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In common with other stereotactic procedures, stereotactic laser thermocoagulation (SLT) promises gentle destruction of pathological tissue, which might become especially relevant for epilepsy surgery in the future. Compared to standard resection, no large craniotomy is necessary, cortical damage during access to deep-seated lesions can be avoided and interventions close to eloquent brain areas become possible. We describe the history and rationale of laser neurosurgery as well as the two available SLT systems (Visualase® and NeuroBlate®; CE marks pending). Both systems are coupled with magnetic resonance imaging (MRI) and MR thermometry, thereby increasing patient safety. We report the published clinical experiences with SLT in epilepsy surgery (altogether approximately 200 cases) with respect to complications, brain structural alterations, seizure outcome, neuropsychological findings and treatment costs. The rate of seizure-free patients seems to be slightly lower than for resection surgery. Due to the inadequate quality of studies, the neuropsychological superiority of SLT has not yet been unambiguously demonstrated.

Background: The aim of the study was an assessment of the tolerability and efficacy of slow release oxcarbazepine (OXC-MR) versus immediate release OXC (OXC-IR) after forced titration in patients with focal epileptic seizures with and without secondary generalization who had previously not become seizure-free under OXC-IR with or without concomitant antiepileptic drugs. The primary study variable was to assess the maximum tolerated dosage with OXC-MR and OXC-IR., Patients and Methods: This was designed as a multicenter, randomized, open, controlled, parallel group phase III study. After randomization patients received OXC-MR or OXC-IR for a study period of 26 days. The initial dosage of 900 mg, 1,200 mg or 1,500 mg OXC was increased every 5 days by 300 mg up to a maximum daily dosage of 2,700 mg. In cases of intolerable adverse events dosage could be reduced by 150 mg 2 days after an increase. Adverse events and executive abilities were assessed with the questionnaire "Adverse Event Profile plus" and with the Epitrack® test protocol. Serum concentrations of OXC and its active metabolite were measured in a part of the patient group., Results: The 71 patients (54% male, age: 19-70 years) enrolled in the study were randomized. The maximum mean daily OXC dosage at the end of the study period was 1,950 mg with OXC-MR and thus statistically significantly higher than in OXC-IR group (1,650 mg, p = 0.022). The number of causally related adverse events was lower in the OXC-MR group (n = 104 versus n = 138 with OXC-IR) and CNS-related adverse events such as dizziness, tremor, somnolence and headache occurred significantly less often with OXC-MR (OXC-MR 65.7%, OXC-IR 88.9%, p = 0.01). Fluctuations of serum concentrations of the active metabolite were less pronounced under the OXC-MR regimen., Conclusions: Due to better tolerability OXC-MR allowed higher maintenance dosages to be reached than OXC-IR. In spite of a higher mean daily dosage adverse events and especially CNS-related adverse events occurred less often than with OXC-IR.

Neurostimulation techniques are applied to reduce the frequency and severity of epileptic seizures. Class I evidence showed that vagus nerve stimulation (VNS) reduces seizure burden by 25-28% compared to 6-15% in placebo controls. Open-label studies, however, reported much greater efficacy. Since 2010 deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is CE approved for epilepsy therapy in Europe. A multicenter randomized controlled trial reported seizure frequency reduction by 40.4% compared to 14.5% in controls. A significant effect was only found in patients with temporal seizure onset. 13% of stimulated patients became seizure-free for at least 6 months. Possible side-effects include depression (14.8%) and memory impairment (13%). Responsive neurostimulation (RNS) combines an automated seizure detection device with on-demand triggered stimulation of the epileptogenic zone. A randomized controlled trial reported seizure frequency reduction by 37.9% compared to 17.3% in controls. There were no relevant neuropsychological or psychiatric side-effects noted.

Background: Patients with psychiatric or neurologic disease often suffer from neuropsychologic problems. The purpose of this study was to present a parental questionnaire (KOPKIJ) that assesses neuropsychologic problems in children and adolescents between 6 and 16 years of age., Methods: We tested theoretical analysis, standardization, and validation of the questionnaire in 352 healthy controls and 116 pediatric patients with epilepsy., Results: The objectivity of this standardized questionnaire can be considered high, and the reliability of the subscales is satisfying. Epileptic patients had higher scores than healthy controls, and the validation displayed reasonable connections with clinical factors and the results of neuropsychological evaluation., Conclusion: The KOPKIJ allows an orientating appraisal clear picture of cognitive problems of children and adolescents at home and at school, simplifies anamnesis, and eases the planning of therapy strategies.

