Search

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.

Background/Aims: Interventional MRI (iMRI) allows real-time confirmation of electrode and microcatheter location in anesthetized patients; however, MRI-compatible pneumatic compression devices (PCD) to reduce the periprocedural venous thromboembolism (VTE) risk are not commercially available. Given the paucity of literature on VTE following iMRI surgery, better characterizing patients suffering this complication and the incidence of this event following iMRI procedures is pivotal for defining best surgical practices. We aim to investigate the incidence of postoperative VTE in iMRI procedures without the use of PCD. Methods: Medical records and operative times of patients were retrospectively reviewed. Patient demographics and mean surgical durations were reported with statistical comparisons via ANOVA and the 2-tailed Student t test, an α of 0.05, and the Bonferroni correction. Patients experiencing postoperative VTE underwent an in-depth chart review. Results: Two out of two hundred ten (0.95%) iMRI procedures resulted in postoperative VTE events. There were statistically significant differences in procedure times between unilateral electrode (157.5 ± 5.7 min), bilateral electrode (193.6 ± 2.9 min), and bilateral gene therapy procedures (467.3 ± 26.5 min). Both patients had longer-than-average operative times for their respective procedures. Conclusions: The incidence of postoperative VTE is low following iMRI procedures, even without the use of PCD during surgery.

Radiation necrosis (RN) is a well described complication seen after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVM). First-line medical therapies are not always successful in alleviating symptoms and management of some cases may require open surgical resection of the lesion. Surgery is often thought of however as a last resort given its associated morbidity especially in the setting of potential concern for residual live AVM. Magnetic resonance imaging (MRI)-guided laser interstitial thermotherapy (LITT) is a minimally invasive surgical procedure that is being increasingly considered for RN lesions and is best established for treatment of symptomatic RN that can develop after stereotactic radiosurgical treatment of metastatic brain tumors. Its ability to treat RN from other primary pathologies remains unclear. Here, we present 2 cases that show successful use of LITT in patients with biopsy-confirmed RN post-radiosurgery for AVMs. As with tumor-associated RN, LITT can result in rapid improvement of symptoms related to reduction in perilesional edema and then shrinkage and eventual stabilization of the RN lesion.

For young children and adolescents with Chiari malformation type I (CM-I), the determinants of extended length of hospital stay (LOS) after neurosurgical suboccipital decompression are obscure. Here, we investigate the impact of patient- and hospital-level risk factors on extended LOS following surgical decompression for CM-I in young children to adolescents.The Kids' Inpatient Database year 2012 was queried. Pediatric CM-I patients (6-18 years) undergoing surgical decompression were identified. Weighted patient demographics, comorbidities, complications, LOS, disposition, and total cost were recorded. A multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree patient comorbidities or post-operative complications correlated with extended LOS.A total of 1592 pediatric CM-I patients were identified for which 328 (20.6%) patients had extended LOS (normal LOS, 1264; extended LOS, 328). Age, gender, race, median household income quartile, and healthcare coverage distributions were similar between the two cohorts. Patients with extended LOS had significantly greater admission comorbidities including headache symptoms, nausea and vomiting, obstructive hydrocephalus, lack of coordination, deficiency anemias, and fluid and electrolyte disorders. On multivariate logistic regression, several risk factors were associated with extended LOS, including headache symptoms, obstructive hydrocephalus, and fluid and electrolyte disorders.Our study using the Kids' Inpatient Database demonstrates that presenting symptoms and signs, including headaches and obstructive hydrocephalus, respectively, are significantly associated with extended LOS following decompression for pediatric CM-I.

The aim of this study was to evaluate regional variations in the management, complications, and total cost of admission for adolescent idiopathic scoliosis (AIS) treated by elective posterior spinal surgery (PSF, ≥4 levels).The Kids' Inpatient Database year 2012 was queried and adolescent patients (age 10-17 years old) with AIS undergoing elective PSF (≥4 levels) were selected. The primary outcome was regional variations for intraoperative and postoperative complications, length of surgery, and total cost of admission after elective PSF intervention.In our cohort of 3759 adolescent patients identified, 704 (18.7%) patients were treated in the Northeast, 917 (24.4%) in the Midwest, 1329 (35.4%) in the South, and 809 (21.5%) in the West (Northeast: n = 704; Midwest: n = 917; South: n = 1329; West: n = 809). The Northeast had the greatest complication rate, followed by the Midwest, South, and West region cohorts (Northeast: 27.7% vs. Midwest: 24.5% vs. South: 23.0% vs. West: 17.2%, P 0.001). On average, length of surgery was shortest in the South (Northeast: 5.3 ± 2.7 days vs. Midwest: 5.3 ± 3.1 days vs. South: 4.9 ± 3.1 days vs. West: 5.3 ± 2.1 days, P 0.001), while the total cost of admission was greatest in the West (Northeast: $51,760 ± $25,177 vs. Midwest: $55,201 ± $23,750 vs. South: $58,847 ± $28,227 vs. West: $60,636 ± $29,372, P0.001).Our study suggests that there may be regional variations in health care resource utilization in AIS patients undergoing multilevel posterior spinal fusions. Further study is warranted to determine the specific factors contributing to disparities in regional outcomes.

