Human CD14hi monocytes and myeloid dendritic cells provide a cell contact-dependent costimulatory signal for early CD40 ligand expression.

CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4(+) T cells is highly dependent on a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus-immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.

Utilizing the Nursing Professional Development Model to create and sustain nursing education aimed at improving the care of patients with Parkinson's Disease in the hospital.

The Nurse Professional Development Model (NPD) has been utilized to improve quality of care for several conditions. Patients with Parkinson's Disease (PD) are susceptible to higher risks while in the hospital. Educational efforts for this patient population are challenged by the small, disbursed number of patients as well as increased turn-over and reliance on temporary nursing staff. To properly care for this patient group, any education has to be hospital wide and ongoing for maintenance of competency. We have used the NPD Model to initiate education for new incoming nurses as well as for continued education for a program that requires hospital-wide reach. Our utilization of the NPD Model for this high risk, low volume patient population has helped us improve the safety of this patient population in the hospital. With this manuscript we detail the need and the educational platform with the hope of it serving as a reference for other institutions facing similar challenges.

Standardizing default electronic health record tools to improve safety for hospitalized patients with Parkinson's disease.

Electronic Health Record (EHR) systems are often configured to address challenges and improve patient safety for persons with Parkinson's disease (PWP). For example, EHR systems can help identify Parkinson's disease (PD) patients across the hospital by flagging a patient's diagnosis in their chart, preventing errors in medication and dosing through the use of clinical decision support, and supplementing staff education through care plans that provide step-by-step road maps for disease-based care of a specific patient population. However, most EHR-based solutions are locally developed and, thus, difficult to scale widely or apply uniformly across hospital systems. In 2020, the Parkinson's Foundation, a national and international leader in PD research, education, and advocacy, and Epic, a leading EHR vendor with more than 35% market share in the United States, launched a partnership to reduce risks to hospitalized PWP using standardized EHR-based solutions. This article discusses that project which included leadership from physician informaticists, movement disorders specialists, hospital quality officers, the Parkinson's Foundation and members of the Parkinson's community. We describe the best practice solutions developed through this project. We highlight those that are currently available as standard defaults or options within the Epic EHR, discuss the successes and limitations of these solutions, and consider opportunities for scalability in environments beyond a single EHR vendor. The Parkinson's Foundation and Epic launched a partnership to develop best practice solutions in the Epic EHR system to improve safety for PWP in the hospital. The goal of the partnership was to create the EHR tools that will have the greatest impact on outcomes for hospitalized PWP.

Custom order entry for Parkinson's medications in the hospital improves timely administration: an analysis of over 31,000 medication doses.

Background: Patients with Parkinson's disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using "custom" ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital. Material and methods: We reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed. Results: 14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group (p<.001). Custom orders had a significantly more recent median date than non-custom default orders (2019-10-07 vs. 2018-01-06, p<0.001). In additional analyses, medication administration delays were significantly improved for custom orders compared to non-custom orders, with likelihoods 1.64 times higher within 1 minute, 1.40 times higher within 15 minutes, and 1.33 times higher within 30 minutes of the due time (p<0.001 for all comparisons). Conclusion: This is the largest study to date examining the effects of order entry type on timely administration of PD medications in the hospital. Orders placed using a custom schedule may help reduce delays in administration of PD medications.

An astrocytic basis of epilepsy.

Hypersynchronous neuronal firing is a hallmark of epilepsy, but the mechanisms underlying simultaneous activation of multiple neurons remains unknown. Epileptic discharges are in part initiated by a local depolarization shift that drives groups of neurons into synchronous bursting. In an attempt to define the cellular basis for hypersynchronous bursting activity, we studied the occurrence of paroxysmal depolarization shifts after suppressing synaptic activity using tetrodotoxin (TTX) and voltage-gated Ca(2+) channel blockers. Here we report that paroxysmal depolarization shifts can be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca(2+) in astrocytes. Two-photon imaging of live exposed cortex showed that several antiepileptic agents, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca(2+) signaling. Our results show an unanticipated key role for astrocytes in seizure activity. As such, these findings identify astrocytes as a proximal target for the treatment of epileptic disorders.

Assessment of Spine Patient Preferences for the Location of Surgery Between a Hospital and an Ambulatory Surgical Center in the Time of COVID-19: An Analysis of Patient Surveys.

