Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes.

Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions.

Proposition: limbic encephalitis may represent limbic status epilepticus. A review of clinical and EEG characteristics.

Limbic encephalitis (LE) with waxing and waning neuropsychiatric manifestations including behavioral, personality, psychiatric, and memory changes can evolve over days to months. Many features of LE show remarkable overlap with the characteristics of mesial-temporal (limbic) status epilepticus (MTLSE or LSE). With LE, these prolonged impaired states are assumed not to be due to ongoing epileptic activity or MTLSE, because scalp EEGs usually show no epileptiform spike-wave activity; cycling behavioral and motor changes are attributed to LE; there may be little immediate improvement with antiepileptic drugs (AEDs); and of course, implanted electrodes are rarely used. Conversely, it is known that in pre-surgical patients with refractory limbic epilepsy, implanted electrodes have revealed limbic seizures that cannot be seen at the scalp. This paper assembles a chain of inferences to advance the proposition that refractory LE might represent LSE more often than is thought, and that implanted electrodes should be considered in some cases. We present two cases that suggest that LE was also LSE, one of which warranted implanted electrodes (case 1).

Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study.

Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.

Selective changes in GABAA receptor subtypes in white matter neurons of patients with focal epilepsy.

Mapping the distribution of GABAA receptor subtypes represents a promising approach to characterize alterations in cortical circuitry associated with neurological disorders. We previously reported subtype-selective changes in GABAA receptor expression in the grey matter of patients with focal epilepsy. In the present follow-up study, we focused on the subcortical white matter in the same tissue specimens obtained at surgery from 9 patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis, 12 patients with TLE associated with neocortical lesions and 5 patients with frontal lobe epilepsy; post-mortem tissue from 4 subjects served as controls. The subunit composition and distribution of three major GABAA receptor subtypes were determined immunohistochemically with subunit-specific antibodies. In all cases, a majority of neurons in the white matter was distinctly labelled, allowing detailed visualization of their dendritic arborization and revealing a differential, cell type-specific expression pattern of alpha-subunit variants. In controls, alpha1-subunit staining was most prominent, displaying a gradient that decreased with depth, in parallel with the density of NeuN-positive cells. Subsets of pyramidal cells were alpha3-subunit-positive, and alpha2-subunit-labelled neurons were rare. In 19 of the 26 patients with focal epilepsy, no changes were detected as compared with controls. In five patients with TLE, striking changes in the dendritic arborization of a subset of white matter neurons were seen with the alpha1-subunit antibody. In two further patients with TLE, we observed a disorganized dendritic network immuno-positive for the alpha1-subunit, cell clusters selectively expressing the alpha2-subunit and small neuronal aggregates that expressed all subunits and appeared to connect to neighbouring white matter neurons. All seven patients with anomalies in the white matter had a selective reduction in alpha3-containing GABAA receptors in the superficial layers of the grey matter. These results demonstrate a distinct organization of GABAA receptors in human white matter neurons, consistent with an inhibitory network that is likely to be integrated functionally with the overlying grey matter. The altered dendritic morphology and changes in GABAA receptor expression in the white matter of a subset of patients with focal epilepsy are suggestive for a rewiring of neuronal circuits.

Altered expression of alpha3-containing GABAA receptors in the neocortex of patients with focal epilepsy.

Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABA(A) receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABA(A) receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABA(A) receptor subtypes using antibodies specifically recognizing the subunits alpha1, alpha2, alpha3, beta2/3 and gamma2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the alpha-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABA(A) receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in alpha3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the alpha1 and alpha2-subunits. Reduced expression in alpha3-containing GABA(A) receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased alpha3-subunit staining. The selective reduction in alpha3-containing GABA(A) receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to alpha3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epilepsy.

Clinical presentation, epidemiology, neurophysiological findings, treatment and outcome of nonconvulsive status epilepticus: a 3-year prospective, hospital-based study.

