Facial nerve function and hearing after microsurgical removal of sporadic vestibular schwannomas in a population-based cohort.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor originating from the vestibulocochlear nerve. The optimal treatment strategy is debated, since surgery may result in iatrogenic facial nerve injury. We report the results of VS surgery in a population-based unselected cohort in a center with access to Cyber Knife (CK) radiosurgery. METHODS: We reviewed 117 consecutive operations and found 95 patients who had their primary operation due to vestibular schwannoma between 2001 and 2017. Facial nerve function was evaluated with the House-Brackmann (HB) scale and hearing with the EU classification. RESULTS: The population consisted of 37 males and 58 females with a median age of 54 years (range 19-79). One year after surgery 67% of patients had a good outcome (HB 1-2). The rate of good outcome was 90% if no facial nerve damage was observed during intraoperative monitoring, the size of the tumor was under 30 mm and no hydrocephalus was present. During the study period, the treatment strategy changed from total to near-total resection after the introduction of CK radiosurgery, which could be used as a second-line treatment in case of residual tumor regrowth. This resulted in an improvement of outcomes (0% HB 5-6) despite the larger tumor sizes (25 ± 14 mm vs. 31 ± 9 mm, p < 0.05). Hearing preservation rates did not increase. CONCLUSIONS: Near-total resection and subsequent CK radiosurgery in case of residual tumor regrowth during follow-up seems to provide a good outcome of facial nerve function even in large VSs.

Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based Case-Control Study.

BACKGROUND AND PURPOSE: To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. METHODS: The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. RESULTS: The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2-3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. CONCLUSIONS: The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication.

MicroRNA-Attenuated Clone of Virulent Semliki Forest Virus Overcomes Antiviral Type I Interferon in Resistant Mouse CT-2A Glioma.

UNLABELLED: Glioblastoma is a terminal disease with no effective treatment currently available. Among the new therapy candidates are oncolytic viruses capable of selectively replicating in cancer cells, causing tumor lysis and inducing adaptive immune responses against the tumor. However, tumor antiviral responses, primarily mediated by type I interferon (IFN-I), remain a key problem that severely restricts viral replication and oncolysis. We show here that the Semliki Forest virus (SFV) strain SFV4, which causes lethal encephalitis in mice, is able to infect and replicate independent of the IFN-I defense in mouse glioblastoma cells and cell lines originating from primary human glioblastoma patient samples. The ability to tolerate IFN-I was retained in SFV4-miRT124 cells, a derivative cell line of strain SFV4 with a restricted capacity to replicate in neurons due to insertion of target sites for neuronal microRNA 124. The IFN-I tolerance was associated with the viral nsp3-nsp4 gene region and distinct from the genetic loci responsible for SFV neurovirulence. In contrast to the naturally attenuated strain SFV A7(74) and its derivatives, SFV4-miRT124 displayed increased oncolytic potency in CT-2A murine astrocytoma cells and in the human glioblastoma cell lines pretreated with IFN-I. Following a single intraperitoneal injection of SFV4-miRT124 into C57BL/6 mice bearing CT-2A orthotopic gliomas, the virus homed to the brain and was amplified in the tumor, resulting in significant tumor growth inhibition and improved survival. IMPORTANCE: Although progress has been made in development of replicative oncolytic viruses, information regarding their overall therapeutic potency in a clinical setting is still lacking. This could be at least partially dependent on the IFN-I sensitivity of the viruses used. Here, we show that the conditionally replicating SFV4-miRT124 virus shares the IFN-I tolerance of the pathogenic wild-type SFV, thereby allowing efficient targeting of a glioma that is refractory to naturally attenuated therapy vector strains sensitive to IFN-I. This is the first evidence of orthotopic syngeneic mouse glioma eradication following peripheral alphavirus administration. Our findings indicate a clear benefit in harnessing the wild-type virus replicative potency in development of next-generation oncolytic alphaviruses.

