FLASH radiotherapy for the treatment of symptomatic bone metastases in the thorax (FAST-02): protocol for a prospective study of a novel radiotherapy approach.

BACKGROUND: FLASH therapy is a treatment technique in which radiation is delivered at ultra-high dose rates (≥ 40 Gy/s). The first-in-human FAST-01 clinical trial demonstrated the clinical feasibility of proton FLASH in the treatment of extremity bone metastases. The objectives of this investigation are to assess the toxicities of treatment and pain relief in study participants with painful thoracic bone metastases treated with FLASH radiotherapy, as well as workflow metrics in a clinical setting. METHODS: This single-arm clinical trial is being conducted under an FDA investigational device exemption (IDE) approved for 10 patients with 1-3 painful bone metastases in the thorax, excluding bone metastases in the spine. Treatment will be 8 Gy in a single fraction administered at ≥ 40 Gy/s on a FLASH-enabled proton therapy system delivering a single transmission proton beam. Primary study endpoints are efficacy (pain relief) and safety. Patient questionnaires evaluating pain flare at the treatment site will be completed for 10 consecutive days post-RT. Pain response and adverse events (AEs) will be evaluated on the day of treatment and on day 7, day 15, months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter. The outcomes for clinical workflow feasibility are the occurrence of any device issues as well as time on the treatment table. DISCUSSION: This prospective clinical trial will provide clinical data for evaluating the efficacy and safety of proton FLASH for palliation of bony metastases in the thorax. Positive findings will support the further exploration of FLASH radiation for other clinical indications including patient populations treated with curative intent. REGISTRATION: ClinicalTrials.gov NCT05524064.

Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

A case of epilepsia partialis continua of abdominal muscles after brain tumor surgery.

Epilepsia partialis continua (EPC) is a rare form of focal motor status epilepticus characterized by continuous muscular twitches or jerks involving a limited part of the body, usually facial region and distal limb. Although the cerebrovascular disease is known to be one of the most common causes of this condition, other reported cases with predominant abdominal involvement have different aetiologies, including, tumors, focal cortical dysplasia, and central nervous system infections. No cases of epilepsia partialis continua of the abdominal wall occurred after brain surgery have been previously reported. We describe the clinical, electrophysiological, and neuroimaging findings in an adult patient presenting with persistent unilateral abdominal myoclonus configuring an EPC as the evolution of a super-refractory hemibody convulsive status epilepticus, occurred after brain tumor surgery.

Subacute cerebellar ataxia as presenting symptom of systemic lupus erythematosus.

Neuropsychiatric manifestations are commonly observed in systemic lupus erythematosus (SLE) patients. In particular, neurological involvement is known to be more common in patients with positive anticardiolipin antibodies and lupus anticoagulants. Nevertheless, cerebellar ataxia has rarely been reported, especially as the first clinical manifestation of this systemic autoimmune disorder. Cerebral vascular infarction or ischemia, vasogenic oedema and antibody-mediated cerebral vasculopathy or vasculitic process have been supposed as possible aetiologies of acute cerebellar ataxia related to SLE. We report the clinical and radiological features of a woman who developed a rapidly progressive cerebellar syndrome as first sign of SLE; no other cause explaining her cerebellar ataxia was found. The patient improved after high-dose steroids. The appearance of a cerebellar syndrome with unknown aetiology with associated features of possible systemic autoimmune dysfunction, should be taken into account in clinical practice for appropriate diagnostic workup in order to provide effective therapeutic options.

Vagal Nerve Stimulation for Drug-Resistant Epilepsy: Adverse Events and Outcome in a Series of Patients with Long-Term Follow-Up.

BACKGROUND: Vagal nerve stimulation (VNS) is a palliative treatment option for drug-resistant epilepsy. The aim of this study was to describe the clinical and demographic features of selected patients scheduled for VNS and to evaluate the long-term efficacy of VNS in seizure control. MATERIALS AND METHODS: Between 2006 and 2013, 32 consecutive epileptic patients (14 male and 18 female) were enrolled at our Institute for VNS implantation. In all cases resective surgery had previously been excluded by the use of a noninvasive presurgical study protocol. Mean age was 32 years (range 18-50), and mean epilepsy duration 23 years (range 11-39). All subjects were followed-up for at least 2 years (mean 6 years, range 2-9) after VNS implantation. Patients were considered responders when a reduction of seizures of more than 50 % was reported. RESULTS: All patients had complex partial seizures, in 81 % of the patients with secondary generalization and in 56 % with drop attacks. Neurological examination revealed focal deficits in 19 % of the patients. Brain magnetic resonance imaging (MRI) was positive in 47 % of the patients. No surgical complications were observed in this series. Three patients were lost to follow-up. Twelve patients were classified as responders. Among the others, 1 patient experienced side effects (snoring and groaning during sleep) and the device was removed. CONCLUSIONS: Our data confirm that VNS is a safe procedure and a valid palliative treatment option for drug-resistant epileptic patients not suitable for resective surgery.

