Pyroptosis activates conventional type I dendritic cells to mediate the priming of highly functional anticancer T cells.

BACKGROUND: Initiation of antitumor immunity is reliant on the stimulation of dendritic cells (DCs) to present tumor antigens to naïve T cells and generate effector T cells that can kill cancer cells. Induction of immunogenic cell death after certain types of cytotoxic anticancer therapies can stimulate T cell-mediated immunity. However, cytotoxic therapies simultaneously activate multiple types of cellular stress and programmed cell death; hence, it remains unknown what types of cancer cell death confer superior antitumor immunity. METHODS: Murine cancer cells were engineered to activate apoptotic or pyroptotic cell death after Dox-induced expression of procell death proteins. Cell-free supernatants were collected to measure secreted danger signals, cytokines, and chemokines. Tumors were formed by transplanting engineered tumor cells to specifically activate apoptosis or pyroptosis in established tumors and the magnitude of immune response measured by flow cytometry. Tumor growth was measured using calipers to estimate end point tumor volumes for Kaplan-Meier survival analysis. RESULTS: We demonstrated that, unlike apoptosis, pyroptosis induces an immunostimulatory secretome signature. In established tumors pyroptosis preferentially activated CD103+ and XCR1+ type I conventional DCs (cDC1) along with a higher magnitude and functionality of tumor-specific CD8+ T cells and reduced number of regulatory T cells within the tumor. Depletion of cDC1 or CD4+ and CD8+ T cells ablated the antitumor response leaving mice susceptible to a tumor rechallenge. CONCLUSION: Our study highlights that distinct types of cell death yield varying immunotherapeutic effect and selective activation of pyroptosis can be used to potentiate multiple aspects of the anticancer immunity cycle.

Determinants for Antitumor and Protumor Effects of Programmed Cell Death.

Cytotoxic anticancer therapies activate programmed cell death in the context of underlying stress and inflammatory signaling to elicit the emission of danger signals, cytokines, and chemokines. In a concerted manner, these immunomodulatory secretomes stimulate antigen presentation and T cell-mediated anticancer immune responses. In some instances, cell death-associated secretomes attract immunosuppressive cells to promote tumor progression. As it stands, cancer cell death-induced changes in the tumor microenvironment that contribute to antitumor or protumor effects remain largely unknown. This is complicated to examine because cell death is often subverted by tumors to circumvent natural, and therapy-induced, immunosurveillance. Here, we provide insights into important but understudied aspects of assessing the contribution of cell death to tumor elimination or cancer progression, including the role of tumor-associated genetics, epigenetics, and oncogenic factors in subverting immunogenic cell death. This perspective will also provide insights on how future studies may address the complex antitumor and protumor immunologic effects of cell death, while accounting for variations in tumor genetics and underlying microenvironment.

Palliation for catastrophic nonlocalizing epilepsy: a retrospective case series of complete corpus callosotomy at a single institution.

OBJECTIVE: In this study, the authors describe their 10-year single-institution experience with single-step complete corpus callosotomy (CCC) for seizure management in pediatric and adult patients with catastrophic, medically refractory, nonlocalizing epilepsy at Advent Health Orlando. METHODS: The authors conducted a retrospective observational study of patients aged 6 months to 49 years who underwent clinically indicated CCC for drug-resistant nonlocalizing epilepsy at Advent Health Orlando between July 2011 and July 2021. Follow-up ranged from 12 months to 10 years. RESULTS: Of the 101 patients (57% of whom were male) who met eligibility criteria, 81 were pediatric patients and 20 were ≥ 18 years. All patients had seizures that appeared poorly lateralized on both electroencephalograms and clinical semiological studies. Of 54 patients with drop seizures before CCC, 29 (54%) achieved stable freedom from drop seizures after CCC. Of the 101 patients, 14 (13.9%) experienced stable resolution of all types of clinical seizures (International League Against Epilepsy classes 1 and 2). The most common postoperative neurological complication was a transient disconnection syndrome, observed in 50% of patients; of those patients, 73% experienced syndrome resolution within 2 months after surgery, and all resolved by the 2-year follow-up. Formal neuropsychological test results were stable in 13 patients assessed after CCC. CONCLUSIONS: CCC is an effective and well-tolerated palliative surgical technique. In this study, drop attacks were reduced after CCC but could recur for the first time as late as 44 months after surgery. Other seizure types were also reduced postoperatively but could recur for the first time as late as 28 months after surgery. Nearly 14% of patients achieved stable and complete freedom from seizures after CCC. Re-evaluation after CCC can reveal lateralized seizure onset in some patients.