Rasmussen encephalitis (RE) is a severe and at the same time pathophysiologically fascinating condition. The chronic inflammation affects one of the two cerebral hemispheres and destroys it during the disease process that lasts from months to years. The patients -- mostly children -- suffer from frequent pharmacoresistant seizures, often in the form of epilepsia partialis continua. In parallel to the atrophy of the affected hemisphere, the neurological functions associated with it decline continuously. This results in a final stage with a usually high-grade sensorimotor hemisyndrome, hemianopia, cognitive impairment and -- if the language-dominant hemisphere is affected -- aphasia. Research results in the last 5 years have contributed to a deeper understanding of the pathogenesis of this condition. Formal diagnostic criteria have been proposed, and new therapeutic options have emerged by which the disease progression can be slowed or stopped. This article summarizes the current research results on the background of older data and gives recommendations regarding diagnostic and therapeutic procedures in RE patients.

Since the initial description of limbic encephalitis (LE) in 1960/1968, several subforms of this clinico-neuropathological syndrome have been identified. The best known is paraneoplastic LE. However, non-paraneoplastic forms have been reported, too. Very recently, autoantibodies against voltage-gated potassium channels have been described in association with LE. The diagnostic workup of such a case and the apparently typical good response to long-term immunotherapy of this LE subform are described.

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.

Oxcarbazepine (OXC, trade names Timox, Trileptal is a new antiepileptic drug (AED) for treatment of mono- and adjunctive therapy of partial seizures with or without secondary generalization for adults and children older than 6 years of age. Although OXC was developed through structural variation of carbamazepine in order to avoid side effects from metabolites, significant differences have emerged between the two drugs. The mechanism of action mainly involves blockade of sodium currents but differs from CBZ by modulating different types of calcium channels. In contrast to CBZ, which is oxidized by the cytochrome P-450 system, OXC undergoes reductive metabolism at its ketomoiety to form MHD, which is glucuronidated and excreted in the urine. Involvement of the hepatic cytochrome P450-dependent enzymes in the metabolism of OXC is minimal. This allows for better combining of OXC with other AEDs such as valproate. In postmarketing experience of over 800,000 patient-years, OXC also showed an advantageous risk-benefit ratio. Oxcarbazepine should be preferred over CBZ and other older AEDs due to its very good efficacy and better side effect profile in children, adolescents, and adults with partial seizures.

Integrins are alphabeta-heterodimers that act as cell-extracellular matrix (ECM) and cell-cell adhesion molecules. During development, they are involved in axonal guidance, synaptogenesis, and in astrocytic maturation and migration. Here, we have examined the potential role of the integrin subunits alpha1-alpha5 and beta1-beta5 in axonal sprouting, synaptogenesis and reactive astrogliosis in the adult rat brain caused by pilocarpine-induced status epilepticus (SE). Strong hippocampal immunoreactivity of alpha1-alpha5, beta1, beta3, beta4, and beta5 was observed in the pia mater, in vascular endothelia, and in astrocytes at the pial surface. beta2 immunoreactivity was found exclusively in vascular endothelia. Pyramidal cells and interneurons of CA3-CA1, as well as hilar neurons revealed moderate alpha5 labeling in their cell bodies. Mossy fibers were immunoreactive for alpha2, beta4, and beta5. After pilocarpine-induced SE, strong immunoreactivity for alpha1, alpha2, alpha4, alpha5, beta1, beta3, and beta4 was observed in reactive astrocytes. Our results show that members of the integrin family are differently distributed in cellular and subcellular compartments of the hippocampus and undergo specific patterns of regulation, which may be important for lesion-induced reactive changes in the adult brain.

