Early Infantile Epileptic Encephalopathy Research Articles

Surgical Treatment of a Case of Early Infantile Epileptic Encephalopathy with Suppression‐Bursts Associated with Focal Cortical Dysplasia

We report a surgically treated case of early infantile epileptic encephalopathy (EIEE) with suppression-bursts associated with focal cortical dysplasia. Tonic-clonic seizures followed by a series of spasms occurred about a hundred times a day at a few days of age. Interictal electroencephalogram (EEG) revealed a suppression-burst pattern that was predominant in the left hemisphere. Magnetic resonance imaging (MRI) suggested focal cortical dysplasia in the left prefrontal area. Combination therapies with antiepileptic treatments showed only partial efficacy. The patient underwent lesionectomy at age 4 months, after which he gradually showed psychomotor development and a decrease of spasms to 0-2 series daily. In cases of EIEE with focal cortical dysplasia, surgical treatment may have beneficial effects on both psychomotor development and seizure control.

Síndrome de Ohtahara

A literature review using the term Ohtahara syndrome and early infantile epileptic encephalopathy revealed 51 cases. The characteristics of these cases were: 1) early onset of seizures; 2) tonic seizures; 3) poor response to treatment; 4) mental retardation; 5) poor prognosis; 6) burst-suppression EEG pattern; 7) evolution to West syndrome, and 8) multiple causes. These characteristics are non specific. No cause was found in most cases. The onset of seizures was between 7 hours and 86 days of age. The most frequent brain imaging abnormality was diffuse atrophy. ACTH was effective in a few cases and hemispherectomy was successful in one case. We believe that Ohtahara syndrome and early myoclonic encephalopathy are the same entity.

Adenylosuccinase deficiency: possibly underdiagnosed encephalopathy with variable clinical features

Adenylosuccinase deficiency is an autosomal recessive inherited defect of purine synthesis. In enzyme deficient patients, two normally undetectable compounds, succinylaminoimidazole carboxamide riboside and succinyladenosine, accumulate in urine, cerebrospinal fluid and, to a minor extent, in plasma. Analysing 150 highly selected urine specimens from patients with unidentified neurogenerative disorders we discovered the first two German cases of adenylosuccinase deficiency. The deficiency causes moderate to severe mental retardation, often accompanied by epileptic seizures and/or autistic features, and is occasionally associated with growth retardation and muscular hypotonia. Of the two German cases we present here, one patient fits into the clinical picture outlined by previous reports. The other patient, however, shows a pattern of symptoms so far undescribed: severe early infantile epileptic encephalopathy with reduced myelination. On mutation analysis this patient is the first to reveal a 39 base pair deletion in the adenylosuccinase gene in contrast to the point mutations detected in previous cases. Adenylosuccinase deficiency may be an underdiagnosed metabolic disorder with variable expression. This should be taken into consideration in patients with unclassified neurological conditions.

Infantile Epileptic Encephalopathy of Ohtahara

A case of infantile epileptic encephalopathy (Ohtahara syndrome) with EEG suppression-bursts at 2 days and associated with diffuse cerebral migrational and maturation disorder, diagnosed at autopsy at 19 months, is reported from Montreal Children’s Hospital, McGill University, Montreal, Canada.

Infantile Epileptic Encephalopathy (Ohtahara Syndrome) and Migrational Disorder

A case of early infantile epileptic encephalopathy (EIEE) with suppression-bursts (Ohtahara syndrome) associated with a diffuse cerebral migrational and maturation disorder evident on microscopic examination is reported. Although virtually all reported cases of EIEE are secondary to a congenital or acquired structural malformation of cortical development, EIEE is sometimes identified only by detailed neuropathologic examination, as confirmed by this case report. In addition to the malformation of cortical development, the patient demonstrated an absence of gamma-aminobutyric acid in the cerebrospinal fluid. All children with EIEE should be thoroughly examined by magnetic resonance imaging, cerebrospinal fluid amino acid level determination, and detailed postmortem neuropathologic examination.

An Electroclinical Study of Epilepsy Associated with Hemimegalencephaly and Focal Cortical Dysplasia with Bulging Lesions

