Brain malformation and infantile spasms in a SCAD deficiency patient

This report presents a case of short-chain acyl-coenzyme A (CoA) dehydrogenase deficiency with a previously unreported presentation with brain malformations and infantile spasms. This female infant developed repeated tonic clonic seizures at the age of 3(1/2) months. She subsequently developed West syndrome at the age of 4 months. Her electroencephalogram disclosed hypsarrhythmia, and video-electroencephalographic monitoring confirmed the presence of infantile spasms. Magnetic resonance imaging revealed a small midline frontal meningocele, abnormal cortical gyration, and partial agenesis of the corpus callosum consistent with neuronal migrational disorder. Metabolic evaluation indicated ethylmalonic acidemia. Muscle biopsy with enzymatic assay of short-chain acyl-coenzyme A revealed low enzymatic activity confirming the diagnosis of short-chain acyl-coenzyme A dehydrogenase deficiency. To our knowledge, this is the first report of the coexistence of short-chain acyl-coenzyme A dehydrogenase deficiency, infantile spasms, and brain malformation. We conclude that short-chain acyl-coenzyme A dehydrogenase deficiency should be considered in the differential diagnosis of gyral abnormality, corpus callosal hypoplasia, and infantile spasms.     

A case of infantile spasms: Epileptic apnea as partial seizures at onset

We report a 2-month-old boy who presented with apneic attacks as a manifestation of epileptic seizures at onset and eventually progressed to infantile spasms. At onset, at 2 months of age, apneic attacks were the sole symptom of epileptic fits. Although these seizures were accompanied by cyanosis, bradycardia was not noted. An ictal electroencephalogram showed focal paroxysmal discharges in the temporal area. Treatment with sodium valproate was not effective to control his seizures. By 6 months of age, he progressed to infantile spasms. Although his seizures could be completely controlled with the use of zonisamide, vitamin B6 or high-dose immunoglobulin, his mental and behavioral development was retarded severely. There have been no previously published cases with infantile spasms that evolved from epileptic apnea as partial seizures.     

Infantile spasms as an adverse outcome of neonatal cortical sinovenous thrombosis

Cerebral sinovenous thrombosis is a rare but potentially serious condition often occurring in children with nonspecific presenting features. Much remains to be learned about the long-term outcome of infants with cerebral sinovenous thrombosis. We report a series of four patients taken from a prospective database of neonates with sinovenous thrombosis who subsequently developed infantile spasms, three with hypsarrythmia on electroencephalography and one with multiple independent spike foci. The first patient presented at 2 weeks of age with hypernatremia, dehydration, and seizures. He was found to have extensive thrombosis and hemorrhagic infarction of the right basal ganglia. The second patient presented at 5 weeks of life and was found to have sagittal sinus thrombosis with bilateral intracranial hemorrhage. The third patient presented with seizures on day 1 of life and was found to have venous thrombosis involving the torcular, extending into the sagittal sinus. The fourth patient presented at 3 weeks with lethargy and seizures. He was diagnosed with bacterial meningitis and also had extensive sinus thrombosis. All patients developed infantile spasms at ages 9, 7, 11, and 10 months, respectively. This is the first report in the English literature describing infantile spasms as a possible outcome of sinovenous thrombosis in early infancy.     

Surgery for the Treatment of Medically Intractable Infantile Spasms: A Cautionary Case

The most appropriate time to consider cortical resection to treat medically intractable infantile spasms has not been clearly defined. The risks that need to be reconciled to make this decision are: What is the risk of loss of developmental potential if surgery is delayed too long versus what is the risk of unnecessary surgery if it is done too soon. We propose that, in addition to evaluation of seizures, developmental assessment is a key factor in the surgical decision. The case report illustrates this concept. CASE REPORT: HC had onset of seizures at 9 days of age and developed infantile spasms due to mild right hemimegancephaly. At 19 months, she was having up to 50 seizures/day and was evaluated and approved for right hemispherectomy but surgery was delayed. Despite the seizures, her development had been much better than most patients with hemimegencephaly and infantile spasms. At 25 months her seizure control was much improved but she had several seizures/week. EcoG at the time of surgery did not demonstrate the usual abnormalities so no resection was performed. She has had only 5 seizures in the 2(1/2) year since. CONCLUSIONS: (a) Hemimegalencephaly is not always associated with severe mental retardation; (b) normal or near-normal development may, in some cases, indicate the possibility of medical control of seizures as the child grows; (c) a localized developmental brain abnormality in a child with intractable seizures should not necessarily lead to cortical resection; and (d) when a child meets developmental milestones, it may be appropriate to delay surgical intervention.     

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.     