SU-E-T-127: Feasibility Study for Using a 2D Array Detector for All Beam Measurements in Monthly Quality Assurance Procedure for a Uniform Scanning Proton Therapy System.

PURPOSE: To develop a more efficient monthly quality assurance (QA) process by utilizing one detector with multiple setups instead of multiple detectors with multiple setups. METHOD: The Sun Nuclear IC Profiler was used to measure machine output, transverse profiles, and depth-dose profiles. The IC Profiler contains 251 ionization chambers aligned in the X, Y, and diagonal axes, and was designed to measure machine output and transverse profiles. In order to measure depth-doses, a Lucite compensator with an angled surface was fabricated. To test the capability of the detector, a proton beam of 10.5 cm range in water was used. The distal edge coincided with the overall water equivalent depth upstream of the detector on central axis. The measurement was repeated with an additional 1.0 mm of solid water placed in front of the detector. The measured profiles from both measurements were compared to quantify the IC Profiler response for a small range change. RESULTS: The IC Profiler performs within vendor specification for measuring machine output and transverse profiles. When measuring depth-doses with an angled compensator, the IC profiler measures a change in profile along central axis of 17.0% for a 1.0mm range change. Based on overall reproducibility of the beam delivery system, the IC profiler is capable of detecting 0.3 mm range shift. Therefore, the sensivity of the IC profiler response is suffficient to detect sub millimeter changes in delivered range. CONCLUSION: The Sun Nuclear IC Profiler is capable of measuring machine output, transverse profiles, and depth-dose profile constancy with a high degree of accuracy and precision. Using a single detector for all beam measurements increases the overall QA efficiency by reducing multiple detector overhead while not sacrificing the accuracy and precision of the measurements.

SU-E-T-301: A Novel Daily QA Device for Proton Therapy.

PURPOSE: We describe the design and use of a daily QA device for proton therapy. The device is designed for therapists to check the readiness of the IBA Proton Therapy System (IBA, Louvain-la-Neuve, Belgium) during morning QA. The checks include connectivity, positioning, mechanical, imaging and dosimetric parameters of the proton therapy system. METHODS: The device consists of a commercial QA device, (rf-DailyQA3 -Sun Nuclear Corporation, Melbourne, FL), in conjunction with a home-made acrylic phantom and mechanical indexing jig. The indexing jig indexes the rf-DailyQA3 to treatment couch. Fiducial markers embedded in the phantom are used for checking the x-ray image and alignment accuracy of the imaging system (VeriSuite, MedCom, Darmstadt- Germany). The rf- DailyQA3 is used to check the proton beam output, range and symmetry, which are acquired during one single beam delivery of 100 monitor units. We developed in-house software to calculate the variation of beam range and symmetry, based on readings from the various ion chambers inside the rf-DailyQA3. RESULTS: The device has been employed to perform daily QA since June 2010 at two operational proton treatment centers and will soon be implemented at ProCure's New Jersey center. All QA tests are performed by radiation therapists and reviewed by the medical physicist on duty. Due to the simplicity of the device and the associated processing software, the QA time is less than 20 minutes per room. The measurement data collected by the device during daily QA are recorded in the OIS. The integrity of the data is validated by comparing against other independent measurements. CONCLUSIONS: The daily QA device has been proven to be robust, reliable and user-friendly. The performance of this system has been proven to be stable and accurate using trend analyses. Key words:proton therapy, daily QA, output, range, symmetry.

MO-A-213AB-03: Commissioning of a Clinical Chair for Patients Treated in the Seated Position Using an Inclined Beam Line Treatment Room.

