Negative Disease-Related Stigma 3-months After Hemorrhagic Stroke is related to Functional Outcome and Female Sex.

OBJECTIVES: The objective of this study was to determine factors associated with negative disease-related stigma after hemorrhagic stroke. MATERIALS AND METHODS: Patients with non-traumatic hemorrhage (ICH or SAH) admitted between January 2015 and February 2021 were assessed by telephone 3-months after discharge using the Quality of Life in Neurological Disorders (Neuro-QoL) Negative Disease-Related Stigma Short Form inventory. We evaluated the relationship between disease-related stigma (T-score>50) and pre-stroke demographics, admission data, and poor functional outcome (3-month mRS score 3-5 and Barthel Index <100). RESULTS: We included 89 patients (56 ICH and 33 SAH). The median age was 63 (IQR 50-69), 43% were female, and 67% graduated college. Admission median GCS score was 15 (IQR 13-15) and APACHE II score was 12 (IQR 9-17). 31% had disease-related stigma. On univariate analysis, disease-related stigma was associated with female sex, non-completion of college, GCS score, APACHE II score, and 3-month mRS score (all p<0.05). On multivariate analysis, disease-related stigma was associated with female sex (OR = 3.72, 95% CI = 1.23-11.25, p = 0.02) and 3-month Barthel Index<100 (OR = 3.46, 95% CI = 1.13-10.64, p = 0.03) on one model, and female sex (OR = 3.75, 95% CI = 1.21-11.58, p = 0.02) and 3-month mRS score 3-5 (OR = 4.23, 95% CI = 1.21-14.75, p = 0.02) on a second model. CONCLUSION: Functional outcome and female sex are associated with disease-related stigma 3-months after hemorrhagic stroke. Because stigma may negatively affect recovery, there is a need to understand the relationship between these factors to mitigate stroke-related stigma.

Poor Accuracy of Manually Derived Head Computed Tomography Parameters in Predicting Intracranial Hypertension After Nontraumatic Intracranial Hemorrhage.

BACKGROUND: The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS: We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS: Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS: More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.

Follow-up Imaging After Thrombolysis: FIAT, A Randomized Trial.

TRIAL DESIGN: Current protocols for treatment of acute ischemic stroke with intravenous thrombolytics, such as alteplase (tPA) and tenecteplase (tNK), recommend the completion of a routine non-contrast head CT at 24 hours post treatment to evaluate for hemorrhage prior to the initiation of antiplatelet therapy for secondary stroke prevention. This guideline was instituted because it had been part of the protocol in the NINDS multicenter randomized placebo-controlled trial that showed the benefit of IV thrombolytics within 3 hours of stroke onset. Recent observational studies indicate that the repeat (stability) head CT rarely alters clinical management, in the absence of neurological worsening or evidence of clinical signs of hemorrhagic conversion, such as seizures, severe headache, or novel acute deficits. A solitary CT carries with it a non-negligible dose of radiation with additive cost to the medical system at large. METHODS: We aimed to identify, with a randomized, blinded outcome assessment trial, if a routine head CT at 24 hours, in the absence of clinical indication, negatively influences clinical outcomes. We enrolled 58 patients, and evaluated differences between groups with t-tests. We also evaluated differences between outcomes (90 day modified Rankin Scale, mRS and change in National Institutes of Health Stroke Scale, NIHSS) from pretreatment to discharge using multivariable logistic regression, including age, baseline NIHSS, and group as independent variables. RESULTS: We found no added benefit of routine CT on either outcome measure. CONCLUSION: It is likely safe to forgo follow up imaging after thrombolysis in the absence of clinical decompensation.

Neuroinflammation in neocortical epilepsy measured by PET imaging of translocator protein.

