Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EPILEPSY”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2004

Juvenile myoclonic epilepsy and idiopathic photosensitive occipital lobe epilepsy: is there overlap?

Although epileptic photosensitivity is well known, its genetics and syndromic associations are incompletely understood. Seizures triggered by photic stimulation are usually a manifestation of the idiopathic generalized epilepsies, especially juvenile myoclonic epilepsy (JME), or of the occipital epilepsies. Idiopathic photosensitive occipital epilepsy (IPOE) is a focal epilepsy with colourful elementary visual auras, often with conscious tonic head and eye version; myoclonus is not a feature. All seizures are induced by photic stimuli. We describe four families with phenotypic overlap between JME and IPOE. Families were identified if two or more affected individuals had visual auras and electro-clinical features of an idiopathic epilepsy. Family members underwent detailed electro-clinical assessment. In addition, 40 unrelated JME probands were investigated systematically for unrecognized features of IPOE (visual aura and conscious head version). There were 12 affected individuals in four families; 11 were female. Clinical onset was at 8-21 years of age. Of 10 patients with visual auras, six had conscious head version and five also experienced myoclonic jerks; eight had non-photic induced tonic-clonic seizures (TCS). Of the remaining individuals, one had myoclonic jerks and occipital spikes; the other had TCS without visual aura or myoclonic jerks. Of 10 patients with EEG studies, eight had generalized spike and wave (GSW) and six had occipital spikes. All had photosensitivity with GSW and four had additional occipital spikes. Of the 40 JME probands, six had visual aura and/or conscious head version; five of these were photosensitive. There is overlap between the clusters of clinical features used to diagnose IPOE and JME. Half of the affected individuals in our families with visual aura had myoclonic jerks; the former is characteristic of IPOE and the latter of JME. Importantly, visual aura is not regarded as part of JME, nor myoclonus part of IPOE, but our data emphasize that these symptoms may occur in both disorders. Moreover, two-thirds of individuals with visual aura had spontaneous TCS; the latter feature is not described in IPOE. Additionally, we demonstrate that visual aura and conscious head version are under-recognized features of JME, particularly among photosensitive patients. These findings could be explained by shared genetic determinants underlying IPOE and JME. Understanding the genetic basis of these disorders must account for the striking female predominance, the variable phenotypes associated with photosensitivity and the overlap of clinical features classically regarded as distinguishing focal and generalized syndromes.

Adolescent↗
PubMedDate not supplied

Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy).

Myoclonic attacks are not characteristic of a specific syndrome. In infancy and early childhood, they are often observed in the context of syndromes that are associated with other types of seizures and with cognitive impairment but no obvious brain lesion. Characterization of the associated seizures and age of expression allows inclusion of a number of cases in two main subgroups: severe myoclonic epilepsy (SME, or Dravet syndrome) and myoclonic-astatic epilepsy (MAE). Severe myoclonic epilepsy is an epileptic encephalopathy with invariably poor outcome in which myoclonic seizures, though frequently observed, may be absent altogether in some children. Prolonged and repeated febrile and afebrile convulsive seizures starting in infancy are the main feature and are probably causally related to cognitive decline. One third of children harbor mutation of the SCN1A gene, but the genetics of SME is probably more complex than expected with simple monogenic disorders. Treatment is usually disappointing. Myoclonic-astatic epilepsy is perhaps more a conceptual category of idiopathic myoclonic epilepsy than a discrete syndrome. Childhood-onset myoclonic-astatic attacks are the characteristic seizures associated in most with episodes of nonconvulsive status and generalized tonic-clonic seizures. Outcome is unpredictable. Either remission within a few years with normal cognition or long-lasting intractability with cognitive impairment is possible. Likewise, the effectiveness of antiepileptic drugs is variable. A number of cases of myoclonic epilepsies in infancy and early childhood, however, remain unclassified, and intermediate forms between the different syndromes exist. They must be distinguished from other syndromes with frequent brief attacks and repeated falls, especially the Lennox-Gastaut syndrome. This differentiation is often difficult and may require extensive neurophysiologic studies.

