Pharmacological outcomes in newly diagnosed epilepsy

The response to antiepileptic drugs (AEDs) has been examined in 780 adult and adolescent patients with newly diagnosed epilepsy presenting with a range of seizure types and epilepsy syndromes over a 20-year period. Carbamazepine (CBZ, n=312), sodium valproate (VPA, n=315), and lamotrigine (LTG, n=249) were the most common AEDs prescribed as monotherapy. More patients with localization-related epilepsies became seizure free with LTG (63%) than with CBZ (45%, P=0.006) or VPA (42%, P=0.006). For idiopathic generalized epilepsies a greater proportion of patients achieved control with VPA (68%) than with CBZ (31%) or LTG (45%). In particular, more patients with juvenile myoclonic epilepsy responded to VPA (75%) compared with LTG (39%, P=0.014). Seizure freedom was achieved with modest or moderate daily doses (median CBZ 400mg, VPA 1000 mg, (LTG) 150 mg) of all three AEDs in the majority of patients achieving remission. Time to first seizure did not differ among these three drugs when given as first treatment. Adverse effects leading to withdrawal were more frequent with CBZ (16%) than with VPA (7%, P=0.03) or LTG (7%, P=0.018). In patients failing initial monotherapy, response to a combination of two AEDs (27%) was not different from that with alternative monotherapy (32%). The majority of patients with newly diagnosed epilepsy responding to treatment did so rapidly and completely with moderate doses of AEDs, with no differences in time to first seizure.     

Drug treatment failures and effectivity in children with newly diagnosed epilepsy

PurposeTo determine the percentage of children whom first-line antiepileptic drug treatment failed and the specific reasons for the treatment failure in newly diagnosed epilepsy.MethodsHospital records were reviewed for 225 children who were newly diagnosed with epilepsy, started on the first antiepileptic drug, and then monitored for approximately 4.2 years.ResultsOf the 225 patients analyzed, the mean age was 7.9 ± 0.6 years at diagnosis. Most of the patients suffered from primarily generalized tonic-clonic seizures (in 84 patients, 37.3%). 114 patients (50.6%) were classified as having idiopathic epilepsy, 64 (28.4%) had symptomatic epilepsy and 47 (20.8%) has cryptogenic epilepsy. Valproic acid (n: 120, 53.3%), carbamazepine (n: 45, 20%) and oxcarbazepine (n: 31, 13.7%) were the most frequently prescribed antiepileptic drugs. Overall, 67.5% (n: 152) patients were treated successfully with the first antiepileptic drug. Seventy-three patients failed with the first-line antiepileptic drug. Of these patients, 28 discontinued medication because of adverse effects (38.3%), 26 because of lack of efficacy (35.6%) and 19 (26.02%)because of a combination of inefficacy and adverse effects. Age at diagnosis, seizure, etiology and antiepileptic drug selection are considered to be associated with drug treatment failure in childhood epilepsy. There was no statistically significant effect of any of these variables on first-line treatment outcome.ConclusionApproximately one-third of the children with newly diagnosed epilepsy fail the first prescribed antiepileptic drug. Adverse effects and lack of efficacy contributed equally to the treatment failures.     

Early predictors of outcome in newly diagnosed epilepsy

Longitudinal studies of newly diagnosed epilepsy in children and adults have identified prognostic factors that allow early identification of patients whose seizures are likely to remain uncontrolled with antiepileptic medication. Results from outcome studies may be subject to bias, depending on the setting (community versus clinic), design (retrospective versus prospective) and characteristics of the patient cohort studied (age, types of epilepsy, specific comorbidities). Nevertheless, factors such as early response to medication, underlying aetiology, and number of seizures prior to initiation of treatment have consistently been found to be predictive of seizure outcomes. Other variables such as age, electroencephalographic findings and the presence or absence of psychiatric co-morbidities have been correlated with outcomes in some analyses. This review has examined studies of seizure outcomes in adults and children with newly diagnosed epilepsy identifying the risk factors that are associated with subsequent refractory epilepsy.     