Approximately 10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer's disease (AD) both exhibit sleep disturbances, build-up of brain metabolic wastes and amyloid-β (Aβ) plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte aquaporin-4 (AQP4). The glia–lymphatic (glymphatic) system facilitates brain fluid clearance and waste removal during sleep via glia-supported perivascular channels. Human studies have implicated impaired glymphatic function in both AD and iNPH. Continued investigation into the role of glymphatic system biology in AD and iNPH models could lead to new strategies to improve brain health by restoring homeostatic brain metabolism and CSF dynamics.

A 10-year-old girl presented with excessive sweating overlying her right scapula (figure) and stable right leg weakness due to an underlying solid cystic pilocytic astrocytoma spanning T3–T12, debulked 5 months earlier, subsequently re-decompressed with syringosubarachnoid shunt placement secondary to intrasyrinx hemorrhage. MRI demonstrated mild tumor and syrinx progression at T5–T8, limited to the right side (figure, B–E). Focal segmental hyperhidrosis is rare, previously reported in Chiari and trauma-related syringomyelia.1,2 Here, unilateral hyperhidrosis was caused by ipsilateral tumor and syrinx progression. The pathophysiology may be from local tissue damage causing hyperactivity of preganglionic sympathetic neurons or disinhibition of inhibitory local interneurons.2

Racial disparities in spine surgery have been shown to impact surgical management and postoperative complications. However, for adolescent patients with idiopathic scoliosis (AIS) treated by posterior spinal fusion (PSF), the influence of race on postoperative outcomes remains unclear. The aim of the study was to investigate the differences in baseline patient demographics, inpatient management, and postoperative complications for adolescents with AIS undergoing elective, posterior spinal surgery (≥ 4 levels).The Kids' Inpatient Database year 2012 was queried. Adolescent patients (age 10-17 years old) with AIS undergoing elective, PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were divided into 4 cohorts: Black, White, Hispanic, and Other. Patient demographics, comorbidities, complications, length of hospital stay (LOS), discharge disposition and total cost were recorded. The primary outcome was the rate of intraoperative and postoperative complications and resource utilization after elective PSF intervention.Patient demographics significantly differed between the four cohorts. While age was similar (p = 0.288), the White cohort had a greater proportion of female patients (White: 79.0%; Black: 72.1%; Hispanic: 78.2%; Other: 75.9%, p = 0.006), and the Black cohort had the largest proportion of patients in the 0-25th income quartile (White: 16.1%; Black: 43.3%; Hispanic: 28.0%; Other: 15.3%, p 0.001). There were significant differences in hospital region (p 0.001) and bed size (p 0.001) between the cohorts, with more Hispanic adolescents being treated in the West (White: 21.9%; Black: 8.9%; Hispanic: 40.3%; Other: 29.3%) at small hospitals (White: 14.0%; Black: 13.9%; Hispanic: 16.2%; Other: 7.1%). Baseline comorbidities were similar between the cohorts. The use of blood transfusions was significantly greater in the Black cohort compared to the other racial groups (White: 16.7%; Black: 25.0%; Hispanic: 24.5%; Other: 22.7%, p 0.001). The number of vertebral levels involved differed significantly between the cohorts (p 0.001), with the majority of patients having 9-levels or greater involved (White: 80.9%; Black: 81.7%; Hispanic: 84.3%; Other: 67.3%). The rate of complications encountered during admission was greatest in the Other cohort (White: 21.9%; Black: 23.6%; Hispanic: 22.2%; Other: 34.9%, p 0.001). While LOS was similar between the cohorts (p = 0.702), median total cost of admission was highest for Hispanic patients (White: $49,340 [37,908-65,078]; Black: $47,787 [37,718-64,670]; Hispanic: $54,718 [40,689-69,266]; Other: $54,110 [41,292-71,540], p 0.001).Our study suggests that race may not have a significant impact on surgical outcomes after elective posterior spine surgery for adolescent idiopathic scoliosis. Further studies are necessary to corroborate our findings.

