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Epilepsy is the most frequent additional handicap in children with mental retardation, with a reported prevalence between 5 and 50 percent. Demographics, issues of control of epilepsy and general attitudes to the care of these youngsters are considered in an effort to increase the availability of needed dental services.
Zonisamide is a new type of benzisoxazole derivative, first marketed in Japan in 1989. This study analyzed: (1) the drug's efficacy by seizure and epilepsy type in a total of 1008 patients treated during the development of zonisamide in Japan; (2) the effectiveness of zonisamide for 726 newly-diagnosed patients treated with zonisamide postmarketing; and (3) 50 patients with generalized epilepsies and epileptic syndromes (idiopathic generalized epilepsies, symptomatic generalized epilepsies, Lennox-Gastaut syndrome, Doose syndrome, and West syndrome), and 19 patients with undetermined epilepsies and specific syndromes (refractory grand mal in childhood, severe myoclonic epilepsy in infancy, other undetermined epilepsy, familial essential myoclonic epilepsy, and mitochondrial encephalomyopathy with ragged-red fibers). Analysis of study results showed that among all patients treated, zonisamide was highly effective for the treatment of idiopathic generalized epilepsy, temporal lobe epilepsy, and other partial epilepsies. The compound was also effective for other symptomatic generalized epilepsies. In 50 patients with generalized epilepsies, and 19 with undetermined epilepsies and specific syndromes, seizure frequency was reduced by >50% with monotherapy or two-drug therapy with zonisamide. Zonisamide was effective not only for partial epilepsies and generalized epilepsies but also for undetermined epilepsies and specific syndromes such as myoclonus epilepsy.
The recent and increasing interest for previously undescribed forms of epilepsy has been due to the description of families in which several affected members presented specific forms of epilepsy. Most epilepsies representing the description of new epilepsy phenotypes are partial epilepsies, although a new form of generalized epilepsy (generalized epilepsy with febrile seizures plus or GEFS+) has also been described. Our understanding of the clinical and genetic characteristics of the new familial epilepsy syndromes and the identification of informative families should accelerate the discovery of the basic mechanisms implicated in the production of partial seizures. The recent description of the syndrome of autosomal dominant nocturnal frontal lobe epilepsy, its localization to chromosome 20, the identification of the responsible gene (the alpha 4 subunit of the nicotinic cholinergic receptor) and the characterization of a mutation in two families are a good example. The recognition of the new epilepsy syndromes is of great interest for clinical neurologists and should lead to the establishment of more precise prognoses and therapies. In those families with several affected members, genetic knowledge may be important for genetic counseling purposes.
OBJECTIVE: To evaluate the relationship between epilepsy and sleep macrostructure in children. METHODS: Totally 31 children with idiopathic epilepsy aged 6-13 (mean 9.5) years were enrolled in this study, including 18 with idiopathic focal epilepsy and 13 with idiopathic generalized epilepsy. Sixteen age-and gender-matched children were also included as the control group. Polysomnogram (PSG) was recorded in all the children for analysis. RESULTS: Children with idiopathic partial epilepsy had increased total recording time (P<0.05) and those with idiopathic generalized epilepsy exhibited reduced non-rapid eye movement sleep in comparison with the control group. The efficiency of the different phases in the total sleep was also lowered in children with idiopathic generalized epilepsy (P<0.05), whose total sleep time had also been significantly reduced (P<0.05). CONCLUSIONS: Significant changes occur in the sleep macrostrcture of children with idiopathic epilepsy. Children with idiopathic generalized epilepsy presents poorer sleep quality, whereas those with idiopathic partial epilepsy tend to require excessive time for sleep.
Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is fundamental not only to allow correct management of patients but also to avoid the burden of unnecessary antiepileptic medication. The focus of this chapter is limited to imitators of idiopathic generalized epilepsies (IGE) which are expressed through myoclonic, tonic-clonic, tonic, atonic, and absence seizures. Apparent losses of consciousness and drop attacks also have to be considered. Benign myoclonus of early infancy is the main nonepileptic disorder in the differential diagnosis of infantile spasms, but is not dealt with here because West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic myoclonus, and disturbed responsiveness caused by the use of drugs are listed in Table 1. Other conditions that may imitate more focal epileptic seizures are omitted. Benign neonatal sleep myoclonus, apnea and apparent life-threatening events in infants, cyanotic and pallid breath-holding spells, syncope, staring spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been selected based on frequency or difficulties in differential diagnosis with the intention to cover the most conspicuous imitators of IGE in different ages.
The efficacy of treatment with lamotrigine (LTG) was evaluated in 92 patients with refractory epileptic seizures (46 women and 46 men aged 14-80 years, median 32 years). Seventy-one patients had partial epilepsy and 21 had primary generalized epilepsy. Patients were treated from zero to four (most frequently two) other antiepileptic drugs (AEDs). Maintenance dose of LTG was 50-800 mg daily (median 300 mg). Fifteen percent of the patients became seizure-free (13% of patients with partial epilepsy, 24% with primary generalized epilepsy). Thirty-eight percent of patients experienced at least 50% reduction in seizure frequency. Twenty-six percent of patients had a significant increase in seizure frequency (the same percentage in the two groups). Adverse events were recorded in 61% of patients, but most symptoms disappeared after dose reduction in concomitant AEDs. LTG was discontinued in 22% of patients, either because of adverse events or lack of effect. We conclude, that LTG is effective in reducing seizure frequency in patients with therapyresistant primary generalized epilepsy or partial epilepsy. Toxicity appears to be limited.
Although there have been major advances in the understanding of the molecular bases of certain inherited epilepsy syndromes, clinical studies are still needed to verify the possible genetic contributions to common epilepsies. We examined the proportions of positive family histories of epilepsy (within second-degree relatives) and consanguinity (within first-degree relatives) in 311 probands with childhood-onset epilepsy, and found that they had high family history rates of epilepsy (19.3%) and consanguinity (6.1%). A positive family history of epilepsy was found more in probands with generalized epilepsy than in ones with localization-related epilepsy, and more in probands with idiopathic/cryptogenic epilepsy than in ones with symptomatic epilepsy. However, on analysis after the symptomatic epilepsies had been divided into two categories, probands with pre- or perinatal symptomatic generalized epilepsy and ones with postnatal symptomatic localization-related epilepsy showed high positive family history rates, similar to ones with idiopathic/cryptogenic epilepsy. On the other hand, a positive family history of consanguinity was noted more in probands with generalized epilepsy than in ones with localization-related epilepsy, but there was no significant difference between probands with idiopathic/cryptogenic epilepsy and ones with symptomatic epilepsy. These findings suggest that in addition to the hereditary effect on idiopathic/cryptogenic epilepsy, a genetic susceptibility may contribute to the development of pre- or perinatal symptomatic generalized epilepsy, and to that of postnatal symptomatic localization-related epilepsy. Furthermore, a genetic predisposition seems to have an influence through consanguinity on the etiologies of both idiopathic/cryptogenic and symptomatic generalized epilepsies.
Approximately three-quarters of epileptic patients seen in consultation by specialists can easily be assigned to one of the diagnostic categories of the International League against Epilepsy. When patient age is taken into account, such a distribution shows that partial epilepsy is more common than generalized epilepsy (62% versus 38%) in patients of all ages, especially in those over 15 years of age (78% versus 22%). In contrast, generalized epilepsy is more frequent in subjects under 15 than partial epilepsy (55% versus 45%). In this younger age group the rarity of partial epilepsy is primarily due to the infrequency of temporal lobe epilepsy (21% of cases, as opposed to 56% in subjects over 15), whereas both primary and secondary generalized epilepsy contribute to the frequency of generalized epilepsy in this group.
