Single-level laminoplasty approach to selective dorsal rhizotomy with conus localization by rapid spine MRI.

INTRODUCTION: While selective dorsal rhizotomy (SDR) was originally described as a multilevel approach, single-level approaches are now popularized. Conus localization is beneficial for operative planning in single-level selective dorsal rhizotomy. Our approach to SDR involves minimal exposure for a single-level laminoplasty, preserving one attached interspinous ligament. Pre-operative conus localization is required for this tailored approach to determine the laminoplasty level and dictate rostral or caudal division of the superior spinus ligament. While rapid MRI sequences have been popularized for pediatric cranial imaging, its utility for spinal imagining is less well-described, and specific application for conus localization has not been reported. OBJECTIVE: Illustrate that rapid MRI without sedation is sufficient to identify conus level for tailored single-level laminoplasty SDR. MATERIAL AND METHODS: Patients undergoing SDR from 2014 to 2022 at one institution were reviewed for type of pre-operative MRI (rapid vs full), conus level, procedural time for MRI, and radiology report. The typical rapid MRI has four sequences utilizing single-shot technique (scout, sagittal T2, axial T2, and axial T1) that typically take less than 1 min each of acquisition time, with non-single-shot sequences added periodically in cooperative patients. To include time for patient positioning, pre-scan shimming, procedural incidentals, and other patient-specific variations, MRI procedure length was recorded as documented in the electronic medical record. RESULTS: N = 100 patients had documentation of an MRI for pre-operative imaging. Seventy-nine of these had a rapid MRI, and 21 required a full MRI with anesthesia for their treatment plan. Mean total procedure time for rapid MRI was 21.5 min (median 17). Mean procedure time for MRI under general anesthesia was 91.2 min (median 94). Of patients with rapid MRI imaging, 2/79 had an ambiguous conus level (1 from motion artifact, 1 from spinal hardware) vs 1/21 with a full MRI under anesthesia (due to spinal hardware). CONCLUSION: Rapid spinal MRI without sedation can be used for conus localization in a pediatric population. This may be routinely used as pre-operative imaging for a single-level approach to selective dorsal rhizotomy, without sedation or intubation procedures.

Intraventricular meningioma resection and visual outcomes.

OBJECTIVE: Intraventricular meningiomas (IVMs) of the lateral ventricle are rare tumors that present surgical challenges because of their deep location. Visual field deficits (VFDs) are one risk associated with these tumors and their treatment. VFDs may be present preoperatively due to the tumor and mass effect (tumor VFDs) or may develop postoperatively due to the surgical approach (surgical VFDs). This institutional series aimed to review surgical outcomes following resection of IVMs, with a focus on VFDs. METHODS: Patients who received IVM resection at one academic institution between the years 1996 and 2021 were retrospectively reviewed. Diffusion tensor imaging (DTI) reconstructions of the optic radiations around the tumor were performed from preoperative IVM imaging. The VFD course and resolution were documented. RESULTS: Thirty-two adult patients underwent IVM resection, with gross-total resection in 30 patients (93.8%). Preoperatively, tumor VFDs were present in 6 patients, resolving after surgery in 5 patients. Five other patients (without preoperative VFD) had new persistent surgical VFDs postoperatively (5/32, 15.6%) that persisted to the most recent follow-up. Of the 5 patients with persistent surgical VFDs, 4 received a transtemporal approach and 1 received a transparietal approach, and all these deficits occurred prior to regular use of DTI in preoperative imaging. CONCLUSIONS: New surgical VFDs are a common neurological deficit after IVM resection. Preoperative DTI may demonstrate distortion of the optic radiations around the tumor, thus revealing safe operative corridors to prevent surgical VFDs.

Update on Pediatric Mild Traumatic Brain Injury in Rural and Underserved Regions: A Global Perspective.