The aim of this study was to investigate the national impact of demographic, hospital, and inpatient risk factors on post-traumatic seizure (PTS) development in pediatric patients who presented to the ED following a traumatic brain injury (TBI).The Nationwide Emergency Department Sample database years 2010-2014 was queried. Patients (21 years old) with a primary diagnosis of TBI and subsequent secondary diagnosis of PTS were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. We identified demographic variables, hospital characteristics, pre-existing medical comorbidities, etiology of injuries, and type of injury. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with post-traumatic seizures.We identified 1,244,087 patients who sustained TBI, of which 10,340 (0.83%) developed PTS. Of the patients who had seizures, the youngest cohort aged 0-5 years had the greatest proportion of seizure development (p0.001). Compared to those TBI patients with loss of consciousness (LOC), patients encountering no LOC after TBI had the smallest proportion of seizures while Prolonged LOC with baseline return had the greatest proportion. On univariate analysis of the effect of in-hospital complication on rate of seizures, respiratory, renal and urinary, hematoma, septicemia, and other neurological complications were all significantly associated with seizure development. On multivariate regression, age 6-10 years (OR: 0.48, p0.001) 11-15 years (OR: 0.41, p0.001), and 16-20 years (OR: 0.51, p0.001) were independently associated with decreased risk of developing seizures. Extended LOC with baseline return (OR: 6.33, p0.001), extended LOC without baseline return (OR: 1.95, p = 0.009), and Other LOC (OR: 3.02, p0.001) were independently associated with increased risk of developing seizures. Subarachnoid hemorrhage (OR: 4.14, p0.001), subdural hemorrhage [OR: 7.72, p0.001), and extradural hemorrhage (OR: 3.13, p0.001) were all independently associated with increased risk of developing seizures.Out study demonstrates that various demographic, hospital, and clinical risk factors are associated with the development of seizures following traumatic brain injury. Enhancing awareness of these drivers may help provide greater awareness of patients likely to develop post-traumatic seizures such that this complication can be decreased in incidence so as to improve quality of care and decrease healthcare costs.

Impaired breathing, cardiac function, and arousal during and after seizures are important causes of morbidity and mortality. Previous work suggests that these changes are associated with depressed brainstem function in the ictal and post-ictal periods. Lower brainstem serotonergic systems are postulated to play an important role in cardiorespiratory changes during and after seizures, whereas upper brainstem serotonergic and other systems regulate arousal. However, direct demonstration of seizure-associated neuronal activity changes in brainstem serotonergic regions has been lacking. Here, we performed multiunit and single-unit recordings from medullary raphe and midbrain dorsal raphe nuclei in an established rat seizure model while measuring changes in breathing rate and depth as well as heart rate. Serotonergic neurons were identified by immunohistochemistry. Respiratory rate, tidal volume, and minute ventilation were all significantly decreased during and after seizures in this model. We found that population firing of neurons in the medullary and midbrain raphe on multiunit recordings was significantly decreased during the ictal and post-ictal periods. Single-unit recordings from identified serotonergic neurons in the medullary raphe revealed highly consistently decreased firing during and after seizures. In contrast, firing of midbrain raphe serotonergic neurons was more variable, with a mixture of increases and decreases. The markedly suppressed firing of medullary serotonergic neurons supports their possible role in simultaneously impaired cardiorespiratory function in seizures. Decreased arousal likely arises from depressed population activity of several neuronal pools in the upper brainstem and forebrain. These findings have important implications for preventing morbidity and mortality in people living with epilepsy.SIGNIFICANCE STATEMENTSeizures often cause impaired breathing, cardiac dysfunction, and loss of consciousness. The brainstem and, specifically, brainstem serotonin neurons are thought to play an important role in controlling breathing, cardiac function, and arousal. We used an established rat seizure model to study the overall neuronal activity in the brainstem as well as firing of specific serotonin neurons while measuring cardiorespiratory function. Our results demonstrated overall decreases in brainstem neuronal activity and marked downregulation of lower brainstem serotonin neuronal firing in association with decreased breathing and heart rate during and after seizures. These findings point the way toward new treatments to augment brainstem function and serotonin, aiming to prevent seizure complications and reduce morbidity and mortality in people living with epilepsy.