Forensic neuropsychology: History and current status.

Objective:This review provides a summary of historical details and current practice activities related to Forensic Neuropsychology (FN). Under the auspices of the American Board of Clinical Neuropsychology (ABCN), the Forensic Neuropsychology Special Interest Group (FNSIG) views the FN as a subspecialty, which has developed over time as the straightforward result of more than 20 years of numerous publications, extensive continuing education, focused research and growth of forensic practice within neuropsychology. In this article, the FNSIG core work group documents and integrates information that is the basis of efforts to consolidate practice knowledge and facilitate attainment of forensic practice competencies by clinical neuropsychologists. Method:Overview of continuing education topics at professional conferences, search results that identify relevant books and peer-reviewed publications, as well as pertinent findings across years of large-scale national survey results. Results:Relevant evidence has shown for decades that FN is prominent within Clinical Neuropsychology as practiced in the United States and Canada. A majority of U.S. neuropsychologists have received FN training and provide forensic evaluation services. FN practice time per week is considerable for many practitioners, and across survey epochs has been shown to be increasing. Conclusion:The present review leads to the conclusion that in the interest of promoting the acquisition of competence, FN practice should remain a focal point of training and continuing education. Alternate routes to attain competence are discussed, as are ongoing professional activities that undoubtedly will ensure continued growth of, and interest in, the subspecialty of FN.

Viral-mediated activation and inhibition of programmed cell death.

Viruses are ubiquitous intracellular genetic parasites that heavily rely on the infected cell to complete their replication life cycle. This dependency on the host machinery forces viruses to modulate a variety of cellular processes including cell survival and cell death. Viruses are known to activate and block almost all types of programmed cell death (PCD) known so far. Modulating PCD in infected hosts has a variety of direct and indirect effects on viral pathogenesis and antiviral immunity. The mechanisms leading to apoptosis following virus infection is widely studied, but several modalities of PCD, including necroptosis, pyroptosis, ferroptosis, and paraptosis, are relatively understudied. In this review, we cover the mechanisms by which viruses activate and inhibit PCDs and suggest perspectives on how these affect viral pathogenesis and immunity.

Comparison of care accessibility, costs, and quality with face-to-face and telehealth epilepsy clinic visits.

During the COVID-19 pandemic, restrictions on reimbursement for telehealth visits were lifted and this visit type was suddenly available to patients around the United States of America. Telehealth visits offer potential cost savings for patients and families, which may vary by region of the world studied. Also, aggressiveness of the care patients receive may differ, and patients or families may be more likely to choose one visit type over another based on seizure control. This is a prospective face-to-face clinic versus telehealth clinic visit comparison study involving patients with seizures, their legal guardians, and caretakers who attend clinic. We compared travel distance, work-related factors, childcare, satisfaction of care, changes in seizure medication or diagnostics tests ordered, and willingness to cancel appointments to better understand the behavioral patterns of patients, caretakers, and providers. Our results indicate that many patients and families still prefer in-person interactions with their medical providers. Patient and family satisfaction levels were equal with both visit types. No significant difference was seen in medical management between face-to-face and telehealth visits. Also, prior seizure control did not dictate the type of visit chosen. Telehealth participants were significantly more willing to cancel appointments if asked to switch to face-to-face then face-to-face participants asked to complete telehealth visits. Surprisingly, we found that patients and families choosing telehealth were not statistically more likely to be employed or take less time off work. Also, distance from home to office was not significantly shorter for participants choosing face-to-face visits. Offering a combination of telehealth and face-to-face visits appears to be the optimal strategy in caring for patients with controlled and uncontrolled seizure disorders to ensure adherence with clinic visits and satisfaction with care. Our study suggests that providers are equally willing to adjust medications or order additional diagnostic testing regardless of visit type. Patients and families may be less likely to cancel telehealth visits than face-to-face visits; this finding may translate to improved seizure control and long-term decreased cost of care.

Intracranial EEG and laser interstitial thermal therapy in MRI-negative insular and/or cingulate epilepsy: case series.