Unlabelled: Carbamazepine is a standard anticonvulsant in children and adults. Until now there is only little information available on its use in neonates. We investigated the oral administration of carbamazepine in refractory neonatal seizures treated with phenobarbital. Ten preterm infants (gestational age 23 + 6-34 + 6 weeks, birth weight 640 g-3080 g) with neonatal seizures were refractory to a primary therapy with phenobarbital. All patients subsequently received carbamazepine exclusively as a second choice anticonvulsant. A daily dose of 7-23 mg/kg carbamazepine was administered orally in two to three aliquots. All patients reached therapeutic plasma drug levels (3-12 mg/l; 13-50 mumol/l). In nine out of ten patients (complete group of small preterms with gestational age under 30 weeks and weight less than 1000 g), therapeutic success was excellent. Carbamazepine was continued for 1-5 months. After termination of therapy no further seizures occurred, also on EEG recordings. Finally, no carbamazepine-induced adverse effects were observed., Conclusion: This is the first report on the use of carbamazepine in small preterm infants. Carbamazepine may provide a useful and effective oral maintenance therapy in the management of neonatal seizures in these patients.

Oxcarbazepin (OXC; 10,11-dihydro-10-oxo-5H-dibenz-[b,f]azepin-5-carboxamid, trade name Trileptal) is a new antiepileptic drug for treatment of mono- and adjunctive therapy of partial seizures with or without secondary generalization for adults and children above 6 years of age. It was developed through structural variation of carbamazepine. Extensive postmarketing use includes more than 200,000 patient years. The mechanism of action mainly involves blockage of sodium currents. The recommended daily starting dose of oxcarbazepin for both mono- and adjunctive treatment is 8-10 mg/kg (600 mg/day for adults) in two doses and can be titrated according to clinical benefit up to 2400 mg/day. Oxcarbazepin undergoes reductive metabolism at its keto moiety to form MHD, which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes. Thus, OXC has limited drug interactions and does not require slow titration, allowing for better tolerability. Oxcarbazepin compares favorably to presently available new anticonvulsants of the second generation for two reasons: it is available immediately for both mono- and adjunctive therapy in adults and children, and extensive postmarketing experience from many countries is already available. In addition, OXC has been thoroughly tested in an unusually large clinical development program and been shown to be similarly effective as standard antiepileptic drugs.

Little is known about the differential long-term outcome from surgical and nonsurgical therapy in patients with chronic epilepsy. In the present study, 161 surgically or nonsurgically treated patients with drug-resistant temporal lobe epilepsy (TLE) were re-evaluated according to a detailed clinical, neuropsychological, and psychosocial protocol with a mean follow-up interval of 58 months. Freedom from seizures was achieved in 64% of the surgical group; yet 23% of the nonsurgical patients became seizure-free as a result of modifications in drug therapy. Generally, socioeconomic development was poorer in nonsurgical than in surgical patients. Freedom from seizures, employment, and the absence of depression were significant determinants of better quality of life. As for neuropsychological outcome, verbal memory impairment was common after left-sided temporal resection; however, there was no evidence of a marked progression of cognitive impairment after the first postoperative year. In nonsurgical patients, too, cognitive capacities were surprisingly stable over time, although persisting seizures and good baseline performance predicted a poorer neuropsychological outcome.

If continuous seizure activity lasts longer than 5 minutes generalized tonic-clonic seizures require prompt treatment, if significant morbidity and mortality are to be avoided. The mortality varies (mean: 20%) depending on patient age and etiology. Control of status epilepticus is achieved by benzodiazepines in about 80% of cases: Lorazepam is recommended due to its longer-acting effects on the central nervous system. To maintain the anticonvulsive effect phenytoin is usually administered intravenously. Fosphenytoin (not approved in Germany) has advantages over phenytoin, because it can be given three times more rapidly and produces fewer side effects. The IV use of valproic acid in status epilepticus seems to be promising, but needs further evaluation. There is no generally accepted treatment protocol for the therapy of persistent seizure activity lasting more than 60 minutes (i.e., refractory status epilepticus). Usually phenobarbital, or general anesthesia with thiopental or pentobarbital are treatment recommendations. In recent reports, the administration of midazolam or propofol proved to be effective and well-tolerated.