Purpose: It is well known that hemimegalencephaly (HM) is often associated with refractory early‐onset epilepsy and some characteristic EEG features. In addition to the typical HM cases, in which the entire hemisphere shows hypertrophy, there are some mild cases of HM with more localized lesions. On the other hand, a type of focal cortical dysplasia shows relatively large lesions with an accompanying increase in the thickness and volume of the abnormal cortex. The underlying white matter is often thin and abnormal, with an increased between the extent of the lesions and their electroclinical characteristics. Methods: We investigated the electroclinical and magnetic resonance imaging (MRI) characteristics of two patients with typical HM (group 1), one patient with mild HM (group 2), and two patients with the previously mentioned focal cortical dysplasis (group 3). Results: On MRIs, there was generalized hypertrophy of the entire hemisphere in both patients in group 1. There were lesions in the occipital lobe and a part of the temporal lobe in the one patient in group 2 and in the frontal lobe in both patients in group 3. The age at onset of seizures was 3 days after birth and 1 month in the patients in group 1. The onset of seizures was within 24 h after birth in the aforementioned patients of groups 2 and 3, and 7 days after birth in the afore mentioned patients of groups 2 and 3, and 7 days after birth in the remaining group 3 patient. As for epileptic syndromes, one patient in group 1 and one in group 3 showed the electroclinical findings of Ohtahara syndrome. One of them subsequently evolved into West syndrome. Another patient in group 3 showed the symptoms of West syndrome; however, it was not preceded by Ohtahara syndrome. The patient of group 2 showed localization‐related epilepsy throughout the clinical course. Regarding the type of epileptic seizures, the patient in group 2 had only partial seizures. The other four patients had both partial and generalized seizures, such as tonic spasms and myoclonic seizures. The interictal EEGs showed asymmetric barst‐suppression (Paladin, 1989) in all patients except for one in group 1. Alpha‐like activity (Paladin, 1989) was observed in all patients except for one in group 3. The triphasic complex (Paladin, 1989) was observed in every patient in all of the groups. At the end of the follow‐up period, all patients continued to have seizures and had severe mental retardation. Both patients in group 1 were able to walk on their own despite the hemiplegia. The patient in group 2 was a severely handicapped child with a double hemiplegia. Both patients in group 3 showed slight hemiplegias. One of them could walk on his own, and the other was severely handicapped. Conclusions: There was no relation between the type of epilepsy and the volume of the lesions. EEG findings characteristic of HM were observed in the patients in all three groups irrespective of the nature, the volume, and the location of the lesions. The patients in groups 1 and 3 showed early‐onset refractory epilepsies such as Ohtahara and West syndromes. All of them had both generalized and partial seizures. The patients in group 3 showed the same characteristic EEG findings as those in group 1. Therefore it is considered that both groups share a similar mechanism for the occurrence of their epilepsies.

Epileptic encephalopathies in early infancy.

Of the epileptic syndromes beginning in early infancy, we described the clinical and electrical characteristics of early myoclonic encephalopathy (EME) and Ohtahara syndrome (OS), and the differential diagnosis between the two syndromes, reviewing previous articles and our own study of 6 cases with EME and 15 cases with OS. With regard to the clinical seizure types, the main seizure type was tonic spasms in OS while myoclonias, especially erratic myoclonias, and frequent partial seizures were predominant in EME. The suppression-burst (S-B) pattern was a common feature of both syndromes, although their form, time of appearance, and duration of appearance differed considerably. The S-B pattern in OS was characterized by periodic and consistent appearances during both waking and sleeping states, whereas in EME, the S-B pattern was enhanced by sleep and often not manifested in the awake states. OS showed a specific pattern of evolution as age-dependent epileptic encephalopathy with concomitant EEG change while EME had no specific evolution with age. In OS, obvious brain lesions such as brain malformations were often seen. In contrast, frequent occurrence of familial cases suggested some kind of congenital metabolic disorder as the etiological factor in EME.

Clinical analysis of 22 infants with afebrile cluster seizures.

The inclusion criteria for afebrile cluster seizures in infancy are defined as follows: (1) frequency of afebrile seizures at least 2 episodes within 72 hours; (2) seizure onset between 2 months and 3 years of age; (3) excluding febrile convulsion, central nervous system infections, status epilepticus, well-known epileptic syndromes in infancy (e.g. early myoclonic encephalopathy, early infantile epileptic encephalopathy, benign myoclonic epilepsy, infantile spasms. Lennox-Gastaut syndrome), electrolyte imbalance, watery diarrhea, head injury and intoxication. From 1986 to 1996, retrospectively and prospectively 22 patients were collected who fulfilled the above criteria. Based on whether or not a strong family history was present and a history of mild diarrhea was associated with seizure onset, they were divided into three groups: Group I, benign infantile familial convulsions (4 patients); Group II, cluster seizures with mild diarrhea in infancy (5 patients); Group III, cluster seizures without diarrhea in infancy (13 patients). Before seizure onset and during follow-up, all of the patients had normal development. The seizure pattern in all was generalized, most tonic type with duration of seizure less than five minutes in the majority. Recurrence rate was 100% in Group I and no recurrence in Group II. In 16 patients who were seizure-free over 12 months, the duration of persistence varied from 1 day to 8 months, and was shortest in Group II (range, 1 to 3 days). It was concluded that the vast majority of afebrile cluster seizures in infancy are benign in nature. Whether anticonvulsant therapy is justified must be individualized.