OBJECTIVE: The goal of this study was to assess the success rate and complications of stereo-electroencephalogra-phy (sEEG) and laser interstitial thermal therapy (LITT) in the treatment of nonlesional refractory epilepsy in cingulate and insular cortex. METHODS: The authors retrospectively analyzed the treatment response in 9 successive patients who underwent insular or cingulate LITT for nonlesional refractory epilepsy at their center between 2011 and 2019. Localization of seizures was based on inpatient video-EEG monitoring, neuropsychological testing, 3-T MRI, PET scan, magnetoencephalography scan, and/or ictal SPECT scan. Eight patients underwent sEEG, and 1 patient had implantation of both sEEG electrodes and subdural grids for localization of epileptogenic zones. LITT was performed in 5 insular cases (4 left and 1 right) and 3 cingulate cases (all left-sided). One patient also underwent both insular and cingulate LITT on the left side. All of the patients who underwent insular LITT as well as 2 of the 3 who underwent cingulate LITT were right-hand dominant. The patient who underwent insular plus cingulate LITT was also right-hand dominant. RESULTS: Following LITT, 67% of the patients were seizure free (Engel class I) at follow-up (mean 1.35 years, range 0.6-2.8 years). All patients responded favorably to treatment (Engel class I-III). Two patients developed small intracranial hemorrhages during the sEEG implantation that did not require surgical management. One patient developed a large intracranial hemorrhage during an insular LITT procedure that did require surgical management. That patient experienced aphasia, incoordination, and hemiparesis, which resolved with inpatient rehabilitation. No permanent neurological deficits were noted in any of the patients at last follow-up. Neuropsychological status was stable in this cohort before and after LITT. CONCLUSIONS: sEEG can be safely used to localize seizures originating from insular and cingulate cortex. LITT can successfully treat seizures arising from these deep-seated structures. The insula and cingulum should be evaluated more frequently for seizure onset zones.

Telehealth perceptions in patients with epilepsy and providers during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) has required novel solutions for issues that arise with social distancing. Telehealth has become one of those solutions in many clinics around the U.S. As we look beyond, the pandemic telehealth can be utilized as an important tool for clinics in the future. Patient satisfaction will most likely affect reimbursement, while provider perception will affect implementation. We see this as a valuable tool to many epilepsy clinics. The goal of our survey was to determine the perceptions and satisfaction of patients with intractable epilepsy and providers with telehealth during the COVID-19 pandemic; we surveyed patient and providers. We evaluated the first 111 patients who participated in our telehealth visits. We conducted telephone surveys with the first 68 patients who agreed to participate. We also conducted surveys by email with our providers who participated in these telehealth visits. We found that 66% of patients and 67% of providers would use a telehealth visit in the future if given the option. Review of our patients' and providers' comments provides valuable insights for building a long-term successful intractable epilepsy telehealth clinic.

Atypical language representation as a protective factor against verbal memory decline following epilepsy surgery.

OBJECTIVE: An important role of neuropsychology in the preoperative evaluation of epilepsy surgery candidates is to assess risk for postoperative memory decline. One factor associated with postoperative verbal memory decline is surgery in the language-dominant temporal lobe (TL). The aim of the study was to determine whether atypical language representation has a protective effect against verbal memory decline following left temporal, frontotemporal, or hippocampal excision. METHODS: Data from 61 patients with medically refractory epilepsy, Wada testing, and pre- and postsurgical memory assessment from four comprehensive epilepsy surgery centers were gathered and examined for pre- to postsurgical memory change. Wada testing was used to determine language dominance (left vs. atypical [bilateral + right]). Postoperative memory change was examined at both the individual (using nonparametric analyses) and group (using parametric analyses) levels for the two language dominance groups. RESULTS: Significant postoperative verbal memory decline was observed in the left hemisphere language-dominant group, while the atypical language group showed verbal memory improvement. Individuals with left hemisphere language dominance were more likely to show postoperative declines in verbal memory, whereas individuals with atypical language dominance were significantly less likely to decline. As expected, there were no significant differences between language groups with regard to postoperative visuospatial memory outcome. CONCLUSION: Patients with atypical language dominance had better verbal memory outcomes following left hemisphere resections than those with left hemisphere language dominance suggesting that typical memory substrates likely reorganized along with language. Thus, atypical cerebral organization of language may be considered a protective factor against verbal memory decline following epilepsy surgery involving the left TL.

