The role of presurgical EEG parameters and of reoperation for seizure outcome in temporal lobe epilepsy.

PURPOSE: After surgery for intractable mesiotemporal lobe epilepsy (mTLE) seizures recur in 30-40%. One predictor for seizure recurrence is the distribution of seizure onset and interictal epileptiform discharges (IED). Our study focused on lateralization and extent of epileptiform activity regarding postoperative seizure persistence and the effect of reoperation. METHODS: This study comprises 426 consecutive patients operated for intractable mTLE. Impact of preoperative seizure onset and IED on the persistence of seizures and results of reoperation were analyzed. RESULTS: One year after surgery, 27% of patients with mTLE experienced persistent seizures (Engel II-IV). Preoperative bilateral seizure onset in EEG was predictive for postoperative seizure recurrence (Engel II-IV: 64%). Seizure foci and IED exceeding the temporal lobe in the ipsilateral hemisphere were not found to be associated with worse seizure outcome (Engel I: 72% and 75%) compared to patients with seizure foci confined to the ipsilateral temporal lobe (Engel I: 75% and 76%). Moreover, IED exceeding the affected temporal lobe in the ipsilateral hemisphere or even bilateral IED did not negatively affect seizure freedom if seizure onset was strictly limited to the affected temporal lobe (Engel I: 85% and 65%, respectively). 60% of patients reoperated in the ipsilateral temporal lobe for persistent seizures became seizure free. CONCLUSIONS: Preoperative bilateral ictal foci are a negative predictor for seizure outcome. Contrarily, IED exceeding the affected temporal lobe in the ipsilateral hemisphere or even bilateral IED had favorable seizure outcome if seizure onset is strictly limited to the affected temporal lobe. Reoperation for seizure persistence constitutes a promising therapeutic option.

Pure endoscopic management of epileptogenic hypothalamic hamartomas.

Hypothalamic hamartomas (HH) are rare congenital malformations located in the region of the tuber cinereum and third ventricle. Their usual clinical presentation is characterized by gelastic/dacrystic seizures which often become pharmaco-resistant and progress to secondary focal/generalized intractable epilepsy causing mostly in children cognitive and behavioral problems (particularly in cases of progressive epileptic encephalopathy) and precocious puberty. Whereas gelastic seizures can be surgically controlled either by resection of the lesion or disconnection (tissue-destructive) procedures, aimed at functionally prevent the spreading of the epileptic burst; generalized seizures tend to respond better to HH excision rather than isolated neocortical resections, which generally fail to control them. Prospective analysis of 14 consecutive patients harboring HH treated in an 8-year period; 12 patients had unilateral and two bilateral HH. All patients were managed by pure endoscopic excision of the HH. The mean operative time was 48 min and mean hospital stay was 2 days; perioperative blood loss was negligible in all cases. Two patients showed a transient diabetes insipidus (DI); no transient or permanent postoperative neurological deficit or memory impairment was recorded. Complete HH excision was achieved in 10/14 patients. At a mean follow-up of 48 months, no wound infection, meningitis, postoperative hydrocephalus, and/or mortality were recorded in this series of patients. Eight patients became seizure free (Engel class I), 2 other experienced worthwhile improvement of disabling seizures (Engel class II); 2 patients were cured from gelastic attacks while still experiencing focal dyscognitive seizures; and 2, having bilateral HH (both undergoing unilateral HH excision), did not experience significant improvement and required later on a temporal lobectomy coupled to amygdalohyppocampectomy. Overall, the followings resulted to be predictive factors for better outcomes in terms of seizure control: (1) cases of unilateral, Delalande class B, HH, (2) shorter history of epilepsy. Endoscopic resection of HH proved, in our series, to be effective in achieving complete control or in reducing the frequency of seizures. Furthermore, this approach has confirmed its minimally invasive nature with a very low morbidity rate: of note, it allowed to better preserve short-term memory and hypothalamic function.

Long-term outcome characteristics in mesial temporal lobe epilepsy with and without associated cortical dysplasia.