BACKGROUND: Mild traumatic brain injury (MTBI) causes morbidity and disability worldwide. Pediatric patients are uniquely vulnerable due to developmental and psychosocial factors. Reduced healthcare access in rural/underserved communities impair management and outcome. A knowledge update relevant to current gaps in care is critically needed to develop targeted solutions. METHODS: The National Library of Medicine PubMed database was queried using comprehensive search terms (("mild traumatic brain injury" or "concussion") and ("rural" or "low-income" or "underserved") and ("pediatric" or "child/children")) in the title, abstract, and Medical Subject Headings through December 2022. Fifteen articles on rural/underserved pediatric MTBI/concussion not covered in prior reviews were examined and organized into four topical categories: epidemiology, care practices, socioeconomic factors, and telehealth. RESULTS: Incidences are higher for Individuals in rural regions, minorities, and those aged 0-4 years compared to their counterparts, and are increasing over time. Rural healthcare utilization rates generally exceed urban rates, and favor emergency departments (vs. primary care) for initial injury assessment. Management guidelines require customization to resource-constrained settings for implementation and adoption. Decreased community recognition of the seriousness of injury is a consensus challenge to care provision by clinicians. Low parental education and income were correlated with decreased MTBI knowledge and worse outcome. Telehealth protocols for triage/consultation and rehabilitation were feasible in improving care delivery to rural and remote settings. CONCLUSIONS: Pediatric MTBI/concussion patients in rural/underserved regions experience increased risks of injury, geographic and financial healthcare barriers, and poorer outcomes. Globally, under-reporting of injury has hindered epidemiological understanding. Ongoing MTBI education should be implemented for rural caregivers, schools, and low-income populations to improve community awareness. Telehealth can improve care delivery across acuity settings, and warrants judicious inclusion in triage and treatment protocols.

Dissociation of Broca's area from Broca's aphasia in patients undergoing neurosurgical resections.

OBJECTIVE: Broca's aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca's aphasia following surgical lesions. METHODS: Patients were prospectively evaluated with standardized language batteries before and after surgery. Broca's area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca's aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca's aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca's area compared to areas identified using the VLSM algorithm. RESULTS: A total of 289 patients had early language evaluations, of whom 19 had postoperative Broca's aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca's aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area. CONCLUSIONS: Broca's aphasia does not typically arise from neurosurgical resections in Broca's area. When Broca's aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and supramarginal gyri.

Paraparesis caused by intradural thoracic spinal granuloma secondary to organizing hematoma: illustrative case.

BACKGROUND: Spinal granulomas form from infectious or noninfectious inflammatory processes and are rarely present intradurally. Intradural granulomas secondary to hematoma are unreported in the literature and present diagnostic and management challenges. OBSERVATIONS: A 70-year-old man receiving aspirin presented with encephalopathy, subacute malaise, and right lower extremity weakness and was diagnosed with polysubstance withdrawal and refractory hypertension requiring extended treatment. Seven days after admission, he reported increased bilateral lower extremity (BLE) weakness. Magnetic resonance imaging showed T2-3 and T7-8 masses abutting the pia, with spinal cord compression at T2-3. He was transferred to the authors' institution, and work-up showed no vascular shunting or malignancy. He underwent T2-3 laminectomies for biopsy/resection. A firm, xanthochromic mass was resected en bloc. Pathology showed organizing hematoma without infection, vascular malformation, or malignancy. Subsequent coagulopathy work-up was unremarkable. His BLE strength significantly improved, and he declined resection of the inferior mass. He completed physical therapy and was cleared for placement in a skilled nursing facility. LESSONS: Spinal granulomas can mimic vascular lesions and malignancy. The authors present the first report of paraparesis caused by intradural granuloma secondary to organizing hematoma, preceded by severe refractory hypertension. Tissue diagnosis is critical, and resection is curative. These findings can inform the vigilant clinician for expeditious treatment.

Improved psychotic symptoms following resection of amygdalar low-grade glioma: illustrative case.

BACKGROUND: Epilepsy-associated psychoses are poorly understood, and management is focused on treating epilepsy. Chronic, interictal psychosis that persists despite seizure control is typically treated with antipsychotics. Whether resection of a mesial temporal lobe lesion may improve interictal psychotic symptoms that persist despite seizure control remains unknown. OBSERVATIONS: In a 52-year-old man with well-controlled epilepsy and persistent comorbid psychosis, brain magnetic resonance imaging (MRI) revealed an infiltrative, intraaxial, T2 fluid-attenuated inversion recovery intense mass of the left amygdala. The patient received an amygdalectomy for oncological diagnosis and surgical treatment of a presumed low-grade glioma. Pathology was ganglioglioma, World Health Organization grade I. Postoperatively, the patient reported immediate resolution of auditory hallucinations. Patient has remained seizure-free on 2 antiepileptic drugs and no antipsychotic pharmacotherapy and reported lasting improvement in his psychotic symptoms. LESSONS: This report discusses improvement of psychosis symptoms after resection of an amygdalar glioma, independent of seizure outcome. This case supports a role of the amygdala in psychopathology and suggests that low-grade gliomas of the limbic system may represent, at minimum, partially reversible etiology of psychotic symptoms.

