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Anne T Berg

Publications and source records attributed to Anne T Berg.

At least 19 recordsLinked to original sources
PubMed2006

Concepts in classification and their relevance to epilepsy.

The classification of the epilepsies was advanced in order to formalize efforts to identify coherent clinical entities and to develop a standardized set of diagnostic terminology for facilitating communication among workers in the field world-wide. The classification initially was, and still is today, based primarily on description and expert opinion. In the era of genomics, neuroimaging and tremendous technological and scientific advances in the neurosciences, it is time to introduce scientific principles and standards into the classification of the epilepsies. Phylogenetic systematics provides an initial model worth studying in this context. While the classification of species cannot be directly applied to the classification of epilepsy syndromes, three general points can be appreciated. (1) In evolutionary biology, there is an operationalized definition of the end point (a species). There is no such definition of a syndrome. (2) There are rules and criteria for the type of evidence and how it is evaluated to determine whether an entity does or does not represent a separate species. There are currently no such rules or criteria for epilepsy syndromes. (3) There is an underlying model (evolution) that generates the diversity among species. With the possible and only partial exception of the idiopathic generalized epilepsies, there are no models to explain the diversity among the epilepsies. Previously held beliefs and convictions must, in time, give way to dispassionate examination of testable scientific hypotheses examined with rigorously collected scientific evidence. Although current classification is in need of revision, it has also come into common use and has great practical utility. Any changes to its form and to the terminology of the classification must be made only after careful deliberation and broad consensus is reached. The change(s) should be based on agreed upon scientific criteria and processes. Any changes should represent major improvements and not merely incremental steps.

Classification↗
PubMed2006

How long does it take for epilepsy to become intractable? A prospective investigation.

OBJECTIVE: To determine prospectively when in the course of epilepsy intractability becomes apparent. METHODS: Data are from a prospective cohort of 613 children followed for a median of 9.7 years. Epilepsy syndromes were grouped: focal, idiopathic, catastrophic, and other. Intractability was defined in two ways: (1) 2 drugs failed, 1 seizure/month, on average, for 18 months (stringent), and (2) failure of 2 drugs. Delayed intractability was defined as 3 or more years after epilepsy diagnosis. RESULTS: Eighty-three children (13.8%) met the stringent and 142 (23.2%) met the two-drug definition. Intractability depended on syndrome (p < 0.0001): 26 (31.3%) children meeting stringent and 39 (27.5%) meeting the 2-drug definition had delayed intractability. Intractability was delayed more often in focal than catastrophic epilepsy (stringent: 46.2 vs 14.3%, p = 0.003; two-drug: 40.3 vs 2.2%, p <or= 0.0001). Early remission periods preceded delayed intractability in 65.4 to 74.3% of cases. After becoming intractable, 20.5% subsequently entered remission and 13.3% were seizure free at last contact. INTERPRETATION: Intractable epilepsy may be delayed, especially in focal epilepsy. It often is preceded by a quiescent period, followed by further remissions. These findings help explain why surgically treatable epilepsies may take 20 years or longer before referral to surgery.

Adolescent↗
PubMed2006

Reduction of AEDs in postsurgical patients who attain remission.

PURPOSE: Little evidence guides practice regarding the reduction of antiepileptic drugs (AEDs) in individuals who achieve significant periods of remission after resective surgery. METHODS: In a prospective study of 396 individuals who underwent resective surgery for intractable seizures, the impact of reducing AEDs on relapse and predictors of relapse were examined. RESULTS: Of 301 study subjects who attained a 1-year seizure remission after surgery, 129 reduced from two to one or from one to no AEDs after achieving remission, and 162 did not reduce drugs. Ten patients who stopped all AEDs before attaining remission were excluded from analysis. In all, 114 (39%) patients relapsed: 73 (45%) of 162 in the nonreduction group and 41 (32%) of 129 in the reduction group (p = 0.02). Patients who reduced drugs were more likely to have remitted immediately after hospital discharge (p<0.0001). After adjustment for this factor, little or no apparent impact of drug reduction on the rate of relapse was noted [rate ratio (RR), 1.1; 95% CI, 0.72-1.71; p=0.64 for reducing from two to one AED, and RR, 0.85; 95% CI, 0.50-1.45; p=0.56 for reducing from one to no AEDs]. Within the 129 patients who reduced AEDs, only delayed remission after hospital discharge was significantly associated with an increased rate of relapse (RR, 2.26; 95% CI, 1.15- 4.48; p=0.02). Continued auras had a marginally significant association with relapse (RR, 2.06; p=0.07) CONCLUSIONS: Although many relapses in this cohort of postsurgical patients who achieved remission occurred in the context of reducing or completely eliminating AEDs, the risk was no higher than in those who continued AEDs. Randomized studies are needed to test the impact of drug reduction in seizure-free postsurgical patients.

