A case of subacute sclerosing panencephalitis preceded by epileptic seizures: evolutional EEG changes

We reported a patient with subacute sclerosing panencephalitis (SSPE) in whom EEG had been serially performed before the onset. She was referred to our hospital due to epileptic seizures at 2 years of age. Focal spikes were seen on EEG at the time of her first seizure (2 years 4 months). At the time of the second unprovoked seizure (9 years 8 months), EEG showed poorly organized background activity associated with focal spikes and a few diffuse spike-and-waves. Then, diffuse paroxysms became predominant, followed by periodic synchronous discharges. In our case, EEG abnormalities were recognized before mental deterioration. Unexpected EEG changes in a patient with epilepsy could be a clue as to the diagnosis of SSPE.     

Epileptic encephalopathies (including severe epilepsy syndromes)

Epileptic encephalopathies represent a group of devastating epileptic disorders that appear early in life and are characterized by pharmacoresistant generalized or focal seizures, persistent severe electroencephalography (EEG) abnormalities, and cognitive dysfunction or decline. The ictal and interictal epileptic discharges are age-specific and are the main etiologic factors causing cognitive deterioration. This is most obvious in the idiopathic group. In the symptomatic group, the most common causes are structural, congenital, or acquired and rarely some metabolic disorders. In certain cases, clinical and EEG abnormalities persist and may evolve from one type to another as the child grows older. Various factors trigger and sustain the underlying pathophysiologic process and the ongoing epileptic and epileptiform activity during the most critical periods of brain maturation, perpetuating their deleterious effect on the brain. Immune-mediated mechanisms may have a role, suggested by certain encephalopathies responding to immune-modulating treatments and by the finding of various autoimmune antibodies. The chance of a better cognitive outcome improves with early diagnosis and treatment that is appropriate and effective. Current antiepileptic drugs are, in general, not effective: we urgently need new trials in this very special epileptic category. This article briefly reviews the most common epileptic encephalopathies and analyzes the most important clinical issues.     

Focal-onset myoclonic seizures and secondary bilateral synchrony

We present a child with myoclonic seizures, epileptic spasms and generalized epileptiform discharges on scalp EEG. Magnetoencephalography and coherence-phase analysis for scalp EEG suggested focal onset in the left hemisphere. Intracranial video EEG confirmed seizure onset in the left frontal lobe with ictal high-frequency oscillations. Left frontal lobectomy suppressed his seizures. Subsets of myoclonic seizures can be focal in origin despite bilaterally synchronized epileptiform discharges on scalp EEG.     

Intracranial EEG Monitoring in Landau-Kleffner Syndrome Associated with Left Temporal Lobe Astrocytoma

Summary: A 3½-year-old boy developed partial complex seizures with right-sided motor activity, occasionally secondarily generalized at age 18 months. Initial EEG showed left-sided focal epileptiform discharges. Seizures became refractory to antiepileptic drugs (AEDs). At age 3 years, there was severe language deterioration consistent with Landau-Kleffner syndrome (LKS). At that time, an EEG showed almost continual generalized spikes and poly spikes, worse during sleep. Video-EEG showed generalized tonic seizures associated with generalized EEG ictal activity. Magnetic resonance imaging (MRI) showed a cystic and solid lesion of the left hippocampal and parahippocampal gyri without surrounding edema. Subdural strip electrodes under the left temporal and overlying the left frontal lobes demonstrated interictal spikes simultaneously in all recording contacts. Ictal EEG activity occurred in the temporal electrodes 0.2–1 s before appearing in the frontal electrodes. After left temporal lobectomy with subtotal resection of a low-grade astrocytoma, he had an immediate marked decrease in seizures. In 1 month he was seizure-free, and in 6 months had no further seizures and markedly improved language. These findings provide further evidence that left temporal structural epileptogenic lesions may contribute significantly to the pathophysiology of LKS.     

