A young infant with musicogenic epilepsy

Musicogenic epilepsy is a relatively rare form of epilepsy. In its pure form, it is characterized by epileptic seizures that are provoked exclusively by listening to music. The usual type of seizure is partial complex or generalized tonic-clonic. Precipitating factors are quite specific, such as listening to only one composition or the actual playing of music on an instrument. However, simple sound also can be a trigger. We report a 6-month-old infant with musicogenic epilepsy. She manifested right-sided focal seizures with occasional generalization. The seizures were frequently triggered by loud music, especially that by the Beatles. The interictal electroencephalography results were normal. Ictal spikes were present throughout the left temporal area during continuous electroencephalograpic monitoring. Brain magnetic resonance imaging results were normal, whereas single-photon emission computed tomography of the brain revealed hypoperfusion of the left temporal area. The young age and epileptogenic left temporal lobe lesion in this patient with musicogenic epilepsy were unusual characteristics. Theoretically, three levels of integration are involved in music processing in the brain. The involved integration of this infant’s brain may be the sensory level rather than the emotional level. Nevertheless, the personal musicality and musical style of the Beatles might play an important role in this patient’s epilepsy.     

Risks and benefits of epilepsy surgery in a pediatric population: Consequences for memory and academic skills

We examined benefits and risks for memory and academic functioning associated with epilepsy surgery in a pediatric population. A total of 46 patients with intractable seizures and a single seizure focus were divided into four groups according to focus localization: right temporal, left temporal, frontal, and parietal/occipital region. Pre- and postsurgery performance measures were compared across groups and with a fifth group of patients that had intractable seizures but did not undergo surgery. Both groups with temporal lobe epilepsy showed significant declines in memory test scores, while performance of the group with frontal lobe epilepsy improved. These changes were mirrored in parental reports of everyday memory. Consistent with other pediatric studies, no lateralized material-specific declines in the groups with temporal lobe epilepsy were found. When memory improved, the improvement was associated with decreases in seizure frequency and the number of anticonvulsant medications. Presurgical performance was the best predictor of declines in memory test performance. Deterioration of academic test scores in the group that did not have surgery exemplified a potential risk of living with seizures and antiepilepsy medication.     

Ictal singing: case report and reappraisal of the literature.

Singing is a rare ictal symptom of focal epilepsy. We report a case of a left-handed woman, with no musical education, experiencing refractory seizures consisting of the singing of a popular Portuguese folksong, with simultaneous, rhythmic hand clapping. A left mesial temporal sclerosis was successfully treated by selective amygdalohippocampectomy. As in most previously reported cases, the epileptogenic zone was located in the left hemisphere, although the ictal onset zone could not be lateralized on scalp EEG. This clinical case supports the evidence that cerebral music production seems to require both hemispheres, in accordance to the concept that brain specializations for music is associated with a dynamic, well-orchestrated interaction of music-specific neural networks. [Published with video sequences].     

Dual pathology in a patient with temporal lobe epilepsy associated with neocortical glial scar after brain abscess and end folium sclerosis/hippocampal sclerosis type 3

End folium sclerosis or hippocampal sclerosis (HS) type 3 is often associated with another coexisting epileptogenic lesion (dual pathology); however, the pathogenesis of HS type 3 remains elusive. A 46‐year‐old man presented with medically intractable focal aware seizures and focal impaired awareness seizures (FIAS) with occasional focal to bilateral tonic–clonic seizures (FBTCS) two years after surgical treatment with extensive cranial reconstruction for a brain abscess in the right temporal lobe associated with intracranial extension of ipsilateral cholesteatoma. Head magnetic resonance imaging (MRI) at age 49 revealed atrophy of the right cerebral hemisphere including the hippocampus and amygdala. The patient's first epilepsy surgery was a lateral temporal lobectomy, in which the mesial temporal structures were preserved because no epileptiform discharge was detected on the intraoperative electrocorticogram. However, FIAS with FBTCS started 15 months after the operation. The second surgery, amygdalohippocampectomy, at age 52, resulted in the patient being seizure‐free again for one year before seizures of the right lateral temporal origin recurred. He underwent a third surgery, resection of the Heschl's and supramarginal gyri, at age 53, but he continued to have drug‐resistant epilepsy over two years after that. Histopathological examination revealed dual pathology consisting of glial scar in the lateral temporal lobe and ipsilateral HS type 3 with an unusually severe lesion in the subiculum. No significant inflammatory change was observed. The clinicopathological features in the present case indicate that HS developed secondarily in the context of neocortical epilepsy due to glial scar, suggesting a role of repetitive abnormal electrical input from neocortical epileptogenic lesions into the hippocampus finally via the perforant pathway in the pathogenesis of HS type 3. Severe hippocampal atrophy on preoperative MRI together with its silent electrocorticogram recording at initial epilepsy surgery may represent clinically pre‐epileptogenic HS in a seizure‐free “silent or latent period” before completion of hippocampal epileptogenesis to the extent that clinical epileptic seizures occur.     