Carotid Revascularization and Its Effect on Cognitive Function: A Prospective Nonrandomized Multicenter Clinical Study.

BACKGROUND: There is conflicting data on the effect of carotid revascularization on cognitive function. OBJECTIVE: To examine cerebral blood flow and cognitive function after carotid revascularization. METHODS: Patients with unilateral, asymptomatic hemodynamically significant carotid artery stenosis (80% by computed tomography angiography or magnetic resonance angiography) were eligible. Cerebral blood flow was measured preoperatively and 1 month postoperatively using quantitative phase contrast magnetic resonance angiography. Preoperative flow impairment was defined as ipsilateral flow at least 20% less than contralateral flow (ie, an ipsilateral and/or contralateral flow ratio ≤0.8). Significant improvement in blood flow was defined as at least a 0.15 increase in flow ratio from pre- to postoperative. A control group was managed medically. Four cognitive domains were assessed at baseline, 1 month, and 6-12 months postoperatively. RESULTS: Seventy-five patients were enrolled at 6 sites; 53 carotid endarterectomy, 11 carotid artery stenting, and 11 medical management only controls. Preoperative Trails B scores were similar between groups. Revascularization was associated with significant improvement in executive function (Trials B) while no improvement was observed in controls (P = .007). Of patients with improvement in middle cerebral artery (MCA) flow, 90% had improved Trails B scores compared to 46.5% of patients without MCA flow improvement (P = .01). Greater absolute improvement in mean Trails B scores was observed in patients with MCA flow improvement compared to those without (48 seconds versus 24.7 seconds, P = .001). CONCLUSIONS: In a cohort of patient with asymptomatic carotid stenosis, improvement in MCA flow following carotid revascularization is associated with improvement in executive functioning.

American Academy of Clinical Neuropsychology consensus conference statement on uniform labeling of performance test scores.

Objectives: Descriptive labels of performance test scores are a critical component of communicating outcomes of neuropsychological and psychological evaluations. Yet, no universally accepted system exists for assigning qualitative descriptors to scores in specific ranges. In addition, the definition and use of the term "impairment" lacks specificity and consensus. Consequently, test score labels and the denotation of impairment are inconsistently applied by clinicians, creating confusion among consumers of neuropsychological services, including referral sources, trainees, colleagues, and the judicial system. To reduce this confusion, experts in clinical and forensic neuropsychological and psychological assessment convened in a consensus conference at the 2018 Annual Meeting of the American Academy of Clinical Neuropsychology (AACN). The goals of the consensus conference were to recommend (1) a system of qualitative labels to describe results from performance-based tests with normal and non-normal distributions and (2) a definition of impairment and its application in individual case determinations. Results: The goals of the consensus conference were met resulting in specific recommendations for the application of uniform labels for performance tests and for the definition of impairment, which are described in this paper. In addition, included in this consensus statement is a description of the conference process and the rationales for these recommendations. Conclusions/Importance: This consensus conference is the first formal attempt by the professional neuropsychological community to make recommendations for uniform performance test score labels and to advance a consistent definition of impairment. Using uniform descriptors and terms will reduce confusion and enhance report comprehensibility by the consumers of our reports as well as our trainees and colleagues.

Autoimmune encephalitis and epilepsy: evolving definition and clinical spectrum.

Advances in autoimmune encephalitis studies in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to the disorder. The disorder or syndrome has been linked to a wide variety of pathologic processes associated with the neuron-specific autoantibodies targeting intracellular and plasma membrane antigens. However, current criteria for autoimmune encephalitis are quite dependent on antibody testing and responses to immunotherapy, which might delay the diagnosis. This form of encephalitis can involve the multifaceted presentation of seizures and unexpected behavioral changes. The spectrum of neuropsychiatric symptoms in children is less definitive than that in adults, and the incorporation of clinical, immunological, electrophysiological, and neuroradiological results is critical to the diagnostic approach. In this review, we document the clinical and immunologic characteristics of autoimmune encephalitis known to date, with the goal of helping clinicians in differential diagnosis and to provide prompt and effective treatment.

Successful Intrathecal Rituximab Administration in Refractory Nonteratoma Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report.