[Update on Current Care Guideline: epilepsies (adult]. / Epilepsiat (aikuiset).

First epileptic seizure is an indication for an urgent referral to a neurology care unit. Diagnosis of epilepsy is based on medical history and clinical examination, supplemented with MRI, EEG and laboratory tests. Exact diagnosis of the epilepsy type and etiology are the basis of the treatment. Patient education improves outcomes. The goal is complete long-term seizure control without significant adverse effects. Antiepileptic medication is usually initiated after the second epileptic seizure. If the patient does not respond to two appropriate drug schedules, patient should be evaluated for surgical treatment options.

Detection improvement of gliomas in hyperspectral imaging of protoporphyrin IX fluorescence - in vitro comparison of visual identification and machine thresholds.

BACKGROUND: 5-aminolevulinic acid (5-ALA) - precursor of protoporphyrin IX (PpIX) - is utilized in fluorescence guided surgery (FGS) of high-grade gliomas. PpIX is used to identify traces of glioma during resection. Visual inspection of the fluorescence seems inaccurate in comparison to optic techniques such as hyperspectral imaging (HSI). AIM: To characterize the limits of PpIX fluorescence detection of (i) visual evaluation and (ii) HSI analysis and to (iii) develop a classification system for visible and non-visible PpIX fluorescence. METHODS: Samples with increasing concentrations (C) of PpIX and non-fluorescent controls were evaluated using a surgical microscope under blue light illumination. Similar samples were imaged with a HSI system tuned to PpIX fluorescence peak wavelength (635 nm) and control (RGB) channels. Samples' intensities were defined, leading to 96 analysed pixels after batching. RESULTS: Three expert neurosurgeons assessed the PpIX samples (n = 16) and controls (n = 8) with unanimous decisions (ICC = 0.704), resulting in 63% recognition rate, 48% sensitivity, 92% specificity, 92% positive predictive value (PPV) and 47% negative predictive value (NPV). HSI image analysis, comparing mean relative values, resulted in 96%, 100%, 86%, 94%, 100%, respectively. Minimum PpIX concentration detection for experts was 0.6-1.8 µmol/l and HSI's 0.03-0.15 µmol/l. CONCLUSIONS: PpIX concentrations of low-grade gliomas, and those reported on glioblastoma infiltration zones, are below experts' detection threshold. HSI analysis exceeds the performance of expert's visual inspection nearly by 20-fold. Hybrid FGS-HSI systems should be investigated in parallel to long-term outcomes. Described methods are applicable as a standard for calibration, testing and development of subvisual FGS techniques.

Late-onset Rasmussen's encephalitis and long-term remission.

We describe an adult man with biopsy-proven Rasmussen's encephalitis and intractable epilepsy, who underwent excellent recovery. To our knowledge, this is the first report of a patient with Rasmussen's encephalitis who has become completely symptomless, at least for three years, on enhanced antiepileptic and immunological medication.

Lentivirus vector­mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain.

Translation of promising experimental therapies from rodent models to clinical success has been complicated as the novel therapies often fail in clinical trials. Existing rodent glioma models generally do not allow for preclinical evaluation of the efficiency of novel therapies in combination with surgical resection. Therefore, the aim of the present study was to develop a larger animal model utilizing lentivirus vector­mediated oncogenic transformation in the rabbit brain. Lentiviruses carrying constitutively active AKT and H­Ras oncogenes, and p53 small interfering (si)RNA were introduced into newborn rabbit neural stem cells (NSCs) and intracranially implanted into rabbits' brains to initiate tumor formation. In one of the ten rabbits a tumor was detected 48 days after the implantation of transduced NSCs. Histological features of the tumor mimic was similar to a benign Grade II ganglioglioma. Immunostaining demonstrated that the tissues were positive for AKT and H­Ras. Strong expression of GFAP and Ki­67 was also detected. Additionally, p53 expression was notably lower in the tumor area. The implantation of AKT, H­Ras and p53 siRNA transduced NSCs for tumor induction resulted in ganglioglioma formation. Despite the low frequency of tumor formation, this preliminary data provided a proof of principle that lentivirus vectors carrying oncogenes can be used for the generation of brain tumors in rabbits. Moreover, these results offer noteworthy insights into the pathogenesis of a rare brain tumor, ganglioglioma.

Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy.

PURPOSE: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long-term outcomes of consecutive true MRI-negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. METHODS: In this study we present all adult MRI-negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high-resolution MRI were included in this study. RESULTS: Among the 38 patients who finally underwent surgery, at the latest follow-up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure-free (Engel class IA). Twenty-one (55%) of 38 patients had poor outcomes (Engel class III-IV). Outcomes did not change compared to 12-month follow-up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR-negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). DISCUSSION: Our results suggest that epilepsy surgery outcomes in MRI-negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long-term also remain stable. Modern imaging techniques could further improve the postsurgical seizure-free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.

[Video-EEG in epilepsy diagnostics--when and why?]. / Video-EEG epilepsian diagnostiikassa--milloin ja miksi?

Video-EEG (V-EEG) refers to the recording of video picture simultaneously with EEG. A major part of epilepsy patients have to be diagnosed without V-EEG. For a patient having recurrent seizures, the aim is to accomplish V-EEG recording during a seizure. Of the indications of V-EEG, the most important one is diagnosis and differential diagnosis of epilepsy. V-EEG is able to differentiate epileptic seizures from cardiogenic seizures, motor disorders or functional seizures, for example. Essential clinical indications include a more exact classification of epilepsies, evaluation of therapeutic response, and localization of the seizure focus prior to epilepsy surgery.

Increased expression of caspase 2 in experimental and human temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is often caused by a neurodegenerative brain insult that triggers epileptogenesis, and eventually results in spontaneous seizures, i.e., epilepsy. Understanding the mechanisms of cell death is a key for designing new drug therapies for preventing the neurodegeneration associated with TLE. Here, we investigated the expression of caspase 2, a protein involved in programmed cell death, during the course of epilepsy. We investigated caspase 2 expression in hippocampal samples derived from patients operated on for drug refractory TLE. To understand the evolution of altered-caspase 2 expression during the epileptic process, we also examined caspase 2 expression and activity in the rat hippocampus after status epilepticus-induced acute damage, during epileptogenesis, and after the onset of epilepsy. Caspase 2 expression was enhanced in the hippocampal neurons in chronic TLE patients. In rats, status epilepticus-induced caspase 2 labeling paralleled the progression of neurodegeneration. Proteolytic activation and cleavage of caspase 2 was also detected in the rat brain undergoing epileptogenesis. Our data suggest that caspase 2-mediated programmed cell death participates in the seizure-induced degenerative process in experimental and human TLE.

Epilepsy-associated long-term mortality after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To elucidate the epilepsy-associated causes of death and subsequent excess long-term mortality among 12-month survivors of subarachnoid hemorrhage from saccular intracranial aneurysm (SIA-SAH). METHODS: The Kuopio SIA Database (kuopioneurosurgery.fi) includes all SIA-SAH patients admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The study cohort consists of 779 patients, admitted from 1995 to 2007, who were alive at 12 months after SIA-SAH. Their use of reimbursable antiepileptic drugs and the causes of death (ICD-10) were fused from the Finnish national registries from 1994 to 2014. RESULTS: The 779 12-month survivors were followed up until death (n = 197) or December 31, 2014, a median of 12.0 years after SIA-SAH. Epilepsy had been diagnosed in 121 (15%) patients after SIA-SAH, and 34/121 (28%) had died at the end of follow-up, with epilepsy as the immediate cause of death in 7/34 (21%). In the 779 patients alive at 12 months after SIA-SAH, epilepsy was an independent risk factor for mortality (hazard ratio 1.8, 95% confidence interval 1.1-3.0). CONCLUSIONS: Comorbid epilepsy in 12-month survivors of SIA-SAH is associated with increased risk of death in long-term follow-up. Survivors of SIA-SAH require long-term dedicated follow-up, including identification and effective treatment of comorbid epilepsy to prevent avoidable deaths.