The etiology and pathogenesis of complex focal lesions associated with chronic, intractable epilepsy are largely unknown. Some data indicate that malformative changes of the central nervous system may precede the development of gangliogliomas and other epilepsy-associated neoplasms. In the present immunhistochemical study, we have examined epilepsy-associated lesions for CD34, a stem cell marker transiently expressed during early neurulation. Surprisingly, most tissue samples from patients with chronic epilepsy (n = 262) revealed neural cells immunoreactive for CD34. Prominent immunoreactivity was detected in gangliogliomas (74%), low-grade astrocytomas (62%) and oligodendrogliomas (59%). Only 52% of non-neoplastic, malformative pathologies, such as glio-neuronal hamartias or hamartomas showed solitary or small clusters of CD34-immunoreactive cells. None of the adult control tissues (n = 22), none of the specimens obtained from the developing human brain (n = 44) and none of those tumor samples from patients without epilepsy (n = 63) contained CD34-immunoreactive neural cells. However, a malignant teratoma with microscopic features of early neural differentiation displayed a focal CD34-immunoreactive staining pattern. The majority of CD34-immunoreactive cells co-localized with S-100 protein and a small subpopulation was also immunoreactive for neuronal antigens. CD34 may, thus, represent a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathological changes in epilepsy patients. The CD34 immunoreactivity of these lesions indicates an origin from dysplastic or atypically differentiated neural precursors. Further studies may elucidate the functional significance of CD34 expression during the pathogenesis of epilepsy-related focal lesions as well as during neurogenesis.

Numerous studies indicate that initial precipitating injuries (IPI) such as febrile seizures during early childhood may play a pivotal role in the pathogenesis of temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS). Previous data demonstrate an increase of horizontally oriented neurons in molecular layers of hippocampal subfields, which are immunoreactive for calretinin (CR-ir) and resemble Cajal-Retzius-like cells. Cajal-Retzius cells are transiently expressed in the murine developing hippocampus and are critically involved in neuronal pattern formation. Here we investigated a potential relationship between the distribution of horizontally oriented calretinin-immunoreactive neurons and the clinical history of TLE patients with AHS. Horizontally oriented neurons in the molecular layer of the hippocampal formation have been visualized by antibodies against the calcium-binding proteins calretinin and calbindin D-28k. Cell counts derived from 27 epilepsy patients with AHS were compared with autopsy specimens from developing and adult normal human hippocampus (n = 26). During ontogeny, CR-ir cells showed a marked perinatal peak in the CA1 and dentate gyrus molecular layer (CA1-ML, DG-ML) followed by a gradual postnatal decline. In hippocampal specimens from TLE patients with AHS and seizure onset before the age of 4 years, significantly higher levels of CR-ir neurons in CA1-ML (P = 0.05) and DG-ML (P < 0.05) were encountered than in AHS patients without precipitating seizures or with an uneventful early medical history. However, all three groups had higher levels of CR-ir neurons compared to adult controls obtained at autopsy (P < 0.01). In addition, AHS specimens showed increased CR-ir neuropil staining throughout the DG-ML compared with the restricted distribution of CR-ir fibers within the superficial granule cell layer visible in controls. These findings suggest that a considerable number of TLE patients with AHS display signs of impaired hippocampal maturation and circuitry formation as indicated by increased numbers of Cajal-Retzius like cells. It remains to be elucidated, how these changes contribute to the pathogenesis of TLE.

Valproate is a frequently used antiepileptic drug. It is associated with rare but serious adverse effects like liver failure. The first symptom is impairment of the patient's well being. Isolated changes of standard laboratory liver parameters are not reliable early indicators. Thus, according to the knowledge of today, prophylactic blood screening cannot predict complications. On the contrary, clinical symptoms are the most relevant indicators of impending complications, eventually supported by laboratory findings. An abrupt withdrawal of valproate and administering carnitin in parallel can interrupt the otherwise fatal course of the complication and induce a subsequent recovery. At a Consensus Conference the current knowledge about early detection and therapy of the valproate-induced serious hepatotoxicity was discussed. The results regarding recommended laboratory screening, as well as diagnostic and therapeutic strategies are reported.