OBJECTIVES: Neuroinflammation, implicated in epilepsy, can be imaged in humans with positron emission tomography (PET) ligands for translocator protein 18 kDa (TSPO). Previous studies in patients with temporal lobe epilepsy and mesial temporal sclerosis found increased [11C]PBR28 uptake ipsilateral to seizure foci. Neocortical foci present more difficult localization problems and more variable underlying pathology. METHODS: We studied 11 patients with neocortical seizure foci using [11C]PBR28 or [11C] N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA) 713, and 31 healthy volunteers. Seizure foci were identified with structural magnetic resonance imaging (MRI) and ictal video-electroencephalography (EEG) monitoring. Six patients had surgical resections; five had focal cortical dysplasia type 2A or B and one microdysgenesis. Brain regions were delineated using FreeSurfer and T1-weighted MRI. We measured brain radioligand uptake (standardized uptake values [SUVs]) in ipsilateral and contralateral regions, to compare calculated asymmetry indices [AIs; 200% *(ipsilateral - contralateral)/(ipsilateral + contralateral)] between epilepsy patients and controls, as well as absolute [11C]PBR28 binding as the ratio of distribution volume to free fraction (VT /fP ) in 9 patients (5 high affinity and 4 medium affinity binders) and 11 age-matched volunteers (5 high-affinity and 6 medium affinity) who had metabolite-corrected arterial input functions measured. RESULTS: Nine of 11 patients had AIs exceeding control mean 95% confidence intervals in at least one region consistent with the seizure focus. Three of the nine had normal MRI. There was a nonsignificant trend for patients to have higher binding than volunteers both ipsilateral and contralateral to the focus in the group that had absolute binding measured. SIGNIFICANCE: Our study demonstrates the presence of focal and distributed inflammation in neocortical epilepsy. There may be a role for TSPO PET for evaluation of patients with suspected neocortical seizure foci, particularly when other imaging modalities are unrevealing. However, a complex method, inherent variability, and increased binding in regions outside seizure foci will limit applicability.

Required and Elective Experiences During the 4th Year: An Analysis of ACGME Accredited Psychiatry Residency Program Websites.

OBJECTIVE: The objective of this study was to assess and describe required and elective components of the 4th post-graduate year (PGY4) in psychiatry residency programs. METHODS: We reviewed the websites of all 193 2014-2015 ACGME accredited psychiatry residency programs for content describing the specific components of the PGY4 year. RESULTS: Nearly all residency programs (99 %) had some form of required experiences during the PGY4 year. Ninety-four percent had clinical requirements for PGY4 residents, with longitudinal outpatient clinic being the most common (77 %). All programs offered some elective time during PGY4, but the amount of time ranged from 2 months to 100 %. CONCLUSION: Virtually all residency programs include some requirements in the 4th year (most commonly didactics and outpatient clinic) in addition to a broad array of elective experiences. Although 3 years may suffice for residents to complete ACGME requirements, a variety of factors may motivate programs to include required 4th year curricula. Future studies should explore the rationales for and possible benefits of programmatic requirements throughout 4 versus only 3 years of psychiatric training.

Thoughts of death and self-harm in patients with epilepsy or multiple sclerosis in a tertiary care center.

BACKGROUND: Patients with epilepsy or multiple sclerosis (MS) have high risks of depression and increased risks of suicide, but little is known about their risks of suicidal ideation. OBJECTIVE: We sought to (1) estimate the prevalence of thoughts of being better off dead or of self-harm among patients with epilepsy or MS, (2) identify risk factors for such thoughts, and (3) determine whether any risk factors interact with depression to predict such thoughts. METHODS: A Cleveland Clinic database provided information on 20,734 visits of 6586 outpatients with epilepsy or MS. Outcome measures were thoughts of death or self-harm (Patient Health Questionnaire [PHQ] item-9), and total score ≥10 for the 8 remaining PHQ items (probable major depression). Generalized estimating equations accounted for repeat visits in tests of associations of PHQ item-9 responses with depression, age, sex, race, household income, disease severity, and quality of life. RESULTS: Prevalence of thoughts of death or self-harm averaged 14.4% overall (epilepsy, 14.0% and MS, 14.7%). Factors associated with positive PHQ item-9 responses in epilepsy were depression and male sex, modified by poor quality of life. Factors associated with positive PHQ item-9 in MS were depression, male sex, medical comorbidity, and poor quality of life; the effect of depression was worse with greater MS severity and being unmarried. CONCLUSIONS: Among patients with common neurologic disorders (epilepsy or MS), 14%-15% reported thoughts of death or self-harm associated with illness severity, depression, quality of life, male sex, and being unmarried. Such patients require further evaluation of clinical outcomes and effects of treatment.

Impact of the information age on residency training: communication, access to public information, and clinical care.

Access to technology in practice helps physicians manage information, communicate, and research topics; however, those in training receive almost no formal preparation for integrating web-based technologies into practice. One reason for this is that many faculty-aside from junior faculty or those in recent generations-did not grow up using Internet communication, may use it minimally, if at all, in their own practices, and may know little about its forms and varieties. This report presents a case to illustrate how these disparities may play out in the supervisory situation and makes suggestions about helping supervisors integrate technology-awareness into their teaching.

Recruiting researchers in psychiatry: the influence of residency vs. early motivation.

