Including Lennox-Gastaut Syndrome Research Articles

Current Position of Callosotomy

Callosotomy is widely used today as a treatment option for medically refractory epilepsy in patients with generalized or unknown-onset seizures. Other surgical indications include bilaterally distributed, most often synchronous, epileptiform discharges on EEG and some epilepsy syndromes, including Lennox-Gastaut syndrome and infantile spasms/West syndrome. Patients with drop attacks, mainly caused by epileptic spasms or atonic seizures, are most likely to benefit from this procedure. A more favorable seizure outcome was observed after a one-stage total callosal section in pediatric patients. For older children and adults, anterior callosotomy should initially be applied, and staged complete sections should be considered if the seizure outcome is insufficient. In terms of complications, most surgically associated brain and vascular injuries are avoidable in this era of microsurgery, and some less invasive newer methods, including endoscopic and stereotactic methods, are being explored. Disconnection syndrome is an unavoidable condition. However, it is usually transient in most cases and does not outweigh the improvement in symptoms of epilepsy in most patients, particularly in children who have compensatory functions or plasticity of the developing brain.

Ketogenic Diets in the Management of Lennox-Gastaut Syndrome-Review of Literature.

Epilepsy is an important medical problem with approximately 50 million patients globally. No more than 70% of epileptic patients will achieve seizure control after antiepileptic drugs, and several epileptic syndromes, including Lennox-Gastaut syndrome (LGS), are predisposed to more frequent pharmacoresistance. Ketogenic dietary therapies (KDTs) are a form of non-pharmacological treatments used in attempts to provide seizure control for LGS patients who experience pharmacoresistance. Our review aimed to evaluate the efficacy and practicalities concerning the use of KDTs in LGS. In general, KDTs are diets rich in fat and low in carbohydrates that put the organism into the state of ketosis. A classic ketogenic diet (cKD) is the best-evaluated KDT, while alternative KDTs, such as the medium-chain triglyceride diet (MCT), modified Atkins diet (MAD), and low glycemic index treatment (LGIT) present several advantages due to their better tolerability and easier administration. The literature reports regarding LGS suggest that KDTs can provide ≥50% seizure reduction and seizure-free status in a considerable percentage of the patients. The most commonly reported adverse effects are constipation, diarrhea, and vomiting, while severe adverse effects such as nephrolithiasis or osteopenia are rarely reported. The literature review suggests that KDTs can be applied safely and are effective in LGS treatment.

Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice

ObjectiveDevelopmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox–Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs. MethodsA multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed. ResultsEighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1–70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent. ConclusionThis is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

A.6 Vagus Nerve Stimulation in patients with therapy resistant generalized epilepsy

Background: For patients with generalized epilepsy who do not respond to anti-seizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox Gastaut Syndrome(LGS) and genetic generalized epilepsy(GGE). Methods: We identified patients with a diagnosis of Lennox-Gastaut Syndrome or Genetic Generalized Epilepsy, who underwent VNS implantation, between1997 and July 2018. Results: A total of 46 patients were included in this study with a history of therapy resistant generalized epilepsy. The mean age at implantation was 24 years(IQR= 17.8-31 years) and 50%(n=23) were female. The most common etiologies were GGE in 37%(n=17) and LGS in 63%(n=29). Median follow-up since VNS implantation was 63 months(IQR:31-112.8months). 41.7%(n=12) of the LGS group became responders, and 64.7%(n=11) in the GGE group. The best response in seizure reduction was seen in generalized tonic-clonic seizures. There was a reduction of seizure-related hospital admissions from 89.7%(N=26) pre-implantation, to 41.4%(N=12) post-implantation (p&lt;0.0001). The frequency of side effects due to the stimulation was similar in both groups(62.1% in LGS and 61.1% in GGE). Conclusions: VNS is an effective treatment in patients with therapy resistant generalized epilepsy, especially GGE.

Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions.

