Mesenchymal Stem Cell Therapy in Acute Intracerebral Hemorrhage: A Dose-Escalation Safety and Tolerability Trial.

BACKGROUND: We conducted a preliminary phase I, dose-escalating, safety, and tolerability trial in the population of patients with acute intracerebral hemorrhage (ICH) by using human allogeneic bone marrow-derived mesenchymal stem/stromal cells. METHODS: Eligibility criteria included nontraumatic supratentorial hematoma less than 60 mL and Glasgow Coma Scale score greater than 5. All patients were monitored in the neurosciences intensive care unit for safety and tolerability of mesenchymal stem/stromal cell infusion and adverse events. We also explored the use of cytokines as biomarkers to assess responsiveness to the cell therapy. We screened 140 patients, enrolling 9 who met eligibility criteria into three dose groups: 0.5 million cells/kg, 1 million cells/kg, and 2 million cells/kg. RESULTS: Intravenous administration of allogeneic bone marrow-derived mesenchymal stem/stromal cells to treat patients with acute ICH is feasible and safe. CONCLUSIONS: Future larger randomized, placebo-controlled ICH studies are necessary to validate this study and establish the effectiveness of this therapeutic approach in the treatment of patients with ICH.

Increasing help-seeking among people with depression by self-distancing using mental time-travel.

BACKGROUND: Past research indicates that self-distancing through perspective-taking may increase help-seeking intentions among some people with depression. AIMS: The current pre-registered study tested the effect of self-distancing through mental time-travel on help-seeking attitudes, intentions, outcome expectations, and self-stigma. METHODS: Participants with elevated depressive symptomatology who had not yet sought help for current feelings of depression (n = 859) were randomly assigned to a self-distancing writing task, a self-immersive writing task, or a control condition. RESULTS: Help-seeking attitudes were significantly higher in the distancing condition than in the immersive or control conditions. Additionally, self-distancing through mental time-travel resulted in higher help-seeking intentions compared to the control condition but was not significantly different from the immersive condition. The immersive condition was not significantly different from the control for any outcomes. Interactions show that both self-distancing and the immersive task weakened the negative relationship between depression severity and help-seeking attitudes and intentions. CONCLUSION: Extending scholarship investigating self-distancing and help-seeking intentions, results show that self-distancing through mental time-travel can result in more favorable help-seeking attitudes compared to a control.

Low antispike antibody levels correlate with poor outcomes in COVID-19 breakthrough hospitalizations.

BACKGROUND: While COVID-19 immunization programs attempted to reach targeted rates, cases rose significantly since the emergence of the delta variant. This retrospective cohort study describes the correlation between antispike antibodies and outcomes of hospitalized, breakthrough cases during the delta variant surge. METHODS: All patients with positive SARS-CoV-2 polymerase chain reaction hospitalized at Mayo Clinic Florida from 19 June 2021 to 11 November 2021 were considered for analysis. Cases were analyzed by vaccination status. Breakthrough cases were then analyzed by low and high antibody titers against SARS-CoV-2 spike protein, with a cut-off value of ≥132 U/ml. Outcomes included hospital length of stay (LOS), need for intensive care unit (ICU), mechanical ventilation, and mortality. We used 1:1 nearest neighbor propensity score matching without replacement to assess for confounders. RESULTS: Among 627 hospitalized patients with COVID-19, vaccine breakthrough cases were older with more comorbidities compared to unvaccinated. After propensity score matching, the unvaccinated patients had higher mortality (27 [28.4%] vs. 12 [12.6%], p = 0.002) and LOS (7 [1.0-57.0] vs. 5 [1.0-31.0] days, p = 0.011). In breakthrough cases, low-titer patients were more likely to be solid organ transplant recipients (16 [34.0%] vs. 9 [12.3%], p = 0.006), with higher need for ICU care (24 [51.1%] vs. 22 [11.0%], p = 0.034), longer hospital LOS (median 6 vs. 5 days, p = 0.013), and higher mortality (10 [21.3%] vs. 5 [6.8%], p = 0.025) than high-titer patients. CONCLUSIONS: Hospitalized breakthrough cases were more likely to have underlying risk factors than unvaccinated patients. Low-spike antibody titers may serve as an indicator for poor prognosis in breakthrough cases admitted to the hospital.

