Depth versus surface: A critical review of subdural and depth electrodes in intracranial electroencephalographic studies.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.

In-vivo testing of a novel wireless intraspinal microstimulation interface for restoration of motor function following spinal cord injury.

BACKGROUND: Spinal cord injury causes a drastic loss in motor and sensory function. Intraspinal microstimulation (ISMS) is an electrical stimulation method developed for restoring motor function by activating the spinal networks below the level of injury. Current ISMS technology uses fine penetrating microwires to stimulate the ventral horn of the lumbar enlargement. The penetrating wires traverse the dura mater through a transdural conduit that connects to an implantable pulse generator. OBJECTIVE: A wireless, fully intradural ISMS implant was developed to mitigate the potential complications associated with the transdural conduit, including tethering and leakage of cerebrospinal fluid. METHODS: Two wireless floating microelectrode array (WFMA) devices were implanted in the lumbar enlargement of an adult domestic pig. Voltage transients were used to assess the electrochemical stability of the interface. Manual flexion and extension movements of the spine were performed to evaluate the mechanical stability of the interface. Post-mortem 9T MRI imaging was used to confirm the location of the electrodes. RESULTS: The WFMA-based ISMS interface successfully evoked extension and flexion movements of the hip joint. Stimulation thresholds remained stable following manual extension and flexion of the spine. CONCLUSION: The preliminary results demonstrate the surgical feasibility as well as the functionality of the proposed wireless ISMS system.

Electrophysiological markers of memory consolidation in the human brain when memories are reactivated during sleep.

Human accomplishments depend on learning, and effective learning depends on consolidation. Consolidation is the process whereby new memories are gradually stored in an enduring way in the brain so that they can be available when needed. For factual or event knowledge, consolidation is thought to progress during sleep as well as during waking states and to be mediated by interactions between hippocampal and neocortical networks. However, consolidation is difficult to observe directly but rather is inferred through behavioral observations. Here, we investigated overnight memory change by measuring electrical activity in and near the hippocampus. Electroencephalographic (EEG) recordings were made in five patients from electrodes implanted to determine whether a surgical treatment could relieve their seizure disorders. One night, while each patient slept in a hospital monitoring room, we recorded electrophysiological responses to 10 to 20 specific sounds that were presented very quietly, to avoid arousal. Half of the sounds had been associated with objects and their precise spatial locations that patients learned before sleep. After sleep, we found systematic improvements in spatial recall, replicating prior results. We assume that when the sounds were presented during sleep, they reactivated and strengthened corresponding spatial memories. Notably, the sounds also elicited oscillatory intracranial EEG activity, including increases in theta, sigma, and gamma EEG bands. Gamma responses, in particular, were consistently associated with the degree of improvement in spatial memory exhibited after sleep. We thus conclude that this electrophysiological activity in the hippocampus and adjacent medial temporal cortex reflects sleep-based enhancement of memory storage.

Chronic stability of activated iridium oxide film voltage transients from wireless floating microelectrode arrays.

Successful monitoring of the condition of stimulation electrodes is critical for maintaining chronic device performance for neural stimulation. As part of pre-clinical safety testing in preparation for a visual prostheses clinical trial, we evaluated the stability of the implantable devices and stimulation electrodes using a combination of current pulsing in saline and in canine visual cortex. Specifically, in saline we monitored the stability and performance of 3000 µm2 geometric surface area activated iridium oxide film (AIROF) electrodes within a wireless floating microelectrode array (WFMA) by measuring the voltage transient (VT) response through reverse telemetry. Eight WFMAs were assessed in vitro for 24 days, where n = 4 were pulsed continuously at 80 µA (16 nC/phase) and n = 4 remained in solution with no applied stimulation. Subsequently, twelve different WFMAs were implanted in visual cortex in n = 3 canine subjects (4 WFMAs each). After a 2-week recovery period, half of the electrodes in each of the twelve devices were pulsed continuously for 24 h at either 20, 40, 63, or 80 µA (200 µs pulse width, 100 Hz). VTs were recorded to track changes in the electrodes at set time intervals in both the saline and in vivo study. The VT response of AIROF electrodes remained stable during pulsing in saline over 24 days. Electrode polarization and driving voltage changed by less than 200 mV on average. The AIROF electrodes also maintained consistent performance, overall, during 24 h of pulsing in vivo. Four of the in vivo WFMA devices showed a change in polarization, access voltage, or driving voltage over time. However, no VT recordings indicated electrode failure, and the same trend was typically seen in both pulsed and unpulsed electrodes within the same device. Overall, accelerated stimulation testing in saline and in vivo indicated that AIROF electrodes in the WFMA were able to consistently deliver up to 16 nC per pulse and would be suitable for chronic clinical use.