EEG value in cases of epileptic seizures in early phase of stroke]

The aim of our work was to assess the usefulness of EEG in patients with seizures in acute phase of stroke. EEG patterns of 54 patients with epileptic seizures at the onset of stroke were evaluated: 45 of ischaemic, 6 of haemorrhagic origin and 3 with lacunar stroke as confirmed by CT or MR examination. Out of 40 patients, who had a single or multiple seizures at the onset of stroke, EEG revealed focal slow waves in 90% and in 22.5% they were accompanied by interictal epileptiform discharges. None of those patients had recurrent seizures during the time of hospitalisation irrespectively of applying antiepileptic drugs. In the remaining 14 patients prolonged disturbances of consciousness were observed. EEG examination revealed simple partial status epilepticus (SE) in 10 and complex partial SE in 4 of them. In 11 of those patients EEG disclosed fragments of periodic lateralized epileptiform discharges (PLED) interrupted by seizure activity. The findings indicate that in patients with seizures in the acute phase of stroke EEG examination is very helpful in making the proper therapeutic decision by recognizing the SE. The introduction of antiepileptic drugs is generally not necessary in stroke patients with single seizures.     

Epileptic seizures difficult to differentiate from alternating hemiplegia in infants: a case report

A child with epileptic seizures had a clinical course similar to that of alternating hemiplegia of infancy (AHI). Tonic hemiplegia began at 2 months of age, and atonic alternating hemiplegia and tetraplegic attacks began at 2 years of age. Clinical findings were paroxysmal ocular movement abnormalities, choreoathetotic involuntary movements, and severe developmental retardation. An interictal EEG at 6 years of age showed multiple independent spike discharges. An ictal EEG showed diffuse irregular spike-wave and slow wave bursts following focal spikes. The present case suggests that a long-term extensive follow-up is necessary to differentiate epileptic seizures from AHI.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Subtle behavioural and cognitive manifestations of epilepsy

A subtle behavioural or cognitive manifestation of epilepsy can be defined in two ways. First, epileptiform discharges not presenting as obvious seizures may nevertheless affect cognition and/or behaviour. Second, the actual seizures may be obvious but the way they affect cognition or behaviour may not be. There is a growing body of evidence indicating that the epileptiform discharges in benign epilepsy with centrotemporal spikes can affect behaviour and cognition. The focal discharges in other forms of epilepsy can also be associated with behavioural change. The Landau‐Kleffner syndrome, the CSWS syndrome, transitory cognitive impairment and transient epileptic amnesia provide further examples of cognitive and behavioural manifestations resulting from subtle manifestations of the epilepsy. Prompt, effective antiepileptic treatment with medication or surgery can improve behaviour and cognition in at least some cases.     

A long-term follow-up of 29 cases of benign epilepsy in childhood with central-temporal electroencephalographic foci

29 cases of benign epilepsy in childhood with central-temporal EEG foci (BECCT) were followed up from 2 to 9 years clinically and electro encephalographically. Focal discharges in several cases were found to be changeable from one cerebral hemisphere to another. The subsidence of clinical seizures usually preceded epileptic discharges. Such focal discharges often disappeared before puberty whereas the clinical seizures would not manifest themselves even earlier. Small doses of antiepileptic drugs were effective for the majority of such patients. One patient with occasional seizures but without medication had been observed.     

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 and EEG evaluation of mid-line spikes in childhood

We studied the clinical and electroencephalographic (EEG) characteristics of 45 patients with mid-line spikes. The incidence of mid-line spikes was 3.0% in total EEG population in childhood. Sex incidence was equal. First appearance age of mid-line spikes ranged from one month to 12 years, with a mean of 5.0 years old. Fz focus was in 3 patients, Cz in 31 and Pz in 11. Thirty two of the 45 patients (71%) had a history of clinical seizures; 16 with febrile convulsions and 16 with epileptic seizures. Of the remaining 13 patients without a history of seizures, the EEG was obtained because of post-meningitis in 4, developmental delayed in 4, migraine in 1 and miscellaneous in 4. Mid-line spikes might not have so strong correlations with clinical seizures. Ten patients had a family history of epilepsy and/or febrile convulsion. In the patients with seizures, generalized tonic-clonic seizures were the most frequent type (18; primary GTC and 10; secondary GTC with partial onset). Elementary symptoms of partial seizures were very variable (focal motor in 5, Jacksonian march in 1, aversive in 1, autonomic in 2 and automatism in 5), and which might be related to the other lesions such as temporal and/or frontal lobes. Seizure control was almost good except for two patients with organic brain damage. And other neurological symptoms were not also progressive. On EEG findings, twenty-two patients had midline spikes as their only epileptiform abnormality. The remaining twenty-three had an additional epileptiform feature, either a focal spikes or a generalized spike-wave.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolonged epileptic blindness in an infant associated with cortical dysplasia