Age Factors↗
PubMed2002

Pre-attentive cognitive processing in epilepsy. A pilot study on the impact of epilepsy type and anti-epileptic treatment.

Patients suffering from epilepsy often complain of deficits in attentive cognition affecting, for instance, concentration, reaction time, memory and psychomotor speed. We were interested in the impact of epilepsy and its treatment on pre-attentive cognitive functions and enrolled 107 subjects (50 male, 57 female; mean age 26 years): 50 patients with partial epilepsy, 15 with primary generalised epilepsy and 42 healthy controls. We used a new computer-adapted neuropsychological test (called textest), measuring the pre-attentive visual processing speed. The subjects had to discriminate 5 different stimuli presented on a computer screen. As a primary result, we calculated the time the subject needed to detect 50% of the demonstrated stimuli correctly (t-50 time). We also applied the d2 test. For the textest results, no significant group differences between the different patient and healthy groups could be revealed, except for a significantly increased t-50 time in patients with polytherapy compared with the control group. Compared with healthy controls, significantly worse d2 test results were found in patients with epilepsy in general, a duration of disease >1 year, anti-epileptic drug therapy in general and in patients receiving polytherapy in particular (all p < 0.001). Our data suggest that polytherapy, but not monotherapy or the subtype of epilepsy, might have a slowing impact on pre-attentive cognitive processing.

Adult↗
PubMed1996

Association of HLA class II alleles in patients with juvenile myoclonic epilepsy compared with patients with other forms of adolescent-onset generalized epilepsy.

Reports have suggested an association of juvenile myoclonic epilepsy (JME) with an HLA-DR allele. We examined the HLA-DR and DQ frequencies in two populations of epilepsy patients: (1) JME patients and (2) patients with other forms of adolescent-onset, idiopathic generalized epilepsy (IGE). We did DNA-based HLA typing on 24 JME patients and 24 patients with non-JME forms of adolescent-onset IGE, forms that are clinically similar to JME. In typing the HLA region, we paid particular attention to the alleles contributing to the HLA-DR13 type and also to the DQB1 locus alleles that are in linkage disequilibrium with the alleles that comprise the DR13 type. We also examined the HLA-AP locus, which is centromeric to the DR locus. The frequency of DR13 was significantly higher in JME compared with the non-JME patients. Nine JME patients, compared with two non-JME patients, carried that type (chi 2 = 5.78 [p < 0.017, 1 df]). The odds ratio was 6.6. Furthermore, the DQB1 alleles in linkage disequilibrium with the alleles contributing to the DR13 type were also more frequent in JME than in non-JME epilepsy patients. The chi 2 is highly significant (8.1, p < 0.005) with an odds ratio of 13.8. These results confirm that JME is an HLA-associated form of epilepsy. They also show that the JME locus probably lies within the HLA region, most likely between the HLA-DP and HLA-B loci. The association studies also confirm linkage results showing that JME is genetically different from some other IGEs and emphasize that careful diagnosis is critical to genetic studies of the epilepsies.

Adolescent↗
PubMed2001

Clinical characteristics of adult epilepsy patients in the 1997 Hong Kong epilepsy registry.