A Rebuttal-Based Social Norms-Tailored Cannabis Intervention for At-Risk Adolescents.

Many past cannabis prevention campaigns have proven largely ineffective due in part to the diversity of adolescents' cannabis-relevant beliefs. The current studies evaluated the impact of a sequential multiple message approach tailored to the usage norms of adolescents expressing negative attitudes toward a cannabis prevention appeal. A multiple-message strategy was implemented-initial unfavorable message evaluations were invalidated using attitudinal rebuttal feedback prior to presenting a third tailored communication. Participants were cannabis-abstinent middle and high school students (ages 11 to 16). Study 1 (N = 808) compared effects of gain- and loss-framed messages tailored to each student's normative usage perceptions. In Study 2 (N = 391), students were randomly assigned to receive a tailored or non-tailored message after receiving feedback meant to destabilize anti-message attitudes. For at-risk adolescents in Study 1 who perceived cannabis use as normative, a tailored gain-framed message resulted in the lowest usage intentions (p < .05). In Study 2, a conditional multiple-moderated mediation model showed that for high-risk teens with normative beliefs and pro-cannabis attitudes, exposure to a tailored gain-framed communication was associated with decreased cannabis attitude certainty, and lower usage intentions 2 months later (p < .05). Findings have implications for sequential messaging utilization in mass media campaigns and support the efficacy of tailored messages over a one-size-fits-all media approach. Further, results suggest that systematically weakening resistance to persuasive communications and tailoring messages consistent with individually perceived peer norms is an effective prevention strategy.

Ketamine in seizure management and future pharmacogenomic considerations.

Ketamine is a noncompetitive N-methyl-D-aspartate antagonist with emerging evidence for use in medically refractory epilepsy. We describe the novel use of low-dose intravenous (IV) ketamine transitioning to enteral formulation in a patient with drug-resistant localization-related refractory epilepsy. We performed a National Library of Medicine (NLM) literature review using search terms "ketamine", "low dose", and "seizure" for similar cases, followed by an illustrative clinical case. Our NLM search engine methodology yielded 24 hits, none of which described use of low-dose ketamine for seizures. Anesthetic doses are used for status epilepticus, but we show that in a patient with postoperative worsening of his chronic seizure burden, low-dose IV ketamine can be used to avoid oversedation and intubation. We demonstrate that IV ketamine can be transitioned to oral regimen to shorten length of stay in the intensive care unit and hospital and has future CYP2B6 pharmacogenomic considerations for further dose individualization.

Incorporation of Telestroke into Neurology Residency Training: "Time Is Brain and Education".

Background: With increasing demand for neurologists, nontraditional health care delivery mechanisms have been developed to leverage this limited resource. Introduction: Telemedicine has emerged as an effective digital solution. Over the past three decades, telemedicine use has steadily grown; however, neurologists often learn on the job, rather than as part of their medical training. The current literature regarding telestroke training during neurology training is sparse, focusing on cerebrovascular fellowship curricula. We sought to enhance telestroke training in our neurology residency by incorporating real-life application. Materials and Methods: We implemented a formal educational model for neurology residents to use telemedicine for remote acquisition of the National Institutes of Health Stroke Scale (NIHSS) for patients with suspected acute ischemic stroke (AIS) before arrival at our comprehensive stroke center. This three-phase educational model involved multidisciplinary classroom didactics, simulation exercises, and real-world experience. Training and feedback were provided by neurologists experienced in telemedicine. Results: All residents completed formal training in telemedicine prehospital NIHSS acquisition and had the opportunity to participate in additional simulation exercises. Currently, residents are gaining additional experience by performing prehospital NIHSS acquisition for patients in whom AIS is suspected. Our preliminary data indicate that resident video encounters average 10.6 min in duration, thus saving time once patients arrive at our hospital. Discussion: To our knowledge, this is the first report of a telestroke-integrated neurology residency program in a comprehensive stroke center resulting in shortened time to treatment in patients with suspected AIS. Conclusions: We present a model that can be adopted by other neurology residency programs as it provides real-world telemedicine training critical to future neurologists.

