A neurocomputational theory of action regulation predicts motor behavior in neurotypical individuals and patients with Parkinson's disease.

Surviving in an uncertain environment requires not only the ability to select the best action, but also the flexibility to withhold inappropriate actions when the environmental conditions change. Although selecting and withholding actions have been extensively studied in both human and animals, there is still lack of consensus on the mechanism underlying these action regulation functions, and more importantly, how they inter-relate. A critical gap impeding progress is the lack of a computational theory that will integrate the mechanisms of action regulation into a unified framework. The current study aims to advance our understanding by developing a neurodynamical computational theory that models the mechanism of action regulation that involves suppressing responses, and predicts how disruption of this mechanism can lead to motor deficits in Parkinson's disease (PD) patients. We tested the model predictions in neurotypical individuals and PD patients in three behavioral tasks that involve free action selection between two opposed directions, action selection in the presence of conflicting information and abandoning an ongoing action when a stop signal is presented. Our results and theory suggest an integrated mechanism of action regulation that affects both action initiation and inhibition. When this mechanism is disrupted, motor behavior is affected, leading to longer reaction times and higher error rates in action inhibition.

Perioperative dual antiplatelet therapy for patients undergoing spine surgery soon after drug eluting stent placement.

BACKGROUND: Performing emergent spinal surgery within 6 months of percutaneous placement of drug-eluting coronary stent (DES) is complex. The risks of spinal bleeding in a "closed space" must be compared with the risks of stent thrombosis or major cardiac event from dual antiplatelet therapy (DAPT) interruption. METHODS: Eighty relevant English language papers published in PubMed were reviewed in detail. RESULTS: Variables considered regarding surgery in patients on DAPT for DES included: (1) surgical indications, (2) percutaneous cardiac intervention (PCI) type (balloon angioplasty vs. stenting), (3) stent type (drug-eluting vs. balloon mechanical stent), and (4) PCI to noncardiac surgery interval. The highest complication rate was observed within 6 weeks of stent placement, this corresponds to the endothelialization phase. Few studies document how to manage patients with critical spinal disease warranting operative intervention within 6 months of their PCI for DES placement. CONCLUSION: The treatment of patients requiring urgent or emergent spinal surgery within 6 months of undergoing a PCI for DES placement is challenging. As early interruption of DAPT may have catastrophic consequences, we hereby proposed a novel protocol involving stopping clopidogrel 5 days before and aspirin 3 days before spinal surgery, and bridging the interval with a reversible P2Y12 inhibitor until surgery. Moreover, postoperatively, aspirin could be started on postoperative day 1 and clopidogrel on day 2. Nevertheless, this treatment strategy may not be appropriate for all patients, and multidisciplinary approval of perioperative antiplatelet therapy management protocols is essential.

Postoperative Admission of Adult Craniotomy Patients to the Neuroscience Ward Reduces Length of Stay and Cost.

BACKGROUND: The neurointensive care unit (NICU) has traditionally been the default recovery unit after elective craniotomies. OBJECTIVE: To assess whether admitting adult patients without significant comorbidities to the neuroscience ward (NW) instead of NICU for recovery resulted in similar clinical outcome while reducing length of stay (LOS) and hospitalization cost. METHODS: We retrospectively analyzed the clinical and cost data of adult patients undergoing supratentorial craniotomy at a university hospital within a 5-yr period who had a LOS less than 7 d. We compared those admitted to the NICU for 1 night of recovery versus those directly admitted to the NW. RESULTS: The NICU and NW groups included 340 and 209 patients, respectively, and were comparable in terms of age, ethnicity, overall health, and expected LOS. NW admissions had shorter LOS (3.046 vs 3.586 d, P < .001), and independently predicted shorter LOS in multivariate analysis. While the NICU group had longer surgeries (6.8 vs 6.4 h), there was no statistically significant difference in the cost of surgery. The NW group was associated with reduced hospitalization cost by $3193 per admission on average (P < .001). Clinically, there were no statistically significant differences in the rate of return to Operating Room, Emergency Department readmission, or hospital readmission within 30 d. CONCLUSION: Admitting adult craniotomy patients without significant comorbidities, who are expected to have short LOS, to NW was associated with reduced LOS and total cost of admission, without significant differences in postoperative clinical outcome.

