Adverse antiepileptic drug effects in new-onset seizures: a case-control study.

OBJECTIVE: Adverse effects (AEs) are a major concern when starting antiepileptic drug (AED) treatment. This study quantified the extent to which AE reporting in people with new-onset seizures started on AEDs is attributable to the medication per se, and investigated variables contributing to AE reporting. METHODS: We pooled data from 2 large prospective studies, the Multicenter Study of Early Epilepsy and Single Seizures and the Northern Manhattan Study of incident unprovoked seizures, and compared adverse event profile (AEP) total and factor scores between adult cases prescribed AEDs for new-onset seizures and untreated controls, adjusting for several demographic and clinical variables. Differences in AEP scores were also tested across different AED monotherapies and controls, and between cases and controls grouped by number of seizures. RESULTS: A total of 212 cases and 206 controls were identified. Most cases (94.2%) were taking low AED doses. AEP scores did not differ significantly between the 2 groups. Depression, female gender, symptomatic etiology, younger seizure onset age, ≥2 seizures, and history of febrile seizures were associated with higher AEP scores. There were no significant differences in AEP scores across different monotherapies and controls. AEP scores increased in both cases and controls with increasing number of seizures, the increment being more pronounced in cases. CONCLUSIONS: When AED treatment is started at low doses following new-onset seizures, AE reporting does not differ from untreated individuals. Targeting specific factors affecting AE reporting could lead to improved tolerability of epilepsy treatment.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. METHODS: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. RESULTS: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. RECOMMENDATIONS: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. METHODS: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. RESULTS: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%-92%) of remaining seizure-free during pregnancy. RECOMMENDATIONS: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

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).

How common are the "common" neurologic disorders?

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.

Indentation properties of young and old osteons.

The purpose of this study was to quantify differences in indentation modulus and microhardness between labeled osteons identified by epifluorescent microscopy and neighboring unlabeled osteons. In microradiographs and backscattered images, newly formed osteons appear more radiolucent (darker) than older osteons. This is ascribed to incomplete mineralization of the osteon. However, the mechanical properties of these young osteons are unknown. Nine femoral cross-sectional specimens were obtained from five skeletally mature dogs. Prior to death, the dogs received a pair of calcein bone labels. Labeled osteons were identified under an epiflourescent microscope. Bone specimens were transferred to a nanoindenter specimen holder, and the previous identified labeled osteons were located. Labeled (n = 102) and unlabeled (n = 101) osteons were examined by instrumented indentation testing. Indents were made to a depth of 500 nm at a loading rate of 10 nm/second. There were significant differences in the indentation modulus (P < 0.001) of labeled (10.02 +/- 3.61 gigapascal (GPa), mean +/- standard deviation) and unlabeled (15.11 +/- 3.72 GPa) osteons. Similar differences existed in microhardness measurements. Newly formed osteons had lower modulus (34%) and hardness (41%) than older osteons found in femoral cross sections. These data provide information on the indentation moduli of osteons during an early phase of mineralization compared to osteons that have completed mineralization.

Emergency department visits associated with traumatic brain injury: United States, 1995-1996.

The purposes of this study were to provide a national estimate of the incidence of traumatic brain injuries (TBIs) seen in emergency departments (EDs), but not requiring hospitalization and to determine the causes of these injuries. Using the Centers for Disease Control and Prevention case definition of TBI, ED data was analysed from the National Hospital Ambulatory Medical Care Survey (1995-1996). The average overall incidence rate of TBI-related ED visits for persons who were not hospitalized was 392/100,000 population per year, or 1,027,000 visits to hospital EDs in the US each year. This estimate is nearly twice (392 vs. 216) the previously estimated incidence rate, which was based on data from the 1991 National Health Interview Survey Injury Supplement. It was found that the highest incidence rate occurred among children aged 0-14 years, the rate for males was higher than for females, and the primary reported causes of these injuries were 'falls', motor vehicle-related causes, and 'struck by an object'. Although often considered 'mild' TBIs, these injuries can lead to significant cognitive and emotional impairment. Thus, continued surveillance of TBI-related ED visits is an important part of a comprehensive TBI prevention strategy.

Trends in hospitalization associated with traumatic brain injury.