Objective: This study reports the prevalence of Nonconvulsive Status Epilepticus (NCSE) in patients with altered mental status (AMS), and describes the clinical presentation, etiology, neurophysiological findings, neuroimaging, treatment, and outcome of NCSE in Qatar. Recording duration of continuous EEG monitoring was also discussed. Methods: This was a 3-year, prospective, hospital-based study involving patients with AMS and continuous EEG monitoring admitted to the Emergency and ICUs of Hamad Hospital, Qatar. Patients with confirmed diagnosis of NCSE were compared to the patients who did not show EEG and clinical features compatible with NCSE. Descriptive statistics in terms of mean with standard deviation, as well as frequency and percentages for categorical variables, were calculated; Student's t test as well as Chi-square tests or Fisher's exact tests were applied. Logistic regressions NSCE was performed using significance level 0.05 for independent variables at univariate analysis. Results: Number of patients with AMS and continuous EEG monitoring was 250. Number of patients with EEG compatible with NCSE: 65 (age range, 12-79 ys; m, 37; f, 28). Number of controls (defined as patients with EEG not compatible with NCSE): 185 (age range, 12-80 ys; m, 101; f, 84). Rate of occurrence of NCSE in patients with AMS: 26%. NCSE group was younger than controls (p < .001). Twenty patients with NCSE (31%) and 35 patients in the control group (19%) died. Death was more frequent in comatose NCSE compared to controls (p < .0007). NCSE proper and comatose NCSE had longer hospital stays than controls (p < .02 and p < .03, respectively). Complete recovery occurred in 26 NCSE patients (40%) and in 98 controls (53%) (p < .08). Twenty-one patients (31%) presented with refractory NCSE: 12 patients survived, 9 died. Conclusion: This was the first prospective study reporting a high number of NCSE in Qatar, a small country in the MENA region. This prevalence (26%) was in the middle range. NCSE patients did not perform better than controls, outcome being worse with comatose NCSE. NCSE is an emergent condition warranting expedited diagnosis and management. Three days of continuous EEG monitoring were able to diagnose most cases of NCSE.

EEG in Creutzfeldt-Jakob disease.

Electroecenphalography (EEG) is an integral part of the diagnostic process in patients with Creutzfeldt-Jakob disease (CJD). The EEG has therefore been included in the World Health Organisation diagnostic classification criteria of CJD. In sporadic CJD (sCJD), the EEG exhibits characteristic changes depending on the stage of the disease, ranging from nonspecific findings such as diffuse slowing and frontal rhythmic delta activity (FIRDA) in early stages to disease-typical periodic sharp wave complexes (PSWC) in middle and late stages to areactive coma traces or even alpha coma in preterminal EEG recordings. PSWC, either lateralized (in earlier stages) or generalized, occur in about two-thirds of patients with sCJD, with a positive predictive value of 95%. PSWC occur in patients with methionine homozygosity and methionine/valine heterozygosity but only rarely in patients with valine homozygosity at codon 129 of the prion protein gene. PSWC tend to disappear during sleep and may be attenuated by sedative medication and external stimulation. Seizures are an uncommon finding, occurring in less than 15% of patients with sCJD. In patients with iatrogenic CJD, PSWC usually present with more regional EEG findings corresponding to the site of inoculation of the transmissible agent. In genetic CJD, PSWC in its typical form are uncommon, occurring in about 10%. No PSWC occur in EEG recordings of patients with variant CJD.

Propagation of interictal discharges in temporal lobe epilepsy: correlation of spatiotemporal mapping with intracranial foramen ovale electrode recordings.