Xenotransplantation of porcine progenitor cells in an epileptic California sea lion (Zalophus californianus): illustrative case.

BACKGROUND: Domoic acid (DA) is a naturally occurring neurotoxin harmful to marine animals and humans. California sea lions exposed to DA in prey during algal blooms along the Pacific coast exhibit significant neurological symptoms, including epilepsy with hippocampal atrophy. OBSERVATIONS: Here the authors describe a xenotransplantation procedure to deliver interneuron progenitor cells into the damaged hippocampus of an epileptic sea lion with suspected DA toxicosis. The sea lion has had no evidence of seizures after the procedure, and clinical measures of well-being, including weight and feeding habits, have stabilized. LESSONS: These preliminary results suggest xenotransplantation has improved the quality of life for this animal and holds tremendous therapeutic promise.

Hydrothermal conversion of toilet waste: effect of processing conditions on gas phase emissions.

Globally, many populations suffer from a lack of access to basic sanitation facilities. This is partly caused by a combination of water resource shortages and the high cost of conventional centralised treatment systems. A novel decentralised treatment technology based on sub-critical hydrothermal processing of organic wastes at toilet-scale, contributes to addressing these economic and resource limitations. To be effective, this technology needs to satisfy a broad range of environmental and safety considerations, including the nature and quantity of formed gas products. We investigated the impact of four process parameters (temperature; O2: COD ratio (λ); time; feed solids content) on off-gas composition by quantifying volatile organic compounds (VOCs), CO, H2 and CO2 in factorial experiments. Temperature and λ influenced VOCs generation greatly. The lowest VOC emissions occurred at 200% λ and 300 °C. Aldehydes and ketones were mostly generated at 200% λ and intermediate temperatures, sulphur compounds in the absence of oxygen, and aromatics, furans, and pyrroles at intermediate oxygen levels and elevated temperatures. Most CO was created at 300 °C but its concentration decreased at longer processing times. Processing conditions have complex impacts and require careful consideration when designing for real world deployment.

Plurihormonal PIT-1-Positive Pituitary Adenomas: A Systematic Review and Single-Center Series.

OBJECTIVE: The 2017 World Health Organization classification of pituitary adenomas identified the plurihormonal PIT-1-positive (PP1) adenoma as a distinct subtype. The reported data suggest that PP1 adenomas encompass the former class of silent subtype 3 (SS3) adenomas and might have an aggressive phenotype. In the present study, we summarized the current clinical data on PP1 and SS3 adenomas and compared the reported data with the data from a single institutional cohort. METHODS: Medline and Google Scholar were searched from 1990 to 2020 for clinical series of PP1 and SS3 adenomas in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Studies were included if they had reported pituitary pathology as PP1 or SS3 adenomas and had reported the clinical outcomes after surgical intervention. To better define the PP1 phenotype compared with non-PP1 adenomas, we also reviewed the adenomas treated surgically at our institution from 2012 to 2019. RESULTS: Of all the tumors reported in the studies as PP1 or SS3, 99% were macroadenomas and 18% were giant adenomas (>4 cm). Of the reported patients, 31.8% had received radiotherapy, and 22.9% had undergone multiple surgeries for their pituitary tumor. In our single-center experience, 20 patients had an adenoma that met the criteria for a PP1 adenoma. Compared with the 1146 non-PP1 tumors, the PP1 tumors did not show statistically significant differences in the extent of resection, size, number of previous surgeries, future reoperations, rate of radiotherapy, p53 staining, or MIB-1 labeling index. CONCLUSIONS: The findings from the present large, single-center study comparing PP1 and non-PP1 adenomas do not suggest that PP1 tumors are more aggressive. Further work is warranted to identify the pathologic subtypes of pituitary adenomas that are consistently more clinically aggressive.