CONTEXT: Traumatic brain injury (TBI) is associated with more than 50000 deaths in the United States each year, and recent observations suggest a substantial decline in TBI-related hospitalizations and deaths. OBJECTIVE: To analyze long-term trends in TBI-related hospitalization in the United States. DESIGN, SETTING, AND PARTICIPANTS: Analysis of existing data from 1980 through 1995 from the National Hospital Discharge Survey, an annual survey representing the US general population. The number of participating hospitals ranged from 400 to 494. MAIN OUTCOME MEASURES: Annual rates of TBI-related hospitalization, stratified by age, sex, severity of injury, and outcome. RESULTS: The annual number of TBI cases identified from the sample during the study period ranged from 1611 to 3129. Overall rates of hospitalization for TBI declined an estimated 51%, from 199 to 98 per 100000 per year. When analyzed by severity of injury, mild TBIs declined most during this period, from 130 to 51 hospitalizations per 100000 per year (61% decline; P<.001 compared with intermediate and severe TBI). The decline was greatest among those aged 5-14 years (-66%) and least among those aged 65 years or older (-9%). The ratio of male to female rates showed little variation during the study period (ratio, 1.8; 95% confidence interval [CI], 1.6-2.0), as did the in-hospital mortality rate (mean, 5.3 per 100000; 95% CI, 3.6-7.1). CONCLUSIONS: Changes in hospital practices may be a major factor in the declining rates of TBI-related hospital admissions. These practices increasingly appear to exclude persons with less severe TBI from hospital admission and shift their care to outpatient settings.

Traumatic brain injury in the United States: A public health perspective.

Traumatic brain injury (TBI) is a leading cause of death and disability among persons in the United States. Each year, an estimated 1.5 million Americans sustain a TBI. As a result of these injuries, 50,000 people die, 230,000 people are hospitalized and survive, and an estimated 80,000-90,000 people experience the onset of long-term disability. Rates of TBI-related hospitalization have declined nearly 50% since 1980, a phenomenon that may be attributed, in part, to successes in injury prevention and also to changes in hospital admission practices that shift the care of persons with less severe TBI from inpatient to outpatient settings. The magnitude of TBI in the United States requires public health measures to prevent these injuries and to improve their consequences. State surveillance systems can provide reliable data on injury causes and risk factors, identify trends in TBI incidence, enable the development of cause-specific prevention strategies focused on populations at greatest risk, and monitor the effectiveness of such programs. State follow-up registries, built on surveillance systems, can provide more information regarding the frequency and nature of disabilities associated with TBI. This information can help states and communities to design, implement, and evaluate cost-effective programs for people living with TBI and for their families, addressing acute care, rehabilitation, and vocational, school, and community support.

The epidemiology of sports-related traumatic brain injuries in the United States: recent developments.

We examined recent population-based data from the National Health Interview Survey, Consumer Product Safety Commission, and state-based traumatic brain injury (TBI) surveillance programs that provide estimates of the overall incidence of sports-related TBI in the United States. Available data indicate that sports-related TBI is an important public health problem because of the large number of people who incur these injuries each year (approximately 300,000), the generally young age of patients at the time of injury (with possible long-term disability), and the potential cumulative effects of repeated injuries. The importance of this problem indicates the need for more effective prevention measures. The public health approach can guide efforts in injury prevention and control. The steps in this approach are (1) identifying the problem, (2) identifying risk factors, (3) developing and testing interventions, and (4) implementing programs and evaluating outcomes. Each of these steps requires adequate data. This article examines the limitations of current sports-related TBI data and suggests ways to improve data in order to develop more effective injury prevention strategies. The impact of sports-related TBI on the public indicates that this task deserves a high priority.

The isolation and characterization of type II metallothionein-like genes from tomato (Lycopersicon esculentum L.).

Two cDNAs encoding putative metallothionein (MT)-like peptides have been isolated from tomato (L. esculentum L.). The predicted protein products of these two cDNAs (LeMT(A) and LeMT(B)) are 72 and 83 amino acids respectively and both encode peptides with arrangements of cysteine residues characteristic of type II plant MTs. In other plants which possess more than one gene expressing MT proteins of the same type, the products are closely related or identical, but LeMT(A) and LeMT(B) constitute two different classes of message, and encode two different protein products. Northern blot analysis of LeMT(A) and LeMT(B) showed that transcripts of both MT-like genes were more abundant in leaves than roots in tomato plants grown without addition of extra metal ions, a characteristic of type II MTs. A genomic clone corresponding to LeMT(B) (LeMT(B)) was isolated and sequenced. The 5'-flanking region of LeMT(B) was shown to contain a putative metal regulatory element (MRE) which suggests the possibility of metal-regulated transcription. In addition, the upstream region also contains a G-box like motif (CACGTG) and an 8 bp sequence (AATTCAAA) found within the promoters of genes shown to be ethylene-responsive.

