Catastrophic Epilepsy in Childhood

Summary: Although for most children epilepsy is a relatively benign disorder, for some, epilepsy can be designated as "catastrophic" because the seizures are so difficult to control and because they are strongly associated with mental retardation. The catastrophic childhood epilepsies include uncommon disorders such as early infantile epileptic encephalopathy with suppression burst, severe myoclonic epilepsy of infancy, and epilepsy with myoclonic-astatic seizures. There are other syndromes that are relatively common such as infantile spasms, Lennox-Gastaut syndrome, and Sturge-Weber syndrome. Many children with catastrophic epilepsy have the seizures as a result of underlying brain abnormalities that will inevitably lead to mental retardation whether or not they have seizures. In some patients, however, the mental retardation appears to be caused by the seizures. Developmental plasticity provides children with an opportunity to recover from significant brain injuries. However, the plasticity may also be the cause of the mental retardation. In such patients, control of the seizures may lead to more normal intellectual development. Thus, every effort should be made to control seizures in children with catastrophic epilepsy.     

Imaging epileptic activity using functional MRI

This review concentrates on functional MRI (fMRI) methods to identify the epileptic focus, i.e. ictal and interictal fMRI. First, established clinical applications of fMRI in the field of epilepsy are briefly introduced: fMRI of sensorimotor, language and memory function can already be considered as clinically relevant tools to identify the eloquent cortex and to predict postoperative functional deficits in patients considered for epilepsy surgery. fMRI offers a valid alternative to invasive methods like the Wada test for establishing language dominance, and it is likely that it will also replace the Wada test for assessing presurgical memory function in the nearer future. Ictal fMRI (fMRI studies of epileptic seizures) will remain confined to exceptional cases due to practical limitations. The generators of interictal epileptiform discharges (IED) can be studied with EEG-correlated fMRI. Despite its technical challenges, it has proved useful to provide insights into the generation of IED in patients with focal and generalized epilepsy. In selected patients with focal IED, EEG-correlated fMRI has the potential to reproducibly identify cortical areas involved in generating IED, i.e. the irritative zone. In patients with generalizes IED, suspension of functional networks due to the IED can be demonstrated. The utility of EEG-correlated fMRI in clinical epileptology cannot be definitely determined yet.     

Motor and cognitive functions in newly diagnosed adult seizure patients before antiepileptic medication

OBJECTIVE: Motor and cognitive functions in patients with partial or generalized onset of seizures were evaluated prior to the administration of antiepileptic medication. MATERIAL AND METHODS: Motor function, attention and memory of 52 consecutive newly diagnosed adult patients with partial or generalized seizures were assessed with neuropsychological tests. RESULTS: Patients with partial onset of seizures did not differ from patients with generalized seizures in tests of motor function or attention, nor in tests of learning and memory. Compared to controls patients with epilepsy performed significantly worse on visual motor tasks, mental flexibility and in delayed visual memory. Within the patient group as a whole lower education, higher age and symptomatic epilepsy with more abnormal CT scan findings tended to associate with worse performance in tests of concentration and mental flexibility and tests of memory. CONCLUSION: These findings indicate that newly diagnosed adult patients with partial or generalized onset of seizures prior to treatment with antiepileptic medication experience some problems in visual motor tasks, mental flexibility and memory even without the numerous risk factors for cognitive deficits in epilepsy. In newly diagnosed patients with epilepsy as a whole symptomatic etiology was associated with somewhat more pronounced cognitive problems.     

Functional MRI Studies of Animal Models in Epilepsy

Summary:  Functional magnetic resonance imaging (fMRI) has become a widely used imaging modality in the past decade in both human studies and animal models. Epilepsy presents unique challenges for neuroimaging due to subject movement during seizures, and the need to correlate the timing of often unpredictable seizure events with fMRI data acquisition. These challenges can readily be overcome in animal models of epilepsy. Animal models also provide an opportunity to investigate the fundamental relationships between fMRI signals and brain electrical activity through invasive studies not possible in humans. fMRI studies in animal models of epilepsy can enable us to correctly interpret fMRI signal increases and decreases in human studies, ultimately elucidating specific networks that will be targeted for improved treatment of epilepsy.     

