Thalamic Stimulation Improves Postictal Cortical Arousal and Behavior.

The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy.SIGNIFICANCE STATEMENT The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.

Cortical low-frequency power correlates with behavioral impairment in animal model of focal limbic seizures.

OBJECTIVE: Impairment in consciousness is a debilitating symptom during and after seizures; however, its mechanism remains unclear. Limbic seizures have been shown to spread to arousal circuitry to result in a "network inhibition" phenomenon. However, prior animal model studies did not relate physiological network changes to behavioral responses during or following seizures. METHODS: Focal onset limbic seizures were induced while rats were performing an operant conditioned behavioral task requiring response to an auditory stimulus to quantify how and when impairment of behavioral response occurs. Correct responses were rewarded with sucrose. Cortical and hippocampal electrophysiology measured by local field potential recordings was analyzed for changes in low- and high-frequency power in relation to behavioral responsiveness during seizures. RESULTS: As seen in patients with seizures, ictal (p < .0001) and postictal (p = .0015) responsiveness was variably impaired. Analysis of cortical and hippocampal electrophysiology revealed that ictal (p = .002) and postictal (p = .009) frontal cortical low-frequency 3-6-Hz power was associated with poor behavioral performance. In contrast, the hippocampus showed increased power over a wide frequency range during seizures, and suppression postictally, neither of which were related to behavioral impairment. SIGNIFICANCE: These findings support prior human studies of temporal lobe epilepsy as well as anesthetized animal models suggesting that focal limbic seizures depress consciousness through remote network effects on the cortex, rather than through local hippocampal involvement. By identifying the cortical physiological changes associated with impaired arousal and responsiveness in focal seizures, these results may help guide future therapies to restore ictal and postictal consciousness, improving quality of life for people with epilepsy.

How technology is driving the landscape of epilepsy surgery.

This article emphasizes the role of the technological progress in changing the landscape of epilepsy surgery and provides a critical appraisal of robotic applications, laser interstitial thermal therapy, intraoperative imaging, wireless recording, new neuromodulation techniques, and high-intensity focused ultrasound. Specifically, (a) it relativizes the current hype in using robots for stereo-electroencephalography (SEEG) to increase the accuracy of depth electrode placement and save operating time; (b) discusses the drawback of laser interstitial thermal therapy (LITT) when it comes to the need for adequate histopathologic specimen and the fact that the concept of stereotactic disconnection is not new; (c) addresses the ratio between the benefits and expenditure of using intraoperative magnetic resonance imaging (MRI), that is, the high technical and personnel expertise needed that might restrict its use to centers with a high case load, including those unrelated to epilepsy; (d) soberly reviews the advantages, disadvantages, and future potentials of neuromodulation techniques with special emphasis on the differences between closed and open-loop systems; and (e) provides a critical outlook on the clinical implications of focused ultrasound, wireless recording, and multipurpose electrodes that are already on the horizon. This outlook shows that although current ultrasonic systems do have some limitations in delivering the acoustic energy, further advance of this technique may lead to novel treatment paradigms. Furthermore, it highlights that new data streams from multipurpose electrodes and wireless transmission of intracranial recordings will become available soon once some critical developments will be achieved such as electrode fidelity, data processing and storage, heat conduction as well as rechargeable technology. A better understanding of modern epilepsy surgery will help to demystify epilepsy surgery for the patients and the treating physicians and thereby reduce the surgical treatment gap.

Beyond implantation effect? Long-term seizure reduction and freedom following intracranial monitoring without additional surgical interventions.

The term 'implantation effect' is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients.

A Switch and Wave of Neuronal Activity in the Cerebral Cortex During the First Second of Conscious Perception.

Conscious perception occurs within less than 1 s. To study events on this time scale we used direct electrical recordings from the human cerebral cortex during a conscious visual perception task. Faces were presented at individually titrated visual threshold for 9 subjects while measuring broadband 40-115 Hz gamma power in a total of 1621 intracranial electrodes widely distributed in both hemispheres. Surface maps and k-means clustering analysis showed initial activation of visual cortex for both perceived and non-perceived stimuli. However, only stimuli reported as perceived then elicited a forward-sweeping wave of activity throughout the cerebral cortex accompanied by large-scale network switching. Specifically, a monophasic wave of broadband gamma activation moves through bilateral association cortex at a rate of approximately 150 mm/s and eventually reenters visual cortex for perceived but not for non-perceived stimuli. Meanwhile, the default mode network and the initial visual cortex and higher association cortex networks are switched off for the duration of conscious stimulus processing. Based on these findings, we propose a new "switch-and-wave" model for the processing of consciously perceived stimuli. These findings are important for understanding normal conscious perception and may also shed light on its vulnerability to disruption by brain disorders.