BACKGROUND: The declining numbers of clinician-researchers in psychiatry and other medical specialties has been a subject of growing concern. Residency training has been cited as an important factor in recruiting new researchers, but there are essentially no data to support this assertion. This study aimed to explore which factors have influenced motivation to conduct research among senior psychiatry residents. METHODS: The authors surveyed senior residents, inquiring about their level of interest in research, demographics, background, research experiences, and factors influencing motivation for research. The authors had confirmed participation from 16 of 33 residency programs with a class size of 10 or more. They received 127 responses, a 67% response rate, from participating programs. RESULTS: Residents with high stated interest in research differed from those with low and moderate interest in their research-intense post-residency plans. They were more likely to have graduate degrees. Those planning research careers had a consistent pattern of interest and involvement in research, starting well before residency. The majority of residents had had research exposure in college, but research involvement of those with very high versus lower interest diverged sharply thereafter. Those with high research interest were overwhelmingly male and tended to have lower debt than those with less interest. CONCLUSION: The great majority of residents appear to have decided whether or not to pursue a research career by the time they reached residency, and few of those with less than the highest research interest were enrolled in research tracks. Efforts to increase recruitment into research should center on identifying early developmental influences, eliminating barriers specific to women, and ensuring adequate funding to provide secure careers for talented potential researchers.

Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography.

PURPOSE: Translocator protein (TSPO) is a promising biomarker for neuroinflammation. We developed two new PET ligands, (18)F-PBR06 and (11)C-PBR28, to image TSPOs. Although our prior studies suggest that either of the two ligands could be used to quantify TSPOs in human brain, the studies were done in different sets of subjects. In this study, we directly compared (18)F-PBR06 and (11)C-PBR28 in eight human subjects to determine (1) whether either ligand provides more precise measurements of TSPOs and (2) whether the higher in vitro affinity of PBR06 compared to PBR28 led to higher in vivo binding of (18)F-PBR06 compared to (11)C-PBR28. METHODS: In vivo binding was calculated as total distribution volume (V(T)), using an unconstrained two-tissue compartment model. V(T) was corrected for plasma free fraction (f (P)) to measure ligand binding based on free ligand concentration in brain. RESULTS: Both ligands measured V(T) with similar precision, as evidenced by similarly good identifiability. However, V(T) for both radioligands increased with increasing lengths of data acquisition, consistent with the accumulation of radiometabolites in brain. Despite its higher lipophilicity and higher in vitro affinity, V(T)/f(P) of (18)F-PBR06 was similar to that of (11)C-PBR28. CONCLUSION: Both (18)F-PBR06 and (11)C-PBR28 are similar in terms of precision, sensitivity to accumulation of radiometabolites, and magnitude of in vivo binding. Thus, selection between the two radioligands will be primarily determined by the logistical impact of the different half-lives of the two radionuclides (110 vs 20 min).

Episodic Facial Paresis-An Isolated Presenting Symptom of Multiple Sclerosis.

This case report describes a case of a man in his 30s who presented with episodic right lower facial paresis for 10 days and was diagnosede with an episodic, transient pattern of unilateral facial palsy associated with relapsing remitting multiple sclerosis.

Patients with challenging behaviors: Communication strategies.

Some patients have behaviors that make interactions unpleasant, sometimes contributing to suboptimal outcomes and physician burnout. Understanding common difficult personality types can help doctors plan effective strategies for dealing with each, resulting in more effective communication, less stress, and better health outcomes.

Primary prevention and practical techniques to encourage mental wellness.

Women patients must be made aware that they need to train and perhaps readjust their attitudes and minds to handle and improve their mental wellness. Being their own person, with awareness of whom and how they want to be, strengthens their sense of self and simplifies their lives with awareness and understanding of the choices unique to them as individuals.

Recognizing, managing medical consequences of eating disorders in primary care.

Eating disorders can lead to serious health problems, and as in many other disorders, primary care physicians are on the front line. Problems that can arise from intentional malnutrition and from purging affect multiple organ systems. Treatment challenges include maximizing weight gain while avoiding the refeeding syndrome.

Is peripheral immunity regulated by blood-brain barrier permeability changes?