Surveillance of traumatic brain injuries in Utah.

From 1990 through 1992 we conducted surveillance of cases requiring hospital admission and of fatal cases of traumatic brain injury among residents of Utah and found an annual incidence rate of 108.8 per 100,000 population. The greatest number of injuries occurred among men and persons aged 15 to 24 years. Motor vehicles were the leading cause of injury, followed by falls and assaults. The incidence rate we found is substantially lower than previously published rates of traumatic brain injury. This may be the result of a decrease in the incidence of these injuries in the decade since earlier studies were done, as well as changing hospital admission criteria that serve to exclude less severe cases of injury. Despite the apparent decline in rates, our findings indicate the continued importance of traumatic brain injury as a public health problem and the need to develop more effective prevention strategies that will address the major causes of these injuries.

Incidence of mild and moderate brain injury in the United States, 1991.

The 1991 National Health Interview Survey was analysed to describe the incidence of mild and moderate brain injury in the United States. Data were collected from 46 761 households and weighted to reflect all non-institutionalized civilians. The report of one or more occurrences of head injury resulting in loss of consciousness in the previous 12 months was the main outcome measure. Each year an estimated 1.5 million non-institutionalized US civilians sustain a non-fatal brain injury that does not result in institutionalization, a rate of 618 per 100,000 person-years. Motor vehicles were involved in 28% of the brain injuries, sports and physical activity were responsible for 20%, and assaults were responsible for 9%. Medical care was sought by 75% of those with brain injury; 14% were treated in clinics or offices, 35% were treated in emergency departments, and 25% were hospitalized. The risk of medically attended brain injury was highest among three subgroups: teens and young adults, males, and persons with low income who lived alone. The incidence of mild and moderate brain injury in the United States is substantial. The National Health Interview Survey is an important national source of current outpatient brain-injury data.

Risk factors and mechanisms of occurrence in motor vehicle-related spinal cord injuries: Utah.

The purpose of this paper is to describe the incidence, risk factors, and crash factors of motor-vehicle-related spinal cord injuries in Utah. The Utah Department of Health established a statewide registry of spinal cord injuries (SCIs) occurring in 1989-1991, analyzing data from hospital medical records and police reports. Forty-nine percent of all SCIs involved motor vehicles, including injuries arising from motor vehicle collisions with bicyclists and pedestrians. Adolescent and young adult males were at highest risk of injury. Among occupants of automobiles and trucks with SCI, 70% were involved in a vehicle rollover, while 39% were ejected from the vehicle. Only 25% reported using seatbelts. SCIs were much more likely to be associated with rollover compared with other types of motor vehicle-occupant injuries. These findings suggest areas in which SCI prevention programs and research should be focused.

Surveillance of spinal cord injuries in Utah, USA.

From 1989 through 1991, we conducted surveillance of spinal cord injury (SCI) among residents of Utah. We found an annual incidence rate of 4.3 per 100,000, with the highest rates occurring among males 15-24 years of age. Motor vehicles were the leading cause of injury, followed by falls, and sports and recreation. We also examined the accuracy and completeness of reporting in this surveillance system. We found the predictive value positive of SCI diagnoses reported in hospital discharge data to be only 61%. When we considered only patients who received acute hospital care in-state, we found that the sensitivity of hospital discharge data 89%. These findings indicate serious problems in the reporting of spinal cord injury diagnoses in hospital discharge data and the need to verify case reports based on these data. There is also a need to study this problem in other jurisdictions to determine if overreporting is widespread.

Submersion injuries in children younger than 5 years in urban Utah.

Submersion injuries of children younger than 5 years in 4 urban Utah counties from 1984 through 1988 were studied retrospectively to identify associated risk factors. Infants younger than 1 year had the highest rates of both submersion injuries and deaths. The incidence of bathtub drownings was 2 to 3 times higher than reported national rates. All bathtub drownings occurred while the victim was bathing with a young sibling (10 months to 7 years of age) without adult supervision. All drownings in pools and moving bodies of water (rivers, irrigation ditches) resulted from unintentional falls into the water rather than from swimming and wading activities. Drowning prevention strategies should focus on educating parents about the risk of young children bathing with siblings in the absence of adult supervision and fencing regulations for pools and open bodies of moving water.