The health-related quality of life of childhood epilepsy syndromes

Objective:    There is increasing awareness of the importance of assessing physical, psychological, social and behavioural well-being in chronic disease. The aim of this study was to examine the health-related quality of life (HRQoL) of children with common epilepsy syndromes and to explore if there are HRQoL differences between those syndromes.
Methods:    Each child had their epilepsy syndrome defined according to the International League Against Epilepsy classification. Epilepsy syndromes included symptomatic frontal, temporal, parietal/occipital lobe and partial unlocalized epilepsy, and two idiopathic epilepsies, childhood absence epilepsy (CAE) and benign rolandic epilepsy (BRE). Seizure semiology and ictal/interictal electroencephalogram (EEG) were determined for symptomatic partial epilepsy syndromes by video-EEG monitoring. HRQoL was evaluated with an epilepsy-specific instrument, the Quality of Life in Childhood Epilepsy Questionnaire, and two generic instruments, the Child Health Questionnaire and Child Behavior Checklist.
Results:    Children with symptomatic partial epilepsy syndromes were affected by epilepsy in a similar way and did not have unique HRQoL profiles. However, these children had significantly lower HRQoL scores compared to those with CAE or BRE. All children with epilepsy regardless of syndrome had a higher frequency of behavioural problems compared to normative data.
Conclusion:    These results indicate that children with epilepsy regardless of syndrome require evaluation of the psychosocial implications. There is a greater impact on HRQoL in symptomatic epilepsy compared to idiopathic epilepsy. Specific symptomatic partial syndromes did not differ in the degree they affect HRQoL. These findings have important implications for clinicians caring for children with epilepsy.     

Is the International League Against Epilepsy classification of epileptic syndromes applicable to children in Estonia?

The concept of the epileptic syndrome has had a practical and research impact on the management of patients with epilepsy. The aim of the present study was to verify the applicability of the International Classification of Epilepsies and Epileptic Syndromes in children and adolescents in Estonia. A population-based study was performed between January 1995 and December 1997 in seven counties. Only cases involving children between the ages of 1 month and 19 years with at least two unprovoked seizures were included. In all, 560 children and adolescents were referred to the Children's Hospital of the University of Tartu. A syndrome diagnosis was made in 550 (98.2%) cases: (49.4%) were localization-related (6.4% idiopathic, 18.9% symptomatic, 24.1% cryptogenic). Benign childhood epilepsy with centrotemporal spikes was present in 33 (5.9%) and childhood epilepsy with occipital paroxysms in three (0.5%); 48.4% were generalized (28.8% idiopathic, 5.7% cryptogenic or symptomatic, 14% symptomatic). Childhood absence epilepsy was present in 6.4%, juvenile absence in 2.0%, juvenile myoclonic in 0.7% and epilepsy with generalized tonic-clonic seizures on awakening in 17.7%. West syndrome was diagnosed in 1.4%, Lennox-Gastaut syndrome in 2.9% of the cases. In 0.4% of the cases it was undetermined whether seizures were focal or generalized. In 8.8% of the cases there were atypical features so they were classified as 'other symptomatic generalized epileptic syndromes not defined above' and 1.8% of the cases were unclassified. Specific neurological diseases were diagnosed in 5.0% of cases. Thus, the International Classification of Epilepsies and Epileptic Syndromes was very applicable to children and adolescents in Estonia.     

Derzeitige Behandlungsstrategien bei Anfällen und Epilepsien im Kindesalter

Over the last years the therapy of epileptic seizures and syndromes has become much more effective by the development of new AED and the better knowledge of their pharmacokinetic properties. In addition many patients with lesional epilepsy who are refractory to medication have become seizure-free by epilepsy surgery. Before starting treatment the classification of seizure-type and epilepsy syndrome is absolutely necessary. There is no indication for long-time treatment of febrile seizures, just in the beginning of epilepsy. Therapy of choice for all epilepsies with generalized seizures is valproate, because of side-effects of valproate lamotrigine may be used alternatively. In epilepsy with tonic-clonic seizures phenobarbital and topiramate are drugs of second choice, in infancy and childhood bromide could be used as well. In children with absences, myoclonic and myoclonic-astatic seizures you could use ethosuximide or mesuximide besides lamotrigine. In patients with localisation-related epilepsies carbamazepine is most efficacious; in severe cases one should use oxcarbazepine because of the positive pharmacokinetic properties with regard to combination with other AED. Further drugs should be valporate, sulthiame and topiramate. In severe cases you should involve monitoring for epilepsy surgery at an early stage. The idiopathic (“benign”) partial epilepsies should be treated with sulthiame or further with valproate and clobazam. In these patients the intention is to get the children not only seizure-free but also normalizing or improving the EEG. Evidently there is a relationship between the extent of EEG-abnormalities and the occurrance of cognitive deficits. The West syndrome and Lennox Gastaut syndrome are encephalopathies of (multi-) focal origin and in most cases are drug-resistant. A successful drug therapy will not be sufficient unless it is combined with an adaequate advice on dealing with the epileptic child.     