OBJECTIVE: We have investigated intracerebral propagation of interictal epileptiform discharges (IED) in patients with mesial temporal lobe epilepsy (MTLE) by using spatiotemporal source maps based on statistical nonparametric mapping (SNPM) of low resolution electromagnetic tomography (LORETA) values. METHODS: We analyzed 30 patterns of IED recorded simultaneously with scalp and intracranial foramen ovale (FO) electrodes in 15 consecutive patients with intractable MTLE. The scalp EEG signals were averaged time-locked to the peak activity in bilateral 10-contact FO electrode recordings. SNPM was applied to LORETA values and spatiotemporal source maps were created by allocating the t-values over time to their corresponding Brodmann areas. Propagation was defined as secondary statistically significant involvement of distinct cortical areas separated by >15 ms. The results were correlated with intracranial data obtained from FO electrode recordings and with scalp EEG recordings. All patients underwent subsequent amygdalo-hippocampectomy and outcome was assessed one year after surgery. RESULTS: We found mesial to lateral propagation in 6/30 IED patterns (20%, four patients), lateral to mesial propagation in 4/30 IED patterns (13.3%, four patients) and simultaneous (within 15 ms) activation of mesial and lateral temporal areas in 6/30 IED patterns (20%, five patients). Propagation generally occurred within 30 ms and was always limited to ipsilateral cortical regions. Nine/30 IED patterns (30%) showed restricted activation of mesial temporal structures and no significant solutions were found in 5/30 IED patterns (16.7%). There was no clear association between the number or characteristics of IED patterns and the postsurgical outcome. CONCLUSIONS: Spatiotemporal mapping of SNPM LORETA accurately describes mesial to lateral temporal propagation of IED, and vice versa, which commonly occur in patients with MTLE. SIGNIFICANCE: Intracerebral propagation must be considered when using non-invasive source algorithms in patients with MTLE. Spatiotemporal mapping might be useful for visualizing this propagation.

Source localization of interictal epileptiform discharges: comparison of three different techniques to improve signal to noise ratio.

OBJECTIVE: To investigate the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) using a new relative averaging (RELAVG) technique for noise reduction. METHODS: We analyzed 19 patterns of mesial temporal IED recorded simultaneously with scalp and foramen ovale (FO) electrodes in 15 consecutive patients who underwent presurgical assessment for intractable temporal lobe epilepsy. The scalp signals were time-locked to the peak activity in the FO electrode recordings and source modeling was performed using the RELAVG technique. Random noise of various amounts was then applied. The results were compared to intracranial data obtained from the FO electrode recordings and to LORETA source solutions obtained using two other approaches to improve signal to noise ratio (SNR): statistical non-parametric mapping (SNPM) and the commonly applied averaging (AVG) technique. RESULTS: The RELAVG technique allowed for reasonable mesial temporal localization in 52.6% (10/19) of IED patterns, compared with 73.7% (14/19) using SNPM. The AVG technique provided no strictly mesial temporal solutions. Nine of the IED patterns revealed relative current density quotient changes >10; all of these were accurately localized by RELAVG into mesial temporal structures. Increasing amounts of white and physiological noise had no influence on the accuracy of RELAVG and SNPM solutions, whereas AVG source reconstructions became progressively spurious. CONCLUSION: The RELAVG technique and SNPM, but not the commonly used AVG technique, allow for reasonable source localization of mesial temporal IED. SNPM is the most accurate but also the most time-consuming noise reduction technique. SIGNIFICANCE: The RELAVG LORETA technique might provide a simple and fast semi-quantitative alternative for localizing IED with low single to noise ratio.

Cortical activation with deep brain stimulation of the anterior thalamus for epilepsy.

OBJECTIVE: We studied the relation between thalamic stimulation parameters and the morphology, topographic distribution and cortical sources of the cerebral responses in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. METHODS: Bipolar and monopolar stimuli were delivered at a rate of 2 Hz to the anterior (AN, four patients), the dorsomedian (DM, four patients), and the centromedian nucleus (CM, one patient) using the programmable stimulation device (Medtronic ITREL II). Source modeling was carried out by using statistical non-parametric mapping of low-resolution electromagnetic tomography (LORETA) values. RESULTS: All patients demonstrated reproducible time-locked cortical responses (CRs) consisting of a sequence of components with latencies between 20 and 320 ms. The morphology of these CRs, however, was very heterogeneous, depending primarily on the site of stimulation. Following AN stimulation, cortical activation was most prominent in ipsilateral cingulate gyrus, insular cortex and lateral neocortical temporal structures. Stimulation of the DM mainly showed activation of the ipsilateral orbitofrontal and mesial and lateral frontal areas, but also involvement of mesial temporal structures. Stimulation of the CM showed a rather diffuse (though still mainly ipsilateral) increase of cortical activity. The magnitude of cortical activation was positively related to the strength of the stimulus and inversely related to the impedance of the electrode. CONCLUSIONS: The pattern of cortical activation corresponded with the hodology of the involved structures and may underscore the importance of optimal localization of DBS electrodes in patients with epilepsy. SIGNIFICANCE: The method of analyzing sources of CRs could potentially be a useful tool for titration of DBS parameters in patients with electrode contacts in clinically silent areas. Furthermore, the inverse relation of the cortical activation and the impedance of the electrode contacts might suggest that these impedance measurements should be taken into consideration when adjusting DBS parameters in patients with epilepsy.

Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis.

Multidrug resistance protein, also referred as P-glycoprotein (P-gp, MDR1; ABCB1) and multidrug resistance-associated protein (MRP) 1 (ABCC1) and 2 (ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that MDR1, MRP1 as well as MRP5 (ABCC5) and MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood-brain barrier (BBB).

Magnetic iron compounds in the human brain: a comparison of tumour and hippocampal tissue.

Iron is a central element in the metabolism of normal and malignant cells. Abnormalities in iron and ferritin expression have been observed in many types of cancer. Interest in characterizing iron compounds in the human brain has increased due to advances in determining a relationship between excess iron accumulation and neurological and neurodegenerative diseases. In this work, four different magnetic methods have been employed to characterize the iron phases and magnetic properties of brain tumour (meningiomas) tissues and non-tumour hippocampal tissues. Four main magnetic components can be distinguished: the diamagnetic matrix, nearly paramagnetic blood, antiferromagnetic ferrihydrite cores of ferritin and ferrimagnetic magnetite and/or maghemite. For the first time, open hysteresis loops have been observed on human brain tissue at room temperature. The hysteresis properties indicate the presence of magnetite and/or maghemite particles that exhibit stable single-domain (SD) behaviour at room temperature. A significantly higher concentration of magnetically ordered magnetite and/or maghemite and a higher estimated concentration of heme iron was found in the meningioma samples. First-order reversal curve diagrams on meningioma tissue further show that the stable SD particles are magnetostatically interacting, implying high-local concentrations (clustering) of these particles in brain tumours. These findings suggest that brain tumour tissue contains an elevated amount of remanent iron oxide phases.

Source localization of mesial temporal interictal epileptiform discharges: correlation with intracranial foramen ovale electrode recordings.

OBJECTIVE: We have investigated the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) on a statistical basis by using clinical electroencephalographic (EEG) data of simultaneous scalp and intracranial foramen ovale (FO) electrode recordings. METHODS: We retrospectively analyzed the IED of 15 patients who underwent presurgical assessment for intractable temporal lobe epilepsy. All patients have subsequently undergone amygdalohippocampectomy. The scalp signals were averaged time-locked to the peak activity in bilateral 10-contact FO electrode recordings. Source modeling was carried out by using statistical non-parametric mapping (SNPM) of LORETA values and by calculating raw LORETA values of averaged IED. The results were compared to intracranial data obtained from FO electrode recordings. RESULTS: Two thousand six hundred and fifteen discharges could be attributed to 19 different patterns of intracranial mesial temporal IED. SNPM of LORETA revealed confined ipsilateral mesial temporal solutions for 14 (73.7%) and no significant solutions for five (26.3%) of these patterns. Raw LORETA current density distributions of the 19 averaged IED patterns revealed ipsilateral basal to lateral temporal solutions for the 14 IED patterns with a sufficient signal to noise ratio (SNR), but spurious results for those five IED with a low SNR. CONCLUSIONS: SNPM of LORETA but not LORETA analysis of averaged IED patterns accurately localizes the source generators of mesial temporal IEDs. SIGNIFICANCE: SNPM of raw LORETA values might be appropriate for localizing restricted mesial temporal lobe sources.

Levetiracetam in patients with refractory epilepsy: results of the SKATE trial in Austria, Germany and Switzerland.