Immunohistochemical Characterization and Sensitivity to Human Adenovirus Serotypes 3, 5, and 11p of New Cell Lines Derived from Human Diffuse Grade II to IV Gliomas.

BACKGROUND: Oncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes. METHODS: We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p. To gauge the impact of antiviral defenses, we also compared the infectivity of the oncolytic adenoviruses in interferon (IFN)-pretreated cells with IFN-sensitive Semliki Forest virus (SFV). RESULTS: Immunostaining revealed generally low expression of HAd5 receptor CAR in both primary tumors and derived cell lines. HAd11p receptor CD46 levels were maintained at moderate levels in both primary tumor samples and derived cell lines. HAd3 receptor DSG-2 was reduced in the cell lines compared to the tumors. Yet, at equal multiplicities of infection, the oncolytic potency of HAd5 in vitro in tumor-derived cells was comparable to HAd11p, whereas HAd3 lysed fewer cells than either of the other two HAd serotypes in 72 hours. IFN blocked replication of SFV, while HAds were rather unaffected. CONCLUSIONS: Adenovirus receptor levels on glioma-derived cell lines did not correlate with infection efficacy and may not be a relevant indicator of clinical oncolytic potency. Adenovirus receptor analysis should be preferentially performed on biopsies obtained perioperatively.

Case report: central neurocytoma with concomitant cerebral involvement by acute lymphatic leukemia.

Central neurocytomas are intraventricular tumors composed of round uniform cells. These tumors have usually favorable prognosis. Leukemic infiltrates are occasionally seen as a complication of acute lymphatic leukemia. This report describes a 7-year-old boy who was treated because of diagnosed lymphatic leukemia with central nervous system involvement and concomitant neurocytic tumor located in the fourth ventricle. These two entities might be problematic to differentiate from each other without proper histopathological examination.

Temporal anteroinferior encephalocele: An underrecognized etiology of temporal lobe epilepsy?

OBJECTIVE: To report the increasing frequency with which temporal anteroinferior encephalocele is a cause of adult temporal lobe epilepsy, to illustrate the clinical and imaging characteristics of this condition, and to report its surgical treatment in a series of 23 adult patients. METHODS: Epilepsy patients diagnosed with temporal anteroinferior encephalocele from January 2006 to December 2013 in a national epilepsy reference center were included in this noninterventional study. RESULTS: Twenty-three epilepsy patients (14 female, mean age 43.8 years) were diagnosed with temporal anteroinferior encephalocele in our institute. Thirteen patients had ≥2 encephaloceles; 7 cases presented bilaterally. The estimated frequency of this condition was 0.3% among MRI examinations performed due to newly diagnosed epilepsy (n = 6) and 1.9% among drug-resistant patients referred to our center (n = 17). Nine patients with local encephalocele disconnection (n = 4) or anterior temporal lobectomy and amygdalohippocampectomy (n = 5) have become seizure-free (Engel 1) for a mean 2.8 years (range 3 months-6.2 years) of follow-up. Three patients with local encephalocele disconnection were almost seizure-free or exhibited worthwhile improvement. Histologically, all 12 surgical patients had gliosis at the base of the encephalocele; some had cortical laminar disorganization (n = 5) or mild hippocampal degeneration (n = 1). CONCLUSIONS: The possibility of a temporal encephalocele should be considered when interpreting MRI examinations of patients with medically intractable focal epilepsy. These patients can significantly benefit from unitemporal epilepsy surgery, even in cases with bilateral encephaloceles.

Epilepsy after aneurysmal subarachnoid hemorrhage: A population-based, long-term follow-up study.