The West Syndrome: Developmental Aspects

The electro-clinical characteristics of childhood epilepsy are known to appear during the development of the brain and to change their features with age. Accordingly, developmental viewpoints are indispensable to researches on childhood epilepsy. Age-dependent epileptic encephalopathy has the most remarkable developmental characteristics among childhood epilepsies. Early-infantile epileptic encephalopathy with suppression-burst (EIEE), the West syndrome and the Lennox-Gastaut syndrome, which constitute age-dependent epileptic encephalopathy, have many common features. Each of these three syndromes, however, has its own distinctive clinical and electro-encephalographic specificities, and shows mutual transition with age. Results of developmental studies on the West syndrome are described, confirming it as one type of age-dependent epileptic encephalopathy. 1) On the basis of the long-term follow-up study of 14 cases of EIEE, sequential transition from EIEE to the West, and further to the Lennox-Gastaut syndrome was observed, with reference to critical changing period, transitional patterns and prognoses. 2) Analytical follow-up study of 83 cases of the West syndrome, divided into idiopathic and symptomatic groups showed its evolution into the Lennox-Gastaut syndrome to be important for its prognosis, with reference to the various factors relating to this transition.     

Early classification of childhood focal idiopathic epilepsies: Is it possible at the first seizure?

PurposesTo evaluate the possibility of early syndrome classification of idiopathic partial epilepsies in children at the first seizure.Patients and methodsIn this observational study we prospectively evaluated 298 patients, aged between 1 month and 17 years and consecutively referred for the first unprovoked focal seizure. The whole cohort included 133 patients; the final analysis was carried out on 107 (59 males) individuals. Age at the first seizure ranged between 2.3 and 13.0 years. Clinical and EEG data of all patients were independently reviewed by two medical doctors. Patients were followed-up for at least 5 years, with a mean period of follow-up of 6.9 years.ResultsAfter the first seizure, a specific syndrome could be diagnosed in eighty (74.7%) children. In particular, Childhood Epilepsy with Centro-Temporal Spikes (CECTS) 42.9% of cases, Panayiotopoulos Syndrome (PS) 28.9%, idiopathic childhood occipital epilepsy of Gastaut (ICOE-G) 2.8%. Unclassified cases were 25.4%. At the end of the follow-up, the diagnosis was confirmed in 72 of 80 children (90%): BCECTS 89% of patients, PS 90% and ICOE-G 100%: among the unclassified cases, in 11 patients (40.7%) the diagnosis did not change, whereas 16 patients (59.3%) evolved into other syndromes or into atypical forms.ConclusionsAt the onset an initial diagnosis is possible in the majority of cases; epilepsy syndromes can be identified at the time of the initial diagnosis and at follow up this diagnosis has not to be revised in 90% of the cases.     

Clinical and genetic aspects of idiopathic epilepsies in childhood.

The identification of the first genes associated with idiopathic epilepsy has been an important breakthrough in the field of epilepsy research. In almost all cases these genes were found to encode components of voltage- or ligand-gated ion channels or functionally related structures. For many other idiopathic syndromes, there is linkage evidence to one or more chromosomes, but the genes have not yet been identified. Identification of the responsible genes and their gene products will further increase the knowledge of the pathogenic mechanisms involved in epilepsy, and will hopefully facilitate the development of drug targets for the effective treatment of epilepsy. This review gives an overview of the clinical characteristics and an update of genetic research of those idiopathic childhood epilepsies for which genes have been identified and the monogenic idiopathic childhood epilepsies for which mapping data are available.     