Effect of Gene Mutation on Seizures in Surgery for Tuberous Sclerosis Complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disorder that commonly leads to drug-resistant epilepsy in affected patients. This study aimed to determine whether the underlying genetic mutation (TSC1 vs. TSC2) predicts seizure outcomes following surgical treatments for epilepsy. METHODS: We retrospectively assessed TSC patients using the TSC Natural History Database core registry. Data review focused on outcomes in patients treated with surgical resection or vagus nerve stimulation. RESULTS: A total of 42 patients with a TSC1 mutation, and 145 patients with a TSC2 mutation, were identified. We observed a distinct clinical phenotype: children with TSC2 mutations tended to be diagnosed with TSC at a younger age than those with a TSC1 mutation (p < 0.001), were more likely to have infantile spasms (p < 0.001), and to get to surgery at a later age (p = 0.003). Among this TSC2 cohort, seizure control following resective epilepsy surgery was achieved in less than half (47%) the study sample. In contrast, patients with TSC1 mutations tended to have more favorable postsurgical outcomes; seizure control was achieved in 66% of this group. CONCLUSION: TSC2 mutations result in a more severe epilepsy phenotype that is also less responsive to resective surgery. It is important to consider this distinct clinical disposition when counseling families preoperatively with respect to seizure freedom. Larger samples are required to better characterize the independent effects of genetic mutation, infantile spasms, and duration of epilepsy as they relate to seizure control following resective or neuromodulatory epilepsy surgery.

Novel tonometer device distinguishes brain stiffness in epilepsy surgery.

Complete surgical resection of abnormal brain tissue is the most important predictor of seizure freedom following surgery for cortical dysplasia. While lesional tissue is often visually indiscernible from normal brain, anecdotally, it is subjectively stiffer. We report the first experience of the use of a digital tonometer to understand the biomechanical properties of epilepsy tissue and to guide the conduct of epilepsy surgery. Consecutive epilepsy surgery patients (n = 24) from UCLA Mattel Children's Hospital were recruited to undergo intraoperative brain tonometry at the time of open craniotomy for epilepsy surgery. Brain stiffness measurements were corrected with abnormalities on neuroimaging and histopathology using mixed-effects multivariable linear regression. We collected 249 measurements across 30 operations involving 24 patients through the pediatric epilepsy surgery program at UCLA Mattel Children's Hospital. On multivariable mixed-effects regression, brain stiffness was significantly associated with the presence of MRI lesion (ß = 32.3, 95%CI 16.3-48.2; p < 0.001), severity of cortical disorganization (ß = 19.8, 95%CI 9.4-30.2; p = 0.001), and recent subdural grid implantation (ß = 42.8, 95%CI 11.8-73.8; p = 0.009). Brain tonometry offers the potential of real-time intraoperative feedback to identify abnormal brain tissue with millimeter spatial resolution. We present the first experience with this novel intraoperative tool for the conduct of epilepsy surgery. A carefully designed prospective study is required to elucidate whether the clinical application of brain tonometry during resective procedures could guide the area of resection and improve seizure outcomes.

Patient Safety Analysis in Radiation Burden of Head Computed Tomography Imaging in 1185 Neurosurgical Inpatients.