Plectin is a high molecular weight protein that serves as a versatile cytoskeletal cross-linker molecule. Mutations of the human plectin gene have recently been identified to cause the autosomal recessive disorder epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). A subgroup of EBS-MD patients display signs of a neurodegenerative disorder suggesting that the expression of defective plectin may also interfere with the structural and functional integrity of the human central nervous system. However, the expression pattern of plectin in the human brain is still unknown. We therefore analyzed the immunohistochemical distribution of plectin in normal hippocampal specimens obtained at autopsy and in neocortical and hippocampal tissue of patients who had undergone epilepsy surgery. In general, plectin-immunoreactive cells were identified as capillary endothelia and astrocytes. A striking feature seen in all specimens was the accentuated plectin immunoreactivity of astrocytic end feet abutting on blood vessels and on the pial surface. Furthermore, the analysis of hippocampal tissue of epilepsy patients with Ammon's horn sclerosis (AHS) revealed a strong plectin labeling of reactive astrocytes. The latter finding suggests that the up-regulation of plectin, which parallels the increase of glial fibrillary acidic protein, may be a general feature of reactive astroglia. The predominant expression of plectin at pia/glia and endothelia/glia interfaces in the human brain indicates that plectin may have an integral role in the structural organization of the blood-brain barrier and the leptomeninges.

Epileptic seizures may alter autonomic functions. This is especially the case with complex focal seizures (of temporal lobe origin) and grand mal. Most frequently, such seizures cause ictal tachycardia, sometimes tachypnea, probably caused by the propagation of epileptic discharges to autonomic cerebral structures. Ictal bradycardia and asystole are rare phenomena. However, they may be life threatening. Their differentiation from primary cardiac arrest is possible by the use of ictal EEG and ECG registration. Postictal serum prolactin measurement does not differentiate syncope from seizure. However, a postictal increase of creatine kinase is only measured after epileptic seizures and not after syncope. Treatment of such epileptic seizures includes an optimization of anticonvulsant drug therapy and the implantation of a cardiac demand stimulator. There is growing evidence that ictal asystole is a cofactor in sudden unexplained death in epileptic patients.

Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.

In patients with therapy-refractory temporal lobe epilepsy (TLE), alterations of glutamate receptors have been proposed as a mechanism for enhanced excitability. Using commercially available monoclonal antibodies specific for the N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 and for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4), we have examined the distribution of these polypeptides in human hippocampal tissue that was surgically removed from patients with intractable TLE. Surgical specimens were classified according to the presence of Ammon's horn sclerosis (AHS) or a focal lesion in the temporal lobe. Cell counts and a densitometric analysis of the immunoreactivity patterns were carried out for all hippocampal subfields. NMDAR1 and GluR2(4) levels were markedly reduced in patients with AHS, primarily in those subfields with substantial neuronal cell loss (in particular CA1, CA4 and CA3), compared to those seen in patients with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of the dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 showed no significant up-regulation in this sublayer. When the receptor staining intensity was normalized for alterations in neuronal density, no significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patients with chronic intractable TLE.

Catamenial seizures are defined as epileptic seizures occurring during distinct phases of the menstrual cycle (i.e., periovulatory, premenstrually and during menstruation). The cyclic changes of the gonadotropic hormones are thought to be the main cause of the seizures. This hypothesis is supported by results of animal experiments, which have shown oestrogens to increase neuronal excitability whereas progesterone lowered it. We investigated 21 women with epilepsy who reported a catamenial increase in seizure frequency. Only 24% of these women actually exhibited a catamenial manifestation in more than 75% of seizures. The incidence of catamenial seizures is reported in the literature to be between 10% and 72%. Catamenial seizures are treated with anticonvulsant drugs. However, when anticonvulsants have failed to suppress seizures, progesterone or progesterone-derivates have been administered with success. We treated 16 patients with a synthetic GnRH-analogue to suppress the hormonal release of gonadotropins. Four of the six patients with only catamenial seizure manifestations and no other seizures became seizure free. Ten patients had catamenial seizures as well as seizures not related to the menstrual cycle. A decrease in seizure frequency by more than 50% was achieved in 7 of these 10 patients.