N-methyl-D-aspartate receptor (NMDA-R) antibody encephalitis is an immune-mediated disorder characterized by the presence of anti-NMDA antibody in serum and cerebrospinal fluid, with a characteristic combination of psychological and neurological signs and symptoms. The scientific knowledge pertaining to the management of anti-NMDA-R encephalitis is growing. It is important that neuroscience nurses be aware of treatments as well as the newest novel treatment options available. Early aggressive intervention is imperative to recovery. The first line of treatment often includes high-dose steroids, intravenous immunoglobulin, and therapeutic plasma exchange. Second-line therapy for refractory NMDA-R encephalitis includes intravenous rituximab and cyclophosphamide. Even with these treatments, up to 25% of patients may be left with severe deficits or have a fatal outcome. It is well known that penetration of monoclonal anti-CD20 antibody therapy (rituximab) into the cerebrospinal fluid is 0.1% of that in the serum. Therefore, efficacy of rituximab in the treatment of NMDA encephalitis may be improved by intrathecal administration in selected cases with a poor response to intravenous rituximab. We present a case of anti-NMDA-R encephalitis that was refractory to first- and second-line therapies, who responded to intrathecal rituximab, to highlight a novel treatment that may be able to prevent long-term disability and improve clinical outcomes.

Epilepsy Surgery in Children versus Adults.

Epilepsy is one of the most common chronic neurological disorder affecting 6-7 per 1000 worldwide. Nearly one-third of patients with newly diagnosed epilepsy continue to have recurrent seizures despite adequate trial of more than two anti-seizure drugs : drug-resistant epilepsy (DRE). Children with DRE often experience cognitive and psychosocial co-morbidities requiring more urgent and aggressive treatment than adults. Epilepsy surgery can result in seizure-freedom in approximately two-third of children with improvement in cognitive development and quality of life. Understanding fundamental differences in etiology, co-morbidity, and neural plasticity between children and adults is critical for appropriate selection of surgical candidates, appropriate presurgical evaluation and surgical approach, and improved overall outcome.

Utility of the Behavior Rating Inventory of Executive Function - Preschool version (BRIEF-P) in young children with epilepsy.

Executive functioning deficits are prominent in children with epilepsy. Although instruments, such as the Behavior Rating Inventory of Executive Function (BRIEF), are useful in detecting executive dysfunction in school-age children with epilepsy, little data are available for younger children. The present study evaluates the ability of the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) to detect executive dysfunction in preschool-age children with epilepsy. Parents of 51 clinically referred children with epilepsy (age: M = 1.99 years, SD = 1.29 years, range = 2-5 years) completed the BRIEF-P. Using a cutoff t score of ≥65 as the threshold for impairment, the BRIEF-P's ability to detect executive dysfunction within this clinical population was established. Additionally, correlational analyses were used to assess the relations between epilepsy severity factors and BRIEF-P indices. Epilepsy severity variables that were significantly related to BRIEF-P indices were entered into a linear regression model to explore their predictive ability. Emergent metacognition (emergent metacognition index [EMI]; 59%) and the global executive composite (43%) were the most frequently elevated indices. The most commonly elevated subscales were working memory (65%), inhibition (37%), and planning/organization (35%). Age of seizure onset, seizure frequency, and number of antiepileptic drugs were not significantly correlated with BRIEF-P indices. However, children with lower intellectual ability were rated as having greater executive dysfunction, specifically with EMI (r = -.30). Still, intellectual functioning only accounted for a small percentage (9%) of the variance in EMI scores. The current pilot study demonstrates that the BRIEF-P shows promise in identifying executive dysfunction in preschool-age children with epilepsy.

The role of executive functioning in quality of life in pediatric intractable epilepsy.

OBJECTIVE: Children with epilepsy are vulnerable to executive dysfunction, but the relationship between executive functioning (EF) and quality of life (QOL) in children with epilepsy is not fully delineated. This exploratory study elucidated the relationship between ecological EF and QOL in pediatric intractable epilepsy. METHOD: Fifty-four consecutively referred pediatric epilepsy surgery candidates and their parents were administered IQ measures, the Behavior Rating Inventory of Executive Function (BRIEF), and the Quality of Life in Childhood Epilepsy (QOLCE) as part of a comprehensive neuropsychological evaluation. RESULTS: A significant difference was found in QOL between those with and without clinical impairments on the BRIEF [t(52)=3.93; p<.001]. That is, children with executive dysfunction had lower overall QOL. All seizure variables and BRIEF scales were associated with overall QOL [F(12, 40)=6.508; p=.001; R2=.661]. Working memory from the BRIEF was the most frequently elevated scale in our sample (57%). Those with executive dysfunction had 9.7 times the risk of having poor QOL. CONCLUSIONS: Poor EF control according to behavior ratings is significantly related to QOL in intractable pediatric epilepsy. Identification of executive dysfunction in home environments is an essential component of presurgical evaluations and target for intervention, which may improve QOL.

