Enhanced Electric Dipole Strength for the Weakly Bound States in

An enhanced low-energy electric dipole (E1) strength is identified for the weakly bound excited states of the neutron-rich isotope ^{27}Ne. The Doppler-shift lifetime measurements employing a combination of the γ-ray tracking array GRETINA, the plunger device, and the S800 spectrograph determine the lower limit of 0.030 e^{2} fm^{2} or 0.052 W.u. for the 1/2^{+}→3/2^{-} E1 transition in ^{27}Ne, representing one of the strongest E1 strengths observed among the bound discrete states in this mass region. This value is at least 30 times larger than that measured for the 3/2^{-} decay to the 3/2_{gs}^{+} ground state. A comparison of the present results to large-scale shell-model calculations points to an important role of core excitations and deformation in the observed E1 enhancement, suggesting a novel example of the electric dipole modes manifested in weakly bound deformed systems.

Quasifree (p, 2p) Reactions on Oxygen Isotopes: Observation of Isospin Independence of the Reduced Single-Particle Strength.

Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R^{3}B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type ^{A}O(p,2p)^{A-1}N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.

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.

Early diffusion-weighted MRI predicts regional neuronal damage in generalized status epilepticus in rats treated with diazepam.

We applied diffusion-weighted MRI (DWI) in the pilocarpine-induced status epilepticus (SE) model to investigate the evolution of acute phase changes in brain diffusion with and without early anticonvulsive therapy correlated to long-term SE-induced neuronal cell loss. Hereby, DWI was performed before (baseline) and serially between 3 and 120 min after onset of SE in untreated and treated animals (n=15 in each group). Anticonvulsive-treated animals received 20 mg/kg diazepam at 15 min after onset of SE. Apparent diffusion coefficients (ADC) were calculated for the parietal, temporal and piriform cortex, thalamus, hippocampus and amygdala and compared to baseline. Neuronal cell loss was quantified at 2 weeks after onset of SE utilizing cresyle-violet-staining. The results of ADC-mapping demonstrated a significant transient increase in ADC (to 116+/-4% of baseline) in the very acute phase starting 3 min after SE onset, lasting for 10 min in both groups. In untreated animals, there was a significant gradual decline in ADC to 75+/-12% of baseline while this decline in diazepam-treated animals was significantly less pronounced (P<0.05) and ADC recovered to 93+/-6% of baseline. There was good correlation between neuronal cell loss in specific brain regions at 2 weeks after SE and maximal decrease in ADC (r>0.79). In conclusion, serial DWI is a sensitive noninvasive technique for early detection, monitoring and prediction of SE-induced neuronal alterations. Using ADC-mapping, verification of early anticonvulsive therapy in SE seems to be possible as there is good correlation between the maximal decrease in ACD in the acute phase of SE and late neuronal cell loss.

Monitoring of acute generalized status epilepticus using multilocal diffusion MR imaging: early prediction of regional neuronal damage.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging (DWI) has emerged as tool for noninvasive and early detection of neuronal alterations. The aim of this study was to investigate the evolution of acute phase changes in different brain regions during experimental status epilepticus (SE) using DWI correlated with SE-induced neuronal cell loss. METHODS: DWI was performed in 20 rats before (baseline) and 3, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes after onset of pilocarpine-induced SE. Apparent diffusion coefficients (ADCs) were calculated for the parietal cortex, temporal cortex, pyriform cortex, hippocampus, amygdala, and thalamus and compared with baseline. Neuronal cell loss was quantified at different time points after SE using cresyl-violet-staining. RESULTS: ADC-mapping demonstrated a significant transient increase in ADC (to 116 +/- 4% of baseline) in the very acute phase, starting 3 minutes after SE onset, lasting for 10 minutes, followed by a significant gradual decline in ADC in all animals. Compared with surviving animals (76 +/- 7%), decline in ADC was significantly lower for the animals who died within 2 hours for all regions of interest (63 +/- 6.5%, 0.45 +/- 0.03 x 10(-3) mm(2)/s) except the thalamus (P < .01, analysis of variance). There was good correlation between neuronal cell loss in specific brain regions 2 weeks after SE and maximal decrease in ADC (r > 0.76). CONCLUSION: Serial ultrafast DWI is a sensitive noninvasive technique for early detection and monitoring of seizure-induced neuronal alterations. Using ADC-mapping differentiation of regional severity of neuronal damage may be possible because there is good correlation between the maximal decrease in ADC in the acute phase of SE and late neuronal cell loss.

Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study.

Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR alpha4 or beta2 subunit, which together compose the main cerebral nAChR. Electrophysiological assessment using in vitro expression systems indicated a gain of function of the mutant receptors. However the precise mechanisms by which they contribute to the pathogenesis of a focal epilepsy remain obscure, especially since alpha4beta2 nAChRs are known to be widely distributed within the entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the alpha4beta2 nAChRs, allows the determination of the regional distribution and density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering a unique opportunity to investigate some in vivo consequences of the molecular defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients (from five families) bearing an identified mutation in nAChRs and in seven age-matched non-smoking healthy volunteers using PET and [(18)F]-F-A-85380. Parametric images of volume of distribution (Vd) were generated as the ratio of tissue to plasma radioactivities. The images showed a clear difference in the pattern of the nAChR density in the brains of the patients compared to the healthy volunteers. Vd values revealed a significant increase (between 12 and 21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the cerebellum when compared to control subjects. Statistical parametric mapping (SPM) was then used to better analyse subtle regional differences. This analysis confirmed clear regional differences between patients and controls: patients had increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum, but decreased nAChR density in the right dorsolateral prefrontal region. In five patients who underwent an additional [(18)F]-fluorodeoxyglucose (FDG) PET experiment, hypometabolism was observed in the neighbouring area of the right orbitofrontal cortex. The demonstration of a regional nAChR density decrease in the prefrontal cortex, despite the known distribution of these receptors throughout the cerebral cortex, is consistent with a focal epilepsy involving the frontal lobe. We also propose that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousal.

The AP-1 transcription factor FOSL1 causes melanocyte reprogramming and transformation.

The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown. Here, we show that FOSL1 is the main immediate early AP-1 member induced by melanoma oncogenes. We first examined its role in established melanoma cells. We found that FOSL1 is involved in melanoma cell migration as well as cell proliferation and anoikis-independent growth, which is mediated by the gene product of its target gene HMGA1, encoding a multipotent chromatin modifier. As FOSL1 expression is increased in patient melanoma samples compared to nevi, we investigated the effect of enhanced FOSL1 expression on melanocytes. Intriguingly, we found that FOSL1 acts oncogenic and transforms melanocytes, enabling subcutaneous tumor growth in vivo. During the process of transformation, FOSL1 reprogrammed the melanocytes and downregulated MITF in a HMGA1-dependent manner. At the same time, AXL was upregulated, leading to a shift in the MITF/AXL balance. Furthermore, FOSL1 re-enforced pro-tumorigenic transcription factors MYC, E2F3 and AP-1. Together, this led to the enhancement of several growth-promoting processes, such as ribosome biogenesis, cellular detachment and pyrimidine metabolism. Overall, we demonstrate that FOSL1 is a novel reprogramming factor for melanocytes with potent tumor transformation potential.

Cerebral perfusion alterations during the acute phase of experimental generalized status epilepticus: prediction of survival by using perfusion-weighted MR imaging and histopathology.

BACKGROUND AND PURPOSE: Persistent generalized status epilepticus (SE) is associated with alterations of cerebral perfusion (CP). Because perfusion-weighted MR imaging (PWI) allows noninvasive CP-determination, the aim of this study was to investigate CP alterations during acute experimental SE correlated with SE-induced neuronal cell loss. METHODS: The rat pilocarpine model was used to induce SE. Multilocal PWI was performed before (baseline) and 3, 15, 30, 60, and 120 minutes after onset of SE. Bolus-peak ratio (BPR) was calculated for the retrosplenial and piriform cortex, hippocampus, amygdala, and thalamus and compared with baseline. Neuronal cell loss was quantified at different time points after induction of SE by cresyle violet staining. RESULTS: Immediately after SE onset (3 minutes), BPR temporarily increased to 102%-130% in all regions, with a maximum in the amygdala (129 +/- 16%) and hippocampus (130 +/- 21%). At 15, 30, and 60 minutes, BPR decreased continuously to 57%-76%. BPR values <55% in the parietal and/or temporal cortex resulted in death. In surviving animals, BPR recovered to 66%-79% and there was a good correlation between neuronal cell loss in specific brain regions at 2 weeks after SE onset and maximal decrease in BPR (r > 0.73). CONCLUSION: PWI demonstrated a transient cerebral hyperperfusion immediately after SE onset, followed by a significant continuous decline to different perfusion levels. In our experimental setting, a decline of cortical BPR below 55% of baseline seems to be a prognostic threshold value associated with subsequent death. In surviving animals, there is good correlation between the maximal decrease in BPR in the acute phase of SE and late neuronal cell loss.