Infantile spasms may evolve into persistent epilepsies including Lennox-Gastaut syndrome. We compared adult epilepsy outcomes in models of infantile spasms due to structural etiology (multiple-hit model) or focal cortical inflammation and determined the anti-epileptogenic effects of pulse-rapamycin, previously shown to stop spasms in multiple-hit rats. Spasms were induced in 3-day-old male rats via right intracerebral doxorubicin/lipopolysaccharide (multiple-hit model) infusions. Controls and sham rats were used. Separate multiple-hit rats received pulse-rapamycin or vehicle intraperitoneally between postnatal days 4 and 6. In adult mice, video-EEG (electroencephalography) scoring for seizures and sleep and histology were done blinded to treatment. Motor-type seizures developed in 66.7% of multiple-hit rats, usually from sleep, but were reduced in the pulse-rapamycin-treated group (20%, p=.043 vs multiple-hit) and rare in other groups (0-9.1%, p<.05 vs multiple-hit). Spike-and-wave bursts had a slower frequency in multiple-hit rats (5.4-5.8Hz) than in the other groups (7.6-8.3Hz) (p<.05); pulse rapamycin had no effect on the hourly spike-and-wave burst rates in adulthood. Rapamycin, however, reduced the time spent in slow-wave-sleep (17.2%), which was increased in multiple-hit rats (71.6%, p=.003). Sham rats spent more time in wakefulness (43.7%) compared to controls (30.6%, p=.043). Multiple-hit rats, with or without rapamycin treatment, had right more than left corticohippocampal, basal ganglia lesions. There was no macroscopic pathology in the other groups. Structural corticohippocampal/basal ganglia lesions increase the risk for post-infantile spasms epilepsy, Lennox-Gastaut syndrome features, and sleep dysregulation. Pulse rapamycin treatment for infantile spasms has anti-epileptogenic effects, despite the structural lesions, and decreases the time spent in slow wave sleep.

Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy

BackgroundFor patients with generalized epilepsy who do not respond to antiseizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy-resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox–Gastaut Syndrome (LGS) and genetic generalized epilepsy (GGE). MethodsWe identified patients with a diagnosis of generalized epilepsy (including LGS and GGE), who underwent VNS implantation at the London Health Sciences Centre and Western University, London, Ontario, since this treatment became available in Canada in 1997 until July 2018. We assessed response to the treatment, including admissions to hospital and complications. ResultsA total of 46 patients were included in this study with a history of therapy-resistant generalized epilepsy. The mean age at implantation was 24 years (interquartile range [IQR] = 17.8–31 years), significantly younger in the LGS group (p = 0.02) and 50% (n = 23) were female. The most common etiologies were GGE in 37% (n = 17) and LGS in 63% (n = 29). Median follow-up since VNS implantation was 63 months (IQR: 31–112.8 months). Of the LGS group 41.7% (n = 12) of patients had an overall seizure reduction of 50% or more, and 64.7% (n = 11) in the GGE group without statistical significance between the groups. The best response in seizure reduction was seen in generalized tonic–clonic seizures, with a significant reduction in the GGE group (p = 0.043). There was a reduction of seizure-related hospital admissions from 91.3% (N = 42) preimplantation, to 43.5% (N = 20) postimplantation (p < 0.05). The frequency of side effects due to the stimulation was almost equal in both groups (62.1% in LGS and 64.7% in GGE). ConclusionsVagus nerve stimulation should be considered as a treatment in patients with therapy-resistant generalized epilepsy, especially in cases with GGE.