OBJECTIVE: We performed a retrospective analysis in a cohort of 1185 patients at our institution who were identified as undergoing ≥1 head computed tomography (CT) examinations during their inpatient stay on the neurosurgery service, to quantify the number, type, and associated radiation burden of head CT procedures performed by the neurosurgery service. METHODS: CT procedure records and radiology reports were obtained via database search and directly validated against records retrieved from manual chart review. Next, dosimetry data from the head CT procedures were extracted via automated text mining of electronic radiology reports. RESULTS: Among 4510 identified adult head CT procedures, 88% were standard head CT examinations. A total of 3.65 ± 3.60 head CT scans were performed during an average adult admission. The most common primary diagnoses were neoplasms, trauma, and other hemorrhage. The median cumulative effective dose per admission was 5.66 mSv (range, 1.06-84.5 mSv; mean, 8.56 ± 8.95 mSv). The median cumulative effective dose per patient was 6.4 mSv (range, 1.1-127 mSv; mean, 9.26 ± 10.0 mSv). CONCLUSIONS: The median cumulative radiation burden from head CT imaging in our cohort equates approximately to a single chest CT scan, well within accepted limits for safe CT imaging in adults. Refined methods are needed to characterize the safety profile of the few pediatric patients identified in our study.

Quantitative Analysis of Neural Foramina in the Lumbar Spine: An Imaging Informatics and Machine Learning Study.

PURPOSE: To use machine learning tools and leverage big data informatics to statistically model the variation in the area of lumbar neural foramina in a large asymptomatic population. MATERIALS AND METHODS: By using an electronic health record and imaging archive, lumbar MRI studies in 645 male (mean age, 50.07 years) and 511 female (mean age, 48.23 years) patients between 20 and 80 years old were identified. Machine learning algorithms were used to delineate lumbar neural foramina autonomously and measure their areas. The relationship between neural foraminal area and patient age, sex, and height was studied by using multivariable linear regression. RESULTS: Neural foraminal areas correlated directly with patient height and inversely with patient age. The associations involved were statistically significant (P < .01). CONCLUSION: By using machine learning and big data techniques, a linear model encoding variation in lumbar neural foraminal areas in asymptomatic individuals has been established. This model can be used to make quantitative assessments of neural foraminal areas in patients by comparing them to the age-, sex-, and height-adjusted population averages.© RSNA, 2019Supplemental material is available for this article.

Neuromodulation for substance addiction in human subjects: A review.

Substance abuse is one of the most prevalent and costly health problems in the world today. Standard medical therapy is often not curative, and relapse is common. Research over the past several decades on the neural underpinnings of addiction has implicated a network of structures within the brain shown to be altered in patients with substance abuse. The field of neuromodulation aims to utilize this knowledge to treat dysfunctional circuits by targeting and modulating specific brain circuits. While invasive neuromodulation such as DBS and VNS have proven to be effective in treating movement disorders, OCD and epilepsy, there is increasing interest and data with regards to its potential application for the treatment of severe, intractable addiction. Several neuromodulatory techniques and brain targets are currently under investigation in patients with various substance abuse disorders. This review aims to summarize the current state of evidence for neurosurgical neuromodulation as a therapy for substance abuse and addiction, and to provide additional expert opinions as to the obstacles and future directions of this endeavor.

Autonomous Trajectory Planning for External Ventricular Drain Placement.

BACKGROUND: External ventricular drain (EVD) placement is the most frequently performed neurosurgical procedure for management of various conditions including hydrocephalus, traumatic brain injury, and stroke. State-of-the-art computational pattern recognition techniques could improve the safety and accuracy of EVD placement. Placement of the Kocher's point EVD is the most common neurosurgical procedure which is often performed in urgent conditions. OBJECTIVE: To present the development of a novel computer algorithm identifying appropriate anatomy and autonomously plan EVD placement on clinical computed tomography (CT) scans. METHODS: The algorithm was tested on 2 data sets containing 5-mm slice noncontrast CT scans. The first contained images of 300 patients without significant intracranial pathology (normal), the second of 43 patients with significant acute intracranial hemorrhage. Automated planning was performed by custom 2-tiered heuristic with run-time template selection in combination with refinement using nonlinear image registration. RESULTS: Automated EVD planning was accurate in 297 of 300 normal and 41 of 43 patient cases. In the normal data set, mean distance between Kocher's point and the ipsilateral foramen of Monro was 63 ± 3.1 mm in women and 65 ± 6.5 mm in men (P = .0008). Trajectory angle with respect to the sagittal plane was 91 ± 6° in women and 90 ± 6° in men (obtuse posterior) (P = .15); to the coronal plane, 85 ± 6° and 86 ± 5° in women and men (P = .12), respectively (acute lateral). CONCLUSION: A combination of linear and nonlinear image registration techniques accurately planned EVD trajectory in 99% of normal scans and 95% of scans with significant intracranial hemorrhage.