OBJECT: The intention of our study was to identify predictive characteristics for long-term seizure control and running down phenomenon after surgical treatment of pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated cortical dysplasia. MATERIALS AND METHODS: Our study comprises a consecutive series of 458 patients who underwent surgical treatment for intractable mTLE at the Epilepsy Center Freiburg. Data evaluated included semiology, duration and frequency of seizures, results of presurgical diagnostics including video-EEG monitoring, MRI, PET and SPECT as well as postoperative seizure outcome. Results were evaluated forming two groups: Group A consisted of isolated mesiotemporal lesions. Group B comprised patients with mTLE and additional focal cortical dysplasia (FCD). Statistical evaluation was based on the Kaplan Meier survival analysis, using log-rank-tests and a multivariate regression model. Postoperative running down phenomenon was defined as seizure freedom after a period of gradual reduction of postoperative seizure frequency. This was compared to patients with ongoing epilepsy. RESULTS: Complete seizure freedom was achieved in 65.0% of investigated patients at 1year and in 56.5% at long-term follow-up of ≥5 years after surgery. Corresponding results were 64.2% and 56.8% at 1 and ≥5 years, respectively in group A and 66.4% and 56.0%, respectively in group B. Predictive for favorable postoperative outcome in the total group were younger age at surgery, shorter duration of epilepsy, absence of secondarily generalized tonic-clonic seizures (SGTCS), presence of strictly ipsilateral temporal interictal epileptiform discharges (IEDs), complete resection of the lesion as well as absence of postoperative epileptiform activity and of early postoperative seizures. In subgroup analyses, patients of group A demonstrated longer postoperative seizure-free intervals with adolescent age at surgery, short duration of epilepsy before surgery and absence of SGTCS, whereas in patients of group B ipsilateral temporal seizure onset and strictly unilateral IEDs in EEG as well as complete resection were predictors for favorable seizure outcome. Furthermore, absence of early postoperative seizures and of spikes in EEG were predictive factors for long-term seizure-freedom in both subgroups. The running down phenomenon was found in 33 (7.2%) patients. None of the parameters evaluated demonstrated significant predictive power. Only late seizure onset and neoplastic lesions showed a trend for postoperative gradual seizure reduction in multivariate analyses. CONCLUSION: Depending on the presence or absence of focal cortical dysplasia in addition to mesiotemporal structural alterations, predictors of long-term seizure control differed regarding the relevant clinical and electrophysiological features. This is important for specific patient counseling in respective groups.

The heavy metals cadmium, lead and mercury in raw materials of animal origin: evaluation of data from practice.

Raw materials from animal origin are widely used in homoeopathy. Due to the lack of dedicated limits, the quality requirements for herbal drugs of the European Pharmacopoeia (Ph. Eur.) and/or the German Homoeopathic Pharmacopoeia (Homöopathisches Arzneibuch, HAB), including limits for heavy metals such as cadmium, lead and mercury, have been applied. A recent database evaluation shows that for some raw materials of animal origin the Ph. Eur. limits for herbal drugs cannot be met in practice. For this reason proposals for new limits for cadmium, lead and mercury are made based on recent experiences from the companies' daily practice. These specific limits are suggested to be included in the individual monographs of the Ph. Eur. or at least the German HAB, respectively, for Ambra grisea, Euspongia officinalis, Formica rufa and Sepia officinalis.

Outcome and predictors of interstitial radiosurgery in the treatment of gelastic epilepsy.

BACKGROUND: Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome. METHODS: Twenty-four consecutive patients (3-46 years of age, 7 women, mean age 21.9 years, mean duration of epilepsy 17.6 years) with gelastic epilepsy due to MR-ascertained hypothalamic hamartoma and a minimum follow-up period of 1 year were included in this evaluation. Treatment was performed by interstitial radiosurgery using stereotactically implanted (125)I seeds. Effects of treatment on seizure frequency and possible side effects were assessed prospectively. Factors influencing outcome and side effects were analyzed statistically. RESULTS: After a mean 24-month follow-up period following the last radiosurgical treatment, 11/24 patients were seizure free or had seizure reduction of at least 90% (Engel class I and II), in some cases only after repeated treatment. The duration of epilepsy prior to radiosurgery negatively influenced outcome. Treatment was well tolerated in most patients. Headache, fatigue, and lethargy were transient side effects associated with the development of brain edema extending from the implantation site in five patients. Four patients had a weight gain of more than 5 kg which was severe in two patients. The majority of those patients whose cognitive functions initially deteriorated showed subsequent recovery of cognitive functions, but episodic memory in two patients showed persistent decline at 1 year follow-up. Longer disease duration increased the risk for cognitive side effects, and larger hamartoma size and eccentric seed positioning increased the risk for radiogenic brain edema. Neither perioperative mortality nor neurologic impairments, visual field defects, or endocrinologic disturbances were encountered following treatment. CONCLUSION: Interstitial radiosurgery was efficacious in significantly improving gelastic epilepsy in about half of the patients treated in this series. Weight gain may occur as a side effect, whereas other severe side effects reported following microsurgical removal of the hamartoma were absent. The study results strongly suggest early causal treatment, as chances for seizure control are higher and the risk for cognitive side effects is lower in patients with shorter disease duration.