Practitioner review: use of antiepileptic drugs in children

BACKGROUND: The aim in treating epilepsy is to minimise or control seizures with full respect of quality-of-life issues, especially of cognitive functions. Optimal treatment first demands a correct recognition of the major type of seizures, followed by a correct diagnosis of the type of epilepsy or of the specific syndrome. METHODS: Review of data from literature and personal clinical experience in treating children with epilepsy. RESULTS: After summarising the general aspects on the diagnosis and treatment of the main forms of childhood epilepsy, we review key issues about management of seizure disorders, including when to start treatment, how to proceed when the first treatment fails, and how to set the targets of treatment. A special section is devoted to the new concept of epileptic encephalopathy and to the influence of "interictal" EEG abnormalities on cognition, behaviour, and motor abilities in children, providing some suggestions on why and how to treat these conditions. A second section approaches the choice of treatment according to the specific syndromes including infantile spasms, focal epilepsies, syndromes with typical absence seizures, the myoclonic epilepsies and the Lennox-Gastaut syndrome. CONCLUSIONS: Antiepileptic drugs (AEDs) can efficiently control seizures in most children. However, the specificity of AEDs is relatively limited, although continuing research is leading to a better understanding of the relationship between pathogenesis and the mechanism(s) and site(s) of drug action.     

Estudio de las epilepsias según la edad de inicio,controladas durante 3 años en una unidad de neuropediatría de referencia regional

Objective

A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years.

Epilepsy syndromes of childhood and adolescence

Epilepsy syndromes are defined as distinctive disorders identifiable on the basis of a typical age of onset, specific EEG characteristics, seizure types, and other features. A wide range of epilepsy syndromes present throughout infancy, childhood and adolescence from benign self-limiting syndromes to severe epileptic encephalopathies. Accurate recognition and diagnosis of these syndromes is essential to ensure appropriate investigation and treatment. Recent revisions to the classification of childhood epilepsy and recent scientific, particularly genetic, discoveries have had an impact on our understanding of the childhood epilepsies. In this review we consider the role of syndromic diagnosis and describe the typical features and presentation of the most important epilepsy syndromes of childhood and adolescence.     

Recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy: A prospective study

AimTo study recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy.MethodsAll children younger than 14 with two or more unprovoked seizures 24 h apart who were seen at our Hospital between 1994 and 2004 were included consecutively and prospectively followed. Patients previously examined in other centres were excluded. All patients who entered a remission were proposed to stop medication and were followed.ResultsThree hundred and fifty three children with two or more unprovoked seizures were attended. A total of 238 entered a remission period and were proposed to stop medication, 216 accept. Mean seizure-free time before medication withdrawal was 2.2 years. Kaplan-Meier estimate of recurrence risk was 23% at 2 years (95% CI: 17–29) and 28% at 5 years (95% CI: 22–34). A remote symptomatic etiology, various seizure types and a history of prior febrile seizures or prior neonatal seizures were associated with a significant increase in recurrence risk in univariable and multivariable analyses using Cox proportional hazards model. Recurrence risk at 2 years was 17% (95% CI: 11–23) for idiopathic/cryptogenic epilepsies and 41% (85% CI: 28–54) for remote symptomatic epilepsies. Recurrence risks at 2 years by epileptic syndrome were West syndrome (0%), benign rolandic epilepsy (10%), epilepsy without unequivocal partial or generalized seizures (11%), benign infantile seizures (13%), absence epilepsy (16%), cryptogenic partial epilepsies (20%), symptomatic partial epilepsies (45%), symptomatic generalized epilepsies (54%).ConclusionsRecurrence risk after withdrawal of antiepileptic treatment in children is low. Etiology and syndromic diagnosis are the main predictive factors.     

Sulthiame in childhood epilepsy

BACKGROUND: Sulthiame is a central carbonic anhydrase inhibitor found to be effective for both partial and generalized seizures. It has been in use in some European countries and in Israel for over 30 years. The aim of the present study was to evaluate the efficacy and tolerability of sulthiame in childhood epilepsy by conducting a multicenter, retrospective study of patients who received this drug. METHODS: The charts of 125 consecutive epilepsy patients treated with sulthiame as monotherapy or add-on therapy were reviewed. RESULTS: Twenty-nine out of 39 patients with benign focal epilepsy of childhood became seizure-free. Total seizure control was also achieved in 17 of 42 patients with symptomatic, non-refractory localization-related epilepsy, and in all 10 cases with juvenile myoclonic epilepsy. Complete normalization of the EEG occurred in 13 of 20 patients with benign partial epilepy of childhood. Side-effects were minimal and caused discontinuation of treatment in only seven children. CONCLUSION: The high tolerability, efficacy, convenience of use and low cost suggest that sulthiame should become a first line drug in the benign partial epilepsies of childhood and juvenile myoclonic epilepsy. It also has a role as add-on treatment in other partial and myoclonic epilepsies.     