A Combined Approach to Intracerebral Hemorrhage: Intravenous Mesenchymal Stem Cell Therapy with Minimally Invasive Hematoma Evacuation.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stromal cells currently being tested as therapy for a variety of diseases. MSC therapy and hematoma evacuation using a minimally invasive approach are being studied separately to improve clinical outcomes after stroke. We report the first case of a patient with intracerebral hemorrhage (ICH) treated with combination MSC therapy and endoscopic hematoma evacuation. CASE REPORT: A 36-year-old woman with a past medical history of essential chronic hypertension and right lung bronchial atresia presented to the emergency department with acute neurologic decline (National Institute of Health Stroke Scale [NIHSS] score, 22). Computed tomography showed a 4.4 × 3.5 × 3.5 cm right basal ganglia hemorrhage with intraventricular extension. An external ventricular drain was placed, and she was enrolled in a Phase I clinical trial investigating intravenous MSC therapy for acute ICH. Continued neurologic deterioration due to increased intracranial pressure led to minimally invasive hematoma evacuation using the Artemis Neuro Evacuation Device (Penumbra, Inc.) on hospital day 4. Follow-up scans showed decreased density and extent of hemorrhage. She was discharged on day 41 with improved neurologic function scores (NIHSS score, 2). At 3-month follow-up, she was walking on her own, but had residual left arm and hand weakness (modified Rankin Score, 2). CONCLUSIONS: This case report suggests that the combination of MSC therapy and minimally invasive hematoma evacuation may be safe and well tolerated. Further larger randomized clinical trials are required to identify whether MSC therapy in combination with minimally invasive hematoma evacuation is safe, tolerable, and potentially improves outcomes than either alone.

Cerebrospinal meningitis: a global disease with regional variability?

INTRODUCTION: In this edition, Szymanski et al. present the results of their retrospective study of the clinical differences between patients with meningococcal meningitis and pneumococcal cerebrospinal meningitis at the Regional Specialistic Hospital in Wroclaw, Poland. CLINICAL REFLECTIONS: The authors found that compared to patients with N. meningitidis, patients with S. pneumoniae were older, more frequently had chronic comorbidities, and had higher rates of pneumonia, longer hospitalisations, and higher mortality. Patients with N. meningitidis had higher rates of haemorrhagic rash and DIC. CLINICAL IMPLICATIONS: These characteristics and outcomes reflect previous reports from Western Europe and the United States.

A Mixed Methods Approach to Creating Depression Public Service Announcements by Collaborating with People with Depressive Symptomatology.

Depression is a treatable condition; unfortunately, many do not seek help. Depression public service announcements (D-PSAs) are one means of increasing help-seeking behavior. However, as Beck's cognitive theory of depression indicates, it can be challenging to persuade people with depression. Although there have been successful D-PSAs, some have been ineffective or led to boomerang effects. With the goal of providing guidance for future messages, we use a mixed-methods approach to assess how people with heightened depressive symptomatology perceive motivations and barriers regarding help-seeking. Study 1 participants (N = 186), with and without depressive symptomatology, provided motivations and barriers to seeking help for depression. Study 1's qualitative analysis determined 112 motivations and 124 barriers to help-seeking. Study 2 participants (N= 214), all with heightened depressive symptomatology, rated the motivations and barriers from Study 1 on their attitude function, importance, awareness, and argument strength. This insight guided successful D-PSA creation in a follow-up study, reported elsewhere. The methodological approach utilized, and the specific motivations and barriers revealed, will ideally assist scholars and practitioners seeking to develop future D-PSAs.

Can Mental Health Anti-stigma Messages Have Untoward Effects on Some People with Depression?: An Exploratory Study.

Scholars have warned that mental health anti-stigma campaigns targeting the general public can possibly be detrimental to some who are stigmatized. Scholars also have noted that people with depression respond to some public service announcements (PSAs) differently than those without. Accordingly, the current study explored whether anti-stigma PSAs targeting the general public could cause problematic outcomes for people with depression. Participants with (n = 55) and without (n = 133) heightened depressive symptomatology viewed two mental health anti-stigma PSAs. Participants provided thoughts about the PSAs through a single, open-ended question. To allow for an assessment of convergence, participants rated overall favorability toward each PSA through a close-ended item. Results indicated that most qualitative responses were favorable; however, 23.6% of respondents with heightened depressive symptomatology, compared to 1.5% without, provided responses coded as indicating that at least one PSA caused unintended negative affect, χ2(1) = 25.96, [Formula: see text] p < .001. Evidence of untoward effects primarily came from the Friend PSA and the qualitative responses indicate how this occurred. Moreover, complementing the qualitative coding, the Friend PSA was rated less favorably by participants with heightened depressive symptomatology (M = 5.00, SD = 1.67), than those without (M = 5.64, SD = 1.44), F(1, 186) = 6.99, p = .009, ηp2 = .036. There were no significant differences in quantitative favorability ratings regarding the Labeling PSA. Indicating that further investigation is warranted, results suggest it is possible for an anti-stigma PSA targeting the general public to cause unintended negative affect among some people with depression.