OBJECTIVE: The aim was to elucidate the incidence and risk factors of epilepsy after subarachnoid hemorrhage (SAH) from saccular intracranial aneurysm (sIA) in a population-based cohort. METHODS: The Kuopio sIA Database (www.uef.fi/ns) includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The use of prescribed medicines, including reimbursable antiepileptic drugs, has been entered from the Finnish national registries. The cumulative incidence and independent risk factors of epilepsy and death were analyzed in 876 patients with sIA-SAH admitted from 1995 to 2007. The competing risks analysis was used to correctly estimate the probability of epilepsy, because epilepsy and death after sIA-SAH may share risk factors. RESULTS: The follow-up ended at death (n = 200) or December 31, 2008; median follow-up time was 76 months. Epilepsy was diagnosed in 113 patients in a median of 8 months after sIA-SAH. Cumulative incidence of epilepsy after sIA-SAH was 8% at 1 year and 12% at 5 years. Thirty-three percent of patients with intracerebral hemorrhage (ICH) >15 cm(3) developed epilepsy. In the 876 patients with sIA-SAH, the independent risk factors for epilepsy were ICH >15 cm(3), Hunt and Hess grade III-V, and acute seizures. CONCLUSIONS: Cumulative incidence of epilepsy is 12% at 5 years. Epilepsy and 12-month mortality after sIA-SAH share poor Hunt and Hess grading as an independent risk factor. Epilepsy in the 2-week survivors of sIA-SAH is predicted by signs of primary injury in the brain tissue, most notably ICH.

Locating and Outlining the Cortical Motor Representation Areas of Facial Muscles With Navigated Transcranial Magnetic Stimulation.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) has become established as an accurate noninvasive technique for mapping the functional motor cortex for the representation areas of upper and lower limb muscles but not yet for facial musculature. OBJECTIVE: To characterize the applicability and clinical impact of using nTMS to map cortical motor areas of facial muscles in healthy volunteers and neurosurgical tumor patients. METHODS: Eight healthy volunteers and 12 patients with tumor were studied. The motor threshold (MT) was determined for the abductor pollicis brevis and mentalis muscles. The lateral part of the motor cortex was mapped with suprathreshold stimulation intensity, and motor evoked potentials were recorded from several facial muscles. The patient protocol was modified according to the clinical indication. RESULTS: In all healthy subjects, motor evoked potentials were elicited in the mentalis (mean latency, 13.4 milliseconds) and orbicularis oris (mean latency, 12.6 milliseconds) muscles. At 110% of MT of the mentalis, the motor evoked potentials of facial muscles were elicited mainly in the precentral gyrus but also from one gyrus anterior and posterior to it. The cortical areas applicable for mapping were limited by an artifact attributable to direct peripheral nerve stimulation. The mapping protocol was successful in 10 of 12 tumor patients at locating the representation area of the lower facial muscles. The MT of the facial muscles was significantly higher than that of the abductor pollicis brevis. CONCLUSION: nTMS is an applicable and clinically beneficial noninvasive method to preoperatively map the cortical representation areas of the facial muscles in the lower part of the face. Instead of using the MT of the abductor pollicis brevis, the stimulus intensity during mapping should be proportioned to the MT of a facial muscle.

3-D reconstructed magnetic resonance imaging in localization of subdural EEG electrodes. Case illustration.

We report an illustrative case of presurgical evaluation for epilepsy surgery, where the three-dimensional reconstructed magnetic resonance imaging played a pivotal role in determining the exact location of the subdural strip electrodes in temporomesial area. The tip of one the frontal strip electrodes was actually recording the temporopolar ictal activity. This contributed conclusively to the decision for surgical treatment and to the excellent outcome.

Long-term memory performance after surgical treatment of unilateral temporal lobe epilepsy (TLE).