The development of new antiepileptic drugs in recent years has enlarged the number of anticonvulsant compounds for the treatment of intractable focal epilepsies. The anticonvulsant potency of these drugs is usually compared by the number of patients who achieve a reduction in seizure frequency of more than 50%. Such an effect can be observed in approximately 20-30% of patients with pharmacoresistant focal epilepsies and is about the same with all the new compounds. In addition to the influence on focal seizures some of the novel anticonvulsant drugs exhibit efficacy in generalized seizures or in Lennox-Gastaut syndrome. In general there are fewer side effects in newly developed drugs than in standard anticonvulsants. However, in some cases characteristic side effects may occur: weight gain, depression or psychosis from vigabatrin; lamotrigine may provoke allergic rashes and felbamate may cause gastrointestinal side effects and sleeplessness. Apart from felbamate, there are no interactions with an antiepileptic comedication or they are of little importance. The development of the new anticonvulsants follows a rational design based on pathophysiological aspects: the main aim is to influence synaptic transmission, resulting in an increase in inhibitory and a decrease in excitatory transmitters. Thus, vigabatrin and tiagabine enhance the endogenous GABA amount, whereas felbamate and remacemide interact with the NMDA-receptor complex. Because it is not possible to draw sufficient conclusions from add-on studies in clinical testing it is necessary to establish new forms of trial design. Monotherapy designs are favored because they lack possible interactions with comedication and make the anticonvulsant efficacy of the compound better comparable to those of established anticonvulsants.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical application of technetium-99m bicisate (ethyl cysteinate dimer, ECD) for ictal and interictal studies of regional cerebral blood flow (rCBF) in a patient suffering from medically intractable simple and complex partial seizures is reported. The interictal study was performed 60 min p.i. and the ictal studies were performed at 60 min p.i. using an annular crystal single photon emission tomography (SPET) system dedicated for high-resolution brain SPET imaging. Visual evaluation of the studies was carried out, as well as semiquantitative measurement of regional tracer uptake. Magnetic resonance imaging (MRI) scans revealed atrophy of almost the complete left frontal lobe and the ventral parts of the left temporal lobe, including in part the temporomesial structures. The left parietal and occipital structures and the right hemisphere were normal. The interictal study showed a large perfusion defect involving the whole left frontal lobe as well as the left temporal lobe with remaining small areas of normal cortical tracer uptake. The ictal studies detected circumscribed hyperperfusion within the left mesial temporal lobe (ventral part of the hippocampus). Additionally an increase in perfusion could be seen within the entire remaining left temporal lobe. Semiquantitative evaluation of tracer uptake comparing both studies detected markedly increased uptake within the focus compared to the remaining left temporal lobe. On this basis the newly available tracer for studies of rCBF, 99mTc-bicisate, seems to be of value for the detection of epileptogenic foci. Additionally, the value of ictal rCBF studies in the presurgical evaluation of those patients presenting severe morphological alterations on MRI is clearly underlined by this case.

Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABAA receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the alpha 1 subunit of the GABAA receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABAA receptor immunoreactivity was present in CA1 (92.3%), CA4 (78.2%), the dentate granular cell layer (70.5%) and the molecular layer of the dentate gyrus (65.4%). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABAA receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABAA receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABAA receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.

Petechial eruptions may be the consequence of tonic-clonic seizures. Usually they are located on face, neck or breast. We report on a 25-year-old male patient suffering from unclassified seizures occurring at night. Seizure frequency was one a month over a six-month period. Following the seizures he regularly observed periocular petechial eruptions which disappeared within three days. EEG, MRI and laboratory investigations, including a hematological screening, were normal. We diagnosed an epileptic disorder and treated the patient with phenobarbitone. Within the next seven months he remained free of seizures. The petechial eruptions probably resulted from capillary bleedings during the tonic phase of a tonic-clonic seizure.

The most important causes of focal epilepsy are hippocampal sclerosis, circumscribed tumors, vascular malformations, trauma and perinatal damage. At the moment MRI is the best radiological imaging modality for localizing and characterizing a focus. In many cases, however, even MRI is negative. Especially in hippocampal sclerosis the diagnostic role of MRI is still not well established. Diagnostic criteria are side differences with hippocampal atrophy and circumscribed signal increase on T2-weighted images of the affected temporal lobe. Circumscribed lesions caused by tumors or vascular malformations are demonstrated very reliably by paracoronal T2-weighted sequences. Routine administration of the paramagnetic contrast material Gd-DTPA is not necessary.