Videopolygraphic and functional MRI study of musicogenic epilepsy. A case report and literature review

A 36-year-old right-handed man, who had experienced partial seizures since the age of 24 every time he played or listened to music with a strong emotional charge, underwent videopolygraphic recording, including autonomic variables, and brain fMRI study during which he listened to both “neutral” and “emotionally charged” music. Three right temporal seizures recorded during videopolygraphic monitoring were elicited by listening to the triggering song. The fMRI study disclosed activation in right acoustic areas during “neutral music,” whereas an “emotionally charged melody” provoked widespread activation over the right fronto-temporo-occipital area before seizure onset. The literature review disclosed 110 published cases of musicogenic epilepsy that seemed to suggest a right-sided predominance of the epileptogenic zone. Our results support the role of the right temporal lobe in musicogenic epilepsy and demonstrate that the cerebral areas activated during the period of strong emotion leading to the seizures encompass the auditory cortex activated by neutral music.     

Race/ethnicity: a predictor of temporal lobe epilepsy surgery outcome?

PURPOSE: The success of epilepsy surgery in temporal lobe epilepsy reaches a 64% rate of seizure freedom, based on a randomized control trial. Observational studies from epilepsy centers worldwide indicate seizure freedom rates up to 93% when the etiology is unilateral hippocampal sclerosis. Several risk factors are attributed to the recurrence of seizures following the surgical procedure. Nonetheless, whether race influences the outcome of temporal lobe surgery is unknown. The purpose of this study was to evaluate if race plays a role in outcome following surgery. METHODS: Data were obtained from the discharge database of the University of Alabama at Birmingham video/EEG monitoring unit, between 1998 and 2003, as well as the clinical charts. Seizure recurrence was evaluated 1 year following surgery. The sample consisted of all patients with a primary diagnosis of mesial temporal sclerosis (MTS) who underwent anterior temporal lobectomy. Multiple logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for MTS. Two sets of logistic regression models were estimated to generate odds ratios (ORs) for seizure recurrence after an anterior temporal lobectomy for African-Americans or other possible ethnic/racial group present relative to non-Hispanic Caucasians. The first model incorporated only ethnicity as the independent variable and generated unadjusted ORs for seizure recurrence following the surgical procedure. The second set included the independent variables: duration of epilepsy, history of febrile seizures, lateralization of epileptogenic focus, handedness, and age. RESULTS: Seventy patients underwent surgical treatment and all of them had pathologic confirmation of MTS. Follow-up information for six was not available. Analysis of the remaining 64 patients revealed that African-Americans were more likely than non-Hispanic Caucasians to have seizure recurrence after surgery (OR=2.1, 95% CI=0.6-8.0). After potential confounders (duration of epilepsy, history of febrile seizures, lateralization of epileptogenic focus, handedness, and age) were controlled, this finding did not change (OR=1.7, 95% CI=0.3-10.7). CONCLUSION: Our data suggest that race may be an important factor related to seizure outcome following temporal lobectomy.     

New‐onset musicogenic epilepsy after temporal lobe epilepsy surgery

Musicogenic epilepsy is a reflex epilepsy provoked by listening to or playing music. The epileptogenic network involves temporal regions, usually mesiotemporal structures. We present a 31‐year‐old female patient who experienced musicogenic seizures after a right temporal lobectomy with amygdalohippocampectomy that was performed in order to treat preexisting right mesio‐temporal epilepsy.     

