[DIAGNOSIS AND TREATMENT OF A GIRL SUFFERING FROM DRUG RESISTANT EPILEPSY WITH AN INNOVATIVE MINIMALLY INVASIVE APPROACH].

INTRODUCTION: About one percent (over 81,000 patients) of the Israeli population suffer from epilepsy. The main treatment for this condition is medication, but about a third of the patients suffer from drug-resistant epilepsy (DRE). Each year about 5,000 new patients are diagnosed with epilepsy, of whom 3,000 are children. For these patients, an evaluation in designated centers is required in order to diagnose possible foci and propose neurosurgical treatment alternatives. BACKGROUND: A model for diagnosis and treatment of the epileptic network in a minimally invasive approach is presented through the description of a case study. Phase I: includes diagnosis of the semiology, neuropsychological assessment, video EEG recording and performing a PET-MRI-FMRI-EEG synchronized examination. Phase II: involves stereo-electroencephalography (SEEG) minimally invasive diagnosis to target the epileptic area and accurately map adjacent functional areas and assessment of cortical redundancy. Phase III: includes radiofrequency ablation of the foci without any further surgery. This procedure is performed under clinical monitoring (the patient is awake during treatment) and continuous EEG monitoring. CONCLUSIONS: This case study demonstrates the multi-dimensional model performed by a multidisciplinary team, combining innovative technologies. This model is essential for the precision of the diagnosis and treatment methods of focal epilepsy and allows preservation of function based, among other factors, on the identification of cortical redundancy. DISCUSSION: The preoperative assessment identified focal epilepsy adjacent to the motor area dominating the right hand. A combined PET-FMRI-MRI-EEG examination enabled detecting redundancy of motor functions beyond the epileptic focus. Based on this information, a targeted implantation of depth electrodes (SEEG) was performed, the epileptic foci were identified and targeted ablations were performed during clinical monitoring and continuous EEG. This resulted in the cessation of seizures in parallel with the disappearance of the pathological signal in the EEG, all while preserving the patient's hand function.

Multi-metric predictors of radiofrequency-treated trigeminal neuralgias.

Evaluation of neurovascular compression-related trigeminal neuralgia (NVC-TN) and its resolution through microvascular decompression are demonstrable by MRI and intraoperatively [Leal et al. (Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia due to neurovascular compression and their association with the severity of compression and clinical outcomes: Clinical article. J Neurosurg. 2014;120(6):1484-1495)]. Non-NVC-TNs treated by radiofrequency (RF) lack such detectable features. Multimodal integration of pre-surgical diffusion tensor imaging (DTI) and volumetry (VOL) with intraoperative neurophysiology (ION) could improve understanding and performance of RF among non-NVC-TN. We hypothesized that DTI disturbances' localization (central relay versus peripherally) rather than their values bares the most significant predictive value upon outcome and that ION could quantitatively both localize and assist RF of affected branches. The first pre-surgical step evaluated the differences between affected and non-affected sides (by DTI and VOL). Four TN's segments were studied, from peripheral to central relay: Meckel's cave-trigeminal ganglion (MC-TGN), cisternal portion, root entry zone (REZ) and spinal tract [Lin et al. (Flatness of the Meckel cave may cause primary trigeminal neuralgia: A radiomics-based study. J Headache Pain. 2021;22(1):104)]. In the second intraoperative step, we used both ION and patient's testimonies to confirm the localization of the affected branch, evolving hypoesthesia, pain reduction and monitoring of adverse effects [Sindou (Neurophysiological navigation in the trigeminal nerve: Use of masticatory responses and facial motor responses evoked by electrical stimulation of the trigeminal rootlets for RF-thermorhizotomy guidance. Stereotact Funct Neurosurg. 1999;73(1-4):117-121); Sindou and Tatli (Traitement de la névralgie trigéminale par thermorhizotomie. Neurochirurgie. 2009;55(2):203-210)]. Last and postoperatively, each data set's features and correlation with short-term (3 months) and long-term outcomes (23.5 ± 6.7 months) were independently analysed and blind to each other. Finally, we designed a multimodal predictive model. Sixteen non-NVC-TN patients (mean 53.6 ± SD years old) with mean duration of 6.56 ± 4.1 years (75% right TN; 43.8% V3) were included. After 23.5 ± 6.7 months, 14/16 were good responders. Age, gender, TN duration and side/branch did not correlate with outcomes. Affected sides showed significant DTI disturbances in both peripheral (MC-TGNs) and central-relay (REZ) segments. However, worse outcome correlated only with REZ-located DTI disturbances (P = 0.04; r = 0.53). Concerning volumetry, affected MC-TGNs were abnormally flatter: lower volumes and surface area correlated with worse outcomes (both P = 0.033; r = 0.55 and 0.77, respectively). Intraoperatively, ION could not differ the affected from non-affected branch. However, the magnitude of ION's amplitude reduction (ION-Δ-Amplitude) had the most significant correlation with outcomes (r = 0.86; P < 0.00006). It was higher among responders [68.4% (50-82%)], and a <40% reduction characterized non-responders [36.7% (0-40%)]. Multiple regression showed that ION-Δ-Amplitude, centrally located only REZ DTI integrity and MC-TGN flatness explain 82.2% of the variance of post-RF visual analogue score. Integration of pre-surgical DTI-VOL with ION-Δ-Amplitude suggests a multi-metric predictive model of post-RF outcome in non-NVC-TN. In multiple regression, central-relay REZ DTI disturbances and insufficiently reduced excitability (<40%) predicted worse outcome. Quantitative fine-tuned ION tools should be sought for peri-operative evaluation of the affected branches.