Pedaling automatism in atypical West syndrome: a case report]

A seven-month-old girl with atypical West syndrome with pedaling automatism was reported. She started to have early infantile epileptic encephalopathy with suppression-burst (EIEE) at age 14 days followed by infantile spasms at 3 months of age. She began to have spasms with automatism at 4 month, mainly consisting of pedaling movements of both feet associated with tonic spasms of upper extremities and writhing of trunk. Ictal EEG showed irregular slow waves with occasional spikes predominantly over the right hemisphere mixed with artifacts. Interictal EEG during sleep showed suppression-burst patterns. Cerebral atrophy and microcephaly were revealed on brain CT, immature myelination on MRI and decreased blood flow in the frontal, temporal, and parietal lobes on the right on PET scan. Pedaling automatism is rare in infancy and its clinical significance was discussed in relation to West syndrome and complex partial seizures.     

Aicardi syndrome associated with anterior cephalocele in a female infant

Aicardi syndrome is a triad of abnormalities that includes total or partial agenesis of the corpus callosum, chorioretinal lacunae, and infantile spasms. This syndrome was first described in 1965. A female infant with Aicardi syndrome associated with a nasoethmoidal cephalocele is described in this report. She presented with a history of unilateral nasal discharge since birth and seizures since age 1 week. She was microcephalic and there was visual impairment. A fleshy mass of the left nostril was noted. Ophthalmological evaluation revealed left exotropia, dysplastic optic discs and retina, 'morning glory' appearance of the left optic disc, and bilateral chorioretinal lacunae. Magnetic resonance imaging of the brain showed absence of the corpus callosum, dysmorphic changes of the lateral ventricles, a superiorly located third ventricle, heterotopic grey matter of the frontal lobes, a left nasoethmoidal cephalocele, and closed lip schizencephaly of the left frontal lobe. This female infant developed asymmetric infantile spasms at age 8 weeks. Surgical correction of the cephalocele was declined. She developed recurrent pneumonias secondary to aspiration of feeds and died at age 8 months during one of these events.     

Infantile spasms with basal ganglia MRI hypersignal may reveal mitochondrial disorder due to T8993G MT DNA mutation

PURPOSE: To report three cases of infantile spasms (IS) with an abnormal magnetic resonance imaging signal in the basal ganglia (Leigh-like syndrome), due to T8993G mt DNA mutation. PATIENTS AND RESULTS: The first sign was, at the end of the first year of life, IS in one case and the combination of IS with behavior changes in the two other cases. Video EEG polygraphy demonstrated both spasms and hypsarrhythmia, but no other kind of seizures. Vigabatrin or steroids controlled the spasms with a follow-up of several years. All 3 patients had hyperlactatorrhachia (3.47 to 7 mmol/l). Axial hypotonia and dystonia appeared by the end of the first year of life. As in cases with the NARP mutation and onset later in life, neuropathy and retinopathy could also be demonstrated. DISCUSSION: Although it is well established that symptomatic IS with hypsarrhythmia mainly result from cortical lesions, this epileptic encephalopathy may also be generated by lesions in the basal ganglia without evidence of cortical damage. This finding suggests that West syndrome is likely to be caused by age-related dysfunction at any level of a cortico-putaminal loop of hyperexcitability.     

Facilitation of Infantile Spasms by Partial Seizures

Summary: We report 16 patients with infantile spasms in whom onset of the clusters of spasms appeared to be triggered by close temporal association with partial seizures. Common features included the presence of focal cerebral lesions in 12 infants (3 were classifiable as cryptogenic); all had partial seizures with EEG localization, clusters of bilateral spasms always preceded by partial seizures, and response to adrenocorticotropic hormone (ACTH) and traditional antiepileptic drugs (AEDs) generally was poor. Three had complete agenesis of the corpus callosum, which argues against interhemispheric callosal spread of focal discharges resulting in the generalized spasms. Surgical cortical resections were performed in 6 of the infants, with good outcomes. This group of patients supports a model in which the spasms, although probably generated at a subcortical level, are facilitated or possibly induced by focal discharges from cortical pathology.     

Clinical,EEG, and positron emission tomography features of childhood-onset epilepsy with localized cortical dysplasia detected by magnetic resonance imaging

We studied clinical, EEG, and positron emission tomography (PET) findings in 18 patients with childhood-onset epilepsy with localized cortical dysplasia detected by magnetic resonance imaging. The age at onset of epilepsy was prior to 6 months of age in about half of the patients; the oldest patient was 7 years. Unilateral dysplastic lesions were more frequently associated with partial epilepsy, whereas bilateral dysplasia was associated more with generalized epilepsy. Patients with partial epilepsy had secondarily generalized seizures more often at the onset. Two patients with partial epilepsy presented generalized seizures transiently: undetermined epilepsy with infantile spasms triggered by partial seizures in one and epilepsy with continuous spike waves during slow-wave sleep in the other. The size of the lesion was not correlated with seizure outcome but was significantly correlated with mental outcome. The PET abnormality of glucose metabolism usually corresponded to the areas of cortical dysplasia and EEG focus, but the correspondence was better in partial epilepsy than generalized epilepsy.     