PURPOSES: A chair, coupled to a robotic patient positioning system (PPS) was manufactured to treat an intracranial tumor in a proton incline beam-line system. Treating patients in the seated position as accurately and efficiently as a treatment table requires the essential functions of isocentric rotation and a weight-sagging-correction algorithm for positioning patients in the seated position. METHODS AND MATERIALS: The chair design incorporated a down-slope arm to achieve the desired beam-line height. To overcome this limitation of only 125 degree rotation on PPS, five indexed positions of the seat-base-plate (SBP) were implemented. An in-house developed optical tracking system using a six degree-of-freedom optical camera system was used to align the treatment room coordinate system with the chair coordinate system at all SBP positions. Furthermore, this optical tracking system quantified the sagging effect due to both the height and weight of a variety of patients. RESULTS: The optical tracking system can measure accuracy of 0.1 degree and 0.1 mm. The SBP rotating axis was aligned within 0.1 degree to PPS rotating axis. A residual precession of chair rotation was found to be an ellipse with long axis of 2.0 mm and short axis of 1.0 mm. An additional 0.75 mm deviation occurred between rotating of SBP and PPS axes. Sagging tilt of 0.6 degree was found on the SBP for the home position for every additional 162 lbs load. This resulted in a 1.1cm shift (0.65 cm forward and 0.87 cm) for an isocenter 90 cm away from the SBP plate. CONCLUSIONS: Using in-house developed optical tracking system, the overall maximum displacement of treatment chair system from isocenter is within 3.0 mm with known sagging characteristics. This characterization is essential to reduce the total treatment time and limited the number of X-rays required for accurate patient alignment in the seated position.

SU-E-T-202: Comprehensive Quality Assurance Procedures for Uniform Scanning Proton Therapy Machines.

PURPOSE: Quality assurance (QA) is essential in safe and accurate delivery of radiation therapy. However, QA in proton therapy is challenging due to complicated and often facility-specific beam delivery systems and limited beam time for QA. The purpose of this study is to develop an efficient and comprehensive QA procedure for a multi-room proton therapy center using uniform scanning beams. METHODS: Our proton therapy center is comprised of a 230 MeV cyclotron, one fixed beam room, two inclined beam rooms, and one gantry room. Uniform scanning is employed exclusively in all treatment rooms. A rfDaily QA3 (Sun Nuclear Inc., Melbourne, Florida) together with home-made devices is used for daily QA. Parallel plane chambers, a multi-layer ionization chamber array (Zebra, IBA dosimetry, Schwarzenbruck, German), and an IC profiler (Sun Nuclear Inc., Melbourne, Florida) are used to QA the characteristics of the uniform scanning beams, including output, range, modulation width, flatness, symmetry, and penumbra, for both monthly and annual QA. QA procedures and acceptance criteria were developed, taking into account the likelihood and potential risk of failure, as well as the available equipment, personnel and other resources. RESULTS: QA procedures and tolerances were developed for daily, monthly and annual QA at our proton therapy center. Daily QA is performed by radiation therapists, and can be completed within 30 minutes for all rooms. Monthly QA and annual QA are performed by physicists, taking about 4 hours and a weekend respectively. Trend analysis was performed for various machine characteristics, such as machine output, range, flatness, and symmetry. CONCLUSION: QA standards are desired in Radiation Oncology, but not many standards are developed and available for proton therapy. In the mean time, facility-specific QA procedures should be developed based on the equipment failure modes and available resources.

SU-E-J-76: Clinical Use of a Real-Time Surface Image-Guided Positioning and Tracking System in Proton Therapy.

Topic of interest: Clinical applications of AlignRT 3-cameras real-time surface image-guided positioning system (IGPS) for positioning patients to reduce the number of X-ray images and tracking intra-fractional movements in proton therapy. PURPOSES: To position patients and track the intra-fractional movements, the AlignRT system was implemented in proton incline-beam-line (IBL) at Procure Oklahoma-City center. METHODS: The AlignRT3c system was configured near perpendicular to the gantry rotation for accommodating the X-ray IGPS. To evaluate positioning accuracy, more than 10 surfaces of each patient for ten patients with intracranial tumors were acquired after patients positioned by X-ray IGPS. Displacements between acquired surfaces and the reference surface taken at 1st day of treatment were examined. Intra-fractional movements with respiratory was studied with gated surface that allows setting the reference surface for patient at exhale during breathing. Intra-fractional movements due to respiratory were monitored on 10 sections of each patient for three patients with thoracic tumors. RESULTS: Accuracy of positioning patient is 2.0 mm at both anterior-posterior and lateral directions, and is 3.5 mm in superior-inferior (SI) direction by aligning the surfaces of masks. Observed larger displacements along SI direction can be due to patient's movements within the mask. Periodical displacements within 5 mm compared to its reference were seen for the three patients with thorax tumors. However, 10 mm sharp displacements with a few seconds were observed when patient moved the body. CONCLUSIONS: We have implemented the first AlignRT3c IGPS for proton therapy for positioning patients within 2.0 mm, and successfully tracked intra-fractional respiratory motion during treatment after positioning patient.