The factors relevant to intractability, types of epilepsy and impairment of dexterity in patients with intractable epilepsy were studied independently in different groups of patients. The factors relevant to intractable epilepsy that were disclosed in 202 patients, who required hospitalization more than twice, were as follows: strong seizure propensity, neuropsychiatric disorders including mental deterioration of various degrees, ataxia, personality changes and psychotic episodes, intolerance to antiepileptic drugs due to acute or chronic side effects, idiosyncrasy and internal disorders, self-induced seizure, misdiagnosis and mistreatment, and breakdown of family care of patients. The types of epilepsy in 224 patients with intractable epilepsy whose seizures were not adequately controlled and recurred on a monthly basis in spite of hospitalization were classified as follows: 101 patients with localization-related epilepsies or syndromes, 106 with generalized epilepsies or syndromes, 16 with undetermined epilepsies or syndromes and one with specific syndrome. In regard to partial epilepsies, frontal lobe epilepsy and partial epilepsy with multiple foci were at least partially intractable as temporal lobe epilepsy. With respect to intractable generalized epilepsies, miscellaneous symptomatic generalized epilepsies like intractable grand mal epilepsy with progressive mental retardation in childhood were as important as Lennox-Gastaut or West syndrome though it defies classification into any established syndromes. The proposed International Classification of Epileptic Syndromes and Epilepsies was found adequate for analysis of intractable epilepsy. The disturbance of fine motor performance found in 84 patients who participated in occupational therapy was investigated by test programs comprising nine subbatteries.(ABSTRACT TRUNCATED AT 250 WORDS)
The effectiveness of lamotrigine as a monotherapeutic agent for a variety of pediatric epilepsies was reviewed retrospectively. Children were categorized as having focal vs generalized epilepsy and according to whether they were antiepileptic drug naive or drug exposed. Data collected included dosages, side effects, length of follow-up, number of prior drugs, and treatment response. Treatment was considered successful if the patient was seizure free for 6 months or more. Eighty-three children were identified (average age = 8.7 years); 43 had focal epilepsy, 32 had generalized epilepsy, and eight were not classified. Twenty-nine patients were classified as having specific syndromes. Fourteen patients were drug naive. The median follow-up period was 8 months (mean = 8.5). Overall, 45% were seizure free, 44% with focal epilepsy and 36% with generalized epilepsy. All children with juvenile myoclonic epilepsy and benign rolandic epilepsy of childhood were seizure free, although not all had been treated for at least 6 months. One third of drug-naive patients were seizure free. Rash was the most common side effect and was reported in five patients (6%); two patients discontinued the drug. None had Stevens-Johnson syndrome. One quarter of children experienced nonquantifiable improvements, namely increased alertness and improved behavior regardless of seizure control. Lamotrigine is effective as a monotherapeutic agent in children for both focal and generalized epilepsies. Side effects are relatively uncommon. Lamotrigine may be an effective firstline agent.
To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox-Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.
OBJECTIVE: To report the efficacy and tolerability of the ketogenic diet (KD) in refractory paediatric epilepsy. METHODS: Twenty-six consecutive children were treated with the classical KD from 1996 to 2001. The epilepsy syndromes included symptomatic generalized epilepsy (15), idiopathic generalized epilepsy (4), symptomatic partial epilepsy (1) and unclassified epilepsy (6). One child was lost to follow up. RESULTS: Median age at initiation of the KD was 6.1 years. Median duration of the treatment was 9 months. Twelve children (48%) were treated for >12 months; one still remains on the KD. Four children (16%) became seizure-free. Five children (20%) had 50-99% reduction in seizures, seven (28%) had <50% reduction in seizures and eight (36%) had no improvement. Age, seizure-type and aetiology did not predict response. The medications were decreased in 33% of the children. The KD was discontinued in 64% of the children because of poor efficacy and in 12% because of side-effects. Problems during initiation of the KD included asymptomatic hypoglycaemia (24%) and vomiting (12%). Later complications included poor growth (20%), hyperlipidaemia (16%), hypercalcuria (8%), hypocarnitaemia (8%), constipation (8%), pancreatitis (4%) and decreased bone density (4%). There were no deaths. A 3-month trial of the KD costs A3879 dollars. The first 12 months cost A7275 dollars with a cost of A4528 dollars each year, thereafter. CONCLUSIONS: The KD is an effective treatment for some children with refractory epilepsy, being generally well tolerated and rarely associated with side-effects. Response is not necessarily predicted by age, syndrome or aetiology. A prospective study of the KD is presently underway.