Early infantile epileptic encephalopathy: a long-term follow-up study.

The authors describe the electroclinical aspects and long-term evolution of five (in one male and four female patients) cases of early infantile epileptic encephalopathy in the neonatal period, the most common seizures were tonic spasms (either generalized or lateralized) that, very often, occurred in series. All newborns showed the typical suppression-burst pattern. The neurological status (initially normal) progressively deteriorated in the subsequent months, and all infants suffered from severe mental insufficiency and daily intractable seizures. Four out of the five children developed hypsarrythmia and one, Lennox-Gastaut syndrome. The authors discuss the main problems related to the suppression-burst pattern and the long-term prognosis of this abnormality.

PS-59-13 Influence of temporal lobe focal discharges on verbal memory impairment

The severe epilepsies of childhood are described briefly and information available on the efficacy of newly developed antiepileptic drugs (AEDs) in their control is reviewed. Therapeutic advances are awaited for early infantile epileptic encephalopathy, early myoclonic encephalopathy, progressive myoclonus epilepsies and Kojewnikow syndrome. West syndrome may respond to vigabatrin, and less predictably to lamotrigine. Lamotrigine can be helpful for severe myoclonic epilepsy and myoclonic absences. Astatic seizures may be dramatically controlled by lamotrigine, whereas vigabatrin may worsen myoclonic attacks. In the Lennox-Gastaut syndrome, the efficacy of felbamate has been demonstrated by a controlled trial; vigabatrin and lamotrigine can also be helpful. Non-idiopathic partial and secondary generalized epilepsies are responsive to vigabatrin in a useful percentage of cases, and some children improve with felbamate, lamotrigine or stiripentol.A trial which compares the efficacies of the newer AEDs against each other could provide very useful information for the clinician.

A case of early infantile epileptic encephalopathy with suppression burst associated with cerebral hemihypertrophy and abnormal gray/white matter intensity on MRI

A case of early infantile epileptic encephalopathy with suppression burst associated with cerebral hemihypertrophy and abnormal gray/white matter intensity on MRI

Management issues in severe childhood epilepsies

The severe epilepsies of childhood are described briefly and information available on the efficacy of newly developed antiepileptic drugs (AEDs) in their control is reviewed. Therapeutic advances are awaited for early infantile epileptic encephalopathy, early myoclonic encephalopathy, progressive myoclonus epilepsies and Kojewnikow syndrome. West syndrome may respond to vigabatrin, and less predictably to lamotrigine. Lamotrigine can be helpful for severe myoclonic epilepsy and myoclonic absences. Astatic seizures may be dramatically controlled by lamotrigine, whereas vigabatrin may worsen myoclonic attacks. In the Lennox-Gastaut syndrome, the efficacy of felbamate has been demonstrated by a controlled trial; vigabatrin and lamotrigine can also be helpful. Non-idiopathic partial and secondary generalized epilepsies are responsive to vigabatrin in a useful percentage of cases, and some children improve with felbamate, lamotrigine or striripentol. A trial which compares the efficacies of the newer AEDs against each other could provide very useful information for the clinician.

Vigabatrin monotherapy in resistant neonatal seizures

Seizures in a term infant with Ohtahara syndrome, associated with polymicrogyria, and a pre-term neonate with similar clinical features, failed to respond to conventional anticonvulsants, but were controlled with vigabatrin monotherapy. Another infant with Aicardi syndrome improved with vigabatrin. Autopsy in the first infant showed no evidence of intramyelinic oedema. The developmental outcome in the two survivors was better than expected for their condition.

Effect of the Ketogenic Diet for West Syndrome into Which Early Infantile Epileptic Encephalopathy with Suppression-Burst Was Evolved

Effect of the Ketogenic Diet for West Syndrome into Which Early Infantile Epileptic Encephalopathy with Suppression-Burst Was Evolved

Surface-recorded flash-EPs in man: Topographical distribution of the earlier fast components

This chapter discusses some of the better known myoclonic epilepsies and their treatment. Early myoclonic epilepsies referred to as early infantile epileptic encephalopathy with suppression-burst or Ohtahara syndrome is characterized by a triad of myoclonic, focal, and later tonic seizures. Their clinical manifestations include onset in early infancy, usually within the first three months, with 60% before ten days of age. Erratic and fragmentory myoclonus of the face or limbs, usually asynchronous and asymmetric, are noted early with massive myoclonic jerks appearing later. The main seizures are tonic spasms (similar to West syndrome) with other ictal events being partial and myoclonic. The electroencephalography (EEG) is characterized by suppression-burst pattern with complex bursts of high amplitude spikes and sharp and slow waves both during waking and sleeping states. Multiple etiologies are responsible for the syndrome but the majority of cases are associated with structural brain damage or severe bilateral injury. Early myoclonic encephalopathy is differentiated from Ohtahara syndrome by the main seizure type being erratic myoclonias, focal seizures and clusters of spasms, rather than tonic spasms primarily. Children with severe myoclonic epilepsy in infancy (SMEI), also known as “Dravet syndrome,” have the onset of seizures in the first year of life with development being normal prior to their onset.