Predicting seizure frequency after epilepsy surgery

OBJECTIVE: To identify clinical features related to seizure frequency after epilepsy surgery in patients with recurrent seizures. BACKGROUND: No studies have examined the differences between patients who have rare seizures and patients who experience frequent seizures after epilepsy surgery. Since seizure frequency correlates with morbidity and quality of life, it is desirable to know which preoperative clinical features predict postoperative seizure frequency. METHODS: Patients with recurrent seizures were placed in two categories: rare postoperative seizures (< or =2 per year) and frequent postoperative seizures (> or =12 per year) using seizure frequency in the second postoperative year. Variables included preoperative seizure frequency, age of first risk, age at first seizure, epilepsy duration, age at surgery, history of febrile convulsions, tonic-clonic seizures, status epilepticus, or family history, IQ, magnetic resonance imaging (MRI), and positron emission tomography (PET). Variables were analyzed using non-parametric tests to assess relationship to postoperative seizure frequency. RESULTS: Of 475 patients who had epilepsy surgery, 111 had rare or frequent seizures in the second postoperative year. After anterior temporal lobectomy (ATL), age of first risk< or =5 years and presence of mesial temporal sclerosis on MRI were associated with rare seizures (66% of patients), whereas lack of these risk factors was associated with frequent seizures (75% of patients) (p<0.03). For non-ATL operations, preoperative seizure frequency of > or =20 seizures per month was associated with frequent postoperative seizures (p=0.03). No other variables influenced outcome. CONCLUSIONS: Some preoperative clinical features correlate with postoperative seizure frequency in patients with recurrent seizures after epilepsy surgery. This has implications for the surgical decision making process and early postoperative management.     

Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center

ObjectiveThis study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom.MethodsThis study included 61 children aged between 2 and 18 years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom.ResultsOf the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p < 0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia.SignificanceResective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis indicate that a patient would have better results in terms of seizure freedom.     

Lateralizing value of behavioral arrest in patients with temporal lobe epilepsy

Analysis of ictal semiology is essential to presurgical evaluation of patients with epilepsy. To assess the localizing value of behavioral arrest in temporal lobe epilepsy (TLE), we analyzed 107 video/EEG monitoring-documented seizures of 107 adult patients with TLE for a set of defined seizure phenomena with respect to frequency and sequence of occurrence in relation to epileptogenic (mesial vs extramesial, left vs right) origin. Behavioral arrest was observed more frequently in left-sided temporal seizures: 25.7% of left-sided mesial seizures and 25.0% of left-sided extramesial seizures exhibited behavioral arrest, whereas only 3.4% of right-sided mesial seizures and 10.5% of right-sided extramesial seizures were associated with behavioral arrest. In addition, occurence of behavioral arrest within the sequence of seizure phenomena was remarkably consistent, being observed mainly as the first apparent feature of seizure onset. Thus, behavioral arrest is a valuable early indicator of a left-sided temporal epileptogenic focus in adult patients with TLE.     

Multimodal approach in the surgical treatment of refractory epilepsy associated with tuberous sclerosis complex: a series of three cases

We describe the surgical treatment of tuberous sclerosis complex (TSC)-related refractory epilepsy in three patients. All three had multiple daily seizures, and each had more than three cortical tubers. High-resolution magnetic resonance imaging, ictal and interictal scalp electroencephalogram (EEG), positron emission tomography, magnetoencephalography as well as acute and intracranial video-EEG were used to identify the epileptogenic tubers. After localization, five cortical tubers (two in the right temporal lobe in patient 1; one each in the left frontal and temporal lobes in patient 2; and one in the right frontal lobe in patient 3) were resected. At minimum follow-up of 13 months (range, 13-35 months), patient 3 had seizure remission; patient 2 had only rare seizures; while patient 1 had 60% reduction in seizure frequency. Successful epilepsy surgery is possible in patients of TSC with multiple tubers using the multimodal approach.     