OBJECTIVE: To study the clinical characteristics of 2952 patients with epilepsy who had received drug treatment from the neurology outpatient clinics of eight major hospitals in Hong Kong. METHODS: Retrospective review of outpatient records. RESULTS: 1601 (54.3%) males and 1351 (45.7%) females with a median age of 35.8 years (range, 10-94.8) were studied. Seizure types included generalized tonic-clonic in 80.7% of patients, complex partial in 28.3%, simple partial in 14.4%, atypical absence in 2.6% and myoclonic in 1.4%, and 30.4% of patients had more than one seizure type. EEG, CT brain, MRI brain and neuropsychological evaluation were obtained in 81.2%, 61.7%, 17.0% and 2.2% of patients, respectively. The etiology of epilepsy was cryptogenic in 59.9%, symptomatic in 35.1% and idiopathic in 3.9%; the commonest were intracranial infection, cerebral vascular disease, cranial trauma and perinatal insult. Phenytoin, carbamazepine and valproate were the most frequently used drugs and 25.9% of patients were taking more than two drugs. 48.3% of patients had active seizures in the past six months and 26.4% were considered to have unsatisfactory control of their epilepsy. Medical refractoriness of epilepsy was associated with a history of perinatal insult, intracranial infection, congenital brain malformation, intracranial neoplasm, cerebral vascular disease, hippocampal sclerosis, mental retardation and a history of status epilepticus (P < 0.05). CONCLUSION: In this local cohort of adult patients with epilepsy under specialist care, there were a considerable number of patients falling into the category of cryptogenic epilepsy. Risk factors associated with medical refractoriness are similar to previous studies.

Adolescent↗
PubMed2003

Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center.

OBJECTIVE: To determine the outcome of intermittent left vagal nerve stimulation on the first 100 consecutive patients treated at our pediatric epilepsy center. METHODS: Patients were identified by means of operating room records. Data collected described the patient's epilepsy, previous and subsequent therapies, adverse events, nonepileptic changes, and outcomes. RESULTS: Average age was 10.4 years; years of epilepsy, 8.5; total number of antiepileptic therapies, 8.4; and median monthly seizure frequency, 120. Data on seizure frequency at follow-up were available for 96 of the 100 patients. Forty-five percent of patients achieved greater than 50% reduction; and 18% had had no seizures for the last 6 months. Response was similar in patients with more than 7 years of refractory epilepsy as compared with patients with a shorter history. Magnet-generated, on-demand current reduced seizure intensity in almost half of the patients with available data. Generator infections occurred in 3 patients. Twenty-four patients had their generators removed. Subsequently, 2 of these patients died. CONCLUSIONS: Seizure reduction was the same in patients younger than 12 years and 12 years or older and in patients with shorter and longer histories of refractory epilepsy. Adverse effects were few in this population, particularly in those younger than 12 years. Vagal nerve stimulation appears to be a relatively safe and potentially effective treatment for children with severely intractable epilepsy.

Adolescent↗
PubMed1989

The genetically epilepsy-prone rat. A valuable model for the study of the epilepsies.

In order to develop a rational clinical treatment for any pathological state, the molecular bases for that state must be understood. As simple and logical as that statement appears, it remains the major obstacle to effective treatment of the family of neurological disorders collectively called the epilepsies. Under the term, the epilepsies are grouped as several types of seizure processes that undoubtedly have multiple pathophysiological causes. Thus, the search to elucidate the molecular bases for the epilepsies has as one of its fundamental components the careful selection of an appropriate model system. The search for an "ideal" seizure model has essentially followed two paths. In the first, animals are rendered "epileptic" by artificial methods and then the pathophysiological, electrophysiological, and pharmacological changes are evaluated. In the second, animals are developed with a genetic predisposition to seizures and used to evaluate the molecular bases for the seizure-prone state. Work using both types of models have provided valuable information about the epileptic state. This review describes an epilepsy model developed using the second approach, namely, the Genetically Epilepsy-Prone Rat (GEPR). These animals represent a valuable model for the study of the inborn neurological defect that predisposes these animals to seizures. A brief description of the work done in several laboratories characterizing the model is presented. Finally, the value of the GEPR as a model for studying the pathophysiology of the epilepsies will be described.

Amino Acids↗
PubMed1992

Epilepsy and the quality of everyday life. Findings from a study of people with well-controlled epilepsy.