Outcome of West Syndrome: A Critical Review

AbstractWest syndrome is a genetically heterogeneous electro-clinical syndrome starting in early infancy. Short-term goal of therapy is spasm control and with standard hormonal or vigabatrin treatment, spasms can be controlled in 60 to 80% of patients in 2 weeks to 3 months period. Hormonal treatment with oral steroid is an alternative therapy to injectable adrenocorticotropin hormone, especially in low resource areas. Vigabatrin is preferred in tuberous sclerosis patients. Long-term aim of treatment is sustained remission of seizures and better neurodevelopmental outcome. About 50 to 70% of children are spasm free for prolonged duration, but epilepsy with multiple seizure types including Lennox–Gastaut syndrome is evident in 20 to 40% of children in long-term follow-up. Though hypsarrhythmia is helpful for the diagnosis, prognostic role of the resolution of electroencephalographic abnormalities is still uncertain. Seizures can be controlled in 40 to 60% of the patients, but only 12 to 40% children have normal neurodevelopmental outcome and a third of children are left with severe disabilities. Children with unknown etiology and normal development at spasm onset have better clinical outcome. Young age at onset, nonstandard therapy have less favorable outcome. Surgery is helpful for spasm control in patients with structural lesions and refractory spasms even in the absence of structural lesions.

The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study

PurposeFenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. MethodsHealthy nonsmoking subjects aged 18 to 50 years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9 days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72 hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis. FindingsIn the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma Cmax (59.1 vs 56.7 ng/mL; NS) and AUC0–∞ (1640 vs 1600 ng · h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity. ImplicationsThe bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals.

Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis.

BackgroundEpilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations.MethodsQuantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria.ResultsWithin the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years).ConclusionOrphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.

An unfortunate challenge: Ketogenic diet for the treatment of Lennox–Gastaut syndrome in tyrosinemia type 1

The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed.

Localization of epileptogenic zones in Lennox–Gastaut syndrome (LGS) using graph theoretical analysis of ictal intracranial EEG: A preliminary investigation

Precise localization of epileptogenic zones is essential for the successful surgical treatment of refractory epilepsy including Lennox-Gastaut syndrome (LGS). The surgical resection areas are generally determined by epileptologists based on diverse neuroimaging modalities; however, exact epileptogenic zones cannot be accurately localized in many patients with LGS using the conventional methods. Therefore, new reliable algorithms are still required for enhancing the success rate of the resective epilepsy surgery. In the present study, we introduce an approach to localize epileptogenic zones in LGS based on the graph theoretical analysis of ical intracranial EEG (iEEG). Four patients with LGS who became seizure-free after the resective epilepsy surgery were selected. Before the surgery, their epileptogenic zones were delineated using EEG, iEEG, and several conventional imaging modalities. Phase locking value (PLV) analysis was applied to construct functional connectivity networks during ictal events, and then several graph theoretical indices including betweenness centrality (BC) were evaluated for each iEEG sensor to find the primary hubs of the ictal epileptic network. The graph theoretical index values were then overlaid on 3D individual cortical surface. The iEEG channels with high BC values coincided well with the surgical resection areas. Among various graph theoretical measures such as local efficiency, participation coefficient, and eigenvector centrality, only BC showed fair correspondence with the surgical resection areas. The primary hubs in the ictal epileptic networks coincided well with areas of surgical resection in LGS patients with successful surgical outcomes. This observation warrants further studies to determine if the graph theoretical network analysis of ictal iEEG recordings can serve as a new auxiliary tool to localize epileptogenic zones in LGS.

Epilepsy Surgery in Pediatric Intractable Epilepsy with Destructive Encephalopathy

Background and Purpose:The aim of the current study is to review the clinical features, surgery outcomes and parental satisfaction of children with destructive encephalopathy who underwent epilepsy surgery due to medically intractable seizures.Methods:48 patients who underwent epilepsy surgery from October 2003 to August 2011 at Severance Children’s Hospital have been reviewed. The survey was conducted for functional outcomes and parental satisfaction at least 1 year after the surgery.Results:Epileptic encephalopathy including Lennox-Gastaut syndrome and infantile spasms was more prevalent than symptomatic focal epilepsy. Hypoxic ischemic injury accounted for most of the underlying etiology of the destructive encephalpathy, followed by central nervous system infection and head trauma. 27 patients (56.3%) underwent resective surgery and 21 patients (43.7%) underwent palliative surgery. 16 patients (33.3%) achieved seizure free and 27 parents (87.5%) reported satisfaction with the outcome of their children’s epilepsy surgery. In addition, 14 parents (77.8 %) whose children were not seizure free reported satisfaction with their children’s improvement in cognitive and behavior issues.Conclusions:Epilepsy surgery in destructive encephalopathy was effective for controlling seizures. Parents reported satisfaction not only with the surgical outcomes, but also with improvement of cognitive and behavior issues.