We report a female infant with status epilepticus amauroticus and intractable focal motor seizures associated with congenital cortical dysplasia. EEG demonstrated persistent epileptiform discharges over the right parieto-temporal regions extending to occipital areas. She required cortical resection of the epileptic zone at age 8 months given failure of very high dose antiepileptic combinations. Histological analysis of a sample of cortex resected from the right central parieto-temporal region, identified by electrocorticography as the focus of epileptic activity, showed cortical dysplasia. The seizures ceased and the infant gained full vision after 48 hours. During an 8-year follow-up period she has had a few short-lived seizures, currently controlled with carbamazepine and vigabatrin. Her cognition and speech are intact. This case demonstrates that: (1) resection of a central temporo-parietal focus, which may have spread to the occipital regions, may result in complete visual recovery and cessation of seizures; and (2) EEG should be considered in every infant with alleged delayed visual maturation, to rule out concealed epileptic activity.     

A follow-up study of healthy children with epileptiform EEG discharges

Fifty-two healthy elementary schoolchildren with epileptiform EEGs who were not taking anticonvulsants were followed for an average period of 3 years and 3 months. Thirty-seven had centrotemporal spikes, three had occipital spikes, one had frontal spikes, nine had generalized spike-and-wave complexes, and two had a combination of multiple spike-and-wave complexes and focal spikes. Disappearance of epileptiform discharges was observed in 65% on waking EEGs and in 45% on sleep EEGs. After 5 years, the rate of disappearance was over 80% in waking and sleep EEGs. This study confirms that most epileptiform discharges in healthy children disappear spontaneously during childhood and that age-related development and disappearance occur in healthy children who would otherwise never be subjected to EEG examination. Epileptic seizures occurred in three cases (6%). This low percentage is not considered to be an indication for treating children with epileptiform discharges with anticonvulsants. However, the risk for seizure development may be higher than in the general population. According to the literature, children with multiple spike-wave complexes have a greater tendency to develop seizures. One girl with multiple spike-wave complexes and focal spikes developed generalized tonic-clonic convulsions. Two boys with centrotemporal spikes developed benign childhood epilepsy with centrotemporal spikes (BCECS). This study confirms that some (5%) of healthy children with centrotemporal spikes, the most common epileptiform pattern in healthy children, develop BCECS.     

Stimulus-induced focal motor seizure in a pediatric patient with carbamazepine overdose

IntroductionCarbamazepine (CBZ) is a common antiepileptic drug that may cause overdoses with seizures as a common neurological manifestation. In previous reports, patients with CBZ overdose exhibited stimulus-induced generalized clinical or electrical seizures. To date, no previous cases of focal motor seizures have been reported.Case reportWe report the case of an 11-year-old girl with spontaneous and stimulus-induced clustering of focal motor seizures following CBZ overdose. The patient had been treated with CBZ (150 mg daily) for focal epilepsy since the age of six years. At the age of 11, she forgot to take a morning dose, took ten CBZ pills (CBZ 1000 mg) as compensation, and presented with generalized seizures. The patient arrived at the hospital in a coma. She demonstrated clustering of focal-to-bilateral tonic-clonic seizures induced by pain stimulus or spontaneously, with focal epileptiform discharges observed on EEG. Her CBZ blood concentration measured 40.4 μg/mL and she was diagnosed with CBZ overdose. The patient showed improvement without any specific treatment, and was later discharged without neurological sequelae.ConclusionPrevious cases of CBZ overdose with stimulus-induced generalized seizures resulted in death or required intensive care. Stimulus-induced focal seizures may indicate a favorable prognosis for CBZ overdose.     

Seizure semiology and neuroimaging findings in patients with midline spikes

PURPOSE: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes. METHODS: We reviewed the EEG database of the University of Michigan Medical Center and identified 35 patients with midline spikes. Information about seizure types and neuroimaging results was obtained from a review of medical records. The seizures were classified according to the International League Against Epilepsy (ILAE) criteria and semiologic classification. RESULTS: Twenty-nine (83%) patients had a history of seizures. Complex partial seizures and simple partial seizures were the most common seizure types, experienced by 66% of patients. The age at seizure onset was within the first 10 years in 90% of patients. According to the semiologic seizure classification, automotor seizures and tonic seizures were the most common seizure types. Neuroimaging studies were abnormal in 45% of patients. When focal abnormalities were detected, they were lateralized to one of the frontal lobes in all cases. CONCLUSIONS: Our results indicate that in the majority of patients, midline spikes represent focal epileptiform activity rather than fragments of generalized discharges, and are most commonly associated with seizures of partial onset. Automotor seizures and tonic seizures are the most common semiologies. Focal radiologic abnormalities tend to be lateralized to one of the frontal lobes.     