Default mode and visual network activity in an attention task: Direct measurement with intracranial EEG.

Dynamic attention states are necessary to navigate the ever changing task demands of daily life. Previous investigations commonly utilize a block paradigm to study sustained and transient changes in attention networks. fMRI investigations have shown that sustained attention in visual block design attention tasks corresponds to decreased signal in the default mode and visual processing networks. While task negative networks are anticipated to decrease during active task engagement, it is unexpected that visual networks would also be suppressed during a visual task where event-related fMRI studies have found transient increases to visual stimuli. To resolve these competing results, the current investigations utilized intracranial EEG to directly interrogate visual and default mode network dynamics during a visual continuous performance task. We used the electrophysiological data to model expected fMRI signals and to maximize interpretation of current results with previous investigations. Results show broadband gamma power decreases in the default mode network, corresponding to previous EEG and fMRI findings. Meanwhile, visual processing regions including the primary visual cortex and fusiform gyrus demonstrate both sustained decreases during task engagement and stimuli-driven transient increases in gamma power. Modeled fMRI based on gamma power reproduces signal decreases reported in the fMRI literature, and emphasizes the insensitivity of fMRI to transient, regularly spaced signal changes embedded within sustained network dynamics. The signal processing functions of the dynamic visual and default mode network changes explored in this study are unknown but may be elucidated through further investigation.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Seizure susceptibility and infraslow modulatory activity in the intracranial electroencephalogram.

OBJECTIVE: Studies of infraslow amplitude modulations (<0.15 Hz) of band power time series suggest that these envelope correlations may form a basis for distant spatial coupling in the brain. In this study, we sought to determine how infraslow relationships are affected by antiepileptic drug (AED) taper, time of day, and seizure. METHODS: We studied intracranial electroencephalographic (icEEG) data collected from 13 medically refractory adult epilepsy patients who underwent monitoring at Yale-New Haven Hospital. We estimated the magnitude-squared coherence (MSC) at <0.15 Hz of traditional EEG frequency band power time series for all electrode contact pairs to quantify infraslow envelope correlations between them. We studied, first, hour-long background icEEG epochs before and after AED taper to understand the effect of taper. Second, we analyzed the entire record for each patient to study the effect of time of day. Finally, for each patient, we reviewed the clinical record to find all seizures that were at least 6 hours removed from other seizures and analyzed infraslow envelope MSC before and after them. RESULTS: Infraslow envelope MSC increased slightly, but significantly, after AED taper, and increased on average during the night and decreased during the day. It was also increased significantly in all frequency bands up to 3 hours preseizure and 1 hour postseizure as compared to background icEEG (61 seizures studied). These changes occurred for both daytime and nighttime seizures (28 daytime, 33 nighttime). Interestingly, there was significant spatial variability to these changes, with the seizure onset area peaking at 3 hours preseizure, then showing progressive desynchronization from 3 hours preseizure to 1 hour postseizure. SIGNIFICANCE: Infraslow envelope analysis may be used to understand long-term changes over the course of icEEG monitoring, provide unique insight into interictal electrophysiological changes related to ictogenesis, and contribute to the development of novel seizure forecasting algorithms.

Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation.

Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.

Sharp Wave Ripples during Visual Exploration in the Primate Hippocampus.