Prosopagnosia following nonlanguage dominant inferior temporal lobe low-grade glioma resection in which the inferior longitudinal fasciculus was disrupted preoperatively: illustrative case.

BACKGROUND: Prosopagnosia is a rare neurological condition characterized by the impairment of face perception with preserved visual processing and cognitive functioning and is associated with injury to the fusiform gyrus and inferior longitudinal fasciculus (ILF). Reports of this clinical impairment following resection of right temporal lobe diffuse gliomas in the absence of contralateral injury are exceedingly scarce and not expected as a complication of surgery. OBSERVATIONS: The authors describe the case of a young female patient found to have an incidental diffuse glioma in the right inferior temporal lobe despite evidence of preoperative ILF disruption by the tumor. Following resection of the lesion, despite the preoperative disruption to the ILF by the tumor, the patient developed prosopagnosia. There was no evidence of contralateral, left-sided ILF injury. LESSONS: Given the significant functional impairment associated with prosopagnosia, neurosurgeons should be aware of the exceedingly rare possibility of a visual-processing deficit following unilateral and, in this case, right-sided inferior temporal lobe glioma resections. More investigation is needed to determine whether preoperative testing can determine dominance of facial-processing networks for patients with lesions in the right inferior posterior temporooccipital lobe and whether intraoperative mapping could help prevent this complication.

Paramedian transparietal approach to a dominant hemisphere intraventricular meningioma: illustrative case.

BACKGROUND: Meningiomas of the atrium of the lateral ventricle present a unique operative challenge. Parietal transcortical approaches have been described with an oblique approach, but a strictly paramedian approach may offer advantages in a dominant hemisphere atrial meningioma. OBSERVATIONS: The patient presented with several weeks of intermittent headaches. Magnetic resonance imaging (MRI) showed an enhancing intraventricular mass in the atrium of the left lateral ventricle. Three-dimensional reconstructions were created from a preoperative MRI, with 1-mm slices for neuronavigation. Diffusion tensor imaging (DTI) was obtained, and tracts were reconstructed in the patient's three-dimensional brainspace. DTI tractography delineated a paramedian transparietal corridor devoid of functional white matter tracks. The patient was positioned supine, in a semislouch position. A left parietal craniotomy was performed. Neuronavigation identified a gyrus posterior to the sensory cortex, anterior to the optic radiations and medial to superior longitudinal and arcuate fasciculus fiber tracts. The tumor was debulked to allow mobilization to coagulate capsular blood supply. Gross total resection was achieved. The patient was discharged postoperatively on day 3 without neurological deficits. LESSONS: A paramedian transparietal approach to a dominant hemisphere meningioma of the lateral ventricle can be a safe and effective way to resect tumors in this anatomically unique operative corridor.

Decompression of a Dorsal Arachnoid Web of the Spine: 2-Dimensional Operative Video.

Arachnoid webs of the spine are a relatively rare entity with unique radiological findings, most notably the scalpel-sign on sagittal magnetic resonance imaging (MRI).1-4 To date there have been no videographic descriptions of the surgical treatment for this clinical entity. We present the case of a patient with progressive myelopathy and MRI showing a cervical and thoracic syrinx with a sharp transition point at the level of the T5 vertebral body. On computed tomography myelogram, there was preserved cerebrospinal fluid (CSF) in the ventral subarachnoid space-this space is often interrupted in ventral cord herniation, and preserved in dorsal arachnoid webs.5 A laminectomy with intradural excision of arachnoid web was offered and the patient consented for the procedure. Preoperatively, a fiducial screw was placed at T5. A T4-6 laminectomy was performed. A clearly compressive arachnoid web was encountered on exposure. Bands were dissected under an operating microscope, restoring normal CSF flow. Ventral dural defect was ruled out by passing a delicot beneath the cord and withdrawing it on the contralateral side. The patient did well and has shown improvement in myelopathic symptoms at 1- and 3-mo follow-up. Arachnoid webs of the spine can be treated effectively with a prudent, stepwise approach, and careful microsurgical technique. The neurosurgeon should consult closely with their neuroradiology colleagues to rule out other entities prior to the operation, such as ventral cord herniations, which can mimic dorsal arachnoid webs radiologically and clinically. We have received informed consent of the patient to submit this video.