Measuring Prosociality: The Development of a Prosocial Behavioral Intentions Scale.

Prosociality is a critical issue in behavioral research. In this investigation, we developed a measure of prosocial behavioral intentions. Qualitative responses from two surveys (n = 465) and items from existing measures were used to generate a list of prosocial behaviors in which people might intend to engage. We factor analyzed responses to these items (n = 319) and retained the most common and representative items. The new measure demonstrated adequate internal consistency (n = 247, 147; α = .81, .83); convergent validity with past prosocial behavior (r = .51, .43), moral identity (r = .50, .55), and materialism (r = -.30, -.20). The instrument also predicted prosocial behavior while controlling for a prior measure of prosocial intentions, Exp(B) = 1.99, Wald = 10.59, p = .001, thereby demonstrating incremental predictive validity. This 4-item scale could be used across contexts to advance the study of prosociality.

Acute bacterial meningitis and stroke.

INTRODUCTION: Acute bacterial meningitis remains a common disease, especially in developing countries. Although advances over the last century have improved mortality and morbidity, the neurological adverse effects remain high. Specifically, acute ischaemic stroke is a serious comorbidity that represents both disease severity and poor prognosis. This review presents the clinical connection between meningitis and stroke, and discusses the neuroinflammatory components that have direct ties between these diseases. STATE OF THE ART: Ischaemic stroke is the direct result of the inflammatory response produced to eradicate infectious pathogens. Bacterial virulence factors and pathogen-associated molecular patterns cause direct damage to the blood-brain barrier and trigger leukocytes to react to the infection. Cytokines are released that cause further destruction of the blood-brain barrier, lead to neuronal death, and recruit the prothrombotic effects of the coagulation cascade through the complement system. Unfortunately, this inflammatory response causes vasculopathy and hypercoagulation of the cerebral blood vessels, leading to cerebral ischaemia. CLINICAL IMPLICATIONS: Pharmacological attempts to mitigate this inflammatory response have produced both positive and negative results. On the one hand, corticosteroids have been shown to improve mortality if given early in patients with bacterial meningitis, particularly pneumococcal meningitis. On the other hand, corticosteroids have been linked to delayed cerebral infarction and other adverse effects. FUTURE DIRECTIONS: New targets for specific inflammatory markers have shown success in rodent models, but have not yet been proven beneficial in humans. Genetic markers are on the horizon, and may serve as individualised targets for diagnosis and therapy.

Increasing Help-Seeking Outcomes among People with Elevated Depressive Symptomatology with Public Service Announcements: An Examination of Functional Matching and Message Sidedness.

The current experimental study assessed the utility, and potential harm, of depression public service announcements (D-PSAs) that were matched, moderately matched, or mismatched based on attitude function (i.e., social-adjustive or object-appraisal) and either one-sided or refutational two-sided. US adults (N = 567) with mild to severe depressive symptomatology were randomly assigned to view control messages or one set of D-PSAs. Results indicate that functionally matched D-PSAs, regardless of message sidedness, caused more favorable help-seeking outcome expectations, attitudes, and intentions compared to the control messages. Exposure to the mismatched D-PSAs, particularly refutational, led to less-favorable help-seeking outcome expectations, attitudes, and intentions compared with the control condition. Help-seeking outcomes among those exposed to the moderately matched messages were not significantly different from those exposed to the control messages, with the exception of those exposed to the one-sided moderately matched messages. The one-sided moderately matched messages resulted in lower help-seeking intentions than the control messages. Overall, results indicate that if messages can be tailored to match the recipients' attitude functions, help-seeking outcomes among people with heightened depressive symptomatology can be increased. However, the results also indicate that some D-PSAs can have negative effects.