Adult↗
PubMed2006

Defining intractability: comparisons among published definitions.

PURPOSE: Intractable epilepsy is the focus of much research; however, this concept is defined in no single way. Individual studies use different definitions, creating difficulties for comparisons of results across studies. A head-to-head comparison of definitions could highlight these differences and motivate the development of consensus guidelines. METHODS: Within a single prospective study of 613 children in Connecticut with newly diagnosed epilepsy (1993-1997), six different published definitions or indicators for intractability were applied and compared. All definitions were assessed at various times within the first 5 years after diagnosis, with the exact timing reflecting how they were used in their initial reports. Observed and chance-adjusted agreement (kappa) were computed. The associations of each definition with remission status 7-10 years after diagnosis were quantified with a relative risk. RESULTS: Depending on the specific definition, the epilepsy of 9-24% of children was considered intractable. Observed agreements among the definitions ranged from a low of 0.83 to a high of 0.96. Kappas ranged from low of 0.45 to 0.79. More similar definitions had higher levels of agreement. All definitions were strongly associated with remission status as of last follow-up. CONCLUSIONS: Agreement among the different definitions is strong but imperfect. All definitions were significantly associated with longer-term outcome. No single preferred definition of intractable epilepsy exists. Some discussion within the field of epilepsy and a consensus process should be considered as a future step for enhancing comparability of research efforts and clinical guidelines. Consideration should be given to whether a single definition will suit all purposes or whether different types of definitions are needed for different purposes.

Anticonvulsants↗
PubMed2006

Epilepsy in North America: a report prepared under the auspices of the global campaign against epilepsy, the International Bureau for Epilepsy, the International League Against Epilepsy, and the World Health Organization.

In North America, overall epilepsy incidence is approximately 50/100,000 per year, highest for children below five years of age, and the elderly. The best data suggest prevalence of 5-10/1000. Potential effects of gender, ethnicity, access to care and socioeconomic variables need further study. Studies of epilepsy etiology and classification mainly were performed without modern imaging tools. The best study found an overall standardized mortality ratio (SMR) for epilepsy relative to the general population of 2.3. There is evidence to suggest a greater increase in patients with symptomatic epilepsy, particularly children. People with epilepsy are more likely to report reduced Health-related Quality of Life than controls. They have reduced income, and are less likely to have full-time employment. They suffer from persistent stigma throughout the region, in developed as well as developing countries. Poor treatment access and health care disparities for people with epilepsy may be related to insufficient economic resources, rural isolation, gender, ethnicity, and lack of public and physician knowledge of modern approaches to epilepsy care. Despite high costs and severe disability, epilepsy may attract somewhat less research funding from public and private sources than other less common chronic neurological disorders. A Plan for Epilepsy in North America should address: basic and clinical research; primary prevention research; translation to care; stigma, quality of life, and self-management; industry relations; government and regional relations; and regional integration and resource sharing.

Epilepsy↗
PubMed2006

Defining intractable epilepsy.

There is no single definition of medically refractory epilepsy, and different definitions may be appropriate depending on the form of epilepsy or on the purposes for which the definition is being used. The natural history of the specific form of epilepsy must be accurately characterized to facilitate a meaningful definition of refractory for that form of epilepsy and thereby allow identification as soon as possible in the course of the disorder. Long-term follow-up after appearance of intractable epilepsy (as determined by a variety of definitions) would provide helpful information necessary for refining meaningful definitions of intractability.

Anticonvulsants↗
PubMed2005

Mortality following a first unprovoked seizure in children: a prospective study.