Introduction There has been a recent increase in the number of spinal procedures that can be performed in ambulatory surgical centers (ASCs). Studies have found that patients who undergo procedures at ASCs tend to have lower complication rates following procedures, including lower infection rates. Furthermore, ASCs offer significantly lower costs of procedures to patients and health insurance companies as compared to the costs of procedures performed in a hospital. Despite precautions and screening in place by ASCs, patients may be hesitant to undergo procedures outside of the hospital. Conversely, the ongoing COVID-19 pandemic has created hesitancy for many to go to the hospital for care due to the presence of COVID patients.  Objective To assess patient preferences in the location of elective spine procedures between ASCs and hospitals, the authors conducted a survey of spine surgery candidates in a single practice. Methods A survey measuring patient age, vaccination status, fear of contracting COVID-19, and preference of surgery location was given to spinal surgery candidates at a single practice between fall 2021 and winter 2022. Statistical differences between the means of response groups were measured by a two-sample Z-score test. Results A total of 58 surveys were completed by patients. No difference in preference was observed by age. A difference was observed between genders, with 66% of females preferring ASCs to 40% of males (α=0.03). Patients with a fear of contracting COVID-19 preferred to have their procedure performed in an ASC. No difference was observed in location due to vaccination status, but unvaccinated patients had a significantly lower fear of contracting COVID-19 (α=0.02). Conclusion The differences in patient preferences have no clear cause, highlighting the need for better patient education in regard to the risks and benefits of each location of surgery. The fear of contracting COVID-19 on the day of surgery appears to be more ideological than rational for unvaccinated patients, who had less fear of contracting COVID-19 than vaccinated patients, despite being more likely to contract COVID-19 than vaccinated patients.

Intracranial air correlates with preoperative cerebral atrophy and stereotactic error during bilateral STN DBS surgery for Parkinson's disease.

OBJECTIVE: We examine the effect of intracranial air on stereotactic accuracy during bilateral deep brain stimulation (DBS) surgery for Parkinson's disease (PD). We also assess factors that may predict an increased risk of intracranial air during these surgeries. METHODS: 32 patients with PD underwent bilateral DBS surgery. The technique used for implantation of the leads has been standardized in over 800 subthalamic nucleus (STN) implantations. For lead implantation, the goal of the neurophysiological technique is identification of the STN and its borders with 3 microelectrode recording (MER) tracks. We examined the number of tracks and the degree of deviation from the planned target on each side. Total intracranial air (TIA) was then compared in these groups. We also examined the relationship between the TIA and length of surgery, ventricular volume and the degree of atrophy. RESULTS: Side 2 in this series required more MER tracks. The TIA was larger in patients with more than 3 MER tracks on side 2 of surgery. There was more deviation from the target on side 2. In addition, the TIA in patients with >1 mm of vector deviation on side 2 was more than in those without. The TIA correlated with the number of tracks on side 2 as well as with the degree of the second euclidean deviation on side 2. There was a correlation of degree of atrophy with TIA. CONCLUSION: In bilateral STN DBS for PD, intracranial air may contribute to error in stereotactic accuracy especially on the second side. In addition, there is a correlation between the accumulated volume of intracranial air and the degree of cerebral atrophy.

Neuromodulation for Cognitive Disorders: In Search of Lazarus?

Alzheimer's disease (AD) and other forms of dementia can have a large impact on patients, their families, and for the society as a whole. Current medical treatments have not shown enough potential in treating or altering the course of the disease. Deep brain stimulation (DBS) has shown great neuromodulatory potential in Parkinson's disease, and there is a growing body of evidence for justifying its use in cognitive disorders. At the same time there is mounting interest at less invasive and alternative modes of neuromodulation for the treatment of AD. This manuscript is a brief review of the infrastructure of memory, the current understanding of the pathophysiology of AD, and the body of preclinical and clinical evidence for noninvasive and invasive neuromodulation modalities for the treatment of cognitive disorders and AD in particular.

Treatment of Acute Delirium in a Patient with Parkinson's Disease by Transfer to the Intensive Care Unit and Administration of Dexmedetomidine.

The treatment of delirium or psychosis in patients with Parkinson's disease (PD) can be complicated by the limited number of pharmacological agents that can be used in this population. Typical and atypical antipsychotics are contraindicated, as they can worsen motor symptoms. The treatment of acute delirium is even more complicated in the hospital setting, as many medications deemed safer in this population are only available in oral form. We present a case of acute delirium in a patient with PD, likely precipitated by a polypharmacy interaction of new medications, that was successfully managed by transferring the patient to the intensive care unit and administering dexmedetomidine for 72 hours.

Adherence to a strict medication protocol can reduce length of stay in hospitalized patients with Parkinson's Disease.