CortiQ-based Real-Time Functional Mapping for Epilepsy Surgery.

PURPOSE: To evaluate the use of the cortiQ-based mapping system (g.tec medication engineering GmbH, Austria) for real-time functional mapping (RTFM) and to compare it to results from electrical cortical stimulation mapping (ESM) and functional magnetic resonance imaging (fMRI). METHODS: Electrocorticographic activity was recorded in 3 male patients with intractable epilepsy by using cortiQ mapping system and analyzed in real time. Activation related to motor, sensory, and receptive language tasks was determined by evaluating the power of the high gamma frequency band (60-170 Hz). The sensitivity and specificity of RTFM were tested against ESM and fMRI results. RESULTS: "Next-neighbor" approach demonstrated [sensitivity/specificity %] (1) RTFM against ESM: 100.00/79.70 for hand motor; 100.00/73.87 for hand sensory; -/87 for language (it was not identified by the ESM); (2) RTFM against fMRI: 100.00/84.4 for hand motor; 66.70/85.35 for hand sensory; and 87.85/77.70 for language. CONCLUSIONS: The results of the quantitative "next-neighbor" RTFM evaluation were concordant to those from ESM and fMRI. The RTFM correlates well with localization of hand motor function provided by ESM and fMRI, which may offer added localization in the operating room and guidance for extraoperative ESM mapping. Real-time functional mapping correlates with fMRI language activation when ESM findings are negative. It has fewer limitations than ESM and greater flexibility in activation paradigms and measuring responses.

Real-time functional mapping: potential tool for improving language outcome in pediatric epilepsy surgery.

Accurate language localization expands surgical treatment options for epilepsy patients and reduces the risk of postsurgery language deficits. Electrical cortical stimulation mapping (ESM) is considered to be the clinical gold standard for language localization. While ESM affords clinically valuable results, it can be poorly tolerated by children, requires active participation and compliance, carries a risk of inducing seizures, is highly time consuming, and is labor intensive. Given these limitations, alternative and/or complementary functional localization methods such as analysis of electrocorticographic (ECoG) activity in high gamma frequency band in real time are needed to precisely identify eloquent cortex in children. In this case report, the authors examined 1) the use of real-time functional mapping (RTFM) for language localization in a high gamma frequency band derived from ECoG to guide surgery in an epileptic pediatric patient and 2) the relationship of RTFM mapping results to postsurgical language outcomes. The authors found that RTFM demonstrated relatively high sensitivity (75%) and high specificity (90%) when compared with ESM in a "next-neighbor" analysis. While overlapping with ESM in the superior temporal region, RTFM showed a few other areas of activation related to expressive language function, areas that were eventually resected during the surgery. The authors speculate that this resection may be associated with observed postsurgical expressive language deficits. With additional validation in more subjects, this finding would suggest that surgical planning and associated assessment of the risk/benefit ratio would benefit from information provided by RTFM mapping.

360 Degree advocacy: a model for high impact advocacy in a rapidly changing healthcare marketplace.

In an era of rapid changes in the healthcare marketplace the specialty of clinical neuropsychology faces a substantial increase in advocacy challenges. These include maintaining both access to services and a favorable practice climate as new healthcare structures and payment models evolve. The issue of regional variability complicates an effective response to these challenges from national professional organizations. One response to the challenge of regional variability is to strengthen our national organizations' capacity to engage in coordinated and effective advocacy, and to partner with state and regional neuro/psychological associations. The Inter-Organizational Practice Committee (IOPC) was formed in 2012 to meet this need. The IOPC has developed a model of 360 Degree Advocacy that coordinates local, regional, and national resources for high-impact, efficient advocacy. This paper describes the 360 Degree Advocacy model, and walks readers through an example of the model in action, successfully responding to a threat to patient access and practice climate with a regional Medicare carrier.