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Background: Clinical trial evidence supports patent foramen ovale (PFO) closure to reduce recurrent stroke risk in select patients. Guidelines recommend a multi-disciplinary approach to identify patients who may benefit from PFO closure. We assess factors associated with the decision to close PFO in a real-world cohort. Methods: We studied patients from University of Minnesota Medical Center and Yale-New Haven Hospital with TIA or ischemic stroke and PFOs evaluated by dedicated multidisciplinary teams of vascular neurologists and interventional cardiologists at each institution. Demographic, clinical, radiographic, and echocardiographic information was extracted by chart review. The study outcome was PFO closure. Descriptive analyses were performed comparing characteristics associated with PFO closure using Mann Whitney test and Chi-squared test. Multivariable logistic regression model was built with variables significant in descriptive analyses. Results: The analytic cohort included 173 patients, of whom 58 patients (33.5%) underwent closure (39.8% of Yale and 20% of UMMC patients were closed). Patients who were closed versus not were similar in age (median age 56 [IQR 21] versus 58 [IQR 21] years), sex, race, diagnosis of TIA or stroke, and co-morbidities except malignancy which was significantly less prevalent among closed patients (2.3% versus 12.1%). Closed patients had a higher RoPE score (median 6 versus 5, p=0.032), and were more likely to have a stroke or TIA of undetermined etiology (55.2 versus 49.6%) and high-risk PFO characteristics (p Conclusions and Relevance: In this study of a real-world cohort, we identify patient characteristics that drive decision-making for PFO closure for secondary stroke prevention.

Background and ObjectivesAlthough moderate and severe traumatic brain injury (TBI) can cause posttraumatic epilepsy (PTE), many patients with functional seizures (FS) also report a history of mild TBI. To determine whether features of TBI history differ between patients with epileptic seizures (ES) and FS, we compared patient reports of TBI severity, symptoms, and causes of injury.MethodsWe recruited patients undergoing video-EEG evaluation for the diagnosis of ES, FS, mixed ES and FS, or physiologic seizure-like events at an academic, tertiary referral center. Patients and their caregivers were interviewed before final video-EEG diagnosis regarding their TBI histories, including concussive symptoms and causes of injury.ResultsOf 506 patients, a greater percentage of patients with FS reported a history of TBI than patients with ES (70% vs 59%, aOR = 1.75 [95% CI: 1.00–3.05],p= 0.047). TBI with loss of consciousness (LOC) lasting less than 30 minutes was more frequently reported among patients with FS than with ES (27% vs 13%, aOR = 2.38 [1.26–4.47],p< 0.01). The proportion of patients reporting other neurologic symptoms immediately after TBI was not significantly different between FS and ES (40% vs 29%,p= 0.08). Causes of TBI were found to differ, with TBIs caused by falls from a height (17% vs 10%, aOR = 2.24 [1.06–4.70],p= 0.03) or motor vehicle collisions (27% vs 11%, aOR = 2.96 [1.54–5.67],p< 0.01) reported more frequently in FS than ES.DiscussionOur findings further the association of mild TBI with FS and prompt reconsideration of typical assumptions regarding the significance of a reported TBI history in patients with previously undifferentiated seizures. Although common in both groups, TBI with LOC less than 30 minutes and causes of injury that are commonly believed to be more severe were reported more frequently in FS than ES. This suggests that a patient or caregiver reporting of these features does not imply that PTE is a more probable diagnosis than FS. Although a history of TBI with LOC and presumed high-risk causes of injury intuitively raises suspicion for PTE, clinicians should be cautioned that these historical factors also were a frequent finding in patients with FS.