PURPOSE: To further evaluate the safety, efficacy and optimal dose of levetiracetam (LEV) in daily clinical practice among patients with uncontrolled partial epilepsy with or without secondary generalization. METHODS: In this phase IV, open-label, 16-week community-based study, 178 at least 16-year-old patients with refractory focal epilepsy were treated with 1000, 2000 or 3000 mg levetiracetam as adjunctive therapy. All patients started with 500 mg LEV b.i.d. (1000 mg/day); the dose was adjusted in 2-week intervals up to 1500 b.i.d. (3000 mg/day) depending on seizure control and tolerability. The main objectives were the adverse events, the percentage reduction in partial and total seizure frequency per week from baseline and the retention rate, defined as the percentage of patients taking LEV at the end of the 16-week treatment period. RESULTS: Of the 178 patients who took at least one dose of LEV 151 completed the study. Thus, the retention rate (number of patients taking LEV at the end of the 16-week treatment period) was 84.8%. Most frequently reported adverse events were asthenia, dizziness, headache, nausea, somnolence and hostility; the majority of these events were of mild to moderate intensity. The seizure-free rate of the ITT population with focal seizures was 16.7%, for all seizures 16.6%; the median reduction of focal seizure frequency was 47.6%, and 46.5% for all seizures. The 50% responder rate was 46.6% for focal seizures and 45.1% for all seizures. CONCLUSION: Add-on treatment with LEV in patients with refractory partial epilepsy was safe and effective in this study.

Pilomotor seizures and status in non-paraneoplastic limbic encephalitis.

BACKGROUND AND AIMS: To describe an unusual clinical presentation of a patient with voltage-gated potassium channel Ab- positive, non-paraneoplastic limbic encephalitis. METHODS: We performed video-EEG monitoring, structural MRI, (18)F-FDG-PET, (1)H-MRS, neuropsychological testing and antibody serology. RESULTS: A 42-year-old male patient presented in an acute phase of non-paraneoplastic limbic encephalitis confirmed by MRI, with antibodies to voltage-gated potassium channels. His pilomotor status was pharmacoresistant to antiepileptic drugs, but responded to corticosteroid and azathioprine treatment. The MRI findings improved. The pilomotor seizures recurred when the immunosuppressive therapy was discontinued after 18 months. MRI at that time was consistent with hippocampal sclerosis. Complete seizure control was achieved after reintroduction of steroids. CONCLUSION: Pilomotor seizures were the predominant seizure type in this case of non-paraneoplastic limbic encephalitis. Immunosuppressive therapy may provide recovery including seizure control. However, long-term immunosuppression may be necessary to prevent relapse. Hippocampal sclerosis and chronic epilepsy might evolve as sequelae of limbic encephalitis.

Awake surgery for glioma resection in eloquent areas--Zurich's experience and review--.

Awake surgery was performed in a series of 21 patients with gliomas in eloquent areas with the use of intraoperative electrical mapping. Gross total removal was performed in 18 patients. There was no operative mortality. Postoperative findings included no change in symptoms and signs in 10 patients, improvement of the preoperative deficit in 11 patients. Four patients had improved Karnofsky performance status (KPS) scores after surgery, 17 patients were stable, and no patient had lower KPS score. Extensive radical resection of gliomas prolongs the overall survival and improves the patient's quality of life. However, surgical resection of gliomas located within the sensorimotor or language areas remains a neurosurgical challenge in reducing eloquent neurological sequelae. Awake surgery with intraoperative functional mapping is a safe approach to maximize the extent of tumor removal and to minimize the resultant neurological deficits in the treatment of glioma involving the eloquent cortex.

Epilepsy with severe abdominal pain.

We describe a patient who experienced recurrent episodes of abdominal pain as a prominent feature of his seizure disorder. Treatment with carbamazepine could not prevent these painful sensations, but a selective amygdalohippocampectomy completely controlled the episodic pain and the seizures associated with loss or alteration of consciousness. During the presurgical evaluation, the episodes of abdominal pain correlated with amygdalar seizure discharges.

Music and the brain. Lessons from brain diseases and some reflections on the "emotional" brain.