Clinical characterization of a proton beam continuous uniform scanning system with dose layer stacking.

A proton beam delivery system on a gantry with continuous uniform scanning and dose layer stacking at the Midwest Proton Radiotherapy Institute has been commissioned and accepted for clinical use. This paper was motivated by a lack of guidance on the testing and characterization for clinical uniform scanning systems. As such, it describes how these tasks were performed with a uniform scanning beam delivery system. This paper reports the methods used and important dosimetric characteristics of radiation fields produced by the system. The commissioning data include the transverse and longitudinal dose distributions, penumbra, and absolute dose values. Using a 208 MeV cyclotron's proton beam, the system provides field sizes up to 20 and 30 cm in diameter for proton ranges in water up to 27 and 20 cm, respectively. The dose layer stacking method allows for the flexible construction of spread-out Bragg peaks with uniform modulation of up to 15 cm in water, at typical dose rates of 1-3 Gy/min. For measuring relative dose distributions, multielement ion chamber arrays, small-volume ion chambers, and radiographic films were employed. Measurements during the clinical commissioning of the system have shown that the lateral and longitudinal dose uniformity of 2.5% or better can be achieved for all clinically important field sizes and ranges. The measured transverse penumbra widths offer a slight improvement in comparison to those achieved with a double scattering beam spreading technique at the facility. Absolute dose measurements were done using calibrated ion chambers, thermoluminescent and alanine detectors. Dose intercomparisons conducted using various types of detectors traceable to a national standards laboratory indicate that the measured dosimetry data agree with each other within 5%.

Epidural infusion of levobupivacaine and sufentanil following thoracotomy.

A prospective, randomised, double-blind study was conducted to compare the efficacy of two doses of levobupivacaine combined with sufentanil for continuous epidural infusion following thoractomy. A total of 72 patients undergoing lobectomy or pneumonectomy were enrolled. An epidural catheter was inserted between the levels of T4 and T6 before induction of anaesthesia and a loading dose of levobupivacaine and sufentanil was administered. At the end of surgery an epidural infusion was commenced at 5 mlxh(-1) and continued for 48 h. Patients were randomly allocated to receive either levobupivacaine 0.125% (group A) or 0.0625% (group B) and all patients also received sufentanil (1 microgxml(-1)). Visual analogue pain scores after coughing (VASi) were always higher in group B (p < 0.05); VAS pain scores at rest were higher for the first 4 h and at 16 and 28 h in group B (p < 0.05). Total morphine consumption and requests number was lower in group A (p < 0.05). Better pain relief was achieved using epidural 0.125% levobupivacaine.

Experiences with an application of industrial robotics for accurate patient positioning in proton radiotherapy.

BACKGROUND: Protons beams deliver targeted radiation doses with greater precision than is possible with electrons or megavoltage X-ray photons, but to retain this advantage, patient positioning systems at proton clinics must meet tighter accuracy requirements. For this and other reasons, robots were incorporated into the treatment room systems at MPRI. METHODS: The Midwest Proton Radiotherapy Institute (MPRI) is the first radiotherapy facility in the United States to use commercial robots with six degrees of freedom for patient positioning, rather than a traditional bed with four degrees of freedom. RESULTS: This paper outlines the ways in which robots are used at MPRI and attempts to distil insights from the experience of treating over 200 radiotherapy patients with a robotic system from February 2004 to late 2006. CONCLUSIONS: The system has performed well, and with great reliability, but there is room for future improvement, especially in ease of use and in reducing the time to get patients into position.

Severe amnesia following bilateral medial temporal lobe damage occurring on two distinct occasions.