Purpose While certain clinical factors suggest a diagnosis of dissociative seizures (DS), otherwise known as functional or psychogenic nonepileptic seizures (PNES), ictal video-electroencephalography monitoring (VEM) is the gold standard for diagnosis. Diagnostic delays were associated with worse quality of life and more seizures, even after treatment. To understand why diagnoses were delayed, we evaluated which factors were associated with delay to VEM. Methods Using data from 341 consecutive patients with VEM-documented dissociative seizures, we used multivariate log-normal regression with recursive feature elimination (RFE) and multiple imputation of some missing data to evaluate which of 76 clinical factors were associated with time from first dissociative seizure to VEM. Results The mean delay to VEM was 8.4 years (median 3 years, IQR 1–10 years). In the RFE multivariate model, the factors associated with longer delay to VEM included more past antiseizure medications (0.19 log-years/medication, standard error (SE) 0.05), more medications for other medical conditions (0.06 log-years/medication, SE 0.03), history of physical abuse (0.75 log-years, SE 0.27), and more seizure types (0.36 log-years/type, SE 0.11). Factors associated with shorter delay included active employment or student status (-1.05 log-years, SE 0.21) and higher seizure frequency (0.14 log-years/log[seizure/month], SE 0.06). Conclusions Patients with greater medical and seizure complexity had longer delays. Delays in multiple domains of healthcare can be common for victims of physical abuse. Unemployed and non-student patients may have had more barriers to access VEM. These results support earlier referral of complex cases to a comprehensive epilepsy center.

Purpose Video-electroencephalographic monitoring (VEM) is a core component to the diagnosis and evaluation of epilepsy and dissociative seizures (DS)—also known as functional or psychogenic seizures—but VEM evaluation often occurs later than recommended. To understand why delays occur, we compared how patient-reported clinical factors were associated with time from first seizure to VEM (TVEM) in patients with epilepsy, DS or mixed. Methods We acquired data from 1245 consecutive patients with epilepsy, VEM-documented DS or mixed epilepsy and DS. We used multivariate log-normal regression with recursive feature elimination (RFE) to evaluate which of 76 clinical factors interacting with patients’ diagnoses were associated with TVEM. Results The mean and median TVEM were 14.6 years and 10 years, respectively (IQR 3–23 years). In the multivariate RFE model, the factors associated with longer TVEM in all patients included unemployment and not student status, more antiseizure medications (current and past), concussion, and ictal behavior suggestive of temporal lobe epilepsy. Average TVEM was shorter for DS than epilepsy, particularly for patients with depression, anxiety, migraines, and eye closure. Average TVEM was longer specifically for patients with DS taking more medications, more seizure types, non-metastatic cancer, and with other psychiatric comorbidities. Conclusions In all patients with seizures, trials of numerous antiseizure medications, unemployment and non-student status was associated with longer TVEM. These associations highlight a disconnect between International League Against Epilepsy practice parameters and observed referral patterns in epilepsy. In patients with dissociative seizures, some but not all factors classically associated with DS reduced TVEM.

Context Present studies suggested that cultural and religious factors, as well as law and policy, may have impeded the advancement of palliative care in the Middle East. Little is known about health care providers' perceptions of palliative care and the barriers to its development in the Gulf Cooperation Council. Objectives To understand health care professionals' attitudes and beliefs regarding palliative care and highlight current practice barriers in Bahrain. Methods Semistructured interviews with 16 health care providers (physicians and nurses) were conducted. Thematic analysis was then performed after interviews were transcribed verbatim. Results Health care professionals perceived palliative care as a service only delivered to patients at the end of life. Palliative care was only offered to patients who have been diagnosed with cancer and had exhausted all curative treatments. Do-not-resuscitate orders and code status discussions are not currently practiced. Palliative care decisions are usually decided by patients' families. Middle Eastern culture, health care law and policy, conservative interpretations of Islam, and a lack of professional expertise were identified as barriers. Conclusion This study unveiled the perceptions of palliative care among health care professionals in a Gulf Cooperation Council country. Six major barriers that hindered palliative care practice were identified. Future health care policy in the region needs to address these barriers within the current health care system while taking culture, religion, and social factors into consideration.