Cognitive Outcomes in Patients with Chronic Temporal Lobe Epilepsy

Summary:  Cognitive impairment is frequent in temporal lobe epilepsy (TLE). In particular, specific deficits in temporal lobe related functions occur, but deficits in extratemporal lobe functions and global intelligence are also found. The degree and type of the impairment are first determined by structural damage and functionally dynamic factors. Most cognitive problems in TLE are already detectable at, or even before, the onset of the epilepsy. Accumulation of damage during the course of chronic epilepsy may add to this. This additional damage may be caused directly by severe seizures, head trauma, intoxication etc., or indirectly by interference of the epilepsy with mental development. Surgical treatment of TLE may also affect the cognitive outcome of patients with chronic TLE, with a risk of additional impairments on the one hand and functional recovery due to seizure control on the other hand. With regard to patient-associated factors, better baseline performance, younger age, cerebral plasticity, and good mental reserve capacities are associated with a better outcome. With regard to treatment-associated factors, prevention of additional brain dysfunction/damage and successful seizure control are important.     

Siblings with refractory occipital epilepsy showing localized network activity on EEG‐fMRI

The benign occipital epilepsies of childhood include Panayiotopoulos and Gastaut syndromes; a third syndrome, idiopathic photosensitive occipital epilepsy may also begin in childhood or adolescence. We describe siblings with occipital epilepsy characterized by refractory, frequent, brief visual seizures and normal magnetic resonance imaging (MRI). Electroencephalography (EEG) with functional MRI (fMRI) supports localization of interictal epileptiform activity to the occipital lobes. Our hypothesis is that the siblings share a genetic focal epilepsy arising from a localized occipital network. Although they share many features of Gastaut syndrome, their refractory ongoing seizures in adolescence is unusual and likely due to underlying genetic determinants.     

Neurología del éxtasis y fenómenos aledaños: epilepsia extática,orgásmica y musicogénica. Síndrome de Stendhal. Fenómenos autoscópicos

All human experiences, including mystical and religious ones, are the result of brain functional activity. Thanks to the study of cases of ecstatic epilepsy with structural (MRI) and functional neuroimaging (fMRI, PET, SPECT) and neurophysiological technologies (recording and stimulation with intracranial electrodes), we now have a better knowledge of certain mental states which involve pleasant and affective symptoms and clarity of mind. These ecstatic experiences are thought to be caused by the activation of the anterior insular cortex and some neuronal networks (basically related to mirror neurons and salience) participating in introspection, social cognition, memory, and emotional processes. Thus, neuroscience could explain in a retrospective way some facts surrounding the situations of such relevant figures as Paul the Apostle, Teresa de Cepeda y Ahumada, and Dostoevsky, whose origin was previously considered paranormal or supernatural. Ecstatic epilepsy shares symptoms and mechanisms with orgasmic epilepsy (spontaneous orgasms in the course of epileptic seizures), musicogenic epilepsy (epileptic seizures triggered by listening to a certain musical piece), and also with Stendhal syndrome (neuropsychiatric disturbances caused when an individual is exposed to large amounts of art) and some autoscopic phenomena (out-of-body experiences that occasionally take place in imminent death situations). In all these events, there are pleasant and affective symptoms which have a great impact on patients.     

Cortical network dysfunction in musicogenic epilepsy reflecting the role of snowballing emotional processes in seizure generation: an fMRI‐EEG study

Aim. Patients suffering from musicogenic epilepsy have focal seizures triggered by auditory stimuli. In some of these patients, the emotions associated with the music appear to play a role in the process triggering the seizure, however, the significance of these emotions and the brain regions involved are unclear. In order to shed some light on this, we conducted fMRI and EEG in a case of musicogenic epilepsy. Methods. In a 32‐year‐old male patient with seizures induced by a specific piece of Russian music, we performed video‐EEG monitoring as well as simultaneous fMRI and EEG registration. Results. Video‐EEG monitoring revealed a left temporo‐frontal epileptogenic focus. During fMRI‐EEG co‐registration, BOLD signal alterations were not only found in the epileptogenic focus but also in areas known for their role in the processing of emotions. Prior to a seizure in some of these areas, BOLD contrasts exponentially increased or decreased. Conclusion. These results suggest that in our case, dysfunction of the regulation processes of the musically‐induced emotions, and not the musical stimulus itself, led to the seizures.     