Early seizure spread and epilepsy surgery: A systematic review.

OBJECTIVE: A fundamental question in epilepsy surgery is how to delineate the margins of cortex that must be resected to result in seizure freedom. Whether and which areas showing seizure activity early in ictus must be removed to avoid postoperative recurrence of seizures is an area of ongoing research. Seizure spread dynamics in the initial seconds of ictus are often correlated with postoperative outcome; there is neither a consensus definition of early spread nor a concise summary of the existing literature linking seizure spread to postsurgical seizure outcomes. The present study is intended to summarize the literature that links seizure spread to postoperative seizure outcome and to provide a framework for quantitative assessment of early seizure spread. METHODS: A systematic review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A Medline search identified clinical studies reporting data on seizure spread measured by intracranial electrodes, having at least 10 subjects and reporting at least 1-year postoperative outcome in the English literature from 1990 to 2019. Studies were evaluated regarding support for a primary hypothesis: Areas of early seizure spread represent cortex with seizure-generating potential. RESULTS: The search yielded 4562 studies: 15 studies met inclusion criteria and 7 studies supported the primary hypothesis. The methods and metrics used to describe seizure spread were heterogenous. The timeframe of seizure spread associated with seizure outcome ranged from 1-14 seconds, with large, well-designed, retrospective studies pointing to 3-10 seconds as most likely to provide meaningful correlates of postoperative seizure freedom. SIGNIFICANCE: The complex correlation between electrophysiologic seizure spread and the potential for seizure generation needs further elucidation. Prospective cohort studies or trials are needed to evaluate epilepsy surgery targeting cortex involved in the first 3-10 seconds of ictus.

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.

Pure Apraxia of Speech After Resection Based in the Posterior Middle Frontal Gyrus.

BACKGROUND AND IMPORTANCE: Apraxia of speech is a disorder of articulatory coordination and planning in speech sound production. Its diagnosis is based on deficits in articulation, prosody, and fluency. It is often described concurrent with aphasia or dysarthria, while pure apraxia of speech is a rare entity. CLINICAL PRESENTATION: A right-handed man underwent focal surgical resection of a recurrent grade III astrocytoma in the left hemisphere dorsal premotor cortex located in the posterior middle frontal gyrus. After the procedure, he experienced significant long-term speech production difficulties. A battery of standard and custom language and articulatory assessments were administered, revealing intact comprehension and naming abilities, and preserved strength in orofacial articulators, but considerable deficits in articulatory coordination, fluency, and prosody-consistent with diagnosis of pure apraxia of speech. Tractography and resection volumes compared with publicly available imaging data from the Human Connectome Project suggest possible overlap with area 55b, an under-recognized language area in the dorsal premotor cortex and has white matter connectivity with the superior longitudinal fasciculus. CONCLUSION: The case reported here details a rare clinical entity, pure apraxia of speech resulting from resection of posterior middle frontal gyrus. While not a classical language area, emerging literature supports the role of this area in the production of fluent speech, and has implications for surgical planning and the general neurobiology of language.

Up and Down States of Cortical Neurons in Focal Limbic Seizures.

Recent work suggests an important role for cortical-subcortical networks in seizure-related loss of consciousness. Temporal lobe seizures disrupt subcortical arousal systems, which may lead to depressed cortical function and loss of consciousness. Extracellular recordings show ictal neocortical slow waves at about 1 Hz, but it is not known whether these simply represent seizure propagation or alternatively deep sleep-like activity, which should include cortical neuronal Up and Down states. In this study, using in vivo whole-cell recordings in a rat model of focal limbic seizures, we directly examine the electrophysiological properties of cortical neurons during seizures and deep anesthesia. We found that during seizures, the membrane potential of frontal cortical secondary motor cortex layer 5 neurons fluctuates between Up and Down states, with decreased input resistance and increased firing rate in Up states when compared to Down states. Importantly, Up and Down states in seizures are not significantly different from those in deep anesthesia, in terms of membrane potential, oscillation frequency, firing rate, and input resistance. By demonstrating these fundamental similarities in cortical electrophysiology between deep anesthesia and seizures, our results support the idea that a state of decreased cortical arousal may contribute to mechanisms of loss of consciousness during seizures.