Regional cerebral blood flow can be measured using single photon emission computed tomography (SPECT). Hexamethyl propyleneamine oxime (HMPAO) is commercially available as a 99mTc-labeled tracer and has the advantage of fixing a blood flow pattern during its first passage through the capillaries. This can be used, for example, to evaluate a short-term ictal phase. With dedicated SPECT systems a spatial resolution of 5-8 mm can be achieved. Measurement using 133Xe allows absolute quantification of blood flow values, but the spatial resolution is lower. In about 50-70% of patients suffering from temporal lobe epilepsy a decreased blood flow in the focus can be visualized in the interictal phase. Ictally, focal hyperperfusion can be observed in most cases. The sensitivity and specificity of SPECT in the ictal phase are superior compared with interictal study. During the postictal phase a hyperperfusion of the anterior and mesial parts of the affected temporal lobe with simultaneous lateral hypoperfusion can often be demonstrated. At present, receptor SPECT has not yet reached clinical significance in the diagnosis of epilepsy.

Epilepsy in childhood is often caused by morphological abnormalities and is frequently pharmacoresistant. Therefore it represents a challenge to the neuroradiologist because early and accurate diagnosis of abnormal morphology is the basis for planning surgical intervention with a high chance of controlling seizures and a low risk of complications. Both morphological (radiography, CT, MRI and angiography) and functional examinations [intracarotid amobarbital test (IAT)] are essential parts of the presurgical evaluation. In most cases MRI has proved to be most sensitive in detecting lesions except for some calcifications. Routine protocols for brain examinations are not sufficient, missing about 22% of lesions. Therefore a refined MRI and CT protocol is proposed. Even in very young children IAT can be performed at very low risk; these tests contribute highly valuable information about actual hemispheric dominance and other functions in more than 80% of procedures that is indispensable if postoperative neurological and neuropsychological deficits are to be avoided.

Twenty percent of the approximately 800,000 epileptic patients in Germany cannot be treated adequately by pharmacotherapy alone. According to conservative estimates, epilepsy surgery could be of fundamental therapeutic benefit to at least 10-25% of these patients. A complex presurgical diagnostic program is the basis for any epilepsy surgery. Numerous methods are used to create a hypothesis about the location and size of the epileptogenic area. In addition, before surgery is performed, it must be established that no additional serious neurological or neuropsychological deficits will result from the planned resection. For this purpose, electrostimulation of the cortex and temporary anaesthesia of brain areas by amobarbital tests are performed. In intractable epilepsy originating in the temporal lobe about 60% of patients become seizure free after surgery. Another 15-20% benefit from surgery by a significant improvement in their seizure situation. Resections of the dominant temporal lobe result in further impairment of memory functions in about 20-30% of patients.

Epileptic foci in the frontal or parieto-occipital cortex often cause epileptiform EEG changes in both hemispheres. Therefore, delineation of the primary epileptogenic area, which is necessary for epilepsy surgery, is not possible by electrophysiological methods. A temporary inactivation of the epileptogenic area by a selective injection of the short-acting barbiturate amobarbital (selective amobarbital test, SAT) can prove the relation between generalized EEG changes and a circumscribed epileptogenic area. The SAT may also be used for evaluation of the risk for additional functional deficits after epilepsy surgery in certain brain areas. During temporary inactivation of the brain area to be resected, the function of the motor system, speech and memory can be tested.

The technique of magnetic resonance spectroscopy fuses spectroscopic methods with the two-dimensional illustration of the metabolite concentrations by parallel acquisition of multiple single voxels from small tissue compartments. Therefore it is not necessary to define a voxel of interest before data acquisition. The interpretation of metabolite images is much easier than the analysis of single spectra, and metabolite concentrations on the right and left sides can be compared. The method has already proved reliable for brain tumors. The application of the procedure to patients suffering from epilepsy is described here in for the first time. Even in the temporal region, where most epileptogenic foci have their origin, one can obtain metabolite images of diagnostic quality without susceptibility artifacts. The epileptogenic focus is lateralized correctly, in accordance with electrophysiological and surgical evaluation, even in those cases where standard magnetic resonance imaging is normal. According to our preliminary findings the epileptogenic focus is characterized by a signal loss of N-acetyl-aspartate and creatine.