In a prospective study, 407 children with a first unprovoked seizure were followed for a mean of 14.2 years. To date, nine have died. Death was unrelated to seizures in four subjects who had no further seizures and were on no medications. The remaining five subjects all had multiple seizures and were on medications. Treatment following the first seizure would not have altered mortality in any of the nine cases.

Adolescent↗
PubMed2005

Special education needs of children with newly diagnosed epilepsy.

Children with epilepsy often experience poor social and educational outcomes. This study aimed to determine the timing of services with respect to the onset of seizures. It also aimed to identify the aspects of childhood epilepsy (type of epilepsy, etiology, seizure control, and treatment) that are associated with the use of special education services. As part of a prospective community-based study, 613 children were recruited when first diagnosed with epilepsy. Mean age at first seizure was 5 years 11 months (SD 4, range 1mo to 15y 8mo). Parents were interviewed 5 years after children were first diagnosed with epilepsy (n=542; 276 [51%] males). Children's mean age at time of interview was 11 years 10 months (SD 4y 1mo, range 5y 8mo to 21y 8mo). Etiology was classified as idiopathic (n=181, 33.4%), cryptogenic (n=261, 48.2%), and remote symptomatic (n=100, 18.5%). Service use was reported in 315 (58%) children. Compared with neurologically intact children (i.e. cryptogenic and idiopathic etiology; n=415, 77%), children with a remote symptomatic etiology and/or an epileptic encephalopathy (n=127, 23%) received services more frequently (88% vs 49%, p<0.001). In the former group, services were initiated for 66 (15%) children before their first seizure; according to age at onset, services were initiated before the first seizures in 12/164 (7.3%) if <5 years, 34/171 (19.9%) if 5-9 years, and 20/80 (25%) if >10 years. A large proportion of children with epilepsy, even if neurologically otherwise normal, receive special education services. Initiation of services often precedes onset of seizures even in neurologically intact children. This suggests that behavioral and cognitive abnormalities may predate the onset of epilepsy and are not necessarily the direct consequences of epilepsy.

Adolescent↗
PubMed2005

Nonfebrile illness seizures: a unique seizure category?

PURPOSE: To describe the clinical characteristics of children with a first-time nonfebrile seizure in the setting of mild illness and to test the hypothesis that these seizures are associated with illness characterized by diarrhea. METHODS: This retrospective cohort study was performed in a pediatric emergency department. Patients ages 6 months to 6 years who were evaluated with first-time seizures were eligible for inclusion. Subjects were divided into three groups on the basis of symptoms accompanying their seizure: febrile (temperature, >38.0 degrees C with seizure), unprovoked (no symptoms of illness), and nonfebrile illness (no fever at the time of seizure, but other symptoms of illness present). RESULTS: Of the 323 children with first-time seizures, 247 (76%) had febrile seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness seizures. Children with nonfebrile illness seizures were more likely than children with febrile seizures to have diarrheal illnesses accompanying their seizure (44 vs. 16%; p=0.001). Frequency of cough, rhinorrhea, and rash did not differ significantly between children with febrile and nonfebrile illness seizures. Diagnostic testing for infectious etiologies was not performed frequently in either group. CONCLUSIONS: Nonfebrile illness seizures may represent a distinct group of seizures with unique epidemiology. Further study to define this seizure group better is warranted.

Child, Preschool↗
PubMed2004

Mortality in childhood-onset epilepsy.

OBJECTIVES: To evaluate mortality in children with newly diagnosed epilepsy, to determine the risk of death, and to identify predictors of death from the point of diagnosis. DESIGN: Prospective community-based cohort of 613 children with newly diagnosed epilepsy. The outcome measure was death. Chi2 Tests were used for bivariate analyses and the Cox proportional hazards model for multivariable analyses. Standardized mortality ratios were used to quantify the excess mortality in the cohort relative to the population. RESULTS: Thirteen deaths occurred during 4733 person-years of follow-up, for a crude death rate of 2.7 per 1000 person-years (0.52 per 1000 person-years in those with nonsymptomatic epilepsy and 12.6 per 1000 person-years in those with symptomatic epilepsy). Ten deaths were associated with the underlying cause of the seizures, 2 were associated with the occurrence or probable occurrence of seizures, and 1 was unrelated to seizures or the underlying disorder. On multivariable analysis, symptomatic etiology (rate ratio, 10.2; 95% confidence interval [CI], 2.1-49.6) and epileptic encephalopathy (rate ratio, 13.3; 95% CI, 3.4-51.7) were independently associated with mortality. The overall standardized mortality ratio for the cohort was 7.54 (95% CI, 4.38-12.99). In children with symptomatic epilepsy, the standardized mortality ratio was 33.46 (95% CI, 18.53-60.43), and in those with nonsymptomatic epilepsy, it was 1.43 (95% CI, 0.36-5.73). CONCLUSIONS: Children with epilepsy have an increased risk of death. Most deaths occur in children with severe underlying conditions and are not directly related to the occurrence of seizures.