Hippocampal sharp-wave ripples (SWRs) are highly synchronous oscillatory field potentials that are thought to facilitate memory consolidation. SWRs typically occur during quiescent states, when neural activity reflecting recent experience is replayed. In rodents, SWRs also occur during brief locomotor pauses in maze exploration, where they appear to support learning during experience. In this study, we detected SWRs that occurred during quiescent states, but also during goal-directed visual exploration in nonhuman primates (Macaca mulatta). The exploratory SWRs showed peak frequency bands similar to those of quiescent SWRs, and both types were inhibited at the onset of their respective behavioral epochs. In apparent contrast to rodent SWRs, these exploratory SWRs occurred during active periods of exploration, e.g., while animals searched for a target object in a scene. SWRs were associated with smaller saccades and longer fixations. Also, when they coincided with target-object fixations during search, detection was more likely than when these events were decoupled. Although we observed high gamma-band field potentials of similar frequency to SWRs, only the SWRs accompanied greater spiking synchrony in neural populations. These results reveal that SWRs are not limited to off-line states as conventionally defined; rather, they occur during active and informative performance windows. The exploratory SWR in primates is an infrequent occurrence associated with active, attentive performance, which may indicate a new, extended role of SWRs during exploration in primates. SIGNIFICANCE STATEMENT: Sharp-wave ripples (SWRs) are high-frequency oscillations that generate highly synchronized activity in neural populations. Their prevalence in sleep and quiet wakefulness, and the memory deficits that result from their interruption, suggest that SWRs contribute to memory consolidation during rest. Here, we report that SWRs from the monkey hippocampus occur not only during behavioral inactivity but also during successful visual exploration. SWRs were associated with attentive, focal search and appeared to enhance perception of locations viewed around the time of their occurrence. SWRs occurring in rest are noteworthy for their relation to heightened neural population activity, temporally precise and widespread synchronization, and memory consolidation; therefore, the SWRs reported here may have a similar effect on neural populations, even as experiences unfold.

Delta rhythm in wakefulness: evidence from intracranial recordings in human beings.

A widely accepted view is that wakefulness is a state in which the entire cortical mantle is persistently activated, and therefore desynchronized. Consequently, the EEG is dominated by low-amplitude, high-frequency fluctuations. This view is currently under revision because the 1-4 Hz delta rhythm is often evident during "quiet" wakefulness in rodents and nonhuman primates. Here we used intracranial EEG recordings to assess the occurrence of delta rhythm in 18 awake human beings. Our recordings reveal rhythmic delta during wakefulness at 10% of all recording sites. Delta rhythm could be observed in a single cortical lobe or in multiple lobes. Sites with high delta could flip between high and low delta power or could be in a persistently high delta state. Finally, these sites were rarely identified as the sites of seizure onset. Thus rhythmic delta can dominate the background operation and activity of some neocortical circuits in awake human beings.

Neurostimulation to improve level of consciousness in patients with epilepsy.

When drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states. Improving or preventing alterations in level of consciousness may have an effect on morbidity (e.g., accidents, drownings, falls), risk for death, and quality of life. Recent studies may have elucidated underlying networks and mechanisms of impaired consciousness and yield potential novel targets for neuromodulation. The feasibility, benefits, and pitfalls of potential deep brain stimulation targets are illustrated in human and animal studies involving minimally conscious/vegetative states, movement disorders, depth of anesthesia, sleep-wake regulation, and epilepsy. We review evidence that viable therapeutic targets for impaired consciousness associated with seizures may be provided by key nodes of the consciousness system in the brainstem reticular activating system, hypothalamus, basal ganglia, thalamus, and basal forebrain.

Anaesthesia for deep brain stimulation: a review.

PURPOSE OF REVIEW: Deep brain stimulation (DBS) is a well tolerated and efficacious surgical treatment for movement disorders, chronic pain, psychiatric disorder, and a growing number of neurological disorders. Given that the brain targets are deep and small, accurate electrode placement is commonly accomplished by utilizing frame-based systems. DBS electrode placement is confirmed by microlectrode recordings and macrostimulation to optimize and verify target placement. With a reliance on electrophysiology, proper anaesthetic management is paramount to balance patient comfort without interfering with neurophysiology. RECENT FINDINGS: To achieve optimal pain control, generous amounts of local anaesthesia are instilled into the planned incision. During the opening and closing states, conscious sedation is the prevailing method of anaesthesia. The preferred agents are dexmedetomidine, propofol, and remifentanil, as they affect neurocognitive testing the least, and shorter acting. All the agents are turned off 15-30 min prior to microelectrode recording. Dexmedetomidine has gained popularity in DBS procedures, but has some considerations at higher doses. The addition of ketamine is helpful for pediatric cases. SUMMARY: DBS is a robust surgical treatment for a variety of neurological disorders. Appropriate anaesthetic agents that achieve patient comfort without interfering with electrophysiology are paramount.

The spatial and signal characteristics of physiologic high frequency oscillations.