Visual cortex responds to sound onset and offset during passive listening.

Sounds enhance our ability to detect, localize, and respond to co-occurring visual targets. Research suggests that sounds improve visual processing by resetting the phase of ongoing oscillations in visual cortex. However, it remains unclear what information is relayed from the auditory system to visual areas and if sounds modulate visual activity even in the absence of visual stimuli (e.g., during passive listening). Using intracranial electroencephalography (iEEG) in humans, we examined the sensitivity of visual cortex to three forms of auditory information during a passive listening task: auditory onset responses, auditory offset responses, and rhythmic entrainment to sounds. Because some auditory neurons respond to both sound onsets and offsets, visual timing and duration processing may benefit from each. In addition, if auditory entrainment information is relayed to visual cortex, it could support the processing of complex stimulus dynamics that are aligned between auditory and visual stimuli. Results demonstrate that in visual cortex, amplitude-modulated sounds elicited transient onset and offset responses in multiple areas, but no entrainment to sound modulation frequencies. These findings suggest that activity in visual cortex (as measured with iEEG in response to auditory stimuli) may not be affected by temporally fine-grained auditory stimulus dynamics during passive listening (though it remains possible that this signal may be observable with simultaneous auditory-visual stimuli). Moreover, auditory responses were maximal in low-level visual cortex, potentially implicating a direct pathway for rapid interactions between auditory and visual cortices. This mechanism may facilitate perception by time-locking visual computations to environmental events marked by auditory discontinuities.NEW & NOTEWORTHY Using intracranial electroencephalography (iEEG) in humans during a passive listening task, we demonstrate that sounds modulate activity in visual cortex at both the onset and offset of sounds, which likely supports visual timing and duration processing. However, more complex auditory rate information did not affect visual activity. These findings are based on one of the largest multisensory iEEG studies to date and reveal the type of information transmitted between auditory and visual regions.

Hippocampal spikes have heterogeneous scalp EEG correlates important for defining IEDs.

OBJECTIVE: To identify scalp EEG correlates of hippocampal spikes in patients with mesial temporal lobe epilepsy (mTLE). METHODS: We recorded scalp and intracranial EEG simultaneously in 20 consecutive surgical candidates with mTLE. Hippocampal spikes were identified from depth electrodes during the first hour of sleep on the first night of recording in the epilepsy monitoring unit, and their scalp EEG correlates were identified. RESULTS: Hippocampal spiking rates varied widely from 101 to 2187 (556 ± 672, mean ± SD) spikes per hour among the subjects. Of the 16,398 hippocampal spikes observed in this study, 492 (3.0%) of hippocampal spikes with extensive involvement of lateral temporal cortex were associated with scalp interictal epileptiform discharges (IEDs) including spikes and sharp waves; 198 (1.2%) of hippocampal spikes with limited involvement of lateral temporal cortex were associated with sharp transients or sharp slow waves, and 78 (0.05%)of hippocampal spikes with no lateral temporal involvement were associated with small sharp spikes (SSS). SSS were not correlated with independent temporal neocortical spikes. CONCLUSIONS: There are morphologically heterogeneous scalp EEG correlates of hippocampal spikes including SSS, sharp transients, sharp slow waves, spikes, and sharp waves. SSS correlate with hippocampal spikes and are likely an EEG marker for mTLE. These findings have important clinical implications for the diagnosis and localization of mTLE, and provide new perspectives on criteria for defining scalp IEDs.

Visual speech differentially modulates beta, theta, and high gamma bands in auditory cortex.