Previous studies had suggested that the epileptic bursts of feline generalized penicillin epilepsy represent the response of hyperexcitable cortex to thalamocortical volleys normally evoking spindles. If this were the case, it should be possible to convert the epileptic bursts of generalized penicillin epilepsy into spindles by decreasing the excitability of cortical neurons. In cats exhibiting the EEG signs of feline generalized penicillin epilepsy cortical excitability was decreased by hypoxia, by the topical application to the cortex of KCl (inducing spreading depression), barbiturates, GABA, AMP or noradrenaline. During generalized penicillin epilepsy, hypoxia and KCl-induced spreading depression abolished epileptic bursts which were replaced by spindles. When spindles and epileptic complexes occurring in the same animal were compared, a direct correlation between the frequencies of these two rhythms could be demonstrated, that of the epileptic complexes being about half that of the spindle waves. These observations support the hypothesis that the epileptic bursts of feline generalized penicillin epilepsy are induced by thalamocortical volleys normally involved in spindle genesis. Topical cortical applications of barbiturates, GABA, AMP and noradrenaline reduced or inverted the negative spikes of the spike and wave complexes, while augmenting the negative slow waves, or revealing them clearly in instances in which they had been poorly developed. This effect is interpreted as being due to a selective inactivation of the superficial cortical layers. That topical cortical application of barbiturates, GABA, AMP and noradrenaline was capable of transforming into typical spike and wave complex epileptic bursts, which had not previously conformed to this pattern, indicates that the intracortical electrophysiological events of typical and atypical epileptic bursts in feline generalized penicillin epilepsy are fundamentally the same and reflect an alternation between excitatory and inhibitory sequences.
The majority of severe epileptic encephalopathies of early childhood are symptomatic where a clear etiology is apparent. There is a small subgroup, however, where no etiology is found on imaging and metabolic studies, and genetic factors are important. Myoclonic-astatic epilepsy (MAE) and severe myoclonic epilepsy in infancy (SMEI), also known as Dravet syndrome, are epileptic encephalopathies where multiple seizure types begin in the first few years of life associated with developmental slowing. Clinical and molecular genetic studies of the families of probands with MAE and SMEI suggest a genetic basis. MAE was originally identified as part of the genetic epilepsy syndrome generalized epilepsy with febrile seizures plus (GEFS(+)). Recent clinical genetic studies suggest that SMEI forms the most severe end of the spectrum of the GEFS(+). GEFS(+) has now been associated with molecular defects in three sodium channel subunit genes and a GABA subunit gene. Molecular defects of these genes have been identified in patients with MAE and SMEI. Interestingly, the molecular defects in MAE have been found in the setting of large GEFS(+) pedigrees, whereas, more severe truncation mutations arising de novo have been identified in patients with SMEI. It is likely that future molecular studies will shed light on the interaction of a number of genes, possibly related to the same or different ion channels, which result in a severe phenotype such as MAE and SMEI.