OBJECTIVES: To study the incidence, spatial distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptic network. METHODS: We included patients who underwent invasive evaluations at Yale Comprehensive Epilepsy Center from 2012 to 2013, had all major lobes sampled, and had localizable seizure onsets. Segments of non-rapid eye movement (NREM) sleep prior to the first seizure were analyzed. We implemented a semiautomated process to analyze oscillations with peak frequencies >80 Hz (ripples 80-250 Hz; fast ripples 250-500 Hz). A contact location was considered epileptic if it exhibited epileptiform discharges during the intracranial evaluation or was involved ictally within 5 s of seizure onset; otherwise it was considered nonepileptic. RESULTS: We analyzed recordings from 1,209 electrode contacts in seven patients. The nonepileptic contacts constituted 79.1% of the total number of contacts. Ripples constituted 99% of total detections. Eighty-two percent of all HFOs were seen in 45.2% of the nonepileptic contacts (82.1%, 47%, 34.6%, and 34% of the occipital, parietal, frontal, and temporal nonepileptic contacts, respectively). The following sublobes exhibited physiologic HFOs in all patients: Perirolandic, basal temporal, and occipital subregions. The ripples from nonepileptic sites had longer duration, higher amplitude, and lower peak frequency than ripples from epileptic sites. A high HFO rate (>1/min) was seen in 110 nonepileptic contacts, of which 68.2% were occipital. Fast ripples were less common, seen in nonepileptic parietooccipital regions only in two patients and in the epileptic mesial temporal structures. CONCLUSIONS: There is consistent occurrence of physiologic HFOs over vast areas of the neocortex outside the epileptic network. HFOs from nonepileptic regions were seen in the occipital lobes and in the perirolandic region in all patients. Although duration of ripples and peak frequency of HFOs are the most effective measures in distinguishing pathologic from physiologic events, there was significant overlap between the two groups.

Ictal spread of medial temporal lobe seizures with and without secondary generalization: an intracranial electroencephalography analysis.

OBJECTIVE: Secondary generalization of seizures has devastating consequences for patient safety and quality of life. The aim of this intracranial electroencephalography (icEEG) study was to investigate the differences in onset and propagation patterns of temporal lobe seizures that remained focal versus those with secondary generalization, in order to better understand the mechanism of secondary generalization. METHODS: A total of 39 seizures were analyzed in nine patients who met the following criteria: (1) icEEG-video monitoring with at least one secondarily generalized tonic-clonic seizure (GTCS), (2) pathologically proven hippocampal sclerosis, and (3) no seizures for at least 1 year after anteromedial temporal lobe resection. Seizures were classified as focal or secondary generalized by behavioral analysis of video. Onset and propagation patterns were compared by analysis of icEEG. RESULTS: We obtained data from 22 focal seizures without generalization (FS), and 17 GTCS. Seizure-onset patterns did not differ between FS and GTCS, but there were differences in later propagation. All seizures started with low voltage fast activity, except for seven seizures in one patient (six FS, one GTCS), which started with sharply contoured theta activity. Fifteen of 39 seizures started from the hippocampus, and 24 seizures (including six seizures in a patient without hippocampal contacts) started from other medial temporal lobe areas. We observed involvement or more prominent activation of the posterior-lateral temporal regions in GTCS prior to propagation to the other cortical regions, versus FS, which had no involvement or less prominent activation of the posterior lateral temporal cortex. Occipital contacts were not involved at the time of clinical secondary generalization. SIGNIFICANCE: The posterior-lateral temporal cortex may serve as an important "gateway" controlling propagation of medial temporal lobe seizures to other cortical regions. Identifying the mechanisms of secondary generalization of focal seizures could lead to improved treatments to confine seizure spread.

Hemifacial spasm and neurovascular compression.

Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve.

Combined neuromodulation and resection for functional cortex epilepsy: a case series.