Does the effectiveness of the ketogenic diet in different epilepsies yield insights into its mechanisms?

The ketogenic diet (KD) has been used successfully in a variety of epilepsy syndromes. This includes syndromes with multiple etiologies, including Lennox-Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau-Kleffner syndrome; and idiopathic epilepsies, such as myoclonic-astatic (Doose) epilepsy. It also includes syndromes where genetics play a major role, such as Dravet syndrome, tuberous sclerosis, and Rett syndrome. Study of the KD in humans and animals harboring various genetic mutations may yield insights into the diet's mechanisms. Comparison of the diet's effectiveness with other treatments in specific syndromes may be another useful tool for mechanistic studies. The diet's utility in epilepsy syndromes of various etiologies and in some neurodegenerative disorders suggests it may have multiple mechanisms of action.

Interictal regional polyspikes in noninvasive EEG suggest cortical dysplasia as etiology of focal epilepsies

To evaluate the clinical significance of interictal regional polyspikes in focal epilepsies secondary to cortical dysplasia. We performed a data search for the term "regional polyspikes" in the database of our epilepsy-monitoring unit. Patients with generalized epilepsies including Lennox-Gastaut syndrome were excluded. Regional interictal epileptiform discharges were recorded in 513 patients with noninvasive EEG. We identified 29 patients with interictal regional polyspikes and focal epilepsies. Another 484 patients showed regional epileptiform discharges other than polyspikes. The etiology of the epilepsy was significantly more frequently cortical dysplasia in the group of patients with regional polyspikes (35%, 10 of 29 patients) than in the patients with other regional epileptiform discharges (5%, 24 of 484 patients) (p < 0.01). The polyspikes were significantly more frequently localized to the extratemporal (72%; n = 21) than temporal (28%; n = 8) regions (p < 0.01). In contrast, regional epileptiform discharges other than polyspikes were significantly more frequently localized to the temporal lobe (75%; n = 362) than extratemporal regions (25%; n = 122) (p < 0.01). Eight of the 10 patients with focal cortical dysplasia had extratemporal polyspikes. Noninvasively recorded regional polyspikes suggest cortical dysplasias as etiology of predominantly extratemporal epilepsies.

Zonisamide in the management of epilepsy—Japanese experience

Zonisamide (Zonegran ®), a novel antiepileptic drug (AED) approved in Europe for the adjunctive treatment of refractory partial seizures in adults, has undergone extensive evaluation in pre- and post-marketing double-blind and open-label studies in Japan (where zonisamide is used widely to treat partial and generalised seizures in adults and children). These data indicate that the clinical benefit of zonisamide extends across a range of seizure types and patient ages. In an analysis based on a mixture of controlled and open studies in adults and children with partial seizures, 51–57% responded to zonisamide treatment (achieving ≥50% reduction in baseline seizure frequency). Efficacy extends across a range of generalised seizures and 22–66% of adults and children experiencing tonic–clonic, tonic, clonic, myoclonic or absence seizures responded to treatment. Even greater responder rates have been reported when zonisamide was used as monotherapy for partial seizures and generalised seizures in patients refractory to other AEDs or with newly diagnosed epilepsy. Zonisamide is also efficacious in paediatric epilepsy syndromes, including Lennox-Gastaut Syndrome, West Syndrome and Ohtahara Syndrome. Across the spectrum of epilepsy syndromes studied, zonisamide is well-tolerated with a low incidence of adverse events, which are generally mild and CNS-related. These data indicate that zonisamide represents a valuable broad-spectrum option for the treatment of epilepsy.

Clinical spectrum of epileptic spasms associated with cortical malformation.