Speech perception is a central component of social communication. Although principally an auditory process, accurate speech perception in everyday settings is supported by meaningful information extracted from visual cues. Visual speech modulates activity in cortical areas subserving auditory speech perception including the superior temporal gyrus (STG). However, it is unknown whether visual modulation of auditory processing is a unitary phenomenon or, rather, consists of multiple functionally distinct processes. To explore this question, we examined neural responses to audiovisual speech measured from intracranially implanted electrodes in 21 patients with epilepsy. We found that visual speech modulated auditory processes in the STG in multiple ways, eliciting temporally and spatially distinct patterns of activity that differed across frequency bands. In the theta band, visual speech suppressed the auditory response from before auditory speech onset to after auditory speech onset (-93 to 500 ms) most strongly in the posterior STG. In the beta band, suppression was seen in the anterior STG from -311 to -195 ms before auditory speech onset and in the middle STG from -195 to 235 ms after speech onset. In high gamma, visual speech enhanced the auditory response from -45 to 24 ms only in the posterior STG. We interpret the visual-induced changes prior to speech onset as reflecting crossmodal prediction of speech signals. In contrast, modulations after sound onset may reflect a decrease in sustained feedforward auditory activity. These results are consistent with models that posit multiple distinct mechanisms supporting audiovisual speech perception.

Surgical Outcomes and EEG Prognostic Factors After Stereotactic Laser Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy.

Objective: To assess the seizure outcomes of stereotactic laser amygdalohippocampectomy (SLAH) in consecutive patients with mesial temporal lobe epilepsy (mTLE) in a single center and identify scalp EEG and imaging factors in the presurgical evaluation that correlate with post-surgical seizure recurrence. Methods: We retrospectively reviewed the medical and EEG records of 30 patients with drug-resistant mTLE who underwent SLAH and had at least 1 year of follow-up. Surgical outcomes were classified using the Engel scale. Univariate hazard ratios were used to evaluate the risk factors associated with seizure recurrence after SLAH. Results: The overall Engel class I outcome after SLAH was 13/30 (43%), with a mean postoperative follow-up of 48.9 ± 17.6 months. Scalp EEG findings of interictal regional slow activity (IRSA) on the side of surgery (HR = 4.05, p = 0.005) and non-lateralizing or contra-lateralizing seizure onset (HR = 4.31, p = 0.006) were negatively correlated with postsurgical seizure freedom. Scalp EEG with either one of the above features strongly predicted seizure recurrence after surgery (HR = 7.13, p < 0.001) with 100% sensitivity and 71% specificity. Significance: Understanding the factors associated with good or poor surgical outcomes can help choose the best candidates for SLAH. Of the variables assessed, scalp EEG findings were the most clearly associated with seizure outcomes after SLAH.

Toward the development of a color visual prosthesis.

Objective. All of the human prosthetic visual systems implanted so far have been achromatic. Schmidtet al(1996Brain119507-22) reported that at low stimulation intensities their subject reported that phosphenes usually had a specific hue, but when the stimulus intensity was increased, they desaturated to white. We speculate here that previous B/W prosthetic systems were unnecessarily over-stimulating the visual cortex to obtain white phosphenes, which may be why unexpected alterations in phosphenes and seizures were not an uncommon occurrence. A color prosthesis would have the advantage of being elicited by lower levels of stimulation, reducing the probability of causing epileptogenic responses.Approach.A 'hybrid' mode of stimulation is suggested, involving a combination of B/W and color stimulation, which could provide color information without reducing spatial resolution.Main results.Colors in the real world are spread along intensity and chromatic gradients.Significance.Software implementation strategies are discussed, as are the advantages and challenges for possible color prosthetic systems.

Chasing language through the brain: Successive parallel networks.

OBJECTIVE: To describe the spatio-temporal dynamics and interactions during linguistic and memory tasks. METHODS: Event-related electrocorticographic (ECoG) spectral patterns obtained during cognitive tasks from 26 epilepsy patients (aged: 9-60 y) were analyzed in order to examine the spatio-temporal patterns of activation of cortical language areas. ECoGs (1024 Hz/channel) were recorded from 1567 subdural electrodes and 510 depth electrodes chronically implanted over or within the frontal, parietal, occipital and/or temporal lobes as part of their surgical work-up for intractable seizures. Six language/memory tasks were performed, which required responding verbally to auditory or visual word stimuli. Detailed analysis of electrode locations allowed combining results across patients. RESULTS: Transient increases in induced ECoG gamma power (70-100 Hz) were observed in response to hearing words (central superior temporal gyrus), reading text and naming pictures (occipital and fusiform cortex) and speaking (pre-central, post-central and sub-central cortex). CONCLUSIONS: Between these activations there was widespread spatial divergence followed by convergence of gamma activity that reliably identified cortical areas associated with task-specific processes. SIGNIFICANCE: The combined dataset supports the concept of functionally-specific locally parallel language networks that are widely distributed, partially interacting in succession to serve the cognitive and behavioral demands of the tasks.

