Zoomed MRI Guided by Combined EEG/MEG Source Analysis: A Multimodal Approach for Optimizing Presurgical Epilepsy Work-up and its Application in a Multi-focal Epilepsy Patient Case Study.

In recent years, the use of source analysis based on electroencephalography (EEG) and magnetoencephalography (MEG) has gained considerable attention in presurgical epilepsy diagnosis. However, in many cases the source analysis alone is not used to tailor surgery unless the findings are confirmed by lesions, such as, e.g., cortical malformations in MRI. For many patients, the histology of tissue resected from MRI negative epilepsy shows small lesions, which indicates the need for more sensitive MR sequences. In this paper, we describe a technique to maximize the synergy between combined EEG/MEG (EMEG) source analysis and high resolution MRI. The procedure has three main steps: (1) construction of a detailed and calibrated finite element head model that considers the variation of individual skull conductivities and white matter anisotropy, (2) EMEG source analysis performed on averaged interictal epileptic discharges (IED), (3) high resolution (0.5 mm) zoomed MR imaging, limited to small areas centered at the EMEG source locations. The proposed new diagnosis procedure was then applied in a particularly challenging case of an epilepsy patient: EMEG analysis at the peak of the IED coincided with a right frontal focal cortical dysplasia (FCD), which had been detected at standard 1 mm resolution MRI. Of higher interest, zoomed MR imaging (applying parallel transmission, 'ZOOMit') guided by EMEG at the spike onset revealed a second, fairly subtle, FCD in the left fronto-central region. The evaluation revealed that this second FCD, which had not been detectable with standard 1 mm resolution, was the trigger of the seizures.

Epilepsy surgery for insular lesions.

OBJECTIVE: Due to the proximity of eloquent areas of the brain, the surgical treatment of insular lesions causing refractory epilepsy is considered difficult. We report here on our experience in this field. METHODS: We identified 24 patients (age: 1-62 years, mean 27) who underwent epilepsy surgery for an insular lesion from the epilepsy surgery data bank. We analyzed the preoperative diagnostics, surgical strategy and postoperative follow-up (duration: 12-168 months, mean 37.5) for functional morbidity and seizure outcome. RESULTS: Eight patients had strictly insular lesions while, in 16 cases, the lesion extended into the frontal (n=3) or temporal (n=8) lobe, or was multilobar (n=5). Sixteen resections (66.7%) were right-sided. Six patients required invasive EEG with implanted electrodes, while three had the aid of intraoperative electrocorticography. In 12 patients, continuous electrophysiological monitoring was used intraoperatively (phase reversal, motor evoked potentials) and, in seven, neuronavigation. In seven patients, only subtotal resection of the insular lesion was possible due to involvement of eloquent areas, and two patients required repeat surgery to complete the resection. Thirteen patients had glial/glioneural tumours (WHO grades I-III), 11 from non-neoplastic lesions. Postoperatively, two patients (8.3%) had a transient neurological deficit (hemiparesis and dysphasia, respectively). One patient had permanent hemihypaesthesia, another had permanent deterioration of preexistent hemiparesis and two had hemianopia as calculated deficit (16.6% rate of mild permanent morbidity). According to the International League against Epilepsy (ILAE) classification, 15 patients were totally seizure-free (62.5%, ILAE 1) and 79.2% had a satisfactory seizure outcome (ILAE 1-3). CONCLUSION: In selected patients, an individually tailored lesionectomy of insular lesions can be performed, with acceptable safety, to provide a high rate of satisfactory seizure relief. Indeed, even subtotal resection can result in effective seizure control.

Overlap of musical and linguistic syntax processing: intracranial ERP evidence.

The present study investigated the co-localization of musical and linguistic syntax processing in the human brain. EEGs were recorded from subdural electrodes placed on the left and right perisylvian cortex. The neural generators of the early potentials elicited by syntactic errors in music and language were localized by means of distributed source modeling and compared within subjects. The combined results indicated a partial overlap of the sources within the bilateral superior temporal gyrus, and, to a lesser extent, in the left inferior frontal gyrus, qualifying these areas as shared anatomic substrates of early syntactic error detection in music and language.