Stereo electroencephalography-guided radiofrequency ablation in focal epilepsia partialis continua: illustrative case.

BACKGROUND: Epilepsia partialis continua (EPC) is a variant of focal motor status epilepticus that can occur as a single or repetitive episode with progressive or nonprogressive characteristics. OBSERVATIONS: The authors describe the feasibility of identifying focal EPC in a 33-year-old woman using video electroencephalography (VEEG), electroencephalography source localization, [18F]fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, and psychiatric and neuropsychological assessments and of treating it with stereo electroencephalography-guided radiofrequency (SEEG-RF) ablation. EPC comprised recurrent myoclonus of the right thigh and iliopsoas with a progressive pain syndrome after left anterior-temporo-mesial resection. Switching between VEEG under regular and epidural block helped to define myoclonus as the presenting ictal symptom with a suspected seizure onset zone in the left parietal paramedian lobule. After the epileptic network was identified, SEEG-RF ablation abolished all seizures. No correlation was found between pain and VEEG/SEEG abnormalities. Rehabilitation began 3 days after the SEEG-RF ablation. By 1 year of follow-up, the patient had no EPC and could walk with assistance in rehabilitation; however, due to the abrupt abolishment of EPC and underlying psychological factors, the patient perceived her pain as overriding, which prevented her from walking. LESSONS: The application of SEEG-RF ablation is an efficient therapeutic option for focal EPC with special concerns regarding concurrent nonepileptic pain. https://thejns.org/doi/10.3171/CASE23611.

Does aspirin use make it harder to collect seizures during elective video-EEG telemetry?

Aspirin has shown promise as an anticonvulsant drug in animal models. Whether aspirin alters seizure frequency in humans remains unstudied. We retrospectively looked at adults with focal onset epilepsy who took aspirin daily while undergoing elective video-EEG monitoring and compared them with similar age- and sex-matched controls to see if seizure frequencies were different between those two populations. Significantly fewer seizures were seen on day two of monitoring for patients on aspirin therapies. Higher aspirin doses were correlated with fewer seizures collected during the monitoring stay. Further prospective study is needed to determine whether aspirin affects more robust seizure control.

FIRDA, refractory epilepsy, and SEEG-guided RF: A case report.