MRI changes associated with partial status epilepticus.

Neurological disorders of different etiology may cause identical clinical symptoms requiring additional diagnostic procedures for a precise differential diagnosis. Focal epileptic seizures have been shown to cause increased signal intensities in T2 and diffusion-weighted magnetic resonance images (MRI), mimicking other neurological disorders or diseases such as viral encephalitis. In some cases even the combination of neuroimaging and cerebrospinal fluid (CSF) analysis is not sufficient to obtain the final diagnosis, since epileptic seizures may cause pleocytosis as well. Some epilepsy centers presented cases of focal status epilepticus with severe but reversible MRI changes. These cases indicate that MRI-changes following focal seizures are reversible over a different time window compared to MRI changes associated with other etiologies, such as viral infection. This data further suggest that in cases where focal seizures can not be ruled out, a follow-up MRI scan within a few days following the onset of symptoms significantly improves the precision of the differential diagnosis. Recently new scientific data were reported in this review.

In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells.

Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS(61K) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.

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.

Surgical pathology of temporal lobe epilepsy. Experience with 216 cases.

The surgical treatment of chronic epilepsies is increasing rapidly. Here we report the histopathologic findings in 216 consecutive surgical specimens of patients with chronic pharmacoresistant temporal lobe epilepsy. In 75 cases (34.7%) there were tumors, all but two of which were of low histopathological grade (WHO grade I or II). The most common tumors were gangliogliomas (34 cases), pilocytic astrocytomas (17 cases), oligodendrogliomas (9 cases), fibrillary astrocytomas (6 cases), and dysembryoplastic neuroepithelial tumors (6 cases). There were 51 cases with non-neoplastic focal lesions and an additional 13 cases with tumors and non-neoplastic focal lesions within the same specimen. The most frequent non-neoplastic focal lesions were microscopic glioneuronal hamartias (32 cases), glioneuronal hamartomas (7 cases), and vascular malformations (13 cases). The hippocampal formation was structurally well preserved in 71 specimens. In 51 of these (71.8%) there was Ammon's horn sclerosis. Presurgical placement of depth electrodes was invariably associated with circumscribed defects of the brain parenchyma. The implantation of subdural electrodes was sometimes followed by chronic inflammatory changes of the leptomeninges. Our findings indicate that in the majority of patients with medically intractable temporal lobe epilepsy there are significant histopathologic findings, many of which are only rarely encountered otherwise.

Anticonvulsant drugs affect particular steps of verbal memory processing--an evaluation of 13 patients with intractable complex partial seizures of left temporal lobe origin.

Thirteen patients with intractable complex partial seizures of left temporal lobe origin were tested for verbal memory performance under the conditions of full and reduced anticonvulsant medication. As suggested by previous investigations memory performance improved significantly with the reduction of anticonvulsants. However, our observations refute assumptions that the effects of antiepileptic drugs act primarily by non-specific mechanisms affecting attention and/or memory diffusely. Our data rather suggest that very specific and circumscribed steps of verbal memory processing, particularly retrieval abilities after interference, are affected by anticonvulsants. The possible implications of these findings in relation to morphological and electrophysiological aspects in patients with temporal lobe epilepsy are discussed.

Verbal working memory components can be selectively influenced by transcranial magnetic stimulation in patients with left temporal lobe epilepsy.