BACKGROUND: Patients with Parkinson's Disease (PD) are at higher risk of complications when admitted to the hospital. Delays in PD medications and use of contraindicated medications contribute to the increased risk and prolong their lengths of stay (LOS). Using a hospital-wide PD protocol, we aimed to ensure PD medications were placed with "custom" timing to resemble the home schedules, and also to avoid ordering or administering contraindicated medications. MATERIAL AND METHODS: 569 patients admitted in 2017 and 2018, were reviewed retrospectively. Mean age was 76.5 (SD 10.6), 332 were males and 237 were females. Charts were reviewed to assess if A) PD medications were ordered with custom timing, B) if not, were the orders changed to custom timed C) if contraindicated medications were ordered, and D) if they were administered. We also assessed the actual/expected length of stay during this time period. Chi Square and post hoc analyses were done to compare time points. Poisson regression analysis was done to assess relative improvement of variables. RESULTS: There was a 2.7 fold increase in orders placed with custom timing in 2018 compared to 2017 (RR = 2.651, 95%CI: 1.860-3.780, p < 0.0001), and a 3.2 fold increase in correction of non-custom orders in the same time period (RR = 3.246, 95%CI: 1.875-1.619, p < 0.0001). We also observed a decrease in the actual/expected LOS ratio from 1.54  to 1.32  (p < 0.05). CONCLUSION: By utilizing an established platform for quality improvement, we were able to improve adherence to the home medication regimen timing in admitted PD patients. Our findings also suggests that adherence to a strict medication regimen protocol may decrease LOS for this patient population.

The interventional magnetic resonance imaging suite: Experience in the design, development, and implementation in a pre-existing radiology space and review of concepts.

BACKGROUND: Intraoperative magnetic resonance imaging (ioMRI) has led to significant advancements in neurosurgery with improved accuracy, assessment of the extent of resection, less invasive surgical alternatives, and real-time confirmation of targeting as well delivery of therapies. The costs associated with developing ioMRI units in the surgical suite have been obstacles to the expansion of their use. More recently, the development of hybrid interventional MRI (iMRI) units has become a viable alternative. The process of designing, developing, and implementing operations for these units requires the careful integration of environmental, technical, and safety elements of both surgical and MR practices. There is a paucity of published literature providing guidance for institutions looking to develop a hybrid iMRI unit, especially with a limited footprint in the radiology department. METHODS: The experience of designing, developing, and implementing an iMRI in a preexisting space for neurosurgical procedures at a single institution in light of available options and the literature is described. RESULTS: The development of the unit was accomplished through the engagement of a multidisciplinary team of stakeholders who utilized existing guidelines and recommendations and their own professional experience to address issues including physical layout, equipment selection, operations planning, infection control, and oversight/review, among others. CONCLUSION: Successful creation of an iMRI program requires multidisciplinary collaboration in integrating surgical and MR practice. The authors' aim is that the experience described in this article will serve as an example for facilities or neurosurgical departments looking to navigate the same process.

Development of a Joint Commission Disease-Specific Care Certification Program for Parkinson Disease in an Acute Care Hospital.

BACKGROUND: Patients with Parkinson disease (PD) admitted to the hospital for any reason are at a higher risk of hospital-related complications. Frequent causes include delays in administering PD medications or use of contraindicated medications. The Joint Commission Disease-Specific Care (DSC) program has been used to establish a systematic approach to the care of specific inpatient populations. Once obtained, this certification demonstrates a commitment to patient care and safety, which is transparent to the public and can improve quality of care. METHODS: We formalized our efforts to improve the care of hospitalized patients with PD by pursuing Joint Commission DSC. An interprofessional team was assembled to include nurses, therapists, physicians, pharmacists, performance improvement specialists, and data analysts. The team identified quality metrics based on clinical guidelines. In addition, a large educational campaign was undertaken. Application to the Joint Commission for DSC resulted in a successful June 15, 2018 site visit. To our knowledge, this is the first DSC program in PD in an acute care hospital. CONCLUSION: Using the established platform of DSC certification from the Joint Commission, we developed a program based on relevant metrics that aims to address medication management of patients with PD admitted to the hospital. Our hope is to improve the care of this vulnerable patient population.

Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study.

BACKGROUND: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers. METHODS: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration. RESULTS: From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003). CONCLUSION: Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

Interventional magnetic resonance imaging-guided subthalamic nucleus deep brain stimulation for Parkinson's disease: Patient selection.