Childhood epilepsy with neuropsychological regression and continuous spike waves during sleep: epilepsy surgery in a young adult

We describe the case of a man with a history of complex partial seizures and severe language, cognitive and behavioural regression during early childhood (3.5 years), who underwent epilepsy surgery at the age of 25 years. His early epilepsy had clinical and electroencephalogram features of the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia (Landau-Kleffner syndrome), which we considered initially to be of idiopathic origin. Seizures recurred at 19 years and presurgical investigations at 25 years showed a lateral frontal epileptic focus with spread to Broca's area and the frontal orbital regions. Histopathology revealed a focal cortical dysplasia, not visible on magnetic resonance imaging. The prolonged but reversible early regression and the residual neuropsychological disorders during adulthood were probably the result of an active left frontal epilepsy, which interfered with language and behaviour during development. Our findings raise the question of the role of focal cortical dysplasia as an aetiology in the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia.     

Genetics of the epilepsies

Recent molecular insights into the human idiopathic epilepsies have suggested the central role of ligand-gated and voltage-gated ion channels in their etiology. So far, genes coding for sodium and potassium channel subunits as well as a nicotinic cholinergic receptor subunit have been identified for Mendelian idiopathic epilepsies. In vitro and in vivo studies of mutations demonstrate functional changes, allowing new insights in mechanisms underlying hyperexcitability. Similarly, spontaneous murine epilepsy models have been associated with calcium channel molecular defects. The major challenge before us in understanding the genetics of the epilepsies is to identify genes for common forms of epilepsy following complex inheritance. Once such genes are discovered, the gene-gene-environmental interactions producing specific epilepsy syndromes can be explored.     

Paradoxical exacerbation of myoclonic-astatic seizures by levetiracetam in myoclonic astatic epilepsy

Background

Levetiracetam is a broad spectrum antiepileptic drug (AED) with proven efficacy when used as adjunctive therapy against myoclonic seizures. We report two patients suffering from epilepsy with myoclonic-astatic epilepsy (MAE) who experienced a paradoxical worsening of seizures after initiation of treatment with LEV, a finding not previously described.

Case presentation

Patients included were enrolled in an ongoing large prospective study evaluating children and adults with new onset epilepsy in Lebanon conducted at the American University of Beirut Medical Center in association with the Lebanese Chapter of the International League against Epilepsy. Based on an extensive evaluation, these patients were stratified into idiopathic partial, idiopathic generalized, symptomatic partial or symptomatic generalized epilepsies. Whenever possible the electroclinical syndrome was identified according to the ILAE classification of epilepsy syndromes. Patients were subsequently followed up on regular intervals and were assessed for adverse events, and seizure recurrence.MAE was diagnosed in five (1.6%) out of 307 consecutive children enrolled in this study. LEV was used as adjunctive therapy in four of those children with two experiencing a substantial and dose related worsening in the frequency of their myoclonic and atonic seizures.

Conclusion

LEV should be used with caution in children with MAE and an exacerbation of seizure frequency temporally related to the introduction of LEV should alert the clinician to the possibility of a paradoxical seizure exacerbation.     

Diagnosing idiopathic/cryptogenic epilepsy syndromes in infancy

PURPOSE—To determine the characteristics that permit diagnosis of the type of epilepsy beginning in the 1st year of life, and to determine from what age such characteristics are recognisable.PATIENTS—From 430 non-selected patients who began having seizures in the 1st year of life and were referred to the neuropaediatric department of Saint Vincent de Paul Hospital, those with epileptic spasms as the first seizure type, those with recognisable aetiology, and those for whom early history was not reliable were excluded.METHODS—For the remaining 140 patients, the age at which clinical and electroencephalogram (EEG) characteristics met those of recognisable epilepsy syndromes according to the ILAE classification was studied.RESULTS—In most epilepsy syndromes, the diagnosis could be made within three months of onset of the disorder. The most difficult was to distinguish cryptogenic localisation related epilepsy from severe myoclonic epilepsy in infancy. Repeat focal seizures and persisting spike focus were the earliest and most reliable signs of localisation related epilepsy, whereas alternating focal seizures, generalised myoclonus, and/or spike waves appeared before the end of the 1st year in most infants with severe myoclonic epilepsy. However, for 39 patients it was not possible to reach the diagnosis of a precise syndrome.CONCLUSION—For over three quarters of infants with cryptogenic/idiopathic epilepsy, it is possible to reach a syndromic diagnosis within the first months of the disease, based on clinical and EEG characteristics. However, for one quarter, no diagnosis is possible based on the currently available classification.     