There is a paucity of literature describing the predictors associated with extended length of hospital stay (LOS) for patients undergoing anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy. The aim of this study was to identify the patient- and hospital-level factors associated with extended LOS for patients with cervical spondylotic myelopathy undergoing ACDF.The National Inpatient Sample database was queried to identify patients with a diagnosis of cervical spondylotic myelopathy undergoing ACDF between 2010 and 2014. Updated trend weights were used to assess patient demographics, comorbidities, complications, LOS, discharge disposition and total cost. Multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree to which patient comorbidities or postoperative complications correlated with extended LOS (3 days).We identified 144,514 patients with 29,947 (20.7%) experiencing an extended LOS (Normal LOS: 114,567; Extended LOS: 29,947). Comorbidities were overall significantly higher in the extended LOS cohort compared to the normal LOS cohort. Patients with extended LOS had a significantly greater proportion of blood transfusion (p 0.001) and 2-3 vertebral levels fused (p 0.001). The overall complication rates were greater in the extended LOS cohort (Normal LOS: 7.4% vs. Extended LOS: 44.8%, p 0.001). The extended LOS cohort incurred $14,489 more in total cost (Normal LOS: $15,486 [11,787-20,623] vs. Extended LOS: $29,975 [21,286-45,285], p 0.001) and had more patients discharged to non-routine locations (p 0.001) compared to the normal LOS cohort. On multivariate logistic regression, several risk-factors were associated with extended LOS including: age, male gender, Black and Hispanic race, patient income, insurance, multiple comorbidities, blood transfusion, and number of complications. The odds ratio for extended LOS was 5.15 (95% CI: 4.68-5.67) for patients with 1 complication and 25.54 (95% CI: 20.54-31.75) for patients with1 complication.Our national cohort study demonstrated multiple patient- and hospital-level factors associated with extended LOS (3 days) after ACDF for CSM. Specifically, patients with an extended LOS had lower socioeconomic status, higher rate of comorbidities, greater percentage of postoperative complications and non-routine discharges, with greater overall costs. Further investigational studies are necessary to identify quality improvement strategies targeted to better optimizing patients preoperatively and reducing perioperative complications in order to improve quality of patient care and reduce hospital LOS.

Gender has been shown to impact several aspects of spine surgical care. However, the influence of gender disparities on discharge disposition after adult spine deformity correction (ASD) is relatively understudied. The aim of this study was to investigate the influence of gender on discharge disposition after elective spinal fusion involving ≥4 levels for ASD correction.The Nationwide Inpatient Sample database (2011-2014) was queried for patients with ASD (≥26 years-old) and elective spine fusion surgery involving ≥4 levels using ICD-9 codes. Patients were stratified by gender: Male or Female. Multivariate linear and logistic regressions were used to assess the impact of gender on length of hospital stay and discharge disposition.A total of 4972 patients were identified of which 3282 (66.0%) were Female and 1690 (34.0%) were Male. The Male cohort had a higher prevalence of comorbidities than the Female cohort. There was a difference in the number of levels operated on between cohorts, with the Female cohort having fewer 4-8-level fusions (77.6% vs. 86.8%) and more 9+-level fusions (23.0% vs. 13.6%) compared to Males. The Female cohort had greater rates of postoperative UTI (5.5% vs. 2.5%) and surgical site hematomas (2.6% vs. 1.3%), while the Male cohort had more postoperative MI (5.4% vs. 1.5%). The Female cohort spent slightly more time in the hospital than Male cohort (6.2 days vs. 5.9 days, P = 0.035). Female patients had a significantly greater proportion of non-routine discharge disposition (F: 48.5% vs. M: 40.3%, P 0.001) compared to Male patients. However, in a multivariate analysis including patient and hospital factors, gender was not an independent predictor of discharge disposition (OR: 0.976, CI: 0.865-1.101, P = 0.688), but was independently associated with increased LOS [female (RR: 0.331, CI: 0.106-0.556, P = 0.004)].Our study suggests gender disparities may not have a significant impact on discharge disposition after spinal fusion for ASD involving four levels or greater. Further studies are necessary to understand risk factors for non-routine discharges in ASD patients to improve quality of patient care and reduced healthcare costs.