Adolescent↗
PubMed2004

Modeling remission and relapse in pediatric epilepsy: application of a Markov process.

Seizure outcome is frequently described in terms of patients ever attaining remission or being in terminal remission. Outcomes are more complicated and, over many years, repeated remission and relapses may occur. These are difficult to quantify with standard survival techniques used in analysis of remission and relapse. The Markov process, which allows one to track a patient's state (remission or not) over time, provides a suitable approach for studying repeated remission and relapse. In a prospective community-based study of children followed from the point of the initial diagnosis of epilepsy, we examined the probability of repeated remission and relapse over up to three different remission episodes (minimum 1 year each) per patient. The role of epilepsy syndrome was the main determinant of remission-relapse patterns considered in the analysis. Two different Markov models were used, one involving three states and the other seven states. Of 613 children initially recruited into the study, 602 were followed at least 1 year and thus eligible for the analysis. Almost 90% of the cohort experienced a remission; however, almost half then relapsed. Second remissions occurred in 81% of those who relapsed of whom 38% relapsed again. A third remission occurred in 82% of those after a second relapse of whom 58% relapsed yet again. After the first 2 years, approximately 70% of the cohort was in remission, 20% was no longer in remission having relapsed, and 10% had never been in remission. Significant differences were seen by underlying epilepsy syndrome. Children with one of the epileptic encephalopathies were least likely of all syndrome groups ever to remit. Those with symptomatic partial epilepsies were less likely to remit than children with any of the other syndromes, idiopathic partial or generalized, cryptogenic partial, and unclassified. Differences between these last groups became apparent when considering their subsequent remission and relapse histories. These differences were best seen in the seven-state model. For example, idiopathic partial epilepsies were most likely to enter remission and never relapse. By contrast, idiopathic generalized and cryptogenic partial epilepsies were more likely to remit and relapse repeatedly. The Markov approach provides an alternative to standard survival techniques for understanding remission and relapse outcomes in epilepsy. Its advantage is that it allows one to track the individuals' outcome over time even as the condition fluctuates. The technique would also be applicable in virtually any remitting-relapsing disorder.

Adolescent↗
PubMed2004

Understanding the delay before epilepsy surgery: who develops intractable focal epilepsy and when?

Intractable temporal lobe epilepsy that is surgically treated in adulthood is a disorder whose onset frequently occurs during childhood and early adolescence. The average duration of epilepsy prior to surgery is on the order of 20 years. The long delay between onset and surgery has at least two components: time from onset to intractability and time from evidence of intractability to surgery. The first interval is prolonged >10 years especially if the onset is during childhood. This suggests a complex natural history that we have not fully appreciated as well as a potential window of opportunity for early secondary intervention. The second interval is also prolonged, especially if onset was during childhood. Reasons for this are not fully clear but may include a reluctance to consider surgery and perhaps difficulty deciding whether seizures are sufficiently intractable to warrant surgery especially after what may have been a relatively benign initial course. Factors involved in the second delay need to be better understood so that surgical interventions can be appropriately targeted early rather than late, thereby reducing serious social, psychological, and educational consequences associated with uncontrolled seizures.

Adolescent↗
PubMed2004

Longitudinal assessment of adaptive behavior in infants and young children with newly diagnosed epilepsy: influences of etiology, syndrome, and seizure control.