S100B is a reporter of blood-brain barrier (BBB) integrity which appears in blood when the BBB is breached. Circulating S100B derives from either extracranial sources or release into circulation by normal fluctuations in BBB integrity or pathologic BBB disruption (BBBD). Elevated S100B matches the clinical presence of indices of BBBD (gadolinium enhancement or albumin coefficient). After repeated sub-concussive episodes, serum S100B triggers an antigen-driven production of anti-S100B autoantibodies. We tested the hypothesis that the presence of S100B in extracranial tissue is due to peripheral cellular uptake of serum S100B by antigen presenting cells, which may induce the production of auto antibodies against S100B. To test this hypothesis, we used animal models of seizures, enrolled patients undergoing repeated BBBD, and collected serum samples from epileptic patients. We employed a broad array of techniques, including immunohistochemistry, RNA analysis, tracer injection and serum analysis. mRNA for S100B was segregated to barrier organs (testis, kidney and brain) but S100B protein was detected in immunocompetent cells in spleen, thymus and lymph nodes, in resident immune cells (Langerhans, satellite cells in heart muscle, etc.) and BBB endothelium. Uptake of labeled S100B by rat spleen CD4+ or CD8+ and CD86+ dendritic cells was exacerbated by pilocarpine-induced status epilepticus which is accompanied by BBBD. Clinical seizures were preceded by a surge of serum S100B. In patients undergoing repeated therapeutic BBBD, an autoimmune response against S100B was measured. In addition to its role in the central nervous system and its diagnostic value as a BBBD reporter, S100B may integrate blood-brain barrier disruption to the control of systemic immunity by a mechanism involving the activation of immune cells. We propose a scenario where extravasated S100B may trigger a pathologic autoimmune reaction linking systemic and CNS immune responses.

Downregulation of brain phosphodiesterase type IV measured with 11C-(R)-rolipram positron emission tomography in major depressive disorder.

BACKGROUND: Phosphodiesterase type IV (PDE4), an important component of the cyclic adenosine monophosphate (cAMP) cascade, selectively metabolizes cAMP in the brain to the inactive monophosphate. Basic studies suggest that PDE4 mediates the effects of several antidepressants. This study sought to quantify the binding of 11C-(R)-rolipram, a PDE4 inhibitor, as an indirect measure of this enzyme's activity in the brain of individuals with major depressive disorder (MDD) compared with healthy control subjects. METHODS: 11C-(R)-Rolipram brain positron emission tomography scans were performed in 28 unmedicated MDD subjects and 25 age- and gender-matched healthy control subjects. Patients were moderately depressed and about one half were treatment-naive. 11C-(R)-Rolipram binding in the brain was measured using arterial 11C-(R)-rolipram levels to correct for the influence of cerebral blood flow. RESULTS: Major depressive disorder subjects showed a widespread, approximately 20% reduction in 11C-(R)-rolipram binding (p = .002), which was not caused by different volumes of gray matter. Decreased rolipram binding of similar magnitudes was observed in most brain areas. Rolipram binding did not correlate with the severity of depressive or anxiety symptoms. CONCLUSIONS: This study is the first to demonstrate that brain levels of PDE4, a critical enzyme that regulates cAMP, are decreased in unmedicated individuals with MDD in vivo. These results are in line with human postmortem and rodent studies demonstrating downregulation of the cAMP cascade in MDD and support the hypothesis that agents such as PDE4 inhibitors, which increase activity within the cAMP cascade, may have antidepressant effects.

Biodistribution and radiation dosimetry in humans of a new PET ligand, (18)F-PBR06, to image translocator protein (18 kDa).

UNLABELLED: As a PET biomarker for inflammation, translocator protein (18 kDa) (TSPO) can be measured with an (18)F-labeled aryloxyanilide, (18)F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ((18)F-PBR06), in the human brain. The objective of this study was to estimate the radiation absorbed doses of (18)F-PBR06 based on biodistribution data in humans. METHODS: After the injection of (18)F-PBR06, images were acquired from head to thigh in 7 healthy humans. Urine was collected at various time points. Radiation absorbed doses were estimated by the MIRD scheme. RESULTS: Moderate to high levels of radioactivity were observed in organs with high densities of TSPO and in organs of metabolism and excretion. Bone had low levels of radioactivity. The effective dose was 18.5 muSv/MBq. CONCLUSION: The effective dose of (18)F-PBR06, compared with other (18)F radioligands, was moderate. This radioligand had negligible defluorination, as indirectly assessed by bone radioactivity. Doses to the gallbladder wall and spleen may limit the amount of permissible injected radioactivity.

Recruiting and rewarding faculty for medical student teaching.

OBJECTIVE: Finding time to teach psychiatry has become increasingly difficult. Concurrently, changes in medical student education are elevating demands for teaching. Academic psychiatry is challenged by these pressures to find innovative ways to recruit, retain, and reward faculty for teaching efforts. To address this challenge, the authors recommend a multifactorial approach to meeting the medical student educational mission of psychiatry departments. METHODS: This approach includes a variety of efforts including having Chairs serve as role models, enforcing the service requirements of volunteer faculty, expanding teaching venues, providing faculty development, elevating the status of teaching through academies, attending to promotion of faculty educators, establishing and nominating faculty for teaching awards, and using medical center resources to provide rewards for teachers. CONCLUSION: Academic leaders must acknowledge the inherent value of teaching to the academic enterprise and delegate sufficient resources to recruit, retain, and reward educators for the essential work that they perform.