Oxygen Therapy with High-Flow Nasal Cannula as an Effective Treatment for Perioperative Pneumocephalus: Case Illustrations and Pathophysiological Review.

Pneumocephalus (PNC) is a condition in which when air is trapped inside the intracranial vault. The causes are varied, but include trauma and intracranial surgery. Treatment of PNC typically consists of augmenting patient oxygenation with the attempt of washing out pulmonary nitrogen, creating a gradient in which nitrogen in the intracranial air bubble diffuses out of the lungs via the blood. Though several high flow methods have been tested, the ideal mode of oxygenation has not fully been investigated. Here we present 3 cases of post-operative PNC who we felt were symptomatic from PNC. With administration of high-flow nasal cannula (HFNC), all patients improved both clinically and radiographically within a few hours, faster than in both anecdotal experience and published trials. Due to its steady FiO2 administration, positive pressure, comfort, and low side-effect profile, HFNC may be the ideal mode of oxygen delivery in PNC. We present a review of the physiology of PNC and the characteristics of several oxygen delivery systems to build a case for HFNC in this disease process.

Granulomatous Angiitis of the Central Nervous System Associated with Hodgkin's Lymphoma: Case Report and Literature Review.

Granulomatous angiitis of the central nervous system (GACNS) is a rare cerebrovascular disorder. It usually presents with multifocal neurologic symptoms symptoms including stroke, encephalopathy, and headache. A limited number of case reports describe neurological deficits resulting from GACNS as the manifesting symptoms of Hodgkin's lymphoma (HL). We describe the case of a patient with neurological symptoms from GACNS that led to the diagnosis of HL, as well as a literature review focusing on the association between GACNS and HL.

Update on Neurocritical Care of Stroke.

PURPOSE OF REVIEW: This review will highlight the recent advancements in acute ischemic stroke diagnosis and treatment, with special attention to new features and recommendations of stroke care in the neurocritical care unit. RECENT FINDINGS: New studies suggest that pre-hospital treatment of stroke with mobile stroke units and telestroke technology may lead to earlier stroke therapy with intravenous tissue plasminogen activator (tPA), and recent studies show tPA can be given in previously contraindicated situations. More rapid automated CT perfusion and angiography may demonstrate a vascular penumbra for neuroendovascular intervention. Further, the greatest advance in acute stroke treatment since 2014 is the demonstration that neuroendovascular catheter-based thrombectomy with stent retrievers recanalizing intracranial large vessel occlusion (LVO) improves both recanalization and long-term outcomes in several trials. Hemorrhagic transformation and severe large infarct cerebral edema remain serious post-stroke challenges, with new guidelines describing who and when patients should get medical or surgical intervention. The adage "time is brain" directs the most evidence-based approach for rapid stroke diagnosis for tPA eligible and LVO recanalization using an orchestrated team approach. The neurocritical care unit is the appropriate location to optimize stroke outcomes for the most severely affected stroke patients.

Index-finger pointing in generalized tonic-clonic seizures.

OBJECTIVE: Most patients with localization-related epilepsy (LRE) and genetic generalized epilepsy (GGE) are classified based on semiology and video-EEG, but both features occasionally fail to provide a definitive diagnosis. Several reliable lateralizing signs have been described, although hand and finger posturing has received little attention. We sought to investigate the frequency of index-finger pointing (IFP) during generalized motor convulsions as a lateralizing semiology in LRE. METHODS: We retrospectively analyzed 98 videos of generalized convulsions in 64 consecutive patients who were admitted for diagnostic video-EEG (vEEG). Demographics were recorded, and IFP ipsilateral, contralateral, and bilateral to vEEG ictal correlate was compared between LRE, GGE, and nonepileptic attacks (NEAs). The angle of IFP was measured to quantify the mean degree of IFP in "pointers" versus "nonpointers". Statistical analysis was completed using JMP 9.0. RESULTS: Index-finger pointing was more common in epileptic GTC seizures than in convulsive NEAs (83.6% vs 12.0%; p<0.001) and was more common in LRE compared with GGE (96% vs 56.6%; p≤0.001). The frequency of contralateral, ipsilateral, or bilateral IFP did not differ between LRE and GGE. The average angle at the MCP joint in "pointers" was 35.8° (SD 22.0°) and in "nonpointers" 3.0° (SD 7.2°). SIGNIFICANCE: This is the first study to examine hand and finger postures as a clinical sign to help classify epilepsy type. The presence of IFP was more common in patients with LRE than in patients with GGE and very rarely occurred in NEA. Index-finger pointing and other hand semiologies are potentially quantifiable localizing signs to aid in the characterization of patients with GTC seizures.