Long-term cognitive and memory performance after surgical treatment of unilateral temporal lobe epilepsy (TLE) was investigated in a series of 98 patients. Neuropsychological evaluation was performed preoperatively and after one and three years postoperatively. Fifty-eight patients (59%) became seizure-free (Engel's class I). Verbal learning and memory declined in long-term follow-up in both left and right TLE groups. Visual memory remained stable. Ongoing postoperative seizures were related to decline in the immediate recall of logical prose, and postoperative seizure-freedom to improvement in verbal fluency in patients with left TLE. There was significant variability in the individual postoperative long-term memory performance. Left side of surgery, better baseline performance and older age at surgery were identified as risk factors for individual decline in delayed verbal memory. Selected patients undergoing surgery for drug-resistant TLE are at risk for significant postoperative memory decline especially after left temporal lobe surgery. Preoperative counseling and long-term follow-up of cognitive performance in individual patients is recommended. Additionally, more accurate predictors of individual postoperative memory performance would be needed.

Malignant giant cell tumor in the posterior fossa of a neonate.

Giant cell tumors (GCTs) of the bone are rare, usually benign but locally aggressive neoplasms that primarily occur in the epiphyses of long bones. They seldom develop in the cranium; when they do, they involve principally the sphenoid and temporal bones. These tumors usually affect young adults, and few reports in children have been published. Primary malignant GCTs of the skull are even more uncommon. The 3 published cases all involved adults over 40 years of age. Herein, the authors present a case of a highly aggressive primary malignant GCT of the posterior fossa in a 5-week old preterm infant. One month after the gross-total resection of the tumor found in the bone, the infant's condition rapidly deteriorated and she died. Magnetic resonance imaging and postmortem examination revealed a tumor larger than it had been before the operation, with expansion toward the brain. To the best of the authors' knowledge, this is the youngest patient reported with a primary malignant GCT of the skull, and actually the first case in a pediatric patient. In addition, the extremely high growth rate of the tumor in the postoperative period renders this case the most aggressive primary malignant GCT of the cranium described so far.

Non-invasive preoperative localization of primary motor cortex in epilepsy surgery by navigated transcranial magnetic stimulation.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive method to localize the primary motor cortex (M1). OBJECTIVE/HYPOTHESIS: To assess the safety and feasibility of nTMS as a non-invasive preoperative mode of functional localization of M1 in epilepsy surgery candidates with intractable focal epilepsy due to lesions in the vicinity of M1. METHODS: We mapped the muscle representation areas of M1 with nTMS in 10 patients (age 2 to 55 years) with intractable epilepsy. The lesions were focal cortical dysplasia (n=6), ganglioglioma (n=2) polymicrogyria (n=1) or dysembryoblastic neuroepithelial tumour (n=1). The optimal stimulation sites and motor threshold (MT) of the distal hand or leg muscles were determined in both hemispheres. Cortical areas were mapped with stimulation intensities 100-120% of the MT to localize functional M1. Patients were on their stabile antiepileptic medication, and EEG was continuously monitored. The clinical benefit obtained with the preoperative nTMS mapping in the surgical decision making was scored as (1) essential, (2) beneficial, or (3) not beneficial, depending mainly on the difference between the functional and the presumed anatomic M1. RESULTS: The M1 was successfully assessed in all but the 2 youngest patients (aged 2 and 5 years), in whom nTMS was unable to elicit motor responses. nTMS was regarded as essential or beneficial in the localization of M1 in relation to the lesions in 6 out of 10 cases. The optimal motor representation areas were mainly located symmetrically on the precentral gyrus, and corresponded to the presumed location of M1 in MRI. No clinical or EEG evidence of acute epileptogenic adverse effects were observed during the localization procedure. None of the operated patients developed post-operative motor deficits. CONCLUSIONS: nTMS is a safe and feasible clinical tool for the non-invasive preoperative localization of motor cortex in patients with intractable epilepsy due to focal lesions adjacent or within the presumed M1 in MRI.