A comprehensive neuropsychological assessment was performed on a 38-year-old woman with drug-resistant right temporal lobe epilepsy before temporal lobectomy, during a 2-year follow-up period, and approximately 3 years after surgery when she developed a malignant glioma in the left medial temporal lobe (MTL). Both before and after epilepsy surgery, memory function was normal. When the tumour was discovered, the patient suffered from severe retrograde and anterograde amnesia, whereas working memory and the other cognitive abilities were preserved. Compared with other cases of bilateral temporal lesion, this case is peculiar because the damage occurred on two distinct occasions. It suggests that only one MTL can allow normal memory function, or can take over the function normally subserved by a dysfunctional contralateral MTL when the dysfunction is marked and prolonged, such as in chronic epilepsy.

Anomalous levels of Cl- transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory.

The mRNA levels of NKCC1, an inwardly directed Na(+), K(+)-2Cl(-) cotransporter that facilitates the accumulation of intracellular Cl(-), and of KCC2, an outwardly directed K(+)-Cl(-) cotransporter that extrudes Cl(-), were studied in surgically resected brain specimens from drug-resistant temporal lobe (TL) epilepsy (TLE) patients. Quantitative RT-PCR analyses of the mRNAs extracted from the human TLE-associated brain regions revealed an up-regulation of NKCC1 mRNA and a down-regulation of KCC2 mRNA in the hippocampal subiculum, compared with the hippocampus proper or the TL neocortex, suggesting an abnormal transcription of Cl(-) transporters in the TLE subiculum. In parallel experiments, cell membranes isolated from the same TLE-associated brain regions were injected into Xenopus oocytes that rapidly incorporated human GABA(A) receptors into their surface membrane. The GABA currents elicited in oocytes injected with membranes from the subiculum had a more depolarized reversal potential (E(GABA)) compared with the hippocampus proper or the neocortex. The NKCC1 blocker bumetanide or a temperature decrease of 10 degrees C shifted the GABA-current E(GABA) more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the E(GABA) of TL neocortex-injected oocytes. We conclude that the anomalous expression of both Cl(-) transporters, NKCC1 and KCC2 [corrected] in TLE hippocampal subiculum probably causes altered Cl(-) transport in the "epileptic" neurons, as revealed in the microtransplanted Xenopus oocytes, and renders GABA aberrantly "exciting," a feature that may contribute to the precipitation of epileptic seizures.

Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy.

Our aim was to test the lateralizing value of a neuropsychological battery including several memory tests on a large sample of consecutive patients with drug-resistant temporal lobe epilepsy (TLE) evaluated for epilepsy surgery. We studied 73 right-handed patients (56% males, mean age 35.3 +/- 11.2 years, 49% left TLE) aged 16 years or older with normal IQ who underwent a preoperative neuropsychological assessment including several memory tests and were seizure-free after at least 1 year of follow-up. Forty-seven had TLE due to hippocampal sclerosis, whilst 26 had TLE secondary to tumors or other lesions. Receiver Operating Characteristic (ROC) analysis and discriminant function analysis were used to evaluate the lateralization value of selected tests and of the battery as a whole, respectively. In patients with TLE secondary to tumors or other lesions, no test showed significant lateralizing value. In patients with TLE due to hippocampal sclerosis, the immediate (P < 0.01) and delayed (P < 0.001) Rey Auditory Verbal Learning Test (RAVLT) displayed substantial discriminatory ability. The battery as a whole correctly classified 82% of patients with respect to side of epileptogenesis. Our findings suggest that a non-invasive, relatively short and unexpensive neuropsychological battery based on memory tests may profitably complement other well-established diagnostic procedures such as video-EEG or magnetic resonance imaging (MRI), at least in patients with drug-resistant TLE due to hippocampal sclerosis.

A rapid and reliable procedure to localize subdural electrodes in presurgical evaluation of patients with drug-resistant focal epilepsy.