Focal Sleep Spindle Deficits Reveal Focal Thalamocortical Dysfunction and Predict Cognitive Deficits in Sleep Activated Developmental Epilepsy

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common focal epilepsy syndrome, yet the cause of this disease remains unknown. Now recognized as a mild epileptic encephalopathy, children exhibit sleep-activated focal epileptiform discharges and cognitive difficulties during the active phase of the disease. The association between the abnormal electrophysiology and sleep suggests disruption to thalamocortical circuits. Thalamocortical circuit dysfunction resulting in pathologic epileptiform activity could hinder the production of sleep spindles, a brain rhythm essential for memory processes. Despite this pathophysiologic connection, the relationship between spindles and cognitive symptoms in epileptic encephalopathies has not been previously evaluated. A significant challenge limiting such work has been the poor performance of available automated spindle detection methods in the setting of sharp activities, such as epileptic spikes. Here, we validate a robust new method to accurately measure sleep spindles in patients with epilepsy. We then apply this detector to a prospective cohort of male and female children with CECTS with combined high-density EEGs during sleep and cognitive testing at varying time points of disease. We show that: (1) children have a transient, focal deficit in spindles during the symptomatic phase of disease; (2) spindle rate anticorrelates with spike rate; and (3) spindle rate, but not spike rate, predicts performance on cognitive tasks. These findings demonstrate focal thalamocortical circuit dysfunction and provide a pathophysiological explanation for the shared seizures and cognitive symptoms in CECTS. Further, this work identifies sleep spindles as a potential treatment target of cognitive dysfunction in this common epileptic encephalopathy.SIGNIFICANCE STATEMENT Childhood epilepsy with centrotemporal spikes is the most common idiopathic focal epilepsy syndrome, characterized by self-limited focal seizures and cognitive symptoms. Here, we provide the first evidence that focal thalamocortical circuit dysfunction underlies the shared seizures and cognitive dysfunction observed. In doing so, we identify sleep spindles as a mechanistic biomarker, and potential treatment target, of cognitive dysfunction in this common developmental epilepsy and provide a novel method to reliably quantify spindles in brain recordings from patients with epilepsy.     

A pediatric case of intractable complex partial seizures associated with mesial temporal lobe astrocytoma: usefulness of interictal epileptiform discharges in the present case]

The patient was a 10-year-old male with normal developmental milestones. He had medically intractable complex partial seizures since the age of 7 years. At the age of 10 years, he had focal motor seizures of the right face, and a head CT scan showed a calcified lesion in the left mesial temporal region. The tumor exhibited low intensity on T 1-weighted and high intensity on T 2-weighted MR images, and was not enhanced by gadolinium-diethylenetriamine pentaacetic acid. Interictal SPECT showed hypoperfusion in the left temporal region. One-day video/EEG monitoring revealed very frequent epileptiform discharges which occurred only during sleep period exclusively in the left anterior-to-middle temporal region. The patient underwent lesionectomy with the guidance of electrocorticography. The histological study of the resected tissue showed astrocytoma. After surgery he has had no seizures for 10 months. It was concluded that very frequent interictal epileptiform discharges strictly localized to the temporal lobe at which MRI-identified tumor was present could be predictive of epileptogenic zone in the present patient in whom clinical symptoms and the results of other studies were also concordant.     

Chronic Semichronic Limbic Epilepsy Produced by Microinjection of Tetanus Toxin in Cat Hippocampus

We describe an animal preparation in which a semichronic or chronic limbic epileptiform syndrome can be produced reliably by unilateral microinjection of tetanus toxin in cat ventral hippocampus. Injections were given at 1-week intervals until abnormal EEG activity was observed. After two to five injections, the animals abruptly began to exhibit intermittent spikes and subclinical discharges that soon gave way to spontaneous and recurrent behavioral seizures which gradually increased in frequency, duration, and severity in the next 12-48 h. Anticonvulsant therapy (phenobarbital, PB) was required within the first 3 days of the syndrome, since life-threatening generalized tonic-clonic seizures (GTCS) and status epilepticus would develop if the animal were left untreated. If severe seizures were prevented by antiepileptic drugs (AEDs) there was complete remission of the syndrome and repeat injection was necessary to reinitiate seizures. Animals that experienced severe seizures or that were reinjected after remission developed a chronic seizure syndrome and could be maintained with AEDs for long times (greater than 1 year) without significant debilitation. Although early spikes and subclinical discharges were typically focal to ipsilateral limbic sites, initial seizures appeared explosively in the form of a high-amplitude, high-frequency discharge, which often had an apparently bilateral limbic onset. On the other hand, chronic seizures had much more gradual onset and spread, often consisting of periodic sharp waves or low-amplitude sinusoidal discharge that was more clearly focal to ipsilateral limbic sites. Throughout the syndrome, ictal behavioral manifestations were highly stereotyped and very comparable to those described by other investigators in studies of clinical and experimental limbic epilepsy. All animals exhibited signs of independent contralateral involvement during the syndrome, ranging from independent contralateral spikes to subclinical discharges with a clear contralateral onset. None of the animals exhibited structural lesions on histologic examination at the level of light microscopy.     