Beyond seizures and medications: normal activity limitations, social support, and mental health in epilepsy

Although seizure control is a critical goal for persons with epilepsy (PWE) from the biomedical perspective, there is growing support for approaches that take into account the effect of epilepsy on the whole person (the biopsychosocial perspective). We hypothesized that PWE who report normal activity limitations due to epilepsy and poor social/emotional support would report poor mental health regardless of whether they report having seizures in the past 3 months or currently taking medication for their epilepsy. In 2005 and 2006, twenty-two states asked about epilepsy in the Behavioral Risk Factor Surveillance System (BRFSS). A set of survey weight-adjusted logistic regression analyses were conducted to examine self-reported poor mental health. Our findings reveal that both normal activity limitations due to epilepsy and poor social/emotional support are significant predictors of reporting poor mental health. After controlling for social support, demographics, comorbidities, and health behaviors we determined that those reporting normal activity limitations due to epilepsy are more likely to report poor mental health (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.41-6.58). Similarly, after controlling for the same factors, PWE with poor social/emotional support are more likely to report poor mental health (OR 3.22, 95% CI 1.84-5.61). In contrast, reported seizures in the past 3 months (OR 1.12, 95% CI 0.56-2.25) or current use of medication (OR 0.58, 95% CI 0.30-1.10) were not significantly associated with poor mental health. These population-based findings support the need for clinical approaches that address psychosocial issues in addition to seizure control and treatment.     

Cerebro-cerebellar functional connectivity profile of an epilepsy patient with periventricular nodular heterotopia

Periventricular nodular heterotopia (PNH) is a rare malformation of cortical development often associated with drug resistant focal onset epilepsy. The link between nodules and neocortex have been demonstrated with depth electrodes investigations showing that seizures may arise from both structures. In the last years fMRI resting-state (fMRI-RS) have received a surge in interest due to its capability to track non-invasively physiological and pathological relevant differences in brain network organization. We performed a cerebro-cerebellar voxel-wise and region-of-interest resting state fMRI (RS-fMRI) functional connectivity analysis in a seizure-free epilepsy patient with a PNH in the right temporal horn. Our finding confirms a spontaneous synchronization between PNH and its surrounding cortex, specifically in the inferior temporal, fusiform and occipital gyrus. We also found a significant connectivity with bilateral cerebellum, more intense and widespread on the PNH cerebellar contralateral lobule. RS-fMRI confirmed its potential as a promising tool for non-invasive mapping of cortical and subcortical brain functional organization.     

Identification of three distinct groups of patients with both epilepsy and psychogenic nonepileptic seizures

Psychogenic nonepileptic seizures (PNES) can be observed in patients with or without epilepsy (mixed and pure PNES). Patients with mixed PNES are usually considered to be a homogeneous group characterized by the coexistent epilepsy. Our study found that patients with mixed PNES were not homogeneous, but could be divided into three groups based on epilepsy type, mental level, comorbid psychiatric disorders, and history of traumatic experiences. Group 1 patients have pharmacoresistant epilepsy, normal cognition, and comorbid anxiety and/or depressive disorders. Here, PNES etiology is the epilepsy-related problems. In group 2 patients, the epilepsy is associated with mental retardation and dependent personality traits. PNES etiology is represented by the reduction or cessation of seizures. The PNES allow patients to continue receiving attention from caregivers. Group 3 patients have epilepsy, normal cognition, comorbid cluster B personality disorders and anxiety disorders, and psychic trauma. Here, PNES etiology is not related to the epilepsy, but to the psychic trauma.     

An open, nonrandomized clinical comparative study evaluating the effect of epilepsy on learning

Children with epilepsy, as a group, have a greater risk for developing learning problems as comorbid disorders. It is unknown which factors contribute to the development of such learning problems; therefore, our current knowledge does not allow the prediction of educational delay in an individual child with epilepsy. This study aimed at excluding as many factors as possible that could interfere with the analysis of the impact of epilepsy on learning. From patients referred to us in 1997 (N = 123), children were included with mild global learning impairment, defined as educational delay between 6 months and 1 year and no other apparent reason for learning impairment except for epilepsy (ie, excluding children with dyslexia, attention-deficit hyperactivity disorder, or mental handicap). A total of 44 patients fulfilled this criterion: 31 also had epilepsy (experimental group); the remaining 13 patients with similar mild learning impairment but without epilepsy were used as controls. In the experimental group two subgroups were distinguished on the basis of onset of learning impairment: in group A (n = 17) the learning problems are not unexpected as they were preceded by mild developmental delay; in group B (n = 14) the problems are unexpected and had a sudden onset. The two experimental groups differed from the control group on a number of variables, such as gender and the incidence of perinatal complications. More differences have been found between the two experimental groups: group B is selected from a larger group: all children with mild global learning impairment with sudden onset. In this group considerably more children with epilepsy have been found compared to the children with developmental delay; moreover the epilepsy is more often characterized in these children as "unexpected," that is, there was no previous established diagnosis of epilepsy, the symptoms were mostly unclear and behavioral in make-up (attentional lapses, etc); the electroencephalogram plays a much greater role in the diagnosis in this group, especially in demonstrating seizures; finally, the children in this group more frequently have neuropsychologic impairment. Children with epilepsy can have mild global learning difficulties, especially in the period after the onset of seizures. This group can be divided in a group with "trait-dependent learning difficulties," that is learning difficulties based on developmental delay, and a group with "state-dependent learning difficulties." The focus in our study was on this latter group, consisting of children with sudden and unexpected decline of results in school. The crucial finding in this group is the relatively frequent demonstration of difficult-to-detect seizures, demonstrating that an uncontrolled epilepsy can cause a decline in school results even when the seizures are of short duration and have subtle symptoms.     