Mechanisms of decreased cholinergic arousal in focal seizures: In vivo whole-cell recordings from the pedunculopontine tegmental nucleus.

Focal limbic seizures often impair consciousness/awareness with major negative impact on quality of life. Recent work has shown that limbic seizures depress brainstem arousal systems, including reduced action potential firing in a key node: cholinergic neurons of the pedunculopontine tegmental nucleus (PPT). In vivo whole-cell recordings have not previously been achieved in PPT, but are used here with the goal of elucidating the mechanisms of reduced PPT cholinergic neuronal activity. An established model of focal limbic seizures was used in rats following brief hippocampal stimulation under light anesthesia. Whole-cell in vivo recordings were obtained from PPT neurons using custom-fabricated 9-10 mm tapered patch pipettes, and cholinergic neurons were identified histologically. Average membrane potential, input resistance, membrane potential fluctuations and variance were analyzed during seizures. A subset of PPT neurons exhibited reduced firing and hyperpolarization during seizures and stained positive for choline acetyltransferase. These PPT neurons showed a mean membrane potential hyperpolarization of -3.82 mV (±0.81 SEM, P < .05) during seizures, and also showed significantly increased input resistance, fewer excitatory post-synaptic potential (EPSP)-like events (P < .05), and reduced membrane potential variance (P < .01). The combination of increased input resistance, decreased EPSP-like events and decreased variance weigh against active ictal inhibition and support withdrawal of excitatory input as the dominant mechanism of decreased activity of cholinergic neurons in the PPT. Further identifying synaptic mechanisms of depressed arousal during seizures may lead to new treatments to improve ictal and postictal cognition.

Association of Seizure Spread With Surgical Failure in Epilepsy.

Importance: Seizures recur in as many as half of patients who undergo surgery for drug-resistant temporal lobe epilepsy (TLE). Understanding why TLE is resistant to surgery in some patients may reveal insights into epileptogenic networks and direct new therapies to improve outcomes. Objective: To characterize features of surgically refractory TLE. Design, Setting, and Participants: Medical records from a comprehensive epilepsy center were retrospectively reviewed for 131 patients who received a standard anteromedial temporal resection by a single surgeon from January 1, 2000, to December 31, 2015. Thirteen patients were excluded for having less than 1 year of follow-up. Patients at the highest risk for seizure recurrence were identified. Intracranial electroencephalogram (iEEG) analyses generated 3-dimensional seizure spread representations and quantified rapid seizure spread. The final analyses of seizure outcome and follow-up data were performed in June 2017. Main Outcomes and Measures: The Engel class seizure outcome following surgery was evaluated for all patients, defining seizure recurrence as Engel class II or greater. Intracranial recordings of neocortical grids/strips and depth electrodes were analyzed visually for seizure spread. Fast ß power was projected onto reconstructions of patients' brain magnetic resonance imaging scans to visualize spread patterns and was quantified to compare power within vs outside resective margins. Results: Of 118 patients with 1 year of follow-up or more (mean [SD], 6.5 [4.6] years), 66 (55.9%) were women and 52 (44.1%) were men (median age, 39 years [range, 4-66 years]). The cumulative probability of continuous Engel class I seizure freedom since surgery at postoperative year 10 and afterward was 65.6%, with 92% of recurrences in years 1 to 3. Multivariable statistical analyses found that the selection for iEEG study was the most reliable predictor of seizure recurrence, with a mixed-effects model estimating that the Engel score in the iEEG cohort was higher by a mean (SD) of 1.1 (0.33) (P = .001). In patients with iEEG results, rapid seizure spread in less than 10 seconds was associated with recurrence (hazard ratio, 5.99; 95% CI, 1.7-21.1; P < .01). In the first 10 seconds of seizures, fast ß power activity outside the resective margins in the lateral temporal cortex was significantly greater in patients whose seizures recurred compared with patients who were seizure-free (mean [SEM], 137.5% [16.8%] vs 93.4% [4.6%]; P < .05). Conclusions and significance: Rapid seizure spread outside anteromedial temporal resection resective margins plays a significant role in the surgical failure of drug-resistant TLE. Seizure control after epilepsy surgery might be improved by investigating areas of early spread as candidates for resection or neuromodulation.

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.