Epilepsy is a stigmatising disorder and available evidence suggests that its diagnosis can have important psychosocial consequences and severely reduce the quality of an individual's everyday life. A number of studies have examined the psychosocial aspects of living with epilepsy, but these have generally involved groups of patients with severe or intractable epilepsy, so that the prevalence of problems may be over-estimated. The present study examined psychosocial functioning in a group of people in whom epilepsy was well-controlled; the majority had been seizure-free for at least two years. In doing so, it drew upon a model of quality of life which incorporated physical, social and psychological domains. Among this group of people, psychosocial functioning and adjustment to epilepsy appeared high, with low reported levels of distress. This is an important finding, not least for people with epilepsy themselves.

Activities of Daily Living↗
PubMed2006

Developmental outcome in benign myoclonic epilepsy in infancy and reflex myoclonic epilepsy in infancy: a literature review and six new cases.

Benign myoclonic epilepsy in infancy is a rare syndrome with just over 100 cases reported since the first syndromic description by Dravet and Bureau [Dravet, C., Bureau, M., 1981. The benign myoclonic epilepsy of infancy. Rev. Elecroencephalogr. Neurophysiol. Clin. 11, 438-444]. This includes 23 infants with reflex myoclonic epilepsy whose inclusion in the wider syndrome remains debatable. We have reviewed the literature and present data from six further cases. Prognosis in respect of long term seizure freedom is good with sodium valproate being the most effective medication. However, the cognitive outcome is much less certain with cognitive problems present in one-third of children who have long term follow up. The cognitive outcome in reflex myoclonic epilepsy of infancy is normal in all reported cases. The term benign may be appropriately used to describe the myoclonic seizures but must be used cautiously when counselling families about cognitive outcome. The clinical heterogeneity within this syndrome suggests that there may be a variety of genetic mechanisms that underlie the presentation. Clinicians should distinguish the syndrome of reflex myoclonic epilepsy in infancy from benign myoclonic epilepsy of infancy and all patients should continue developmental follow up for several years after diagnosis.

Child Development↗
PubMed2004

Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintainance of epilepsy.

Epilepsy is one of the most common neurological disorders. Although epilepsy can be idiopathic, it is estimated that up to 50% of all epilepsy cases are initiated by neurological insults and are called acquired epilepsy (AE). AE develops in 3 phases: (1) the injury (central nervous system [CNS] insult), (2) epileptogenesis (latency), and (3) the chronic epileptic (spontaneous recurrent seizure) phases. Status epilepticus (SE), stroke, and traumatic brain injury (TBI) are 3 major examples of common brain injuries that can lead to the development of AE. It is especially important to understand the molecular mechanisms that cause AE because it may lead to innovative strategies to prevent or cure this common condition. Recent studies have offered new insights into the cause of AE and indicate that injury-induced alterations in intracellular calcium concentration levels [Ca(2+)](i) and calcium homeostatic mechanisms play a role in the development and maintenance of AE. The injuries that cause AE are different, but they share a common molecular mechanism for producing brain damage-an increase in extracellular glutamate concentration that causes increased intracellular neuronal calcium, leading to neuronal injury and/or death. Neurons that survive the injury induced by glutamate and are exposed to increased [Ca(2+)](i) are the cellular substrates to develop epilepsy because dead cells do not seize. The neurons that survive injury sustain permanent long-term plasticity changes in [Ca(2+)](i) and calcium homeostatic mechanisms that are permanent and are a prominent feature of the epileptic phenotype. In the last several years, evidence has accumulated indicating that the prolonged alteration in neuronal calcium dynamics plays an important role in the induction and maintenance of the prolonged neuroplasticity changes underlying the epileptic phenotype. Understanding the role of calcium as a second messenger in the induction and maintenance of epilepsy may provide novel insights into therapeutic advances that will prevent and even cure AE.

Animals↗
PubMed2006

Erratum to "Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintenance of epilepsy." [Pharmacol. Ther. 105(3) (2005) 229-266].