Aicardi syndrome: a longitudinal clinical and electroencephalographic study.

We report clinical and EEG follow-up of 6 children with Aicardi syndrome. Age at seizure onset was < 3 months in 5 patients and 4 months in 1 patient. All patients had spasms, and these continued at time of follow-up in 5 patients. Five patients had seizures other than spasms which disappeared during early infancy. Bilateral independent bursts (BIBs) characteristic of Aicardi syndrome were noted in 4 patients. In 1, BIBs showed suppression-burst patterns. BIBs converted to hypsarrhythmia or multifocal spikes with a tendency to BIBs during sleep. BIBs disappeared completely during both waking and sleeping states between the ages of 3 years 1 month and 4 years 9 months. After BIB disappearance, the EEG of 1 patient showed diffuse slow spike-and-wave complexes most of which appeared asynchronously. At onset, 1 patient had early-infantile epileptic encephalopathy with suppression-burst which evolved initially into West syndrome (WS) and then Lennox-Gastaut syndrome (LGS). The other 3 children also had WS.

Prenatal etiologies of West syndrome.

We investigated the etiology of West syndrome (WS) with special reference to prenatal factors in 180 cases. Prenatal cause was the most frequent diagnosis (77 cases, 42.8%), followed by perinatal (25 cases, 13.9%) and postnatal factors (12 cases, 6.7%); 48 cases (26.7%) were of uncertain etiology; eighteen cases (10.0%) were idiopathic. Of the three forms of age-dependent epileptic encephalopathy, prenatal cause was present in 12 of 15 cases (80.0%) of early-infantile epileptic encephalopathy with suppression-burst, 77 of 180 cases (42.8%) of WS, and 31 of 123 cases (25.2%) of Lennox-Gastaut syndrome (LGS). Prenatal factors of WS included tuberous sclerosis (23), chromosome abnormalities (10), cerebral dysgenesis (10), porencephaly (7), hydrocephalus (5), Aicardi syndrome (3), Aicardi syndrome associated with chromosome abnormality (1), and other causes (18). Chromosome abnormalities with WS consisted of 6 cases with 21 trisomy and one case each with 18q duplication, t(1;y) translocation, 7q duplication, and partial 2p trisomy. One patient with Aicardi syndrome also had a t(12;21) translocation. No significant difference was observed in the age of onset of WS among the five etiologic groups. The evolution from WS to LGS was not influenced by etiology, except for the idiopathic group. In patients followed for over 3 years, seizure remission occurred in 46.8% (22 of 47 cases) of the prenatal group. This was lower than the other four groups. Intellectual prognosis was also relatively poor in those with prenatal onset. Pyridoxal phosphate (PAL-P) treatment was effective in 9 of 70 (12.9%) prenatal cases and 5 of 18 (27.8%) idiopathic cases.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of early infantile epileptic encephalopathy (EIEE) with anatomical cerebral asymmetry and myoclonus

The authors report a case of early encephalopathy with myoclonus, tonic spasms and a suppression-burst pattern on electroencephalography (EEG) associated with unilateral cerebral hypertrophy following hemiatrophy. This patient showed frequent myoclonus in relation to a suppression-burst pattern resembling that in early myoclonic encephalopathy (EME). Moreover, the case also showed tonic spasms, from the age of 13 days, in series, as seen in Ohtahara syndrome. On the other hand, there was a previously undescribed peculiar CT scan finding, which showed hypertrophy of the right cerebral hemisphere at birth, following hemiatrophy. Neuropathological examination revealed cerebral atrophy associated with heterotopia and an ependymal hyperplasia in the right hemisphere, suggesting hemimegalencephaly. This case should be classified as Ohtahara syndrome accompanied by myoclonus, because of the spasms in series interrupting the suppression-burst pattern, and the etiological factor of brain malformation. The nosological aspects of this epileptic encephalopathy are discussed.

Atypical Early Infantile Epileptic Encephalopathy with Suppression-Burst

Atypical Early Infantile Epileptic Encephalopathy with Suppression-Burst

Early infantile epileptic encephalopathy: A case associated with hemimegalencephaly

The authors report a case of early infantile epileptic encephalopathy (EIEE) associated with hemimegalencephaly. The etiological factors in previously published cases of EIEE are reviewed and attention is focused on the high proportion of cases associated with neuronal migration disorders. We suggest that idiopathic cases of EIEE would be due to such disorders.