The aim of this study was to investigate whether transcranial magnetic stimulation (TMS) can be used for a lateralization of verbal and non-verbal memory functions in candidates for epilepsy surgery by inducing focal, material-specific memory deficits. Twenty patients who underwent presurgical epilepsy evaluation with chronically implanted subdural strip electrodes were submitted to focal TMS over the temporal lobes and the vertex while sequences of items of the Digit Span and the Corsi Block test were presented on a computer screen. TMS was applied synchronously or 200 msec following presentation of each item. The effects of TMS on the memory span and the serial position curve were analysed in comparison to baseline levels. The following results were obtained: the quantitative effects on the verbal (Digit Span) and non-verbal (Corsi Block) memory span were not significant, but there were significant qualitative changes of serial position effects. In the group of six patients with left temporal epilepsy, TMS over the left temporal lobe induced a significant recency effect in the Digit Span test, while TMS over the vertex significantly increased the recency errors. The absolute number of errors remained unchanged. No such effects were observed in the group of nine patients with right temporal lobe epilepsy. These results suggest that in the presence of a left temporal lobe focus TMS can induce qualitative, material specific changes in verbal working memory (phonological loop) which become apparent in the serial position curve. The dissociation of TMS effects for temporal and vertex stimulation imply that TMS can selectively influence specific phonological loop components and that the phonological loop has a functionally and neuroanatomically multimodular structure.

Increased technetium-99m-HMPAO uptake in grade II astrocytoma.

Most brain tumors show decreased uptake of blood flow tracers in brain SPECT imaging and in some cases meningiomas show increased uptake, mainly associated with high regional blood flow values. A reason for regionally increased tracer uptake is partial epilepsy when a tracer is injected during the ictal phase. We present a case of a histologically proven Grade II astrocytoma in the mesial part of the left temporal lobe that caused complex partial seizures. After tracer injection during a phase without signs of clinical seizure, markedly increased uptake of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) occurred, although the tumor was partially calcified.

Evaluation of technetium-99m-ECD in childhood epilepsy.

UNLABELLED: In childhood epilepsy, it is difficult, but of critical importance, to determine whether surgical intervention might be beneficial for an individual patient. Because both established procedures-MRI and electroencephalography (EEG)-have limitations, interictal and ictal regional cerebral blood flow (rCBF) SPECT has proven to be a valuable adjunctive method in the presurgical evaluation of children. METHODS: We evaluated the usefulness of the new rCBF tracer 99mTc-ECD in 14 children with focal epilepsy (mean age 9.7 yr). Eleven interictal and 8 ictal studies were performed. Results were correlated with ictal and interictal surface EEG, MRI and histological findings and the postsurgical outcome. RESULTS: On the basis of the presurgical evaluation, nine patients underwent surgery. MRI studies demonstrated pathological features with possible relation to epilepsy in 50%. Overall, interictal 99mTc-ECD SPECT showed areas of hypoperfusion in 80% of patients. Ictal rCBF SPECT was informative in all patients, including one who showed bifrontal hyperperfusion in accordance with EEG results. CONCLUSION: Technetium-99m-ECD has proven to be of value for interictal and ictal rCBF SPECT in childhood epilepsy. No side effects during or after tracer administration were noticed. Ictal and interictal rCBF SPECT showed good correlation with MRI and EEG results in patients in whom correlation with the postoperative situation was possible and presented additional significant information in those patients with normal MRI and uninterpretable EEG results. No false lateralizations occurred. In children with focal epilepsy, interictal rCBF SPECT may accelerate the application of long-term electrocorticography (ECoG) in patients with normal MRI results. Ictal rCBF SPECT may also help to avoid ECoG, if a focal hyperperfusion correlates with a focal MRI abnormality, and the surface EEG gives no contradictory information.

Ictal and interictal brain SPECT imaging in epilepsy using technetium-99m-ECD.