Factors influencing surgical outcome in patients with focal cortical dysplasia.

A total of 120 patients with histologically proven focal cortical dysplasias (FCD) were retrospectively analysed for prognostic factors for successful epilepsy surgery. Multivariate data analyses showed that older age at epilepsy surgery, occurrence of secondarily generalised seizures and a multilobar extent of the dysplasia were significant negative predictors. In univariate analyses, longer duration of epilepsy, need for intracranial EEG recordings and incomplete resection of the FCD were factors which significantly reduced the chance of becoming seizure free. Histological subtype of the FCD and age at epilepsy onset had no significant predictive value. These findings strongly suggest early consideration of epilepsy surgery in FCD patients.

Emerging drugs for epilepsy and other treatment options.

Epilepsies are amongst the most frequent chronic neurological conditions. Patients suffer from spontaneously recurring seizures because of sudden extensive electrical gray matter discharges. Although the current drug therapy allows many patients at least some degree of a satisfying course of the disease, a substantial number of patients remain without adequate seizure control. Reasons are either refractoriness to anticonvulsant drugs or intolerable drug-related side effects. Epilepsy surgery should be considered in these cases as possible treatment option. Nevertheless, a considerable rate of patients will not be suitable candidates or continue to have seizures despite surgery. Therefore there is a substantial need for better antiepileptic drugs. The aim of this review is to highlight currently emerging different treatment approaches which may ameliorate the perspectives of patients with difficult-to-treat epilepsies.

Assessment of cognitive functions before and after stereotactic interstitial radiosurgery of hypothalamic hamartomas in patients with gelastic seizures.

We assessed cognitive functions before and 3 months after interstitial radiotherapy in 14 patients with gelastic seizures caused by hypothalamic hamartoma. Cognitive functioning was assessed before temporary implantation of (125)I-seed and 3 months after seed explantation. Performance was compared with that of a selected control group of conservatively treated patients with symptomatic focal epilepsy tested before add-on treatment with a new antiepileptic drug and after reaching steady state. No short-term negative side effects of the interstitial radiosurgery could be observed for the domains of attention and executive functions and verbal and figural memory performance. Cognitive development of the patients treated with seeds was comparable to that of the control group at both assessments. Thus, the stereotactic implantation of (125)I-seeds in this patient group with gelastic seizures caused by hypothalamic hamartoma provides a well-tolerated minimally invasive method in the treatment of this severe epileptic syndrome without negative cognitive side effects.

Unsuspected atypical hemispheric dominance for language as determined by fMRI.

PURPOSE: We sought to illustrate the value of functional magnetic resonance imaging (fMRI) in the presurgical assessment of hemispheric dominance for language by means of an illustrative case report. METHODS: fMRI with two language paradigms was performed in a right-handed patient without familial sinistrality suffering from a left frontal focal epilepsy. RESULTS: Both fMRI paradigms revealed unequivocally lateralized right hemispheric activation. Atypical language representation was confirmed by Wada test. The further presurgical workup could be restricted to subdural strip recordings instead of the initially intended grid implantation. After resective surgery, no language deficits were apparent. CONCLUSIONS: Hemispheric dominance for language should be assessed by fMRI in all patients before surgery in areas potentially relevant for language in either cerebral hemisphere. fMRI may influence the further diagnostic workup and should be performed before other invasive diagnostic procedures.

Dipole-source analysis in a realistic head model in patients with focal epilepsy.