PURPOSE: We tried to specify the relation between the photoparoxysmal response (PPR) and the wavelength spectra of flashing light in various photosensitive epileptic syndromes in the physiologic state. METHODS: Intermittent photic stimulation (IPS) by a Grass PS22 photic stimulator was performed with wavelength-specific optical filters in photosensitive patients with epilepsy (idiopathic generalized epilepsy, IGE; hereditary dentatorubral-pallidoluysian atrophy, DRPLA) and photosensitive subjects without epilepsy. RESULTS: Five of 19 normal trichromat patients with IGE and an IGE patient with deuteranomaly showed wavelength-dependent PPRs. The wavelength-dependent PPRs were elicited only by IPS containing wavelength spectra approximately 700 nm in the normal trichromat patients. Two of four patients with DRPLA showed wavelength-dependent PPRs, and two other DRPLA patients showed quantity-of-light-dependent PPRs. Quantity-of-light-dependent PPRs are elicited by IPS containing more than a certain quantity of light, independent of the wavelength composition of the flashing light. Two of five subjects without epilepsy showed wavelength-dependent PPRs. CONCLUSIONS: There are wavelength-dependent and quantity-of-light-dependent pathophysiologic mechanisms for eliciting PPRs by low-luminance IPS. Consideration of the quantity and wavelength composition of light from electronic screens will lead to the prevention of photosensitive seizures induced by electronic screen games.
The authors report 3 cases of gyratory seizures whose epileptic nature was demonstrated on the following features. They appeared with a loss of consciousness. In 2 cases, they ended with a tonic-clonic generalized fit and in the 3 cases, they were mixed with other generalized seizures. From an etiological point of view, in 2 cases, a deep lesion was discovered, the first one near the paracentral lobule, the second in the para-thalamic area. The third one was an idiopathic generalized epilepsy on clinical and electroencephalographic grounds. These 3 cases focus on the difficulties to classify gyratory seizures that may appear in 2 opposite situations, namely in symptomatic partial epilepsy and in idiopathic generalized epilepsy.
To combine both clinical and experimental findings into comprehensive nosological theories is a novel approach in epileptology, the adoption of which seems highly advisable for future research. A selection of problems concerning some well-known epilepsy syndromes are presented which could profit from such an approach. In idiopathic epilepsies, both generalized and localization-related, there seems to be an astonishing amount of variability beyond the acknowledged syndromes when these are looked at in detail. Much of this variance seems to be the consequence of regional expression of the genes which are certainly involved in their pathogenesis. Some of the involved genes seem to have not only a spatial but also a temporal limit of action. In symptomatic and cryptogenic 'generalized' epilepsies the rôle of focal etiological factors needs to be clarified as well as the question why their phenotype seems to depend more upon the manifestation age than the etiology. In relation to the symptomatic and cryptogenic focal epilepsies, it becomes more and more intriguing whether they are all due to more or less identical interactions of a set of basic mechanisms or whether foci in different cortical areas differ in this respect. It appears that there are many syndrome-related or syndrome-specific differences in the rôle of basic mechanisms in human epilepsies. A better understanding of these differences could become most helpful for the development of more specific and more effective therapies.
Feline generalized penicillin-induced epilepsy is a reliable experimental model of epileptic photosensitivity. Binocular photic stimulation at 4-8 flashes/s consistently triggers generalized, bilaterally synchronous spike-and-wave discharges in cats submitted to long-term intramuscular penicillin administration at low dosage (50,000-150,000 IU/kg). The photically induced epileptic activity is first and mainly recorded from the cerebral cortex as compared with the lateral geniculate (GL) body, therefore supporting a cortical onset of epileptic photosensitivity. At this low penicillin dosage, only minimal spontaneous spike-and-wave activity is recorded. Bilateral GL stimulation is more effective than binocular photic stimulation in triggering spike-and-wave discharges, whereas unilateral GL stimulation is grossly ineffective. This observation implies a role of bilateral specific visual thalamocortical volleys in the genesis of epileptic photosensitivity. Five of 12 randomly selected cats receiving long-term penicillin exhibited spontaneous epileptic photosensitivity, a finding that suggests an underlying genetic predisposition of the feline species to this condition.