Insular lesionectomy for refractory epilepsy: management and outcome.

Surgical treatment of deep-seated insular lesions causing refractory epilepsy is thought to be difficult due to the complicated accessibility and close proximity of eloquent areas. Here we report our experience with insular lesionectomies. Twenty-four patients (range 1-62 years, mean 27) who underwent epilepsy-surgery for a lesion involving the insular region, were identified from the epilepsy surgery data bank. We analysed pre-surgical diagnostics, surgical strategy and postoperative follow up concerning functional morbidity and seizure outcome (range 12-168 months, mean 37.5). Eight patients had pure insular lesions, in 16 cases the lesion extended either to the frontal (n = 3) or temporal lobe (n = 8) or was multilobar (n = 5). Sixteen resections (66.7%) were done on the right side. Six patients required invasive EEG-recording, three patients received intra-operative electrocorticography. In seven patients only subtotal resection of the insular lesion was possible due to involvement of eloquent areas. Thirteen patients suffered from glial/glioneural tumours (WHO grades I-III), 11 from non-neoplastic lesions. Postoperatively, one patient had a hemihypesthesia and one patient had a deterioration of a pre-existing hemiparesis; two patients had a hemianopia as calculated deficit (mild permanent morbidity 16.6%). According to the ILAE-classification, 15 patients were completely seizure free (62.5%, ILAE 1). Around 79.2% had satisfactory seizure outcome (ILAE 1-3). In selected patients an individually tailored lesionectomy of insular lesions can be performed, which is acceptably safe and provides a high rate of satisfactory seizure relief. Even subtotal resection can result in good seizure control.

The impact of zonisamide on weight. A clinical study in 103 patients with epilepsy.

OBJECTIVE: To investigate the impact of zonisamide (ZNS) on body weight in patients with epilepsy. METHODS: A retrospective chart analysis of weight changes after initiation of ZNS (103 patients; 54 female; age 17-68 years). For 31 patients follow-up data after ZNS-withdrawal were available. Patients were categorized according to body-mass-index (BMI) <20, 20-25, and >25 kg/m(2). RESULTS: Body weight before ZNS was 78.6 +/- 16.0 kg (range 45-120 kg), BMI 26.5 +/- 5.2 kg/m(2) (range17.6-41.3 kg/m(2)). Within 13 +/- 7.2 months of treatment, mean body weight decreased by -3.7% +/- 9.1%, showing high interindividual variability (-36% to +32%). Weight loss >5% was documented in 35%, weight gain >5% in 14% of patients. Weight loss was more prominent in patients being overweight prior to treatment onset. At the end of follow-up, patients with overweight had decreased by number. Weight changes under ZNS were not correlated to ZNS daily dosage. Following discontinuation of ZNS treatment weight loss proved to be reversible. CONCLUSION: Zonisamide reduced weight in 35% of patients, especially in patients with overweight prior to treatment. Weight loss is reversible following discontinuation of treatment with ZNS.

[Zonisamide as add-on treatment for focal epilepsies. An outcome analysis of 74 patients]. / Zonisamid zur Komedikation fokaler Epilepsien. Eine Behandlungsanalyse von 74 Patienten.

BACKGROUND: Evaluation of efficacy and tolerability of zonisamide (ZNS) used as an add-on treatment in patients with chronic focal epilepsies. MATERIAL AND METHODS: Retrospective data analysis in 74 patients (38 men, 36 women), age 17-61 years (mean 35 years). Duration of epilepsy was 2-50 years (mean 23.3 years). Additional antiepileptic drugs 2-5 (mean 2.7). RESULTS: The ZNS daily dosage varied between 100 mg and 500 mg (mean 368 mg). Seizure frequency could be estimated in 50 patients; it decreased by at least 50% in 11 patients (22%), remained unchanged in 28 patients (56%), and increased by at least 50% in 11 patients (22%). None of the patients achieved complete seizure control. Side effects were seen in 45/74 patients (60.8%). Adverse events resulting in discontinuation of treatment with ZNS were documented in 24 patients (32.4%). Out of 70 patients, 34 (48.5%) remained on ZNS 12 months after the onset of therapy. CONCLUSIONS: In this study, ZNS proved to be an antiepileptic drug with a comparatively low anticonvulsant efficacy as an add-on treatment in patients with chronic focal epilepsies.