Cerebellar volumes in newly diagnosed and chronic epilepsy

Cerebellar atrophy is assumed to be a common finding in patients suffering from epilepsy. Anticonvulsants as well as seizure activity itself have been considered to be responsible for it but many studies have addressed these questions in specialised centres for epilepsy thus having a referral bias towards patients with severe epileptic syndromes. The purpose of this study was: 1. To develop a quantitative method on 3D-MRI data to achieve volume or planimetric measurements (of cerebrum, cerebellum and cerebellar substructures). 2. To investigate the prevalence of cerebellar atrophy (and substructure atrophy) in a prospectively investigated population-based cohort of patients with newly diagnosed and chronic epilepsy. 3. To quantify cerebellar atrophy in clinic-based patients, who had had atrophy previously diagnosed on routine visual MRI assessment. 4. To correlate the measures of atrophy with clinical features in both patient groups. A total of 57 patients with either newly diagnosed or chronic active epilepsy and 36 control subjects were investigated with a newly developed semiautomated method for cerebral as well as cerebellar volume measurements and substructure planimetry, corrected for intracranial volume. We did not find any significant atrophy in the population-based cohort of patients with newly diagnosed epilepsy or with chronic epilepsy. Visually diagnosed cerebellar atrophy was mostly confirmed and quantified by volumetric analysis. The clinical data suggested a correlation between cerebellar atrophy and the duration of the seizure disorder and also the total number of lifetime seizures experienced and the frequency of generalised tonic-clonic seizures per year. Volumetry on 3D-MRI yields reliable quantitative data which shows that cerebellar atrophy might be common in severe and/or longstanding epilepsy but not necessarily in unselected patient groups. The results do not support the proposition that cerebellar atrophy is a predisposing factor for epilepsy but rather are consistent with the view that cerebellar atrophy is the aftermath of epileptic seizures or anticonvulsant medication. Received: 26 September 2001, Received in revised form: 15 February 2002, Accepted: 15 April 2002 Present address: Dept. of Neurology, Friedrich-Schiller University, 07740 Jena, Germany, Tel.: +49-36 41/93 67 64, Fax: +49-36 41/93 46 99, E-Mail: hagemann@med.uni-jena.de Correspondence to G. Hagemann, MD     

Cognitive function in Nigerians with newly diagnosed epilepsy

OBJECTIVE: The objective of this study was to evaluate the pattern of cognitive disturbances in Nigerian Africans with newly diagnosed epilepsy, prior to onset of drug therapy. METHODS: A total of 60 consecutive patients (mean age 31.6 +/- 17.4, range 14-55 years) presenting with a clinical diagnosis of epilepsy were recruited for the study. Sixty healthy volunteers without a history of epilepsy and who were age-, sex- and level of education matched with the epileptic patients, were recruited as controls. The administration of cognitive tests was done with the FePsy computerized neuropsychological test battery. The tests administered were the visual and auditory reaction times, the continuous performance test and the recognition memory tests to assess mental speed, attention and memory respectively. The means of the cognitive performances of the epileptic patients and controls were statistically compared. RESULTS: Epileptic patients performed worse than the controls across the spectrum of cognitive tasks assessed (P = 0.00001; P < 0.025), with the exception of the beta parameter (response bias) of the vigilance test (P = 0.488; P > 0.025). CONCLUSIONS: The cognitive impairments of short-term memory, psychomotor speed and sustained attention observed in this study are similar to those reported in the literature for patients with epilepsy. The results of this study will be useful in the counseling of patients on their educational, social and vocational needs.     

Treating newly diagnosed epilepsy: the Canadian choice

BACKGROUND: Choosing an antiepileptic medication to treat a patient with epilepsy can be a complicated process during which the treating physician must base her or his decision on efficacy and safety of each of many available drugs. The lack of comparative studies between medications is one of the reasons. METHODS: We conducted a survey on the management of newly diagnosed epilepsy in adult patients. The surveyed were adult and pediatric neurologists with a subspecialty interest in epilepsy who were working in academic institutions or private practice across Canada. Scenarios presented were grouped in categories according to the epilepsy syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic partial epilepsy, and unclassified epilepsy), the patient's gender and age. First and second step in medical treatment for status epilepticus were surveyed as well. RESULTS: Forty one of 64 experts responded the survey (responder rate of 66%). The results revealed a consensus among Canadian epileptologists that the first choice of antiepileptic medication in generalized epilepsies was between valproate in men (chosen by 88% of respondents) and lamotrigine in women. In localization-related epilepsies, carbamazepine was the preferred drug of choice (chosen by 90% of respondents). In the treatment of status epilepticus, an initial intravenous dose of lorazepam (95% of respondents), followed by a second dose of lorazepam or intravenous phenytoin in case the initial dose of lorazepam failed, were the treatments preferred.     

Levetiracetam monotherapy for newly diagnosed epilepsy patients.