OBJECTIVES: The outcomes of childhood-onset epilepsy are highly varied and have several potential determinants. We examined the independent effects of syndrome type, seizure control, and etiology over time on adaptive behavior as measured by the Vineland Scales of Adaptive Behavior. METHODS: As part of a prospective community-based study of newly diagnosed epilepsy, parents of children who were younger than 3 years at the time of initial onset of epilepsy completed the Vineland Adaptive Behavior Scales screener version at entry into the study and once a year thereafter for up to 3 years. Longitudinal analyses were performed on the composite score as the primary outcome and on the 4 domain scores (communication, socialization, motor, and daily living) as confirmatory/secondary outcomes to determine the effects of syndrome (epileptic encephalopathy or other), seizure control (intractable or not), and etiology (symptomatic or not) on adaptive behavior at the time of initial diagnosis and over time. RESULTS: A total of 613 children were enrolled in the study, and 191 (31%) of these children met the age criterion for this analysis. Of these, 172 (90%) had adequate follow-up and had completed baseline and at least 1 subsequent Vineland assessment. Overall, Vineland scores (composite and individual domains) were somewhat below average at baseline (initial diagnosis). All declined significantly over time. All of the effects at baseline, however, were limited to children with epileptic encephalopathies and symptomatic etiology. Substantial declines over time occurred in these children, and there was an independent effect of intractable seizures as well. In children with none of these factors ( approximately 75% of the study group), baseline scores were consistent with average performance for the test norms and there was no evidence of any decline over time. CONCLUSIONS: Children with an underlying symptomatic etiology or a syndrome that can be characterized as 1 of the epileptic encephalopathies demonstrate impaired adaptive behavior at the time of initial diagnosis and experience additional declines in assessments of age-adjusted performance over time. Our results suggest that future seizure outcome is not strongly reflected in adaptive behavior at initial diagnosis but that it takes its toll on the child over time. Understanding how each of these factors affects development and how they interact with each other is the next step in designing effective interventions for lessening the impact of these disorders on the child. In the majority of children with onset of epilepsy during infancy or early childhood, adaptive behavior is within the normal range and does not show any evidence of declining over time. Although this is encouraging, it does not contradict other studies that have demonstrated behavioral and relatively subtle cognitive difficulties in school-aged children with epilepsy. Long-term follow-up in this cohort will permit us to examine the predictive value of the Vineland for later behavioral and cognitive difficulties in this group that, so far, seems to be doing well.

Activities of Daily Living↗
PubMed2003

The multicenter study of epilepsy surgery: recruitment and selection for surgery.

PURPOSE: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single-center series with limited sample size. Little information is available about the selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries. METHODS: An observational cohort of 565 surgical candidates was prospectively recruited from June 1996 through January 2001 at six Northeastern and one Midwestern surgical centers. Standardized eligibility criteria and protocol for presurgical evaluations were used at all seven sites. RESULTS: Three hundred ninety-six (70%) study subjects had resective surgery. Clinical factors such as a well-localized magnetic resonance imaging (MRI) abnormality and consistently localized EEG findings were most strongly associated with having surgery. Of those who underwent intracranial monitoring (189, 34%), 85% went on to have surgery. Race/ethnicity and marital status were marginally associated with having surgery. Age, education, and employment status were not. Demographic factors had little influence over the surgical decision. More than half of the patients had intractable epilepsy for >/=10 years and five or more drugs had failed by the time they initiated their surgical evaluation. During the recruitment period, eight new antiepileptic drugs were approved by the Food and Drug Administration for use in the United States and came into increasing use in this study's surgical candidates. Despite the increased availability of new therapeutic options, the proportion that had surgery each year did not fluctuate significantly from year to year. This suggests that, in this group of patients, the new drugs did not provide a substantial therapeutic benefit. CONCLUSIONS: Up to 30% of patients who undergo presurgical evaluations for resective epilepsy surgery ultimately do not have this form of surgery. This is a group whose needs are not currently met by available therapies and procedures. Lack of clear localizing evidence appears to be the main reason for not having surgery. To the extent that these data can address the question, they suggest that repeated attempts to control intractable epilepsy with new drugs will not result in sustained seizure control, and eligible patients will proceed to surgery eventually. This is consistent with recent arguments to consider surgery earlier rather than later in the course of epilepsy. Postsurgical follow-up of this group will permit a detailed analysis of presurgical factors that predict the best and worst seizure outcomes.

Adolescent↗