The widespread over-use of narcotics has been increasing. However, whether narcotic use impacts surgical outcomes after complex spinal fusion remains understudied. The aim of this study was to evaluate whether there is an association between preoperative narcotic use with perioperative complication rates, patient-reported pain scores, and ambulatory status after complex spinal fusions.The medical records of 134 adult (age ≥18 years) patients with spinal deformity undergoing elective, primary complex spinal fusion (≥5 levels) for deformity correction in a major academic institution from 2005-2015 were reviewed. Patient demographics, comorbidities, intraoperative and postoperative complication rates, pain scores, and ambulatory status were collected for each patient.Patient demographics and comorbidities were similar between both cohorts, except that the Narcotic-User cohort had a greater mean age (57.5 years vs. 50.7 years; P = 0.045) and prevalence of depression (39.4% vs. 16.2%; P = 0.003). Complication rates were similar between both cohorts. The Narcotic-User cohort had significantly higher pain scores at baseline (6.7 ± 2.4 vs. 4.0 ± 3.4; P0.001) and at the first postoperative pain score reported (6.7 ± 2.8 vs. 5.3 ± 2.9; P = 0.013), but had a significantly greater improvement from baseline to last pain score (Narcotic-User: -2.5 ± 3.9 vs. Non-User: -0.5 ± 4.7; P = 0.031). The Narcotic-User cohort had significantly greater ambulation on the first postoperative ambulatory day compared with the Non-User cohort (103.8 ± 144.4 vs. 56.4 ± 84.0; P = 0.031).Our study suggests that the preoperative use of narcotics may impact patient perception of pain and improvement after complex spinal fusions (≥5 levels). Consideration of patients' narcotic status preoperatively may facilitate tailored pain management and physical therapy regimens.

Objective In the past decade, prevalence of obesity in the United States have been soaring at a disparaging rate. Previous spine studies have associated obesity with inferior surgical outcomes, increased complication and 30-day readmission rates, and worsening patient-reported outcomes. However, there is a paucity of data identifying whether the impact of obesity is sustained in patients undergoing complex deformity correction involving 7 levels or greater. The aim of this study was to determine whether obesity impacts surgical outcomes, patient-reported pain scores, and 30-day readmission rates after complex spinal fusions ≥7 levels. Methods The medical records of 112 adult patients (≥18 years old) with spine deformity undergoing elective, primary complex spinal fusion (≥7 levels) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. Preoperative body mass index greater than or equal to 30 kg/m2 was classified as obese. Patient demographics, comorbidities, and intraoperative and postoperative complication rates were collected for each patient. Inpatient patient-reported pain scores and ambulatory status also were collected. The primary outcomes of this study were surgical outcomes, patient-reported pain scores, and 30-day readmission rates. Results Of the 112 patients, 33 (29.5%) were obese (obese: n = 33 vs. non-obese: n = 79). Patient demographics and comorbidities were similar between both cohorts, including age, sex, diabetes, hypertension, and home narcotic use. The median number of fusion levels operated, length of surgery, estimated blood loss, transfusion, and complication rates were similar between both cohorts. Moreover, the postoperative complication profiles between the cohorts also were similar, with a comparable length of hospital stay (obese: 6.5 ± 4.6 days vs. non-obese: 7.0 ± 3.9 days, P = 0.5833) and 30-day readmission rates (obese: 12.1% vs. non-obese: 13.9%, P = 0.7984). Baseline (P = 0.6826), first (P = 0.9691), and last (P = 0.9583) postoperative patient-reported pain scores were similar between cohorts. Analogously, ambulatory status was similar between the cohorts, including days from operating room to ambulation (P = 0.3471) and number of steps on first (P = 0.9173) and last (P = 0.1634) ambulatory day before discharge. Conclusions Our study suggests that obesity does not significantly affect surgical outcomes, patient-reported pain scores, and 30-day readmission rates after complex spinal surgery requiring ≥7 levels of fusion. Further studies are necessary to corroborate our findings.

A 5-month-old boy had bilateral intracranial subdural hematomas from nonaccidental trauma with a poor neurologic examination limited to extremity withdrawal. Spinal imaging (figure) demonstrated a subdural hematoma spanning T4-L5 with cord compression. He underwent L3-5 laminectomies, durotomy, and subdural irrigation, resulting in excellent evacuation of cephalad blood products. Postoperatively, he developed CSF leakage, prompting burr-hole drainage of intracranial subdural hematomas to relieve a suspected pressure gradient between brain and spine. Subdural spinal hematomas are underrecognized but highly morbid injuries that may warrant further imaging workup in cases of severe intracranial injury or poor neurologic examination in suspected nonaccidental trauma.1,2

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.

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.