The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

[Oral treatment of vitamin B12 deficiency in subacute combined degeneration]. / Orale Vitamin-B12-Substitution bei funikulärer Myelose.

Vitamin B12 deficiency due to malnutrition or malabsorption may lead to pernicious anemia and neurological disorders. Although randomized prospective studies have shown that pernicious anemia can be safely treated with oral vitamin B12 even in the absence of intrinsic factor, it is still common practice to treat patients with neurological symptoms with intramuscular cyancobalamin injections. We report the successful oral treatment of subacute combined degeneration of the spinal cord in a 24-year-old woman closely monitored clinically with MRI and plasma levels of vitamin B12, homocysteine, and methylmalonic acid. We suggest monitored oral substitution therapy as first-line therapy for neurological disorders related to vitamin B12 deficiency.

Neurochemical profile of glioneuronal lesions from patients with pharmacoresistant focal epilepsies.

Gangliogliomas, dysembryoplastic neuroepithelial tumors (DNT) and glioneuronal malformations are frequently encountered in patients with pharmacoresistant focal epilepsies. In order to characterize the neurochemical profile of these neoplastic and malformative glioneuronal lesions, we have examined the presence of the alpha 1 subunit of the GABAA receptor, the N-methyl-D-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, tyrosine hydroxylase, somatostatin, parvalbumin, and calretinin in 60 gangliogliomas, 11 DNT, 10 tuberous sclerosis-like lesions and 17 non-tuberous sclerosis-like glioneuronal malformations. All DNT and tuberous sclerosis-like lesions, 59 gangliogliomas (98%), and 13 non-tuberous sclerosis-like hamartias (76%) were positive for at least one of the markers. Despite a great variation between and within the different entities, the neurochemical profile was generally reminiscent of normal neocortex: glutamate decarboxylase, GABAA receptor and NR1 which are common in neocortical neurons were present in the great majority of the lesions and often showed high labeling indices. There were three tuberous sclerosis-like lesions (30%) that contained both NR1 and glutamate decarboxylase immunoreactive giant cells in addition to well-differentiated ganglion cells. This supports the idea that at least some of these giant cells are of neuronal origin. The oligodendroglia-like cells of DNT and glioneuronal hamartias did not show immunoreactivity for any of the markers. The very high incidence of ganglioglial lesions in patients with chronic focal epilepsies and the presence of neurotransmitter-producing enzymes, neurotransmitter receptors, neuropeptides, and calcium-binding proteins in many of these lesions suggests that they may play an active role in the pathogenesis of epileptic seizures.

Glioneuronal malformative lesions and dysembryoplastic neuroepithelial tumors in patients with chronic pharmacoresistant epilepsies.

Malformative glioneuronal lesions were examined in surgical specimens from 43 patients with chronic focal epilepsies in order to determine the scope of histopathological changes and to better understand their pathogenesis. The most common lesions were hamartias composed of randomly oriented neurons and astrocytes (24 cases). Most of these lesions also contained clustered oligodendrocyte-like cells which were often strongly immunoreactive for the developmentally regulated embryonal form of the neural cell adhesion molecule (E-NCAM). These hamartias were typically minute, multifocal, and arranged in a pattern suggestive of a migration disorder. There were eight cases with aggregates of large disfigured neurons, oversized atypical astrocytes and ballooned multinucleated giant cells reminiscent of tuberous sclerosis-associated changes. Finally, there were 11 dysembryoplastic neuroepithelial tumors (DNT), an entity which has been proposed to be malformative rather than neoplastic. The oligodendroglia-like cells in DNT were negative for E-NCAM. However, strong E-NCAM expression was present in many dysplastic neurons of tuberous sclerosis-like lesions, hamartias and DNT and in reactive astrocytes. Significant immunoreactivity for the proliferation associated Ki-67 antigen was not observed. No similar lesions were observed in 500 consecutive autopsies from patients without epilepsy. Malformative glioneuronal lesions appear to be highly epileptogenic and most likely result from a disordered cell migration and differentiation.