Epilepsy is one of the most common neurological disorders. Although epilepsy can be idiopathic, it is estimated that up to 50% of all epilepsy cases are initiated by neurological insults and are called acquired epilepsy (AE). AE develops in 3 phases: (1) the injury [central nervous system (CNS) insult]. (2) epileptogenesis (latency), and (3) the chronic epileptic (spontaneous recurrent seizure) phases. Status epilepticus (SE), stroke, and traumatic brain injury (TBI) are 3 major examples of common brain injuries that can lead to the development of AE. It is especially important to understand the molecular mechanisms that cause AE because it may lead to innovative strategies to prevent or cure this common condition. Recent studies have offered new insights into the cause of AE and indicate that injury-induced alterations in intracellular calcium concentration levels ([Ca(2+)](i)) and calcium homeostatic mechanisms play a role in the development and maintenance of AE. The injuries that cause AE are different, but the share a common molecular mechanism for producing brain damage--an increase in extracellular glutamate and are exposed to increased [Ca(2+)](i) are the cellular substrates to develop epilepsy because dead cells do not seize. The neurons that survive injury sustain permanent long-term plasticity changes in [Ca(2+)](i) and calcium homeostatic mechanisms that are permanent and are a prominent feature of the epileptic phenotype. In the last several years, evidence has accumulated indicating that the prolonged alteration in neuronal calcium dynamics plays an important role in the induction and maintenance of the prolonged neuroplasticity changes underlying the epileptic phenotype. Understanding the role of calcium as a second messenger in the induction and maintenance of epilepsy may provide novel insights into therapeutic advances that will prevent and even cure AE.

Animals↗
PubMed2004

Review of the legal obligations of the doctor to discuss Sudden Unexplained Death in Epilepsy (SUDEP)--a cohort controlled comparative cross-matched study in an outpatient epilepsy clinic.

INTRODUCTION: Acknowledging informed consent and warning of material risk, the present study examined the current debate regarding early discussion of Sudden Unexplained Death in Epilepsy (SUDEP). It sought to confirm the profile of those prone to SUDEP and to determine the basis for disclosure to patients. METHODS: Patients with SUDEP attending an Australian outpatient epilepsy clinic between 1985 and 2000 were compared to an age, gender and epilepsy type cross-matched control group to ascertain risk factors for SUDEP and similarities to published parameters. These were evaluated as the basis for actions in negligence for either disclosure or failure to disclose. RESULTS: Twenty-one SUDEP patients were identified: aged 18-70 years; the majority had localisation-related epilepsy (13:8, 62%); male to female ratio was 3:1; and 15/21 used polypharmacy, compared with 8/21 controls (P = 0.02951). Handedness, alcohol use or deterioration of epilepsy were unrelated. DISCUSSION: This population mirrored the literature and confirmed an absence of risk factors amenable to modification. As discussion of SUDEP with males with localisation-related epilepsy on polypharmacy could not alter outcome it is unlikely that failure to disclose could be causal and hence successful in an action for negligence. Conversely, disclosure, in the absence of the patient seeking the information, may causally adversely affect quality of life hence providing successful action in negligence. Duty of care dictates open and frank discussion with those seeking the information. Thus, each case must be managed individually and doctors are advised to document the decision-making process.

Adolescent↗
PubMed2005

Elementary school epilepsy survey (ESES): a new measure of elementary school students' knowledge and attitudes about epilepsy.