Atypical presentation in Rasmussen encephalitis: delayed late-onset periodic epileptic spasms

A five-and-a-half-year-old girl started experiencing progressive left hemiparesis at age two and a half years. At age five years and four months she started presenting clusters of asymmetric periodic epileptic spasms with no hypsarrhythmia. The ictal EEG showed periodic, constant and stereotyped complexes. Serial brain imaging revealed progressive atrophy of the right hemisphere with increased T2 signal on MRI. She underwent a right hemispherotomy, and histological examination showed signs of inflammation and features of focal cortical dysplasia (FCD). She has been seizure-free for 16 months. This case is unique in the following aspects: the presence of typical Rasmussen encephalitis features of progressive unilateral brain involvement without seizures, a delay of almost three years prior to seizure onset; an atypical seizure type presentation with periodic epileptic spasms and the presence of FCD associated with inflammatory changes. [Published with video sequences].     

A 9-year-old boy with a history of large perinatal stroke, infantile spasms, and high academic achievement

The prognosis for intellectual development in children with symptomatic infantile spasms is usually poor. We report a 9-year-old boy with a history of a large, presumed perinatal, left middle cerebral artery infarct discovered when he developed infantile spasms at 6 months of age. The infantile spasms responded to treatment with adrenocorticotropic hormone. He attained cognitive milestones at normal times, requiring only speech therapy for dysarthric speech. At 9 years of age, he has seizures and a severe right hemiparesis but is an articulate honor roll student in advanced English classes. The development of infantile spasms after large-branch middle cerebral artery stroke does not always predict future mental retardation.     

Alexander disease with mild dorsal brainstem atrophy and infantile spasms

We present the case of a Japanese male infant with Alexander disease who developed infantile spasms at 8 months of age. The patient had a cluster of partial seizures at 4 months of age. He presented with mild general hypotonia and developmental delay. Macrocephaly was not observed. Brain magnetic resonance imaging (MRI) findings fulfilled all MRI-based criteria for the diagnosis of Alexander disease and revealed mild atrophy of the dorsal pons and medulla oblongata with abnormal intensities. DNA analysis disclosed a novel heterozygous missense mutation (c.1154 C>T, p.S385F) in the glial fibrillary acidic protein gene. At 8 months of age, tonic spasms occurred, and electroencephalography (EEG) revealed hypsarrhythmia. Lamotrigine effectively controlled the infantile spasms and improved the abnormal EEG findings. Although most patients with infantile Alexander disease have epilepsy, infantile spasms are rare. This comorbid condition may be associated with the distribution of the brain lesions and the age at onset of Alexander disease.     

Outcome of Epilepsy Surgery in the First Three Years of Life

PURPOSE: We analyzed our experience over a 6-year period with early-childhood patients who had undergone epilepsy surgery, and investigated the surgical outcomes. METHOD: We reviewed the medical records of 23 children, ages 0-3 years, who underwent epilepsy surgery between 1991 and 1996. RESULTS: Twenty children had partial seizures; two had infantile spasms; and one had generalized tonic-clonic seizures at onset. The mean age at onset of seizures was 4.7 months, and the mean age at time of surgery was 15.3 months. A total of 32 operations (21 focal cortical resections and 11 hemispherectomies) was performed. Five of 12 children with seizures secondary to a neuronal migration disorder had reoperations, including three who ultimately underwent complete hemispherectomy. The pathology consisted of hemimegalencephaly in three patients, focal cortical dysplasia (FCD) in eight, tuberous sclerosis in one, Sturge-Weber syndrome (SWS) in five, infarction in two, low-grade glioma (LGG) in three, and post-herpes simplex virus encephalitis (HSE) in one. The follow-up period ranged from 1 to 6.5 years (mean, 3.2 years) from patients' last operation. The seizure outcome according to Engel's criteria was class I in 12 patients, class II in three, class III in six and class IV in two. CONCLUSIONS: Seizure outcomes after surgery were less favorable in infants with FCD than in those with SWS and LGG. Seizure outcome for the patients with hemispherectomies was excellent, compared with those who had focal cortical resections.     