Effect of Deep Brain Stimulation on Cerebellar Tremor Compared to Non-Cerebellar Tremor Using a Wearable Device in a Patient With Multiple Sclerosis: Case Report.

Tremor of the upper extremity is a significant cause of disability in some patients with multiple sclerosis (MS). The MS tremor is complex because it contains an ataxic intentional tremor component due to the involvement of the cerebellum and cerebellar outflow pathways by MS plaques, which makes the MS tremor, in general, less responsive to medications or deep brain stimulation (DBS) than those associated with essential tremor or Parkinson's disease. The cerebellar component has been thought to be the main reason for making DBS less effective, although it is not clear whether it is due to the lack of suppression of the ataxic tremor by DBS or else. The goal of this study was to clarify the effect of DBS on cerebellar tremor compared to non-cerebellar tremor in a patient with MS. By wearing an accelerometer on the index finger of each hand, we were able to quantitatively characterize kinetic tremor by frequency and amplitude, with cerebellar ataxia component on one hand and that without cerebellar component on the other hand, at the beginning and end of the hand movement approaching a target at DBS Off and On status. We found that cerebellar tremor surprisingly had as good a response to DBS as the tremor without a cerebellar component, but the function control on cerebellar tremor was not as good due to its distal oscillation, which made the amplitude of tremor increasingly greater as it approached the target. This explains why cerebellar tremor or MS tremor with cerebellar component has a poor functional transformation even with a good percentage of tremor control. This case study provides a better understanding of the effect of DBS on cerebellar tremor and MS tremor by using a wearable device, which could help future studies improve patient selection and outcome prediction for DBS treatment of this disabling tremor.

Caffeine reverses the unconsciousness produced by light anesthesia in the continued presence of isoflurane in rats.

Currently no drugs are employed clinically to reverse the unconsciousness induced by general anesthetics. Our previous studies showed that caffeine, when given near the end of an anesthesia session, accelerated emergence from isoflurane anesthesia, likely caused by caffeine's ability to elevate intracellular cAMP levels and to block adenosine receptors. These earlier studies showed that caffeine did not rouse either rats or humans from deep anesthesia (≥ 1 minimum alveolar concentration, MAC). In this current crossover study, we examined whether caffeine reversed the unconsciousness produced by light anesthesia (< 1 MAC) in the continued presence of isoflurane. The primary endpoint of this study was to measure isoflurane levels at the time of recovery of righting reflex, which was a proxy for consciousness. Rats were deeply anesthetized with 2% isoflurane (~1.5 MAC) for 20 minutes. Subsequently, isoflurane was reduced to 1.2% for 10 minutes, then by 0.2% every 10 min; animals were monitored until the recovery of righting reflex occurred, in the continued presence of isoflurane. Respiration rate, heart rate and electroencephalogram (EEG) were monitored. Our results show that caffeine-treated rats recovered their righting reflex at a significantly higher inspired isoflurane concentration, corresponding to light anesthesia, than the same rats treated with saline (control). Respiration rate and heart rate increased initially after caffeine injection but were then unchanged for the rest of the anesthesia session. Deep anesthesia is correlated with burst suppression in EEG recordings. Our data showed that caffeine transiently reduced the burst suppression time produced by deep anesthesia, suggesting that caffeine altered neuronal circuit function but not to a point where it caused arousal. In contrast, under light anesthesia, caffeine shifted the EEG power to high frequency beta and gamma bands. These data suggest that caffeine may represent a clinically viable drug to reverse the unconsciousness produced by light anesthesia.

RTTBD-like activity in association with hippocampal ictal discharges in patients with temporal lobe epilepsy.

To determine clinical and intracranial EEG correlates of rhythmic temporal theta bursts of drowsiness (RTTBD) and assess its clinical significance in patients with temporal lobe epilepsy (TLE). A retrospective review of simultaneous scalp and intracranial video-EEG recordings from 28 patients with TLE was evaluated for epilepsy surgery. Scalp RTTBD patterns were identified and their clinical and intracranial EEG correlates were then determined on video-EEG recording using depth and subdural electrodes. Thirty-one RTTBD patterns on scalp EEG were observed in six (21%) of the 28 patients. Five (16%) of the RTTBD patterns occurred during wakefulness and 26 (84%) occurred during drowsiness and light sleep. The mean duration of RTTBD was 10 seconds (range: 3-28 seconds). RTTDB consistently correlated with hippocampal ictal discharges and was time-locked to the hippocampal seizures in which the ictal discharges evolved into rhythmic theta frequency (4-7-Hz) range. Ictal automatisms were observed during five (16%) RTTBD patterns, while cognitive impairment was observed in four (13%) of the 31 RTTBD patterns. Our findings show that scalp EEG correlates of hippocampal ictal discharges can resemble RTTBD and may be associated with ictal symptoms and cognitive impairment, indicating that RTTBD may rarely be an ictal EEG pattern in patients with TLE.