We retrospectively reviewed the charts of all of our patients with a history of partial seizures, with and without secondarily generalisation, who received levetiracetam (LEV; Keppra) for treatment of their seizures during the years 2000-2002. Forty-five patients were identified, 13 of whom began LEV as first line therapy. Eleven patients continued on LEV for at least 6 months; six of whom became seizure free and five had >50% reduction in their seizures. The remaining two patients discontinued LEV because of adverse effects. LEV monotherapy can be effective and well tolerated in adults with new onset seizures. A prospective, large, double-blind monotherapy study for newly diagnosed patients is needed to confirm this finding.     

Negative emotions in children with newly diagnosed epilepsy

PURPOSE: To understand the emotional predicament in children with recently diagnosed idiopathic or cryptogenic epilepsy. METHODS: We used the well-tried method of structured projection for the first time in children with epilepsy. Thirty-six children with epilepsy, aged 7-15 years (mean age, 9.5 years) and in 35 control children aged 7-15 years (mean age, 9.4 years), attributed shame and guilt in relation to three types of situation (non-illness related, illness related, and epilepsy related). Children were evaluated twice: shortly after diagnosis, before antiepileptic drug (AED) use and after an interval of 3 months. RESULTS: Children with epilepsy and healthy controls were similar in their way of attributing shame and guilt. However, the type of situation was of influence: Both children with epilepsy and healthy children attributed more shame to incompetence due to epilepsy than to incompetence due to other illnesses. CONCLUSIONS: Increased affective problems in childhood epilepsy cannot be explained by excessive attribution of shame and guilt, affects known to be important precursors of psychopathology, yet both healthy children and children with epilepsy attribute more shame to epilepsy than to other illnesses. Epilepsy is not like any other disease.     

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.     

Medical care costs of newly diagnosed children with structural-metabolic epilepsy: A one year prevalence-based approached

PurposeAims of this study were to estimate the first-year medical care costs of newly diagnosed children with structural-metabolic epilepsy and to determine the cost-driving factors in the selected population.MethodThis was a prevalence-based retrospective chart review that included patients who attended a pediatric neurology clinic in a tertiary referral center in Malaysia. The total first-year medical care costs were estimated from the provider (i.e., hospital) perspective, using a bottom-up, microcosting analysis. Medical chart/billing data (i.e., case reports) obtained from the hospital (i.e., provider) were collected to determine the resources used. Prices or cost data were standardized for the year 2010 (One Malaysian Ringgit MYR is equivalent to 0.26 Euro or 0.32 USD).ResultsThe most expensive item in the costs list was antiepileptic drugs, whereas ultrasound examination represented the cheapest item. Hospitalization and the use of non-antiepileptic drugs were the second and third most costly items, respectively. The cost of therapeutic drug monitoring comprised only a small proportion of the total annual expenditure. None of the demographic variables (i.e., gender, race, and age) significantly impacted the first-year medical care costs. Similarly, child development, seizure type, therapy type (i.e., polytherapy versus monotherapy), and therapeutic drug monitoring utilization were also not associated with the cost of management. The first-year medical care costs positively correlated with seizure frequency (r_s = 0.294, p = 0.001). However, the only variable that significantly predict the first-year medical care costs was the type of antiepileptic drugs (R² = 0.292, F = 7.772, p < 0.001).ConclusionThis investigation was the first cost analysis study of epilepsy in Malaysia. The total first-year medical care costs for 120 patients with structural-metabolic epilepsy were MYR 202,816 (i.e., MYR 1690.13 per patient per year). The study findings highlight the importance of optimizing seizure control in reducing the cost of management.     

Status epilepticus in children with newly diagnosed epilepsy.

Status epilepticus (SE) constitutes a neurological emergency and may be of prognostic value in individuals with epilepsy. Little is known about the associations between other prognostic factors in epilepsy and the occurrence of SE. The following study examines associations between clinical characteristics of children with newly diagnosed epilepsy and the occurrence of SE when epilepsy is first diagnosed. Children were recruited prospectively from the practices of physicians throughout Connecticut. Information was collected via standardized interviews with parents and review of pertinent records. Analyses were performed for any SE, unprovoked SE only, and previous provoked SE. Of 613 children, 56 (9.1%) had one or more episodes of SE by the time the diagnosis of epilepsy was established. Factors correlated with SE during an unprovoked seizure were partial seizures and previous craniotomy. For SE during a provoked seizure, correlates were primarily young age at onset of epilepsy and nonidiopathic epilepsy syndrome. To date, subsequent SE has occurred in 4.3% of children without and in 19.6% of those with SE at diagnosis. By the time epilepsy is first diagnosed in children, SE has already occurred in a substantial minority. It is correlated with specific clinical characteristics in the children, which differ depending on whether the SE was provoked or unprovoked. SE has a high risk of recurring.