Autistic regression associated with seizure onset in an infant with tuberous sclerosis

We report here on a male diagnosed with tuberous sclerosis at 6 months of age. The child was treated with vigabatrin at age 6 months after an abnormal electroencephalogram but before onset of seizures. Vigabatrin was discontinued at age 13 months to avoid possible visual field defects. At 21 months, the child developed partial seizures with secondary generalization and infantile spasms. Standardized developmental assessments were performed at 12, 18, 24, 30, and 36 months of age. Cognitive and social development were normal until age 21 months and the onset of seizures. When assessed at 24 months, the child met criteria for autism and learning disability. This case indicates that the onset of epilepsy during an early stage in brain development can be associated with autistic regression and persistent developmental disorder. The case suggests the need to consider if possible visual field defects with vigabatrin outweigh the potentially deleterious effects of uncontrolled seizures.     

Spontaneous resolution of intractable epileptic seizures following HHV-7 infection

Purpose: We report a three-year-old female with intractable epilepsy post West syndrome whose seizures disappeared following an acute viral infection, without changes in anti-epileptic therapy. Methods: The female infant was born at term to a healthy mother after an uneventful pregnancy and delivery. At the age of five months, she developed intractable brief tonic spasms which had a series of infantile spasms, and an electroencephalogram indicated hypsarrhythmia. She was diagnosed with West syndrome. The seizures were uncontrollable with conventional therapy, including ACTH, vigabatrin, sodium valproate, clonazepam, zonisamide, and ketogenic diet. Daily multiple generalized tonic seizures and brief tonic spasms were observed before an episode of viral infection. Results: At the age of three years, the intractable seizures disappeared after a febrile rash illness due to human herpesvirus 7 (HHV-7) infection, without changes in anti-epileptic drugs. Conclusions: The disappearance of intractable epileptic seizures following acute viral infections might be related to the inflammatory or immunologic processes associated with viral infections. This is the first documented case of spontaneous remission of intractable epileptic seizures following HHV-7 infection.     

Benign familial neonatal convulsions in a family with one member with infantile spasms]

A pedigree of benign familial neonatal convulsions (BFNC) was reported. Seven members of two generations experienced convulsions in the neonatal period and/or in early infancy. All of these members except one had a good prognosis. One member who had infantile spasms was uneventfully delivered at 37 weeks of gestation, with a birth weight of 2,562 g and, without trouble during pregnancy. At the age of 20 days, she began to have adversive seizures. Later, she developed complex partial seizures and infantile spasms at 1 month and 10 days of age. Interictal EEG showed hypsarrhythmia. Biochemical investigations and MRI of the head revealed no abnormality. Treatment with sodium valproate and carbamazepine succeeded in stopping the seizures and she had no seizures after 3 months. But her psychomotor development was moderately delayed at 8 months. No case with severe epilepsy such as infantile spasms has been reported in the previous literature on BFNC. From our experience, early treatment and careful follow-up are considered to be important for BFNC.     

A case of malignant migrating partial seizures in infancy as a continuum of infantile epileptic encephalopathy

The syndrome of malignant migrating partial seizures in infancy (MMPSI) is characterized by onset before the age of 6 months, nearly continuous electrographic seizures involving multiple independent areas of onset in both hemispheres, and poor developmental outcome. This report presents a case involving a patient with MMPSI, who later developed West syndrome. At the age of 2 months old, he showed multifocal partial seizures, which were refractory to antiepileptic drugs. His electroencephalogram (EEG) revealed characteristic migrating multifocal epileptiform activities and neuroimaging finding was normal. The focal seizures were refractory to antiepileptic drugs and ketogenic diet. When he was 9 months old, epilepic spasms were observed with hypsarrhythmia on EEG. He also showed severe developmental delay. MMPSI may be a continuum of infantile epileptic encephalpathy and could evolve to West syndrome.     

Clinical experience with open-label topiramate use in infants younger than 2 years of age

To assess the efficacy, safety, and tolerability of topiramate in infants younger than 24 months of age, we conducted an open-label, multicenter chart review study of infants who received topiramate. Twenty-eight patients were evaluated. All had refractory epilepsy. The mean age of seizure onset was 3.8 months (range 0-10 months). Refractory infantile spasms were the most common epilepsy syndrome. Among infants without infantile spasms, complex partial seizures were the prominent seizure type in eight, followed by simple partial seizures in six. Topiramate was prescribed as add-on therapy in 25 cases and a s monotherapy in 3 cases. Seven of the eight infantile spasms cases improved on topiramate therapy, attaining topiramate monotherapy in three infants. Half of the infants with other seizure types responded to topiramate. The average treatment duration among topiramate responders was 11 months. Topiramate was prescribed after a mean of 3.3 antiepilepsy drugs had been used in these infants. In no case was topiramate the first prescribed antiepilepsy drug. Adverse effects occurred only in five patients, leading to topiramate discontinuation in two patients. Topiramate was efficacious and well tolerated in infants younger than 24 months of age with refractory epilepsy. Prospective data are needed to corroborate this observation.