Postmortem investigation of a human cortical visual prosthesis that was implanted for 36 years.

Objective: Postmortem analysis of the brain from a blind human subject who had a cortical visual prosthesis implanted for 36 years (Dobelle 2000 Asaio J. 46 3­9) Approach: This provided insight into the design requirements for a successful human cortical visual prosthesis by revealing, (a) unexpected rotation of the electrode array 25 to 40 degrees away from the midsagittal plane, thought to be due to the torque of the connecting cable, (b) degradation of the platinum electrodes, and (c) only partial coverage of the primary visual cortex by the rectangular array. The electrode array only overlapped with the anterior 45% of primary visual cortex (identified by the line of Gennari), largely missing the posterior foveal representation of visual cortex. Main results: A significantly greater proportions of electrodes outside of V1 elicited phosphenes than did electrodes within of V1. Histology did not reveal appreciable loss of neurons in cortex that surrounded the migrated array, perhaps due to the very slow rotation of this implant. Significance: This pioneering effort to develop a cortical visual prosthesis suggests that to maximize efficacy, the long-term effects of implanted alien materials on nervous tissue, and vice versa, need to be considered in detail, and that electrode array design considerations need to optimally match the electrodes to the patient's cortical anatomy. Modern pre-implant imaging can help optimize future implants by identifying the location and extent of bridging veins with MRI and even map the location of the V1/V2 border in vivo with PET.

DC shifts, high frequency oscillations, ripples and fast ripples in relation to the seizure onset zone.

Efforts to improve epilepsy surgery outcomes have led to increased interest in the study of electroencephalographic oscillations outside the conventional EEG bands. These include fast activity above the gamma band, known as high frequency oscillations (HFOs), and infraslow activity (ISA) below the delta band, sometimes referred to as direct current (DC) or ictal baseline shifts (IBS). HFOs in particular have been extensively studied as potential biomarkers for epileptogenic tissue in light of evidence showing that resection of brain tissue containing HFOs is associated with good surgical outcomes. Not all HFOs are conclusively pathological, however, as they can be recorded in nonepileptic tissue and induced by cognitive, visual, or motor tasks. Consequently, efforts to distinguish between pathological and physiological HFOs have identified several traits specific to pathological HFOs, such as coupling with interictal spikes, association with delta waves, and stereotypical morphologies. On the opposite end of the EEG spectrum, sub-delta oscillations have been shown to co-localize with the seizure onset zones (SOZ) and appear in a narrower spatial distribution than activity in the conventional EEG frequency bands. In this report, we review studies that implicate HFOs and ISA in ictogenesis and discuss current limitations such as inter-observer variability and poor standardization of recording techniques. Furthermore, we propose that HFOs and ISA should be analyzed in addition to activity in the conventional EEG band during intracranial presurgical EEG monitoring to identify the best possible surgical margin.

Joint Encoding of Auditory Timing and Location in Visual Cortex.

Co-occurring sounds can facilitate perception of spatially and temporally correspondent visual events. Separate lines of research have identified two putatively distinct neural mechanisms underlying two types of crossmodal facilitations: Whereas crossmodal phase resetting is thought to underlie enhancements based on temporal correspondences, lateralized occipital evoked potentials (ERPs) are thought to reflect enhancements based on spatial correspondences. Here, we sought to clarify the relationship between these two effects to assess whether they reflect two distinct mechanisms or, rather, two facets of the same underlying process. To identify the neural generators of each effect, we examined crossmodal responses to lateralized sounds in visually responsive cortex of 22 patients using electrocorticographic recordings. Auditory-driven phase reset and ERP responses in visual cortex displayed similar topography, revealing significant activity in pericalcarine, inferior occipital-temporal, and posterior parietal cortex, with maximal activity in lateral occipitotemporal cortex (potentially V5/hMT+). Laterality effects showed similar but less widespread topography. To test whether lateralized and nonlateralized components of crossmodal ERPs emerged from common or distinct neural generators, we compared responses throughout visual cortex. Visual electrodes responded to both contralateral and ipsilateral sounds with a contralateral bias, suggesting that previously observed laterality effects do not emerge from a distinct neural generator but rather reflect laterality-biased responses in the same neural populations that produce phase-resetting responses. These results suggest that crossmodal phase reset and ERP responses previously found to reflect spatial and temporal facilitation in visual cortex may reflect the same underlying mechanism. We propose a new unified model to account for these and previous results.