OBJECTIVE: No peer-reviewed, published, psychometrically tested scales are available to assess elementary school students' general knowledge and attitudes about epilepsy. Such a scale is needed for evaluation of the effectiveness of classroom education programs. The purpose of this work was to develop and validate a brief, reliable scale for grades 4-6 to assess students' knowledge and attitudes about epilepsy and persons diagnosed with epilepsy. METHODS: Development of the 22-item Elementary School Epilepsy Survey (ESES) followed standard protocol for scale development. It includes a 12-item Knowledge subscale and a 10-item Attitudes subscale. The ESES was administered during regular classroom time given and repeated 1 week later. No educational intervention took place. RESULTS: Mean age of the 155 students was 11 years (range 9.8-13.9): grade 4, 56 students; grade 5, 36; and grade 6, 63 students. The ESES Total scale and Attitudes subscale had good internal consistency (Cronbach's alpha=0.72 and 0.81, respectively). As expected, the Knowledge subscale had low internal reliability (Cronbach's alpha=0.50). Test-retest scores indicated good reliability and strong discriminant validity, with significant increases noted in all ESES scores with increasing age and in those who knew someone with epilepsy. CONCLUSION: The ESES detects developmental and experiential trends in students' knowledge and attitude about epilepsy. It has good internal consistency and test-retest reliability.

Child↗
PubMed1998

Epilepsy: comprehensive care, quality of life, and factors preventing people with epilepsy from being employed.

This article reviews several studies of patients with intractable epilepsy carried out at the National Epilepsy Center, Shizuoka, Japan. These studies have evaluated the factors that affect the employment status of people with epilepsy and the effect of resective surgery for epilepsy on quality of life. It has been shown that although seizure status is a major factor in determining whether a person with intractable epilepsy finds employment, other factors also play a role. These other factors include intellectual impairment, psychological and psychiatric disorders, and physical disabilities. Thus even patients who are rendered seizure free may not be able to find employment. This is perhaps reflected in the finding that some patients who were rendered seizure free by resective surgery and their families were dissatisfied with the postoperative outcome. A number of special factors affecting the quality of life and employment opportunities available to people with epilepsy in Japan are also discussed.

Adolescent↗
PubMed1999

Promoting self-care in epilepsy: the views of patients on the advice they had received from specialists, family doctors and an epilepsy nurse.

The aim of the study was to examine patients' satisfaction with information and advice on epilepsy and self-care provided by medical specialists, general practitioners and a special nurse. We interviewed patients following a trial of nurse-run clinics for epilepsy in general practice. 44 patients, two-thirds of whom had at least one epilepsy attack in the prior 6 months were seen in their homes in the south of England. A recurring theme from interview data was that patients perceived the doctors' time as too limited to explain the condition and how to manage it, whilst the nurse had the time and expertise to do so. Overall the nurse trained in epilepsy care was valued highly for providing advice and support, especially in explaining the social aspects of epilepsy. Patients expressed the belief that they would have benefited most by seeing a special nurse at the time when epilepsy was first diagnosed.

Adolescent↗
PubMed1996

Cost analysis of epilepsy surgery and of vigabatrin treatment in patients with refractory partial epilepsy.

In this study the direct actual costs associated with epilepsy-related health care, treatment with the novel antiepileptic drug vigabatrin (gamma-vinyl GABA, GVG), epilepsy surgery evaluation (ESE) and epilepsy surgery were analysed in 52 patients with intractable partial epilepsy who were on a waiting-list for ESE while trying GVG. Sixty percent of the 52 patients obtained a reduction in seizure frequency of 50% or more with GVG. Of the twenty-one operated patients 57% became seizure free, 10% had more than 75%, 5% had 50-75% and 29% had less than 50% reduction of seizure frequency. Of the 17 patients who did not go through ESE (the "GVG responders"), the corresponding outcome was 6%, 59%, 29% and 6%. For the 14 patients who were neither operated nor GVG responders, the outcome was 0%, 0%, 36% and 64%. The mean yearly costs (expressed in 1991 prices) of epilepsy-related health care including antiepileptic drug treatment was US $1,594 the year before starting GVG therapy, and US $2959 the first year of GVG treatment including a mean yearly cost of GVG of US $1,572. The mean total cost for ESE and surgery was US $46,778 (N = 21), while the mean cost of ESE in patients evaluated but not accepted for surgery (N = 14) was US $24,054. Considering the costs for ESE and surgery in the whole patient series, the mean total cost of rendering one patient seizure free with surgery was US $110,000. Surgery is the most effective treatment option in selected cases of severe partial epilepsy. If its costs are distributed over the patient's expected lifetime, the yearly cost is comparable to the present yearly cost of medication with GVG. However, since many patients achieve satisfactory seizure control with GVG, and considering the risks of surgery, we consider it a rational policy to let patients try this drug (or another of the new generation of antiepileptic drugs) before entering ESE.