Repetitive transcranial magnetic stimulation for the treatment of drug-resistant epilepsy: A systematic review and individual participant data meta-analysis of real-world evidence.

Objective: To perform a systematic review and meta-analysis of real-world evidence for the use of low-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of drug-resistant epilepsy. Methods: We systematically searched PubMed, Scopus, Medline, and clinicaltrials.gov for all relevant articles. Relevant patient and stimulation predictors as well as seizure outcomes were assessed. For studies with and without individual participant data (IPD), the primary outcomes were the rate of "favorable response" (reduction in seizure frequency ≥50%) and pooled event rate of mean reduction in seizure frequency, respectively. Outcomes were assessed with comparative statistics and random-effects meta-analysis models. Results: Of 3,477 identified articles, 12 met eligibility and were included in this review. We were able to obtain IPD for 5 articles constituting 34 participants. Univariate analysis on IPD identified greater favorable response event rates between participants with temporal seizure focus versus extratemporal (50% vs. 14%, p = 0.045) and between participants who were stimulated with a figure-8 coil versus other types (47% vs. 0%, p = 0.01). We also performed study-level meta-analysis on the remaining 7 studies without IPD, which included 212 participants. The pooled mean event rate of 50% seizure reduction using low-frequency rTMS was 30% (95% confidence interval [CI] 12-57%). Sensitivity analysis revealed that studies with a mean age ≤21 years and studies using targeted stimulation had the highest seizure reduction rates compared to studies with a mean age >21 years (69% vs. 18%) and not using a targeted stimulation (47% vs. 14-20%). Moreover, we identified high interstudy heterogeneity, moderate study bias, and high publication bias. Significance: Real-world evidence suggests that low-frequency rTMS using a figure-8 coil may be an effective therapy for the treatment of drug-resistant epilepsy in pediatric patients. This meta-analysis can inform the design and expedite recruitment of a subsequent randomized clinical trial.

Current and Expected Advances in Deep Brain Stimulation for Movement Disorders.

Deep brain stimulation (DBS) has become an established treatment for medically refractory movement disorders including Parkinson's disease, essential tremor, and dystonia. The field of DBS continues to evolve with advances in patient selection, target identification, electrode and pulse generator technology, and the development of more effective stimulation paradigms such as closed-loop stimulation. Furthermore, as the safety and efficacy of DBS improves through better hardware design and deeper understanding of its mechanisms of action, the indications for DBS will continue to expand to cover a wider range of disorders. Finally, the recent approval of MR-guided focused ultrasound for the treatment of essential tremor and potentially other movement disorders heralds a resurgence in lesion creation as a viable alternative to DBS for selected patients.

Prospective and retrospective study of videoconference telemedicine follow-up after elective neurosurgery: results of a pilot program.