Small sharp spikes as EEG markers of mesiotemporal lobe epilepsy.

OBJECTIVE: Mesial temporal lobe epilepsy (mTLE) is the most common type of focal epilepsy, but often lacks scalp EEG correlates. We ask if hippocampal epileptiform discharges that are characteristic of mTLE are associated with small sharp spikes (SSS) recorded on scalp EEG. SSS are considered benign waveforms, so are not currently used as markers of epilepsy. METHODS: To determine if there is a relationship between SSS and hippocampal discharges, simultaneous scalp and hippocampal depth electrode EEGs were recorded from 27 patients being evaluated for possible mTLE. Scalp EEG waveforms were assessed at the time of hippocampal discharges identified on intracranial hippocampal depth electrodes. RESULTS: 15 of 27 patients had SSS on scalp EEG that were time locked to hippocampal epileptiform discharges measured intracranially. These hippocampal spikes tended to have overlying high frequency oscillations and to co-localize with a seizure onset zone, suggesting that they were pathological discharges. CONCLUSIONS: There is a tight coupling between a subset of pathological hippocampal discharges and SSS. SIGNIFICANCE: SSS can be scalp EEG markers of mTLE rather than normal EEG variants.

Antiglutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy.

Glutamic acid decarboxylase (GAD) antibody-associated encephalitis causes both acute seizures and chronic epilepsy with predominantly temporal lobe onset. This condition is challenging in diagnosis and management, and the incidence of GAD antibody (Ab)-related epilepsy could be much higher than commonly believed. Imaging and CSF evidence of inflammation along with typical clinical presentations, such as adult onset temporal lobe epilepsy (TLE) with unexplained etiology, should prompt testing for the diagnostic antibodies. High serum GAD Ab titer (≥2000U/mL or ≥20nmol/L) and evidence of intrathecal anti-GAD Ab synthesis support the diagnosis. Unlike other immune-mediated epilepsies, antiglutamic acid decarboxylase 65 (GAD65) antibody-mediated epilepsy is often poorly responsive to antiepileptic drugs (AEDs) and only moderately responsive to immune therapy with steroids, intravenous immunoglobulin (IVIG), or plasma exchange (PLEX). Long-term treatment with more aggressive immunosuppressants such as rituximab (RTX) and/or cyclophosphamide is often necessary and may be more effective than current immunosuppressive approaches. The aim of this review is to review the physiology, pathology, clinical presentation, related ancillary tests, and management of GAD Ab-associated autoimmune epilepsy by searching the keywords and to promote the recognition and the initiation of proper therapy for this condition.

Insights Into the Therapeutic Effect of Responsive Neurostimulation Assessed With Scalp EEG Recording: A Case Report.

The responsive neurostimulation system (RNS) is the first closed-loop neurostimulator approved as an adjunctive treatment for adults with medically refractory focal epilepsy from no more than two seizure foci. In addition to its therapeutic effect, it provides chronic intracranial EEG recordings, with limited storage capacity. Long-term monitoring with scalp EEG recordings can provide additional information regarding seizure patterns, the efficacy of RNS stimulation in aborting individual seizures, and the net effect of RNS on seizure control. We present a 34-year-old woman with medically intractable right temporoparietal lobe epilepsy who failed two resective epilepsy surgeries and MR-guided laser interstitial thermal therapy (MRgLITT), after which RNS was implanted. Long-term scalp EEG performed 16 months after implantation showed continuous right hemisphere slowing and right temporal sharp waves. In addition, RNS stimulation produced bursts of high-voltage, broad-field, surface-negative activity, which allowed correlation of RNS stimulation with scalp EEG patterns. Twenty-seven seizures were captured. Responsive neurostimulation system stimulation did not abort any of the seizures recorded on the scalp EEG. However, the frequency of seizures doubled after RNS stimulation was discontinued and returned to baseline once it was turned back on. This observation supports the neuromodulation effect of RNS.