Subdural strip electrodes or intracerebral electrodes are required in order to precisely localize epileptic foci, which is mandatory for epilepsy surgery. The subdural electrodes are inserted via a borehole and thus precise positioning cannot be directly monitored. Therefore, the location of the electrodes in relation to the gyri and sulci has to be determined by imaging techniques. In this study, a three-dimensional magnetic resonance imaging (3D MRI) technique was used for visualization of intracranial EEG electrodes. A 3D gradient echo sequence with thin slices of 1 mm is required for the assessment of the gyral anatomy of the brain surface. Using a short repetition time of 30 ms good image quality within an acceptable acquisition time of about 15 min was possible. Post-processing with 3D surface reconstruction was performed using a Sun workstation. Three-dimensional reconstruction allows a more precise delineation of the localization of the EEG electrodes and the simultaneous display of the adjacent brain structures. Misplacement of intracranial electrodes is readily detected. 3D MRI with 3D surface reconstruction proved superior to 2D imaging and CT for the assessment of EEG electrode localization.

We present clinical, electrophysiological and neuropsychological data of a patient with an extraordinary type of frontal lobe epilepsy. In addition to complex partial and secondary generalized seizures the patient had 183 non-convulsive states per day. Chronical electrocorticography via subdural electrodes clearly revealed that the complex partial seizures and the secondary generalized seizures originated within the right frontal lobe. During the non-convulsive states a constantly increasing spike frequency which showed characteristics of secondary bilateral synchrony was noticed within both frontal lobes. After a period of 20-40 min a sudden transition into a clinically generalized seizure occurred. In contrast to the clinical generalization the onset of bilateral motor phenomena was paralleled by a "secondary focalisation" of the pre-existent high frequency interictal bifrontal epileptiform activity within the right frontal lobe.

The surgical treatment of chronic pharmacoresistant epilepsies is increasing rapidly. Although several studies have reported on histopathological findings in temporal lobe epilepsy, little is known about the surgical pathology of other seizure disorders. Here we report the histopathological findings in 63 consecutive surgical specimens of patients who were operated for chronic pharmacoresistant epileptic seizures other than temporal lobe epilepsy (37 corticectomies, 19 functional hemispherectomies, 5 lobectomies, 1 multilobectomy, and 1 frontal lobe deafferentiation combined with a temporal lobectomy). There were structural lesions in 85.7% of the specimens. In 16 cases (25.4%) the predominant lesions were malformative (focal glioneuronal hamartias and hamartomas, vascular malformations, abundant ectopic neurons in the white matter, microgyria, and arachnoid cyst). Lesions indicating pre- or perinatal necrosis such as porencephaly, ulegyria, and congenital hemiatrophy were present in 7 cases (11.1%). Twelve specimens (19.0%) contained low-grade neoplasms (7 gangliogliomas, 3 astrocytomas, 1 oligodendroglioma and 1 oligoastrocytoma). There were 3 cases of Rasmussen encephalitis, 1 specimen with atrophy and gliosis due to previous herpetic encephalitis and 1 case with an old abscess wall. Posttraumatic or postoperative changes were the predominant finding in 7 specimens (11.1%). In 7 patients there were only nonspecific changes such as cortical atrophy and gliosis or old hemorrhage. No structural alterations were identified in 9 specimens (14.3%). The findings suggest that the structural lesions observed in the great majority of the specimens were closely related to the pathogenesis of intractable seizures.

The neurosurgical treatment of therapy-resistent patients with epilepsy has gained a new and increasing interest in Germany over the recent years. In the context of the extensive, multidisciplinary preoperative work-up of these patients the neuropsychological and psychosocial evaluation has become more and more important. Therefore the aim of this article is to discuss in detail the relevance of these aspects for the selection of appropriate surgical candidates, their prognostic and localizing value as well as their importance for the control of the postoperative outcome.