Existing literature suggests that use of telemedicine during postoperative appointments can increase access to care and is valued by patients and providers alike. While research examining the clinical equivalency of telemedicine visits for postoperative care has been growing, few studies have reported on telemedicine follow-up after neurosurgery. This study examined if a videoconferencing visit could substitute for an in-person clinic visit for elective neurosurgical cases in the USA. This was a single-center prospective study of patients who underwent elective neurosurgical procedures (aneurysm clipping, resection of cavernous angiomas, resection of arterial venous malformation, microvascular decompression for trigeminal neuralgia and hemifacial spasm, and certain benign brain tumors) and were offered telemedicine follow-up care by an allied health professional during the first 90 days after neurosurgery. Prospective data was compared to a historical group of patients who underwent the same procedures and received in-person postoperative follow-up. Patients in the prospective group were contacted by telephone 2-6 weeks after surgery by a nurse practitioner and assessed using a standard template that included incidence of reported postoperative seizures, fever, and performance of activities of daily living. Primary outcome measures included percentage of patients accepting telemedicine, clinical and functional status, complications, patient satisfaction, patient travel time and distance, and rates of emergency room care or hospitalization within 90 days of discharge. Ninety-nine patients were included in the study, with 57 in the prospective group and 42 in the historical group. Of the 57 prospective patients, 47 accepted telemedicine in lieu of an in-person clinic visit. Emergency room visits and readmission rates at 30 and 90 days postoperatively did not differ significantly between the study groups, nor was there any significant difference in clinical variables that were recorded in the electronic medical record more than 80% of the time. This study demonstrates the safety and value of telemedicine as an alternative method of postoperative clinical care for patients undergoing elective neurosurgery. Telemedicine avoids unnecessary travel time and was welcomed by the majority of patients without compromising clinical or functional outcomes.

In-hospital weekend outcomes in patients diagnosed with bleeding gastroduodenal angiodysplasia: a population-based study, 2000 to 2011.

BACKGROUND AND AIMS: GI angiodysplastic (GIAD) lesions are an important cause of blood loss throughout the GI tract, particularly in elderly persons. The aim of this study was to determine whether mortality rates in patients with GIAD were higher for weekend compared with weekday hospital admissions. METHODS: We performed a retrospective study using the National Inpatient Sample database from 2000 to 2011 including inpatients with an International Classification of Diseases, Ninth Revision, Clinical Modification code for gastrointestinal GIAD (code 537.82 or 537.83). We assessed rates of delayed endoscopy (examinations performed >24 hours after admission), intensive care unit (ICU) admissions, and in-hospital mortality rates. Bivariate and multivariate logistic regression analyses were performed to identify risk factors for mortality. RESULTS: There were 85,971 discharges for GIAD between 2000 and 2011, of which 69,984 (81%) were weekday hospital admissions and 15,987 (19%) were weekend admissions. Patients with weekend versus weekday admissions were more likely to undergo delayed endoscopic examination (35% vs 26%, P ≤ .0001). Mortality rates were higher for patients with weekend admissions (2% vs 1%, P = .0002). The adjusted odds ratio (aOR) for inpatient mortality associated with weekend admissions was elevated (2.4; 95% confidence interval [CI], 1.5-3.9; P = .0005). Rates of delayed endoscopic examinations were lower in patients with higher socioeconomic status (aOR = 0.77; 95% CI, 0.68-0.88). ICU admission rates were higher for weekend compared with weekday admissions (8% vs 6%, P = .004). The presence of a delayed endoscopic examination was associated with an increased length of stay of 1.3 days (95% CI, 1.2-1.4 days). CONCLUSIONS: Weekend admissions for angiodysplasia were associated with higher odds of mortality, ICU admissions, higher rates of delayed endoscopic procedures, longer lengths of stay, and higher hospital charges.

Dementia in the Oldest-Old: A Nationwide Inpatient Sample Database Analysis.

OBJECTIVE: The aim of this study was to explore gender and race-specific mortality and comorbidities associated with dementia hospitalizations among the oldest-old. METHOD: Using the 1999-2008 Nationwide Inpatient Sample, we identified the association between dementia mortality and hospital characteristics in the oldest-old population. RESULTS: The oldest-old population was mostly comprised of Whites (81.1%) and women (76.0%), had shorter length of hospital stay (6.12 days), and lower hospital charges (US$18,770.32) than the young-old, despite the higher in-hospital mortality. Crude in-hospital mortality was higher for White males in the young-old population, followed by Hispanics and African Americans. However, Hispanic males had the highest mortality, followed by Whites then African Americans in the oldest-old group. After adjusting for different variables, these relationships did not change. DISCUSSION: There should be a greater focus on potential pre-existing biases regarding hospital care in the elderly, especially the oldest-old and elderly minority groups.