBJECTIVE: This pharmacologic protection trial was conducted to test the hypothesis that allopurinol, a scavenger and inhibitor of oxygen free radical production, could reduce death, seizures, coma, and cardiac events in infants who underwent heart surgery using deep hypothermic circulatory arrest (DHCA). DESIGN: This was a single center, randomized, placebo-controlled, blinded trial of allopurinol in infant heart surgery using DHCA. Enrolled infants were stratified as having hypoplastic left heart syndrome (HLHS) and all other forms of congenital heart disease (non-HLHS). Drug was administered before, during, and after surgery. Adverse events and the clinical efficacy endpoints death, seizures, coma, and cardiac events were monitored until infants were discharged from the intensive care unit or 6 weeks, whichever came first. RESULTS: Between July 1992 and September 1997, 350 infants were enrolled and 348 subsequently randomized. A total of 318 infants (131 HLHS and 187 non-HLHS) underwent heart surgery using DHCA. There was a nonsignificant treatment effect for the primary efficacy endpoint analysis (death, seizures, and coma), which was consistent over the 2 strata. The addition of cardiac events to the primary endpoint resulted in a lack of consistency of treatment effect over strata, with the allopurinol treatment group experiencing fewer events (38% vs 60%) in the entire HLHS stratum, compared with the non-HLHS stratum (30% vs 27%). In HLHS surgical survivors, 40 of 47 (85%) allopurinol-treated infants did not experience any endpoint event, compared with 27 of 49 (55%) controls. There were fewer seizures-only and cardiac-only events in the allopurinol versus placebo groups. Allopurinol did not reduce efficacy endpoint events in non-HLHS infants. Treated and control infants did not differ in adverse events. CONCLUSIONS: Allopurinol provided significant neurocardiac protection in higher-risk HLHS infants who underwent cardiac surgery using DHCA. No benefits were demonstrated in lower risk, non-HLHS infants, and no significant adverse events were associated with allopurinol treatment.congenital heart defects, hypoplastic left heart syndrome, induced hypothermia, ischemia-reperfusion injury, neuroprotective agents, allopurinol, xanthine oxidase, free radicals, seizures, coma.
Subject(s)
Allopurinol/therapeutic use , Cardiac Surgical Procedures/methods , Free Radical Scavengers/therapeutic use , Heart Arrest, Induced , Heart Defects, Congenital/surgery , Hypothermia, Induced , Neuroprotective Agents/therapeutic use , Oxygen/metabolism , Coma/prevention & control , Death, Sudden, Cardiac/prevention & control , Female , Heart Arrest, Induced/methods , Heart Defects, Congenital/blood , Humans , Infant , Male , Seizures/prevention & control , Single-Blind Method , Treatment Outcome , Uric Acid/blood , Xanthine Oxidase/metabolismABSTRACT
OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient management based on analysis of evidence. For this practice parameter, the authors reviewed available evidence on evaluation of the first nonfebrile seizure in children in order to make practice recommendations based on this available evidence. METHODS: Multiple searches revealed relevant literature and each article was reviewed, abstracted, and classified. Recommendations were based on a three-tiered scheme of classification of the evidence. RESULTS: Routine EEG as part of the diagnostic evaluation was recommended; other studies such as laboratory evaluations and neuroimaging studies were recommended as based on specific clinical circumstances. CONCLUSIONS: Further studies are needed using large, well-characterized samples and standardized data collection instruments. Collection of data regarding appropriate timing of evaluations would be important.
Subject(s)
Epilepsy/diagnosis , Adolescent , Adult , Child, Preschool , Humans , Infant , Infant, Newborn , Seizures, Febrile/diagnosis , Time FactorsABSTRACT
We previously reported that IQ was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n = 217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p = 0.007). There was a nonsignificant mean difference of 3.71 IQ points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p = 0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile seizures.