The spectrum of clinico-electrical characteristics of epileptic spasms associated with cortical malformation was studied in detail. The subjects were 15 patients suffering from spasms and cortical malformation demonstrated by MRI. The types of cortical malformation causing spasms were various, including hemimegalencephaly, diffuse pachygyria, focal cortical dysplasia, and polymicrogyria. Ohtahara syndrome was diagnosed in 3 patients, and West syndrome in 8. Symptomatic localization-related epilepsy preceded West syndrome in 4 patients, and a transition from Ohtahara syndrome to West syndrome was observed in one. West syndrome was followed by symptomatic generalized epilepsy including Lennox-Gastaut syndrome in 4 patients. Nine patients showed a condition which was labeled "epilepsy with partial seizures and spasms" (EPS) and characterized by the coexistence of partial seizures and spasms, and multifocal epileptic discharges on EEG. Spasms occurred only as EPS in 5 patients. EPS appeared following Ohtahara syndrome or West syndrome in 4 patients, and showed a transition to symptomatic localization-related epilepsy in 4. However, EPS did not evolve into generalized epilepsy, and persisted until the time of last follow-up in 5 patients. Therefore, the clinico-electrical pictures of patients with spasms and cortical malformation were diverse and not always limited within those of typical generalized epilepsy.

Vagus Nerve Stimulation in Children with Refractory Seizures Associated with Lennox–Gastaut Syndrome

Vagus nerve stimulation (VNS) is approved for use for refractory partial seizures. Nevertheless, information regarding VNS therapy for special populations, including Lennox-Gastaut syndrome (LGS) is limited. We discuss the effectiveness, tolerability, and safety of VNS therapy in patients with LGS. A six-center, retrospective study evaluated the effectiveness of VNS therapy in patients with LGS at 3 and 6 months and compared preimplant and postimplant seizure frequency. Adverse effects and quality of life (QOL) were included as secondary measures. Fifty patients, median age 13 years, with medically refractory epilepsy, were implanted. Median age at onset of seizures was 1.4 years, and a median of nine anticonvulsants (AEDs) had been tried before implantation. Data-collection forms were designed for retrospectively gathering data on each patient's preimplant history, seizures, implants, device settings, QOL, and adverse events. Median reductions in total seizures were 42% at 1 month, 58.2% at 3 months, and 57.9% at 6 months. The most common adverse events reported were voice alteration and coughing during stimulation. Other uncommon adverse events included increased drooling and behavioral changes. Investigators noted that QOL had improved for some patients in the study. VNS is an effective treatment for medically refractory epilepsy in LGS. This treatment is well tolerated, safe, and may improve QOL.

Community-based study of Lennox-Gastaut syndrome.

Before 1986, the spectrum of childhood epilepsies, including Lennox-Gastaut syndrome (LGS) and Doose syndrome (DS), known collectively as "epilepsia myoclonica astatica," was believed to represent a single disease. More recently, some investigators have considered these syndromes to be parts of a continuum. To clarify these theories, neurobiologic factors of the syndromes were studied to determine which qualities were shared and which were unique. A retrospective (1975-1985), community-based (Helsinki metropolitan area and the province of Uusimaa) study was designed to seek children with features of LGS and DS. It was assumed that recall bias and the selection of documented history would be similar throughout the group. Ranks of increasing pathology were assigned to different seizure types, EEG results, and drug treatments. A similar procedure was applied to epidemiologic data. Spearman rank-order correlations were calculated to determine which features correlated with LGS and which correlated with less severe epilepsy. The survey comprised 75 patients with broadly defined LGS. The annual incidence was 2 in 100,000 children aged 0 to 14 years. Prenatal or perinatal abnormalities did not correlate with severity of epilepsy. As compared with the relatively favorable ranks, the severe epilepsy ranks were more often associated with an early onset of epilepsy, an infectious disease at the onset, delayed development before epilepsy, abnormalities in neurologic or neuroradiologic examinations, and a deteriorating course of the condition. Patients with LGS are more likely than patients with less severe epilepsy to have a younger age at onset of epilepsy, an infection or both, and a deteriorating course of the condition.