OBJECTIVES: We will demonstrate that FIRDA (frontal intermittent rhythmic delta activity)-otherwise related to systemic disorders and encephalopathy-has a role as an epileptic biomarker of deep-seated midline SOZ. Its abolishment following SEEG-guided radiofrequency of such SOZ correlates with clinical improvement suggesting its role as a noninvasive biomarker of otherwise inaccessible SOZs. METHODS: We report the case of AK who was admitted with "psychiatric and gastrointestinal complaints." AK's complaints were further associated with FIRDA during VEEG. His previous refractoriness to AEDs, the clinico-electroencephalographic correlation, MRI showing bilateral hippocampal atrophy (more to the left) and severe memory deficits, prompted us to suggest a left temporo-mesial SOZ, for which SEEG was done. Dual SEEG and scalp electrodes were used primarily for diagnostic purposes but taking into account an option for a therapeutic action by RF ablation. RESULTS: The dual array demonstrated a clear association between left hippocampal high voltage spikes and HFOs on SEEG recordings with FIRDA on concomitant scalp EEG parallel to behavioral changes, as suspected in our preliminary hypothesis. A further RF ablation eliminated the epileptiform activity (Spikes, HFOs, and FIRDA) followed by clinical improvement. SIGNIFICANCE: This is the first report showing the clinical significance of FIRDA associated with behavioral changes as a marker for latent refractory mesial epilepsy. SEEG exploration has the potential to uncover deep sources, which are manifested as FIRDA on scalp EEG. These abnormalities and clinical symptoms can be eliminated by RF ablation.

SEEG-RF for revealing and treating Geschwind syndrome's epileptic network: A case study.

Stereotypic neural networks are repeatedly activated in drug-refractory epilepsies (DRE), reinforcing the expression of certain psycho-affective traits. Geschwind syndrome (GS) can serve as a model for such phenomena among patients with temporal lobe DRE. We describe stereo-electroencephalogram (SEEG) exploration in a 34-year-old male with DRE and GS, and his treatment by SEEG-radiofrequency (SEEG-RF) ablation. We hypothesized that this approach could reveal the underlying epileptic network and map eloquent faculties adjacent to SEEG-RF targets, which can be further used to disintegrate the epileptic network. The patient underwent a multi-modal pre-surgical evaluation consisting of video EEG (VEEG), EEG source localization, 18-fluorodexyglucose-PET/MRI, neuropsychological and psychiatric assessments. Pre-surgical multi-modal analyses suggested a T4-centered seizure onset zone. SEEG further localized the SOZ within the right amygdalo-hippocampal region and temporal neocortex, with the right parieto-temporal region as the propagation zone. SEEG-RF ablation under awake conditions and continuous EEG monitoring confirmed the abolishment of epileptic activity. Follow-up at 20 months showed seizure suppression (Engel 1A/ILEA 1) and a significantly improved and stable psycho-affective state. To the best of our knowledge this is the first description of the intracranial biomarkers of GS and its further treatment through SEEG-RF ablation within the scope of DRE.

Secreted semaphorins modulate synaptic transmission in the adult hippocampus.

Modulation of synaptic activity is critical for neural circuit function and behavior. The semaphorins are a large, phylogenetically conserved protein family with important roles in neural development. However, semaphorin function in the adult brain has yet to be determined. Here, we show that the coreceptors for secreted semaphorins, the neuropilins, are found at synapses and localize to molecular layers of the adult mouse hippocampus and accessory olfactory cortex. Moreover, application of the secreted semaphorin Sema3F to acute hippocampal slices modulates both the frequency and amplitude of miniature EPSCs in granule cells of the dentate gyrus and pyramidal neurons of CA1. Finally, we show that mice lacking Sema3F are prone to seizures. These results suggest a novel role for semaphorins as synaptic modulators and illustrate the diverse repertoire of these guidance cues in both the formation and function of neural circuits.

A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy.

The predominant neuronal glutamate transporter, EAAC1 (for excitatory amino acid carrier-1), is localized to the dendrites and somata of many neurons. Rare presynaptic localization is restricted to GABA terminals. Because glutamate is a precursor for GABA synthesis, we hypothesized that EAAC1 may play a role in regulating GABA synthesis and, thus, could cause epilepsy in rats when inactivated. Reduced expression of EAAC1 by antisense treatment led to behavioral abnormalities, including staring-freezing episodes and electrographic (EEG) seizures. Extracellular hippocampal and thalamocortical slice recordings showed excessive excitability in antisense-treated rats. Patch-clamp recordings of miniature IPSCs (mIPSCs) conducted in CA1 pyramidal neurons in slices from EAAC1 antisense-treated animals demonstrated a significant decrease in mIPSC amplitude, indicating decreased tonic inhibition. There was a 50% loss of hippocampal GABA levels associated with knockdown of EAAC1, and newly synthesized GABA from extracellular glutamate was significantly impaired by reduction of EAAC1 expression. EAAC1 may participate in normal GABA neurosynthesis and limbic hyperexcitability, whereas epilepsy can result from a disruption of the interaction between EAAC1 and GABA metabolism.