Studies are reviewed from the perspective of a neurologist and epileptologist interested in "music and the brain." At the neurocognitive level, deficits in pitch discrimination of patients with brain lesions and those during the intracarotid amobarbital test are outlined, because they show that the temporal lobe and, in particular, the right acoustic cortex are crucial. Hallucinations of music during epileptic seizures as well as the analysis of musicogenic epilepsy point to the same gross localization and lateralization. At the esthetic level, music theoretical concepts on the consonance-dissonance dichotomy and related EEG examinations are reported, which illustrate the importance of mesiolimbic temporal lobe structures for the pleasure that we might experience when listening to music. The complex interaction of many neuronal circuits and assemblies of both hemispheres in musical perception and performance is illustrated by musical analysis of a recording by an organ player who experienced a right temporal lobe seizure. This analysis revealed that the seizure-induced errors of the left hand were compensated with the right hand in a musically meaningful way.

Functional neuroimaging predicts individual memory outcome after amygdalohippocampectomy.

We examined memory-related activity within to-be-resected medial temporal lobe (MTL) structures in 12 epilepsy patients with PET before amygdalohippocampectomy and studied the reallocation of memory functions to the contralateral MTL before and after surgery. Learning tasks were designed to activate predominantly the right or left MTL. Those patients who significantly activated to-be-resected ipsilateral MTL structures during the ipsilateral learning task (i.e. the left MTL during verbal learning or the right MTL during nonverbal learning) experienced a postoperative memory decline. Preoperative activation in the contralateral MTL during the ipsilateral learning task positively correlated with the postoperative outcome for ipsilateral memory. There was no significant postoperative reallocation of ipsilateral memory functions to the contralateral MTL.

Event-related brain potentials in memory: correlates of episodic, semantic and implicit memory.

OBJECTIVE: To study cognitive evoked potentials, recorded from scalp EEG and foramen ovale electrodes, during activation of explicit and implicit memory. The subgroups of explicit memory, episodic and semantic memory, are looked at separately. METHODS: A word-learning task was used, which has been shown to activate hippocampus in H(2)(15)O positron emission tomography studies. Subjects had to study and remember word pairs using different learning strategies: (i) associative word learning (AWL), which activates the episodic memory, (ii) deep single word encoding (DSWE), which activates the semantic memory, and (iii) shallow single word encoding (SSWE), which activates the implicit memory and serves as a baseline. The test included the 'remember/know' paradigm as a behavioural learning control. During the task condition, a 10-20 scalp EEG with additional electrodes in both temporal lobes regions was recorded from 11 healthy volunteers. In one patient with mesiotemporal lobe epilepsy, the EEG was recorded from bilateral foramen ovale electrodes directly from mesial temporal lobe structures. Event-related potentials (ERPs) were calculated off-line and visual and statistical analyses were made. RESULTS: Associative learning strategy produced the best memory performance and the best noetic awareness experience, whereas shallow single word encoding produced the worst performance and the smallest noetic awareness. Deep single word encoding performance was in between. ERPs differed according to the test condition, during both encoding and retrieval, from both the scalp EEG and the foramen ovale electrode recordings. Encoding showed significant differences between the shallow single word encoding (SSWE), which is mainly a function of graphical characteristics, and the other two strategies, deep single word (DSWE) and associative learning (AWL), in which there is a semantic processing of the meaning. ERPs generated by these two categories, which are both functions of explicit memory, differed as well, indicating the presence or the absence of associative binding. Retrieval showed a significant test effect between the word pairs learned by association (AWL) and the ones learned by encoding the words in isolation of each other (DSWE and SSWE). The comparison of the ERPs generated by autonoetic awareness ('remember') and noetic awareness ('know') exhibited a significant test effect as well. CONCLUSIONS: The results of behavioural data, in particular that of the 'remember/know' procedure, are evidence that the task paradigm was efficient in activating different kinds of memory. Associative word learning generated a high degree of autonoetic awareness, which is a result of the episodic memory, whereas both kinds of single word learning generated less. AWL, DSWE and SSWE resulted in different electrophysiological correlates, both for encoding as well as retrieval, indicating that different brain structures were activated in different temporal sequence.