Defining epileptogenic networks: Contribution of SEEG and signal analysis

Epileptogenic networks are defined by the brain regions involved in the production and propagation of epileptic activities. In this review we describe the historical, methodologic, and conceptual bases of this model in the analysis of electrophysiologic intracerebral recordings. In the context of epilepsy surgery, the determination of cerebral regions producing seizures (i.e., the “epileptogenic zone”) is a crucial objective. In contrast with a traditional focal vision of focal drug‐resistant epilepsies, the concept of epileptogenic networks has been progressively introduced as a model better able to describe the complexity of seizure dynamics and realistically describe the distribution of epileptogenic anomalies in the brain. The concept of epileptogenic networks is historically linked to the development of the stereoelectroencephalography (SEEG) method and subsequent introduction of means of quantifying the recorded signals. Seizures, and preictal and interictal discharges produce clear patterns on SEEG. These patterns can be analyzed utilizing signal analysis methods that quantify high‐frequency oscillations or changes in functional connectivity. Dramatic changes in SEEG brain connectivity can be described during seizure genesis and propagation within cortical and subcortical regions, associated with the production of different patterns of seizure semiology. The interictal state is characterized by networks generating abnormal activities (interictal spikes) and also by modified functional properties. The introduction of novel approaches to large‐scale modeling of these networks offers new methods in the goal of better predicting the effects of epilepsy surgery. The epileptogenic network concept is a key factor in identifying the anatomic distribution of the epileptogenic process, which is particularly important in the context of epilepsy surgery.     

Parahippocampal epilepsy with subtle dysplasia: A cause of “imaging negative” partial epilepsy

Purpose: Lesion‐negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging‐negative frontal or temporal lobe epilepsy. Methods: We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Results: Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T₁‐ and T₂‐weighted images with relative preservation of the gray–white matter boundary on T₁‐weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure‐free (one has occasional auras only, follow‐up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. Discussion: In patients with lesion‐negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features.     

Epilepsy surgery in children with pervasive developmental disorder

Pervasive developmental disorder (PDD) is occasionally associated with medically intractable complex partial seizures. The outcome of PDD was explored in three males and two females who underwent epilepsy surgery at 32 months to 8 years of age (mean = 4 years) after onset of epilepsy at 1 week to 21 months of age (mean = 11 months). Four children had temporal lobe resections (three right, one left; two for focal cortical dysplasia, and two for tumors), and one had a right temporoparieto-occipital resection (for focal cortical dysplasia). Each child underwent repeated evaluations by a pediatric neuropsychologist and psychiatrist. Fourteen to 47 months (mean = 23 months) after operation, one child with persistent seizures had moderate developmental and behavioral improvement, three children (two seizure free, one with rare staring spells) had mild developmental and behavioral improvement, and the remaining child (seizure free) experienced a worsening of her PDD. The four children with mild-to-moderate improvement in postoperative cognitive and behavioral development still demonstrated persistent delay. Cognitive gains were confirmed by neuropsychologic testing in the oldest patient but were not reflected in test results from the three younger children, who had more modest improvement. The child with worsening of her PDD had cognitive and emotional deterioration to babbling, echolalia, aggressiveness, decreased social interaction, and increased mouthing of objects beginning several months postoperatively. These results suggest that families should be counseled that PDD symptoms in children with focal epileptogenic lesions may or may not improve after epilepsy surgery, even if the surgery is successful with respect to seizure control.     

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.     

Two magneto-encephalographic epileptic foci did not coincide with the electrocorticographic ictal onset zone in a patient with temporal lobe epilepsy.

To evaluate the usefulness and limitations of magneto-encephalography (MEG) for epilepsy surgery, we compared 'interictal' epileptic spike fields on MEG with ictal electrocorticography (ECoG) using invasive chronic subdural electrodes in a patient with intractable medial temporal lobe epilepsy (MTLE) associated with vitamin K deficiency intracerebral hemorrhage. A 19-year-old male with an 8-year history of refractory complex partial seizures, secondarily generalized, and right hemispheric atrophy and porencephaly in the right frontal lobe on MRI, was studied with MEG to define the interictal paroxysmal sources based on the single-dipole model. This was followed by invasive ECoG monitoring to delineate the epileptogenic zone. MEG demonstrated two paroxysmal foci, one each on the right lateral temporal and frontal lobes. Ictal ECoG recordings revealed an ictal onset zone on the right medial temporal lobe, which was different from that defined by MEG. Anterior temporal lobectomy with hippocampectomy was performed and the patient has been seizure free for two years. Our results indicate that interictal MEG does not always define the epileptogenic zone in patients with MTLE.     