BACKGROUND: Interventional magnetic resonance imaging (iMRI) guided deep brain stimulation (DBS) for Parkinson's disease (PD) has been shown to be effective. The costs of a dedicated intraoperative MRI may be prohibitive. The procedure can also be performed in a diagnostic scanner, however this presents challenges for utilization of time when the scanner is used both as a diagnostic and an interventional unit. This report outlines our novel methodology for patient selection for implantation in a diagnostic MR scanner, as an attempt to streamline the use of resources. A retrospective review of our outcomes is also presented. METHODS: DBS candidacy evaluation included a PD questionnaire-39. Anxiety, age, difficulties in communication and body habitus were factors that were assessed in selecting patients for this technique. Eleven patients underwent iMRI-guided DBS implantation in the subthalamic nucleus. All patients were implanted bilaterally. Unified PD rating scale (UPDRS) part III and L-dopa dose were compared pre- and post-stimulation. A cohort of 11 DBS patients not selected for iMRI-guided DBS were also reported for comparison. RESULTS: For the iMRI-guided patients, mean "Off" UPDRS III score was 47.6 (standard deviation [SD] 8.26). Postoperative "On" medication, "On" stimulation UPDRS III was 13.6 (SD 5.23). Mean preoperative L-dopa dose was 1060 mg (SD 474.3) and mean postoperative L-dopa dose was 320 (SD 298.3). CONCLUSION: iMRI-guided DBS is a newly emerging technique for surgical treatment of patients with PD. We present a novel scoring system for patient selection assessing anxiety, age, ability to communicate, and body habitus to identify patients who will be benefited most from this technique.

Surgery for postarthrodesis adjacent-cervical segment degeneration.

Anterior cervical decompression and fusion has gained popularity because of its applicability to a variety of cervical spine disorders. The authors of long-term follow-up studies have demonstrated the development of degenerative changes in segments adjacent to fusion. So-called adjacent-segment disease causes symptomatic deterioration in up to 25% of the patients who have undergone anterior cervical decompression and fusion for cervical spondylotic myelopathy. The causes of this condition are debated in the literature. The authors provide a review of the available literature on the pathogenesis, prevention, and treatment of postarthrodesis adjacent-segment degenerative disease.

Surgery for movement disorders.

Movement disorders, such as Parkinson's disease, tremor, and dystonia, are among the most common neurological conditions and affect millions of patients. Although medications are the mainstay of therapy for movement disorders, neurosurgery has played an important role in their management for the past 50 years. Surgery is now a viable and safe option for patients with medically intractable Parkinson's disease, essential tremor, and dystonia. In this article, we provide a review of the history, neurocircuitry, indication, technical aspects, outcomes, complications, and emerging neurosurgical approaches for the treatment of movement disorders.

Functional imaging in a low-field, mobile intraoperative magnetic resonance scanner: expanded paradigms.

OBJECTIVE: We previously demonstrated the capability to obtain functional magnetic resonance imaging (MRI) scans of the motor cortex in healthy volunteers using a low-field mobile operating room-based MRI scanner with 0.12-T field strength. Using an expanded (0.15-T), but still mobile, version of this system, our goal was to acquire data showing activation of other areas of functionally important cortex. METHODS: Five healthy volunteers were scanned with the low-field scanner using finger tapping, hand touch, silent word generation, text listening, and visual stimulation paradigms. The data was analyzed offline using publicly available software. For comparison, the volunteers were then scanned with a 3-T diagnostic MRI scanner. RESULTS: Significant cortical activation was demonstrated on 16 out of 22 images obtained on the operating room-based scanner. Motor activation was most robust, followed by silent word generation, text listening, and hand touch paradigms. The correlation coefficients compared favorably with the images obtained on the 3-T scanner. The signal changes were higher for images obtained with the low-field, mobile scanner compared with those performed with the 3-T diagnostic MRI scanner. CONCLUSION: Functional MRI scans of multiple cortical areas can be acquired with a low-field strength magnet designed for intraoperative imaging. Further refinement of this technique may allow for the acquisition of true intraoperative functional MRI scans immediately, before, and even during cranial surgery in select patients.

Direct inhibition of CD40L expression can contribute to the clinical efficacy of daclizumab independently of its effects on cell division and Th1/Th2 cytokine production.

Humanized anti-CD25 antibodies (eg, daclizumab) have been successfully used to treat several autoimmune diseases. Paradoxically, IL-2 blockade in mice can induce autoimmunity. An interspecies difference in the relative contribution of IL-2 to CD25(+) T regulatory cell (CD25(+)Treg) versus CD25(+) effector cell function might explain this conundrum. Consistent with this are reports that daclizumab inhibits human CD25(+) effector cell cytokine production by blocking the expression of CD40L. However, in mice, IL-4 and IL-12 regulate CD40L expression. As human Th1/Th2 cytokine production is also dependent on IL-2, daclizumab's inhibition of CD40L expression could be due to an indirect, rather than a direct, effect of IL-2. Here, we clarify the mechanisms underlying CD40L expression. In contrast to the mouse, human CD40L is regulated by CD28 signaling and IL-2, not the principal Th1/Th2-polarizing cytokines. We find that CD40L is expressed on naive and memory cells and inhibited by daclizumab independently of cell division. Collectively, our results indicate that daclizumab could inhibit CD25(+) effector T-cell function in vivo by directly blocking CD40L expression. This difference between mice and human may help explain the paradoxical effects of IL-2R blockade in the 2 species.