Spinal glutamate uptake is critical for maintaining normal sensory transmission in rat spinal cord.

Glutamate is a major excitatory neurotransmitter in primary afferent terminals and is critical for normal spinal excitatory synaptic transmission. However, little is known about the regulation of synaptically released glutamate in the spinal cord under physiologic conditions. The sodium-dependent, high-affinity glutamate transporters are the primary mechanism for the clearance of synaptically released glutamate. In the present study, we found that intrathecal injection of glutamate transporter blockers DL-threo-beta-benzyloxyaspartate (TBOA) and dihydrokainate produced significant and dose-dependent spontaneous nociceptive behaviors, such as licking, shaking, and caudally directed biting, phenomena similar to the behaviors caused by intrathecal glutamate receptor agonists. Intrathecal TBOA also led to remarkable hypersensitivity in response to thermal and mechanical stimuli. These behavioral responses could be significantly blocked by intrathecal injection of the NMDA receptor antagonists MK-801 and AP-5, the non-NMDA receptor antagonist CNQX or the nitric oxide synthase inhibitor L-NAME. In vivo microdialysis analysis showed short-term elevation of extracellular glutamate concentration in the spinal cord after intrathecal injection of TBOA. Furthermore, topical application of TBOA on the dorsal surface of the spinal cord resulted in a significant elevation of extracellular glutamate concentration demonstrated by in vivo glutamate voltametry. The present study indicates that defective spinal glutamate uptake caused by inhibition of glutamate transporters leads to excessive glutamate accumulation in the spinal cord. The latter results in persistent over-activation of synaptic glutamate receptors, producing spontaneous nociceptive behaviors and sensory hypersensitivity. Our results suggest that glutamate uptake through spinal glutamate transporters is critical for maintaining normal sensory transmission under physiologic conditions.

Spatial neglect during electrocortical stimulation mapping in the right hemisphere.

Spatial processing was assessed following implantation of subdural electrodes in the nondominant hemisphere with electrocortical stimulation mapping (ESM) in two patients before epilepsy surgery. The first patient had mild hemispatial neglect/extinction during ESM of posterior temporal and inferior parietal areas. These areas were resected, and the patient had postoperative deficits that were similar to those occurring with ESM. The second patient was found to have marked hemispatial neglect during stimulation of parietal areas. These areas were not resected, and the patient had no neglect following surgery. These results suggest that ESM can help predict spatial processing deficits associated with cortical resection, and may help prevent postoperative impairments following resection in right parietal or temporal regions.

Multimodal functional mapping of sensorimotor cortex prior to resection of an epileptogenic perirolandic lesion.

The effects of chronic epileptogenic lesions on functional anatomy are under debate. Our recent experience during mapping and resection of a lesion in sensorimotor cortex supports the idea that epileptogenic lesions may prompt development of alternate cortical motor representations. Multimodal mapping may uncover alternate areas of functionality that make surgery feasible even when conventional neuroanatomy suggests otherwise. Newer methods such as electrocorticographic spectral analysis may complement traditional electrical cortical stimulation mapping.

Optimizing parameters for terminating cortical afterdischarges with pulse stimulation.

PURPOSE: We previously reported that brief pulses of electrical stimulation (BPSs) can terminate afterdischarges (ADs) during cortical stimulation. We investigated conditions under which BPS is more likely to suppress ADs. METHODS: We analyzed parameters altering BPS effectiveness on 200 ADs in seven patients with implanted subdural electrodes. RESULTS: The odds of BPSs stopping ADs was 8.6 times greater at primary sites (directly stimulated electrodes) than at secondary sites (adjacent electrodes) (p = 0.016). BPS applied within 4.5 s after onset of AD had 2 times greater odds of stopping ADs (p = 0.014). BPS applied when AD voltage was negative was 1.9 times more likely to stop ADs (p = 0.012). ADs with rhythmic pattern responded best (p < 0.0001). BPS stopped 100% of ADs not starting immediately after localization stimulus (LS) versus 29% of those starting immediately (p < 0.0001). CONCLUSIONS: BPS is more likely to terminate ADs at primary electrodes, if given early, if applied to the negative peak of the AD waveform, if AD has a rhythmic pattern, and if AD did not start immediately after LS.