A functional polymorphism in the prodynorphin gene promotor is associated with temporal lobe epilepsy

The prodynorphin gene (PDYN) encoding the anticonvulsant peptide dynorphin is a strong candidate for a seizure suppressor gene and thus a possible modulator of susceptibility to temporal lobe epilepsy. We performed a case control association study in 155 patients with nonlesional temporal lobe epilepsy and 202 controls and found that PDYN promotor low-expression L-alleles confer an increased risk for temporal lobe epilepsy in patients with a family history for seizures. Irrespective of the familial background, L-homozygotes display a higher risk for secondarily generalized seizures and status epilepticus.     

fMRI of triggerable aurae in musicogenic epilepsy

The authors studied a patient with musicogenic epilepsy triggered by one specific musical piece using 3D PRESTO fMRI. During epileptic aurae initiated by the stimulus, signal increases were found in the left anterior temporal lobe, correlating with ictal EEG and SPECT showing a left anterior temporal focus, and the right gyrus rectus. Because fMRI indicated a cascade of recruitment of the ventral frontal lobes by epileptogenic music, left anterior temporal lobe activity could be secondary to a right gyrus rectus focus, possibly triggered by emotional processing of music.     

Localizing and lateralizing features of auras and seizures

The symptomatology of auras and seizures is a reflection of activation of specific parts of the brain by the ictal discharge, the location and extent of which represent the symptomatogenic zone. The symptomatogenic zone is presumably, though not necessarily, in close proximity to the epileptogenic zone, the area responsible for seizure generation, the complete removal or disconnection of which is necessary for seizure freedom. Knowledge about the symptomatogenic zone in focal epilepsy is acquired through careful video/EEG monitoring and behavioral correlation of seizures and electrical stimulation studies. Ictal symptomatogy provides important lateralizing and/or localizing information in the presurgical assessment of epilepsy surgery candidates. As the initial symptoms of epileptic seizures, many types of auras have highly significant localizing or lateralizing value. Similarly, motor signs during focal and secondary generalized seizures, language manifestations, and autonomic features offer reliable clues to the delineation of the epileptogenic zone. Some focal epilepsies (e.g., neocortical temporal lobe epilepsy, insular lobe epilepsy, temporal-plus epilepsies, and parieto-occipital lobe epilepsy) generate seizure manifestations that mimic temporal lobe epilepsy, potentially contributing to surgical failure. To optimize surgical outcome, careful interpretation of ictal symptomatology in conjunction with other components of the presurgical evaluation is required.     

Functional interactions in brain networks underlying epileptic seizures in bilateral diffuse periventricular heterotopia.

OBJECTIVE: Our aim was to investigate relationships between heterotopic and remote cortical structures at seizure initiation, in a patient with bilateral periventricular nodular heterotopias (BPNH) explored by intracerebral electrodes. METHODS: Stereoelectroencephalography (SEEG) was performed in a man with BPNH and refractory epilepsy to investigate the hypothesis of right temporal lobe epilepsy and the possible involvement of heterotopic structures during seizures. SEEG signals were analyzed with quantification of functional coupling between different brain structures during seizures, using nonlinear regression. We have used Z-score transformation of correlation values to reflect the change from the preictal period. Relationships between BPNH and cortical structures were investigated using analysis of stimulation-induced potentials. RESULTS: Three spontaneous seizures were recorded and analyzed. Signal analysis of interdependencies in two seizures demonstrated a large initial network involving both heterotopia and cortical structures. Stimulations of heterotopia induced responses in remote cortical structures. CONCLUSIONS: Distinct epileptogenic networks were identified, in which leader structures were either the heterotopic or the mesial temporal structures, with functional connections between heterotopic and cortical areas. SIGNIFICANCE: These results confirm that a vast epileptogenic network, including heterotopic and cortical neurons, may be responsible for seizure generation in BPNH. This may explain certain surgical failures in this group.