UNLABELLED: The aim of this study was to evaluate the use of 99mTc-ethyl cysteinate dimer (ECD), also known as 99mTc-bicisate, in the presurgical evaluation of patients suffering from medically intractable epilepsy. METHODS: Twenty-three brain SPECT studies (8 ictally and 15 interictally) were performed on 16 patients with a high-resolution annular SPECT system (CERASPECT). For the ictal studies, the tracer was injected in the very early phase of the seizure. The delay between seizure onset and 99mTc-ECD injection was 2-20 sec. RESULTS: Interictally, all patients showed circumscribed hypoperfusions. In four patients, the SPECT lesion represented only structural defects. Circumscribed increased tracer uptake was observed in all ictal studies. For all patients with temporal lobe epilepsy without significant mass lesion, in whom an interictal and ictal 99mTc-ECD-SPECT study could be obtained, the asymmetry index was 0.88 +/- 0.03 for the interictal and 1.23 +/- 0.08 for the ictal studies. CONCLUSION: The data suggest that 99mTc-ECD is an effective marker of cerebral perfusion imaging in epilepsy. In comparison to other tracers, it has a high in vitro stability and is therefore particularly useful for ictal studies in the very early phase after seizure onset.

Short-term memory: no evidence of effect of rapid-repetitive transcranial magnetic stimulation in healthy individuals.

The effect of rapid-repetitive transcranial magnetic stimulation (rr-TMS) on the immediate verbal and visuospatial memory span was assessed by computerized neuropsychological testing in 11 healthy volunteers. The objective was to test whether rr-TMS may be utilized as a non-invasive tool for evaluation of memory function. The subjects had to memorize series of numbers (Digit-Span test) or the position of cubes (Corsi-Block test) shown to them on a computer screen and actively reproduce them immediately after the presentation. Synchronous with the appearance of each item an rr-TMS train of 550 ms duration was delivered to the left or right anterolateral parietal as well as superior and posterior lateral temporal region at 50 Hz and with approximately 1.0 T stimulation intensity. Statistical comparison of memory performance during rr-TMS and baseline testings without stimulation revealed no significant changes. No adverse effects were observed. Thus, rr-TMS does not affect short-term memory performance in healthy individuals under the stimulation conditions described above.

Transcranial magnetic stimulation: specific and non-specific facilitation of magnetic motor evoked potentials.

Different physiological mechanisms of facilitation of latencies and amplitudes of magnetic motor evoked potentials (MEPs) were evaluated in a cohort of 140 healthy volunteers. The potentials were induced at the vertex and recorded at the abductor pollicis brevis. The aim of the present investigation was to compare physiological mechanisms which presumably facilitate motor pathways at the cortical level with those known to occur during contraction of small hand muscles. When compared with MEPs at rest, the maximum average decrease of latencies (1.5, SD 1.1 ms) as well as the highest increase of peak to peak amplitudes (2.6, SD 2.1 mV) was observed during exertion of a voluntary background force, at the muscle recorded from. Pre-innervation of a neighbouring muscle (abductor digiti minimi) led to a lesser average decrease of latencies by 1.0, SD 1.1 ms and an average increase of amplitudes by only 0.5, SD 1.5 mV. Non-specific manoeuvres, like sticking out the tongue or counting aloud, reduced mean latencies slightly by 0.4 ms, SD 0.8 ms and 0.3 SD 0.85 ms respectively, but increased amplitudes markedly by an average of 1.0, SD 1.6 mV and 0.8, SD 1.4 mV respectively. It is concluded that facilitation of MEPs by non-specific manoeuvres occurs and must be taken into account when evaluating MEPs.

Activation of epileptic foci by transcranial magnetic stimulation: effects on secretion of prolactin and luteinizing hormone.

Transient elevation of serum levels of prolactin has been observed following several types of epileptic seizures and after electrical stimulation of limbic temporal lobe structures via implanted electrodes. Transcranial magnetic stimulation has been found to selectively induce epileptiform afterdischarges in the epileptic focus of candidates for epilepsy surgery who suffered from temporal lobe epilepsy. Lateralized serial transcranial magnetic stimulation was therefore used and serum levels of prolactin or luteinizing hormone were measured to find if it could be used as a non-invasive diagnostic tool. The investigation was performed on six patients and five healthy volunteers. In the patients the induction of epileptiform potentials was continuously monitored via subdural electrodes. A transient surge of prolactin and luteinizing hormone was found in only one patient, in whom a complex partial seizure was induced. Thus, transcranial magnetic stimulation appeared not to be helpful for the lateralization of the (primary) epileptic focus during presurgical evaluation.