Diagnosing idiopathic/cryptogenic epilepsy syndromes in infancy.

PURPOSE: To determine the characteristics that permit diagnosis of the type of epilepsy beginning in the 1st year of life, and to determine from what age such characteristics are recognisable. PATIENTS: From 430 non-selected patients who began having seizures in the 1st year of life and were referred to the neuropaediatric department of Saint Vincent de Paul Hospital, those with epileptic spasms as the first seizure type, those with recognisable aetiology, and those for whom early history was not reliable were excluded. METHODS: For the remaining 140 patients, the age at which clinical and electroencephalogram (EEG) characteristics met those of recognisable epilepsy syndromes according to the ILAE classification was studied. RESULTS: In most epilepsy syndromes, the diagnosis could be made within three months of onset of the disorder. The most difficult was to distinguish cryptogenic localisation related epilepsy from severe myoclonic epilepsy in infancy. Repeat focal seizures and persisting spike focus were the earliest and most reliable signs of localisation related epilepsy, whereas alternating focal seizures, generalised myoclonus, and/or spike waves appeared before the end of the 1st year in most infants with severe myoclonic epilepsy. However, for 39 patients it was not possible to reach the diagnosis of a precise syndrome. CONCLUSION: For over three quarters of infants with cryptogenic/idiopathic epilepsy, it is possible to reach a syndromic diagnosis within the first months of the disease, based on clinical and EEG characteristics. However, for one quarter, no diagnosis is possible based on the currently available classification.     

The classification and differential diagnosis of absence seizures with short-term video-EEG monitoring during childhood

Absence seizures are idiopathic epilepsies characterized by impairment of consciousness and generalized 2.5-4 Hz spike and slow wave discharges. This prospective study was performed to classify and define properties of subgroups of absence epilepsies. We included 31 patients, of whom seven were in the differential diagnosis group. On admission, absence epilepsy provisional diagnosis was considered in 16 patients clinically and in the other 15 patients based on routine EEG findings. Ictal EEGs were recorded by video-EEG monitoring in 23 of the patients (totally 202 ictal recordings). Patients were diagnosed as childhood absence epilepsy (n=8), juvenile absence epilepsy (n=10), juvenile myoclonic epilepsy (n=3), eyelid myoclonia with absences (n=2), and perioral myoclonia with absences (n=1). Neuroimaging, video-EEG monitoring and especially ictal recordings are important for classification of epilepsies in addition to history, physical examination and routine EEG findings. Video-EEG monitoring is required to classify, to make differential diagnosis and to determine the treatment plan and prognosis.     

Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy

Lamotrigine (LTG) has shown to confer broad-spectrum, well-tolerated control of epilepsy. Monotherapy is preferable over polytherapy because of better compliance, fewer adverse events, less interactions, lower teratogenicity and lower cost. The aim of this study is to evaluate the efficacy and safety of LTG monotherapy on seizure control in a cohort of children and adolescents with epilepsy.We retrospectively reviewed the records of children and adolescents treated with LTG monotherapy at our institution between 2001 and 2006. Data collected included demographics, seizure type, etiology of seizures, age at onset of seizures and at initiation of LTG treatment, number of antiepileptic drugs (AEDs) prior to LTG, dose of LTG, length of follow-up, treatment response, and adverse events.Seventy-two children and adolescents were identified (mean age 12.1 years); 37.5% had mental retardation. Age at onset of epilepsy was 5.7 years (0–16). Twenty three percent had symptomatic focal epilepsy, 15.5% idiopathic focal epilepsy, 19.4% symptomatic generalized epilepsy and 41.6% idiopathic generalized epilepsy. LTG was used as first-line monotherapy in 26.4% of patients and as a second-line monotherapy in 73.6%. Age at initiation of LTG therapy was 10 years (2.8–19). Mean number of AEDs tried prior to LTG was 1.3 (0–6). Mean dose of LTG was 5.5 mg/kg/day (1.1–13.7). Mean follow-up period was 33 months (3 weeks to 11.5 years).The degree of seizure reduction was as follows: seizure free in 42%, 75–90% reduction in 17.4%, 50–74% in 11.6%, 25–49% in 10%. Sixteen percent had no change in seizure control and 3% became worse. The most common adverse event was rash (6.9%). Six (8.3%) patients discontinued LTG because of the adverse events. No patient had Stevens–Johnson syndrome.In conclusion, LTG was effective and well-tolerated as monotherapy in children and adolescents for both focal and generalized epilepsies.