PURPOSE: By the use of three different head models in EEG dipole analysis, we tried to model the origin of interictal and ictal epileptic activity as precisely as possible. Further, as a control, a second evaluation was made by an independent group to control for interindividual reliability of the dipole source analysis. With the realistic head model (CURRY) considering cortex, skull, and skin segmentation, the spike source was located. METHODS: In five patients with mesial temporal epileptogenesis, confirmed by successful epilepsy surgery, the spike source was close to the hippocampus, with a mean distance of the dipole source from the hippocampus of 13.6 mm (range, 9-17.2 mm). In one case the ictal EEG also could be analyzed and resulted in a dipole-source localization comparable to the interictal source. RESULTS: In both head models using either pure cortex segmentation only or a concentric three-shell model, the dipole source was systematically dislocated in a more superior position. Data analysis by a second group with independently chosen EEG samples and identical individual head model resulted in deviations of <5.3 mm. Data analysis using independently selected spikes and independently segmented head models resulted in deviations < or =16.7 mm. CONCLUSIONS: In four cases of extratemporal epileptogenesis, the origin of interictal epileptiform discharges was localized to the suspected primary epileptogenic zone.

How to improve the clinical diagnosis of Creutzfeldt-Jakob disease.

This paper describes a prospective follow-up of 364 patients initially notified as suspected Creutzfeldt-Jakob disease to a Surveillance Unit in Göttingen, Germany. Six patients were diagnosed as having genetic prion disease by blood analysis and were excluded from the study. After examination and review of the remaining 358, 193 were classified as probable Creutzfeldt-Jakob disease. However, autopsy revealed that five of the 193 did not have Creutzfeldt-Jakob disease (four cases, Alzheimer's disease; one case, cerebral lymphoma). Of the 54 patients classified as possible Creutzfeldt-Jakob disease, 10 had another diagnosis made at autopsy. Two of the 111 cases originally classified as having other diseases were found to have Creutzfeldt-Jakob disease on autopsy. Autopsy evidence, together with follow-up of the patients still living and those who died without autopsy, revealed a broad range of other diagnoses. In the younger age groups, the commonest were chronic inflammatory diseases including Hashimoto encephalitis, whilst rapidly progressive Alzheimer's disease was most common in the older age groups. The presence of 14-3-3 protein in the CSF discriminated better between Creutzfeldt-Jakob disease and other rapidly progressive dementias than did the EEG pattern or the MRI. The inclusion of this CSF protein in the criteria of Masters and colleagues (Ann Neurol 1979; 5: 177-88) improves the accuracy and confidence in the clinical diagnosis of Creutzfeldt-Jakob disease.

Cisternal S100 protein and neuron-specific enolase are elevated and site-specific markers in intractable temporal lobe epilepsy.

In the brain, S100 protein and neuron-specific enolase (NSE) are mainly found in glial cells and neurons, respectively. We investigated concentrations of S100 protein and NSE in cisternal cerebrospinal fluid obtained during implantation of foramen ovale electrodes in eight patients with temporal lobe epilepsy (TLE). In addition, the meningeal markers cystatin-C and beta-trace as well as total protein were measured. Patients with trigeminal neuralgia (TN) undergoing glycerol rhizotomy served as controls. S100 protein and NSE levels ipsilateral to the site of seizure onset were significantly higher than in TN. Contralateral TLE values were also markedly but not significantly elevated. The meningeal markers cystatin-C and beta-trace protein as well as total protein did not differ in TLE and TN. We conclude that interictal temporal lobe dysfunction corresponds with neuronal and glial marker elevations in the extracellular space and that site-specific elevations may predict the site of seizure origin biochemically.

Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: During an epidemiological study of Creutzfeldt-Jakob disease in Germany, Hashimoto's encephalitis was encountered as a differential diagnosis, which has not yet been described in this context. METHODS: The symptoms and findings of seven patients who fulfilled the criteria for "possible" Creutzfeldt-Jakob disease are presented. RESULTS: A Hashimoto's thyroiditis with antibodies against thyroglobulin or thyroid peroxidase, or both and a hypoechoic thyroid ultrasonogram were found in all cases. Analysis of CSF disclosed an increased leucocyte count in three patients, and a raised CSF:serum concentration ratio of albumin (QA1b) in four patients. The 14-3-3 protein, typical of Creutzfeldt-Jakob disease, could not be detected in any of our patients. No periodic sharp wave complexes, which are typical of Creutzfeldt-Jakob disease, were detected on EEG in any of the cases. By contrast with Creutzfeldt-Jakob disease, which leads to death within a few months, the patients with Hashimoto's encephalitis often recover quickly when treated adequately. All the patients improved after administration of corticosteroids. CONCLUSION: The clinical symptomatology of both diseases may be very similar: dementia, myoclonus, ataxia, and personality change or psychotic phenomena are characteristic symptoms.