Epilepsy in the elderly

There are many unique characteristics in elderly patients with epilepsy. The incidence of seizure in this age group is the highest of any age group and continues to increase as people live longer. Etiology of seizures is different than for adults and includes cerebrovascular disease, dementia, closed head injury, and metabolic encephalopathies. The elderly patient with epilepsy most often presents with complex partial seizures that have a higher recurrence rate than the younger population. The seizures are often difficult to diagnose since they present with atypical symptoms, particularly prolonged postictal symptoms, including memory lapses, confusion, altered mental status, and inattention. There are also therapeutic challenges due to age-related changes in pharmacokinetics, including variations in absorption, distribution, metabolism, and excretion. These must be considered when selecting antiepileptic drug (AED) therapy to avoid harmful side effects. In addition, several of the AEDs have drug-drug interactions, a problem potentially exacerbated in this population of patients due to the use of medications for comorbid conditions.     

Lamotrigine treatment of a patient affected by epilepsy and anxiety disorder

Epilepsy often occurs in comorbidity with mental diseases and disorders. Early detection and/or treatment of such disorders in patients affected by epilepsy, as well as their socialisation are crucially important since epileptic patients tend to suffer more due to lack of social support than to frequent epileptic seizures. Prevalence of psychiatric disorders is higher in patients with epilepsy than in general population, the most frequent being: anxiety, depression, panic attacks, behavioural disorders as well as psychotic states with paranoid elements. The efficacy of AE treatment of patients affected by epilepsy and mood disorders has also directed clinicians to investigate possible AE benefits in treating other mental disorders such as anxiety states, depression and bipolar disorder. The examined case displays complex partial epilepsy and comorbid mental disorder. The use of lamotrigine, a fourth-generation antiepileptic, which is also a mood stabilizer, has assured a favourable remission of symptoms related to both epilepsy and mood disorders. Side-effects caused by lamotrigine were only temporary and dose reduction was sufficient to eliminate their symptoms.     

Benign partial epilepsy in infancy long-term outcome and marginal syndromes

Benign partial epilepsy in infancy (BPEI) is an infantile epilepsy with excellent seizure and developmental outcome proposed by Watanabe et al. Our telephone interview survey revealed that the long-term outcome of patients with BPEI was also excellent over 8 years of age. Six of 39 patients did not fulfill the criteria of BPEI by the last follow-up. Two patients had a recurrence of unprovoked seizure beyond 2 years of age, three had cognitive problems (mild mental retardation in two and Asperger syndrome in one) and the other had both a recurrence of seizure and mild mental retardation. These results indicates that a large majority of patients diagnosed as possible BPEI at 2 years of age did not have a recurrence of unprovoked seizures and mental problems beyond 8 years of age. Our study also suggested a presence of some marginal syndromes of BPEI. An association of paroxysmal kinesigenic choreoathetosis was observed in three patients. Another three patients had experienced seizures with mild gastroenteritis. The seizure outcome of three patients with mild cognitive problems was quite excellent. These patients can be grouped as a marginal syndrome of BPEI.     