OBJECTIVES: To evaluate a novel method for localization of subdural electrodes in presurgical assessment of patients with drug-resistant focal epilepsy. METHODS: We studied eight consecutive patients with posterior epilepsy in whom subdural electrodes were implanted for presurgical evaluation. Electrodes were detected on post-implantation brain CT scans through a semiautomated procedure based on a MATLAB routine. Then, post-implantation CT scans were fused with pre-implantation MRI to localize the electrodes in relation to the underlying cortical structures. The reliability of this procedure was tested by comparing 3D-rendered MR images of the electrodes with electrode position as determined by intraoperative digital photography. RESULTS: In each patient, all electrodes could be correctly localized and visualized in a stereotactic space, thus allowing optimal surgery planning. The agreement between the procedure-generated images and the digital photographs was good according to two independent raters. The mean mismatch between the 3D images and the photographs was 2 mm. CONCLUSIONS: While our findings need confirmation on larger samples including patients with anterior epilepsy, this procedure allowed to localize subdural electrodes and to establish the spatial relationship of each electrode to the underlying brain structure, either normal or damaged, on brain convessity, basal and medial cortex. SIGNIFICANCE: Being simple, rapid, unexpensive, and reliable, this procedure holds promise to be useful to optimize epilepsy surgery planning.

Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy.

Pharmacotherapeutic strategies have been difficult to develop for several forms of temporal lobe epilepsy, which are consequently treated by surgical resection. To examine this problem, we have studied the properties of transmitter receptors of tissues removed during surgical treatment. We find that when cell membranes, isolated from the temporal neocortex of patients afflicted with drug-resistant mesial temporal lobe epilepsy (TLE), are injected into frog oocytes they acquire GABA type A receptors (GABA(A)-receptors) that display a marked rundown during repetitive applications of GABA. In contrast, GABA(A)-receptor function is stable in oocytes injected with cell membranes isolated from the temporal lobe of TLE patients afflicted with neoplastic, dysgenetic, traumatic, or ischemic temporal lesions (lesional TLE, LTLE). Use-dependent GABA(A)-receptor rundown is also found in the pyramidal neurons of TLE neocortical slices and is antagonized by BDNF. Pyramidal neurons in cortical slices of a traumatic LTLE patient did not show GABA(A)-receptor rundown. However, the apparent affinity of GABA(A)-receptor in oocytes microtransplanted with membranes from all of the epileptic patients studied was smaller than the affinity of receptors transplanted from the nonepileptic brain. We conclude that the use-dependent rundown of neocortical GABA(A)-receptor represents a TLE-specific dysfunction, whereas the reduced affinity may be a general feature of brains of both TLE and LTLE patients, and we speculate that our findings may help to develop new treatments for TLE and LTLE.

Laser evoked potentials and carbamazepine in epileptic patients.

AIMS OF THE STUDY: Nerve conduction studies have demonstrated that carbamazepine (CBZ), as well as other antiepileptic drugs (AEDs), can affect peripheral nerve conduction; reports on conventional somatosensory evoked potentials and CBZ are controversial. In a previous study, assessing laser-evoked potentials (LEPs) in CBZ-treated patients with idiopathic trigeminal neuralgia, we found that LEPs were dampened even after stimulation of the non-painful side, with a strong correlation between LEP latency and daily CBZ dose. No other study investigated the influence of AEDs on LEPs. In order to clarify the effect of CBZ on LEPs we sought possible LEP changes in epileptic patients taking CBZ. MATERIALS AND METHODS: We studied LEPs after trigeminal and hand CO(2)-laser stimulation in 20 patients with epilepsy taking CBZ and 20 age-matched controls. RESULTS: Although the trigeminal LEP mean latency was slightly longer in epileptic patients (P=0.11), we did not find significant differences between epileptic patients and controls for any LEP data. LEP data did not correlate with the daily CBZ dose, CBZ blood concentration, or duration of therapy (P>0.3). CONCLUSION: The lack of a CBZ-induced dampening of LEPs suggests that small-fibre pathways, compared to large-fibre, might be less susceptible to AED's toxic effect. Although the TN patients in our previous study were older than the epileptic patients in the present study, a possible combined effect induced by drug and age in patients with TN is unlikely because LEP latency is reportedly unaffected by age. The CBZ-induced effect in patients with trigeminal neuralgia is possibly related to pathophysiological changes specific to this disease.

Temporal lobe epilepsy surgery: different surgical strategies after a non-invasive diagnostic protocol.

AIM: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on "anatomo-electro-clinical correlations". METHODS: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. "Tailored" surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. RESULTS: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a "hippocampal sclerosis/cryptogenic" group (n = 57) and a "tumours/cortical organisation disorders" group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. CONCLUSIONS: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo-electro-clinical data and can be treated effectively and safely with tailored surgery.