[Semiologic classification of epileptic seizures]. / Die semiologische Klassifikation epileptischer Anfälle.

Recent advances in epileptology and epilepsy surgery require revision of the currently used International Classification of Epileptic Seizures, which was published 1981. We present a classification of epileptic seizures which is based purely on the clinical seizure semiology. The advantages of a semiological seizure classification are stressed.

The lateralizing value of ictal clinical symptoms in uniregional temporal lobe epilepsy.

In order to assess the lateralizing value of several ictal and postictal clinical symptoms in temporal lobe epilepsy (TLE), we analyzed 89 seizures of 20 left dominant patients with intractable left (n = 9) versus right (n = 11) TLE who had undergone successful anterior temporal lobectomy. In left TLE, movement arrest at seizure onset, postictal dysphasia > 120 s and postictal dyslexia > 180 s were the most typical findings and associated with a sensitivity of 94, 94, and 100%, respectively. The highest specificity of 100% each was evident for contralateral versions of eyes and head and dystonic posturing. In right TLE, the highest sensitivity was seen for whole-body movements at seizure onset, postictal dysphasia < 120 s and postictal dyslexia < 180 s with figures of 82, 87, and 93%, respectively. As compared to left TLE, contralateral version and dystonic posturing, ictal speech, and postictal dyslexia < 180 s each had a specificity of 100%. The careful combined analysis of certain ictal clinical signs combined with consistent findings of interictal EEG and neuroimaging studies may be often sufficient to proceed with epilepsy surgery without invasive recordings even if ictal scalp EEG is not unambiguous.

[The magnetic resonance tomography of Ewing's sarcomas: the morphology and tumor extension]. / Magnetresonanztomographie von Ewing-Sarkomen: Morphologie und Tumorausdehnung.

PURPOSE: The morphology and delineation of Ewing sarcoma in magnetic resonance imaging was investigated. METHODS AND MATERIALS: Magnetic resonance images (spin-echo techniques; T1-w pre/post gadolinium, T2-w) of 59 patients as part of a multicenter study were evaluated retrospectively. Qualitative image analysis was performed: signal intensity (point of reference extraosseous: muscle, intraosseous: bone marrow), enhancement patterns, lesion delineation and differentiation between tumor and oedema. RESULTS: Signal intensity: T1-w: extraosseous: 75% isointense, intraosseous: 92% hypointense; T2-w extraosseous: 100% hyperintense, intraosseous: 93% hyperintense. Enhancement pattern: 97% both extra- and intraosseous. Best delineation intraosseous in T1-w (53% good, 36% very good), extraosseous in gadolinium enhanced T1-w (46% good, 37% very good) and T2-w (55% good, 33% very good). Differentiation between tumour and oedema was intraosseous not possible, extraosseous in T2-w in 61%. CONCLUSION: Morphology of Ewing sarcoma in magnetic resonance imaging is rather uniform. The lesion is intra- and extraosseous sharply delineated, though tumour and oedema can be rarely differentiated.

Ictal scalp EEG in temporal lobe epilepsy with unitemporal versus bitemporal interictal epileptiform discharges.

We investigated the ictal scalp EEG in 228 seizures of 36 patients with unitemporal (n = 25) or bitemporal independent (n = 11) interictal epileptiform discharges (IED). All patients had proven temporal lobe epilepsy since they became seizure-free or only had auras after temporal lobectomy with a minimum follow-up of 1 year. Ictal patterns at seizure onset or later in the course of the seizure were lateralized significantly more often in patients with unitemporal IED (90%, at seizure onset and 96%, later) compared with those with bitemporal independent IED (75%, at seizure onset and 78%, later). Furthermore, scalp ictal EEGs, when lateralized at seizure onset or later in the course of the seizure, were significantly more likely to predict the correct side for surgery in patients with unitemporal (98%, at seizure onset and 100%, later) than bitemporal (64%, at seizure onset and 77%, later) IED. Bilateral independent seizure onsets, asynchrony of ictal activity over the two temporal lobes, and switch of ictal activity from one to the other hemisphere are ictal patterns that are strongly correlated with bitemporal excitability.