The Effect of Inconsistency Appeals on the Influence of Direct-to-Consumer Prescription Drug Advertisements: An Application of Goal Disruption Theory.

Scholars across multiple domains have identified the presence of inconsistency-arousing information in direct-to-consumer prescription drug advertisements and have suggested that these appeals, which highlight differences between people's actual and desired lives, may create psychological disequilibrium. However, experimental assessment of the distinct influence of inconsistency-arousing information in this domain is rare. Guided by goal disruption theory-a framework that outlines people's reactions to goal expectation violations-we created direct-to-consumer advertisements designed to make people's life inconsistencies salient. The influence of these ads on people's perceptions of, and intentions to use, prescription drugs was then assessed. Results from a structural equation modeling analysis supported the proposed model, indicating that compared to a control ad, an ad containing a goal expectation violation manipulation resulted in higher levels of psychological disequilibrium; in turn, psychological disequilibrium led to positive evaluations of the ad and the drug, positive outcome expectations of the drug, increased purposive harm endurance, and increased usage intentions. The current results suggest a psychological pathway that begins with a negative goal expectation violation and ends with increased usage intentions and a greater willingness to endure harm to make use possible.

State Psychological Reactance to Depression Public Service Announcements Among People With Varying Levels of Depressive Symptomatology.

Campaigns seeking to help people with depression can be effective, but they can also backfire. Psychological reactance is proposed as a partial explanation. Two experimental studies examined the effect of two depression messages (i.e., autonomy-supportive language, controlling language) for participants (n = 2027, n = 777) with varying levels of depressive symptomatology. For Study 1, two versions of a print public service announcement about seeking help for depression served as the experimental stimulus. Study 2 used an existing video public service announcement about seeking help for depression, but the text was altered to create the two conditions. In both studies, increased depressive symptomatology was associated with reduced help-seeking attitudes and intentions, as well as greater state reactance to a public service announcement about depression. Increased state reactance mediated the relationship between increased depressive symptomology and unfavorable help-seeking outcomes. Further, across the two studies, participants with high levels of depressive symptomatology who were exposed to the autonomy-supportive language ad reported either as much, or more, state reactance than participants with high levels of depressive symptomatology who were in the control condition. These results warn that language perceived as autonomy-supportive by people without depression might be perceived as controlling among people with depression.

The Potential (F)utility of a Passive Organ Donor Registration Opportunity: A Conceptual Replication.

CONTEXT: Approximately 22 people die each day in the United States as a result of the shortage of transplantable organs. This is particularly problematic among Spanish-dominant Hispanics. Increasing the number of registered organ donors can reduce this deficit. OBJECTIVE: The goal of the current set of studies was to conceptually replicate a prior study indicating the lack of utility of a lone, immediate and complete registration opportunity (ICRO). DESIGN AND SETTING: The study, a quasi-experimental design involving a total of 4 waves of data collection, was conducted in 2 different Mexican consulates in the United States. Guided by the IIFF Model (ie, an ICRO, information, focused engagement, and favorable activation), each wave compared a lone ICRO to a condition that likewise included an ICRO but also included the 3 additional intervention components recommended by the model (ie, information, focused engagement, and favorable activation). PARTICIPANTS: Visitors to the Mexican consulates in Tucson, Arizona, and Albuquerque, New Mexico, constituted the participant pool. MAIN OUTCOME MEASURE: New organ donor registrations represented the dependent variable. RESULTS: When all 4 components of the IIFF Model were present, approximately 4 registrations per day were recorded; the lone ICRO resulted in approximately 1 registration every 15 days. CONCLUSION: An ICRO, without the other components of the IIFF Model, is of minimal use in regard to garnering organ donor registrations. Future studies should use the IIFF Model to consider how the utility of ICROs can be maximized.