OBJECTIVE: Medically refractory epilepsy (MRE) often requires resection of the seizure onset zone (SOZ) for effective treatment. However, when the SOZ is in functional cortex (FC), achieving complete and safe resection becomes difficult, due to the seizure network overlap with function. The authors aimed to assess the safety and outcomes of a combined approach involving partial resection combined with focal neuromodulation for FC refractory epilepsy. METHODS: The authors performed a retrospective analysis of individuals diagnosed with MRE who underwent surgical intervention from January 2015 to December 2022. Patients whose SOZ was located in FC and were treated with resection combined with simultaneous implantation of a focal neuromodulation device (responsive neurostimulation [RNS] device) with more than 12 months of follow-up data were included. All patients underwent a standard epilepsy preoperative assessment including intracranial electroencephalography and extraoperative stimulation mapping. Resections were performed under general anesthesia, followed by the concurrent implantation of an RNS device. RESULTS: Seven patients (4 males, median age 32.3 years, all right-handed) were included. The median interval from seizure onset to surgery was 17.4 years. The epileptogenic network included sensorimotor areas (cases 2, 3, and 6), visual cortex (case 1), language areas (cases 4 and 7), and the insula (case 5). The median follow-up was 3 years (range 1-5.8 years). No significant changes in neuropsychological tests were reported. One permanent nondisabling planned neurological deficit (left inferior quadrantanopia) was observed. Six patients had stimulation activated at a median of 4.7 months after resection. All patients achieved good seizure outcomes (5 with Engel class I and 2 with Engel class II outcomes). CONCLUSIONS: Maximal safe resection combined with focal neuromodulation presents a promising alternative to stand-alone resections for MRE epileptogenic zones overlapping with functional brain. This combined approach prioritizes the preservation of function while improving seizure outcomes.

7T MR spectroscopic imaging in the localization of surgical epilepsy.

PURPOSE: With the success that surgical approaches can provide for localization-related epilepsy, accurate seizure localization remains important. Although magnetic resonance (MR) spectroscopy has had success in earlier studies in medial temporal lobe epilepsy, there have been fewer studies evaluating its use in a broader range of localization-related epilepsy. With improvements in signal-to-noise with ultra-high field MR, we report on the use of high resolution 7T MR spectroscopic imaging (MRSI) in 25 surgically treated patients studied over a 3.5-year period. METHODS: Patients were included in this analysis if the region of MRSI study included the surgical resection region. Concordance between region of MRSI abnormalities and of surgical resection was classified into three groups (complete, partial, or no agreement) and outcome was dichotomized by International League Against Epilepsy (ILAE) I-III and IV-VI groups. MRSI was performed with repetition time/echo time 1.5 s/40 msec in two-dimensional (2D) or three-dimensional (3D) encoding for robust detection of singlets N-acetyl aspartate (NAA), creatine (Cr), and choline with abnormalities in NAA/Cr determined with correction for tissue content of gray matter. KEY FINDINGS: The concordance between MRSI-determined abnormality and surgical resection region was significantly related to outcome: Outcome was better if the resected tissue was metabolically abnormal. All 14 patients with complete resection of the region with the most severe metabolic abnormality had good outcome, including five requiring intracranial electroencephalography (EEG) analysis, whereas only 3/11 without complete resection of the most severe metabolic abnormality had good outcome (p < 0.001). SIGNIFICANCE: This is consistent with the seizure-onset zone being characterized by metabolic dysfunction and suggests that high resolution MRSI can help define these regions for the purposes of outcome prediction.

Unexpected recovery of function after severe traumatic brain injury: the limits of early neuroimaging-based outcome prediction.

BACKGROUND: Prognostication in the early stage of traumatic coma is a common challenge in the neuro-intensive care unit. We report the unexpected recovery of functional milestones (i.e., consciousness, communication, and community reintegration) in a 19-year-old man who sustained a severe traumatic brain injury. The early magnetic resonance imaging (MRI) findings, at the time, suggested a poor prognosis. METHODS: During the first year of the patient's recovery, MRI with diffusion tensor imaging and T2*-weighted imaging was performed on day 8 (coma), day 44 (minimally conscious state), day 198 (post-traumatic confusional state), and day 366 (community reintegration). Mean apparent diffusion coefficient (ADC) and fractional anisotropy values in the corpus callosum, cerebral hemispheric white matter, and thalamus were compared with clinical assessments using the Disability Rating Scale (DRS). RESULTS: Extensive diffusion restriction in the corpus callosum and bihemispheric white matter was observed on day 8, with ADC values in a range typically associated with neurotoxic injury (230-400 × 10(-6 )mm(2)/s). T2*-weighted MRI revealed widespread hemorrhagic axonal injury in the cerebral hemispheres, corpus callosum, and brainstem. Despite the presence of severe axonal injury on early MRI, the patient regained the ability to communicate and perform activities of daily living independently at 1 year post-injury (DRS = 8). CONCLUSIONS: MRI data should be interpreted with caution when prognosticating for patients in traumatic coma. Recovery of consciousness and community reintegration are possible even when extensive traumatic axonal injury is demonstrated by early MRI.