Pointed rhythmic theta waves: a unique EEG pattern in KCNQ2‐related neonatal epileptic encephalopathy

We report the case of an infant with KCNQ2‐related neonatal epileptic encephalopathy presenting with intractable seizures beginning on the second day of life, which were resistant to multiple antiepileptic drugs. Continuous EEG recordings starting on the sixth day of life demonstrated a unique pattern of inter‐and postictal focal rhythmic pointed theta waves of lambdoid morphology in the immediate postictal period, localizing to the side of the antecedent seizure. Interictal EEG exhibited discontinuous background, including patterns of burst suppression and multifocal discharges, predominantly in the centrotemporal regions, which were aggravated during sleep. MRI demonstrated T1 signal abnormalities in the basal ganglia, bilaterally. Genetic testing revealed a de novo missense mutation in KCNQ2 at position c.545 T>G, encoding a previously unreported substitution (p.Val182Gly). Seizure control was achieved immediately after starting a lidocaine infusion at age 4 weeks. The patient remained largely seizure‐free following add‐on oral carbamazepine for maintenance therapy and weaning off lidocaine. This is the first report of a patient with KCNQ2‐related neonatal epileptic encephalopathy and therapy‐refractory seizures aborted by lidocaine, demonstrating a unique EEG pattern of inter‐ and postictal focal rhythmic pointed theta waves. Whether this pattern could be an early EEG marker for this disorder remains to be confirmed. [Published with video sequences on www.epilepticdisorders.com ]     

Late-onset temporal lobe epilepsy in a patient with juvenile myoclonic epilepsy

We report a patient with longstanding, severe juvenile myoclonic epilepsy who subsequently developed features of temporal lobe epilepsy, which gradually became clinically dominant. Over the years, there was an electrographic evolution from the typical generalised epileptiform patterns, characteristic of juvenile myoclonic epilepsy, to the novel appearance of interictal temporal spikes immediately preceding bisynchronous discharges, and subsequently to temporal intermittent rhythmic delta activity and temporal lobe-onset seizures. In this rare case of coexistent primary generalised epilepsy and focal epilepsy, the epileptic networks of the two forms of epilepsy appear to overlap.     

Longitudinal study of epileptiform EEG patterns in normal children

EEG were recorded in 3,726 children, from 6 to 13 years of age who were neurologically normal and had no history of epileptic seizures. The records were taken during wakefulness, at rest, and during hyperventilation. In 131 cases (3.54%) epileptiform patterns were found. They consisted of 3 count/sec spike and slow waves discharges (4 cases), multiple spike and slow wave complexes (37 cases), midtemporal spikes (50 cases), rolandic or parietal spikes (27 cases), occipital spikes (2 cases), and multifocal spikes (11 cases). Half of the subjects with EEG abnormalities had behavior problems and/or slight psychomotor ability disturbances. Follow-up studies over an 8 to 9 year period were performed. These demonstrated the spontaneous disappearance of the EEG abnormalities, usually within school age or, at the latest, during adolesence. Only seven individuals developed epileptic seizures of the primary generalized type which responded well to anticonvulsant drug treatment. From this study we can deduce that the epileptiform EEG patterns that often are found in children during school age have no clinical relationship to epilepsy in the great majority of cases. The relationship with epilepsy exists probably on a genetic level for the generalized discharges. The spike foci are non-epileptic in nature in all probability, especially if they emerge from a fairly normal background activity and their duration is very similar to that of the constituents of the background activity, as found in the majority of these subjects. On the contrary, it is probable that these alterations express difficulties in affective or motor adaptation during childhood.