Viral encephalitis and epilepsy

Viral encephalitis presents with seizures not only in the acute stage but also increases the risk of late unprovoked seizures and epilepsy. Acute symptomatic and late unprovoked seizures in different viral encephalitides are reviewed here. Among the sporadic viral encephalitides, Herpes simplex encephalitis (HSE) is perhaps most frequently associated with epilepsy, which may often be severe. Seizures may be the presenting feature in 50% patients with HSE because of involvement of the highly epileptogenic frontotemporal cortex. The occurrence of seizures in HSE is associated with poor prognosis. In addition, chronic and relapsing forms of HSE have been described and these may be associated with antiepileptic drug-resistant seizures. Among the epidemic (usually due to flaviviruses) viral encephalitides, Japanese encephalitis (JE) is most common and is associated with acute symptomatic seizures, especially in children. The reported frequency of acute symptomatic seizures in JE is 7–46%. Encephalitis due to other flaviviruses such as equine, St. Louis, and West Nile viruses may also manifest with acute symptomatic seizures. In Nipah virus encephalitis, seizures are more common in relapsed and late-onset encephalitis in comparison to acute encephalitis (4% vs. 1.8%). Other viruses like measles, varicella, mumps, influenza, and entero-viruses may cause seizures depending on the area of brain involved. There is no comprehensive data regarding late unprovoked seizures in different viral encephalitides. Prospective studies are required to document the risk of late unprovoked seizures and epilepsy following viral encephalitis due to different viruses as well as to determine the clinical characteristics, course, and outcome of post-encephalitic epilepsy.     

Reflex writing seizures in two siblings with juvenile myoclonic epilepsy

We report on two siblings who presented with juvenile myoclonic epilepsy, and in whom myoclonic jerks of the right arm and hand were also triggered by writing tasks. Both patients underwent intensive video-electroencephalography monitoring, with simultaneous neuropsychological tests. In both patients, reflex epileptic myoclonus was more easily triggered by writing that required a higher degree of concentration. Conversely, other cognitive tasks, such as reading, typing, thinking, or calculation never elicited any seizures or myoclonus. Valproate was effective in controlling both spontaneous and reflex epileptic seizures. The results of this study further support the notion that 'praxis-induced' reflex epilepsy precipitated by specific stimuli occurs in the context of idiopathic generalized epilepsy. Our results also illustrate that writing tasks are more effective in eliciting seizures when they require higher levels of concentration and mental elaboration.     

Symptomatic generalized epilepsy associated with an inverted duplication of chromosome 15.

An inverted duplication of chromosome 15 (inv dup[15] chromosome) is the most common supernumerary marker chromosome in humans. Inv dup(15) chromosomes are commonly associated with mental retardation, epilepsy, behavioral problems and structural malformations. Though epilepsies associated with inv dup(15) chromosomes are often intractable, there have been very few reports regarding the seizure manifestations or types. We report a patient with severe mental retardation and intractable epilepsy, associated with an inv dup(15) chromosome. The seizures recorded with EEG-VTR monitoring were axial and generalized tonic seizures, and our case was diagnosed as symptomatic generalized epilepsy. Molecular and cytogenetic analysis showed an inv dup(15) chromosome containing the Prader-Willi syndrome/Angelman syndrome region mapped within bands 15q 11-q13.     

Epilepsy and psychiatric disorder in the mentally retarded adult

302 mentally retarded adults, sampled by epidemiological criteria, were examined with regard to epilepsy and psychiatric disorder. Each of the complications was frequent and related to degree and origin of mental retardation. In 55 (18.2%) epilepsy had occurred at some time during their lives, in 25 (8.3%) of these in the past year. In 52% of persons with seizures in the past year a present state psychiatric diagnosis was established, compared to 26% in those without seizures. The nature of the combination of epilepsy and psychiatric disorder is complex, but in the mentally retarded most often reflecting underlying brain pathology in the form of widespread cortical and subcortical cerebral damage causing epilepsy of generalised or mixed type, and predominantly interictal psychiatric disorders unrelated in time to seizures and dominated by behaviour problems.     

Childhood absence epilepsy with clinically apparent genetic and acquired burdens: a diagnostic consideration

Both genetic and acquired factors play important roles in the development of childhood absence epilepsy. This article describes a girl with mental retardation, probably due to a perinatal complication, who had typical absence seizures with characteristic electroencephalographic findings of childhood absence epilepsy, including normal background activity. This patient was subsequently found to have a strong genetic predisposition, which was suggested by the fact that childhood absence epilepsy also developed in her younger brother. Except for the mental subnormality, the electroclinical features of this patient satisfied the diagnostic criteria for childhood absence epilepsy. This case raises the question about diagnostic consideration of childhood absence epilepsy in association with cerebral pathology for genetically predisposed individuals.