Adult↗
PubMed2002

Epilepsy surgery outcome in children with focal epilepsy due to tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is frequently associated with focal epilepsy due to cerebral tubers. Seizures are the first symptoms in most patients with brain involvement. These epilepsies are frequently severe, drug-resistant and may have a negative impact on the child's global development. Although most epilepsies are multicentric, these patients may be candidates for epilepsy surgery, if it is possible to determine a leading epileptogenic tuber. Nine patients with TSC were examined with long-term video-EEG monitoring, different neuroimaging techniques and neuropsychological tests. A main epileptogenic tuber could be identified in all of our patients. We found good correlations between neuroimaging and EEG. Surgery was performed in eight patients. Seizure outcome was good in all. Two patients became seizure-free, one patient had a single prolonged seizure five days postoperatively, four patients had a significant seizure reduction of more than 75 % and one patient had a seizure reduction of more than 50 % after surgery without additional neurologic deficits. In conclusion, patients with TSC and drug-resistant epilepsy may benefit from epilepsy surgery with reduction in frequency and severity of seizures as well as improved mental and behavioural development leading to a better quality of life. In view of recent developments in functional and metabolic imaging, primary epileptogenic lesions will be more easily detectable in patients with diffuse brain involvement in TSC and surgical treatment may be more specifically applied at an earlier age to a selected subgroup of patients with this disorder.

Child↗
PubMed2002

Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy.

Epilepsy is resistant to drug treatment in about one-third of cases, but the mechanisms underlying this drug resistance are not understood. In cancer, drug resistance has been studied extensively. Amongst the various resistance mechanisms, overexpression of drug resistance proteins, such as multi-drug resistance gene-1 P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1), has been shown to correlate with cellular resistance to anticancer drugs. Previous studies in human epilepsy have shown that MDR1 and MRP1 may also be overexpressed in brain tissue from patients with refractory epilepsy; expression has been shown in glia and neurones, which do not normally express these proteins. We examined expression of MDR1 and MRP1 in refractory epilepsy from three common causes, dysembryoplastic neuroepithelial tumours (DNTs; eight cases), focal cortical dysplasia (FCD; 14 cases) and hippocampal sclerosis (HS; eight cases). Expression was studied immunohistochemically in lesional tissue from therapeutic resections and compared with expression in histologically normal adjacent tissue. With the most sensitive antibodies, in all eight DNT cases, reactive astrocytes within tumour nodules expressed MDR1 and MRP1. In five of eight HS cases, reactive astrocytes within the gliotic hippocampus expressed MDR1 and MRP1. Of 14 cases of FCD, MDR1 and MRP1 expression was noted in reactive astrocytes in all cases. In five FCD cases, MRP1 expression was also noted in dysplastic neurones. In FCD and DNTs, accentuation of reactivity was noted around lesional vessels. Immunoreactivity was always more frequent and intense in lesional reactive astrocytes than in glial fibrillary acidic protein-positive reactive astrocytes in adjacent histologically normal tissue. MDR1 is able to transport some antiepileptic drugs (AEDs), and MRP1 may also do so. The overexpression of these drug resistance proteins in tissue from patients with refractory epilepsy suggests one possible mechanism for drug resistance in patients with these pathologies. We propose that overexpressed resistance proteins lower the interstitial concentration of AEDs in the vicinity of the epileptogenic pathology and thereby render the epilepsy caused by these pathologies resistant to treatment with AEDs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