Purpose Differentiating psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES) can be difficult, even when expert clinicians have video recordings of seizures. Moreover, witnesses who are not trained observers may provide descriptions that differ from the expert clinicians’, which often raises concern about whether the patient has both ES and PNES. As such, quantitative, evidence-based tools to help differentiate ES from PNES based on patients’ and witnesses’ descriptions of seizures may assist in the early, accurate diagnosis of patients. Methods Based on patient- and observer-reported data from 1372 patients with diagnoses documented by video-elect roencephalography (vEEG), we used logistic regression (LR) to compare specific peri-ictal behaviors and seizure triggers in five mutually exclusive groups: ES, PNES, physiologic non-epileptic seizure-like events, mixed PNES plus ES, and inconclusive monitoring. To differentiate PNES-only from ES-only, we retrospectively trained multivariate LR and a forest of decision trees (DF) to predict the documented diagnoses of 246 prospective patients. Results The areas under the receiver operating characteristic curve (AUCs) of the DF and LR were 75% and 74%, respectively (empiric 95% CI of chance 37–62%). The overall accuracy was not significantly higher than the naive assumption that all patients have ES (accuracy DF 71%, LR 70%, naive 68%, p > 0.05). Conclusions Quantitative analysis of patient- and observer-reported peri-ictal behaviors objectively changed the likelihood that a patient’s seizures were psychogenic, but these reports were not reliable enough to be diagnostic in isolation. Instead, our scores may identify patients with “probable” PNES that, in the right clinical context, may warrant further diagnostic assessment.

Post-stroke cognitive impairment is associated with poor long-term outcomes and increased functional dependency. The overall study aim was to explore the relationships between global cognition, executive function and metacognition in a stroke population, to examine correlates and potential predictors of cognitive impairment and to determine the relationship between cognitive impairment and stroke in a Bahraini stroke sample in comparison to an age- and sex- matched control group. A sample of 130 stroke patients (case group) were recruited from the largest medical complex in Bahrain and 55 control participants from the non-stroke general population were recruited from two primary local health centres in the country. General demographic data, clinical assessment and neuropsychological battery of cognitive assessments was conducted on participants. The study found that individuals not affected by stroke have proportional risk factors to a stroke population in Bahrain. Approximately 48% of the stroke sample group had some degree of cognitive impairment with greater stroke severity being more significantly associated with worse overall cognitive impairment. Poorer performance on global cognition was correlated with executive dysfunction and more functional dependency. Stroke patients with higher levels of cognitive impairment were more likely to report lower cognitive self-consciousness levels, indicating an impairment in their metacognitive thought processes. Similarly, participants who performed poorly in the memory components of cognitive testing tended to subjectively report higher confidence in their memory skills, indicating an impairment in metamemory. Though no significant correlations were reported between total Metacognitive Questionnaire-30 scores and executive function and global cognition, the Metacognitive Questionnaire-30 was shown to be a good predictor of anxiety and depression post-stroke. The development of a tool that can consolidate both subjective and global objective assessment and thereby measure the full breadth of metacognitive function is necessary and may have important implications for future rehabilitation.

Purpose Descriptions of seizure manifestations (SM), or semiology, can help localize the symptomatogenic zone and subsequently included brain regions involved in epileptic seizures, as well as identify patients with dissociative seizures (DS). Patients and witnesses are not trained observers, so these descriptions may vary from expert review of seizure video recordings of seizures. To better understand how reported factors can help identify patients with DS or epileptic seizures (ES), we evaluated the associations between more than 30 SMs and diagnosis using standardized interviews. Methods Based on patient- and observer-reported data from 490 patients with diagnoses documented by video-electoencephalography, we compared the rate of each SM in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic seizure-like events (PSLE), mixed DS and ES, and inconclusive testing. Results In addition to SMs that we described in a prior manuscript, the following were associated with DS: light triggers, emotional stress trigger, pre-ictal and post-ictal headache, post-ictal muscle soreness, and ictal sensory symptoms. The following were associated with ES: triggered by missing medication, aura of deja vu, and leftward eye deviation. There were numerous manifestations separately associated with mixed ES and DS. Conclusions Reported SM can help identify patients with DS, but no manifestation is pathognomonic for either ES or DS. Patients with mixed ES and DS reported factors divergent from both ES-alone and DS-alone.

Objective To develop a Dissociative Seizures Likelihood Score (DSLS), which is a comprehensive, evidence-based tool using information available during the first outpatient visit to identify patients with “probable” dissociative seizures (DS) to allow early triage to more extensive diagnostic assessment. Methods Based on data from 1616 patients with video-electroencephalography (vEEG) confirmed diagnoses, we compared the clinical history from a single neurology interview of patients in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic nonepileptic seizure-like events (PSLE), mixed DS plus ES, and inconclusive monitoring. We used data-driven methods to determine the diagnostic utility of 76 features from retrospective chart review and applied this model to prospective interviews. Results The DSLS using recursive feature elimination (RFE) correctly identified 77% (95% confidence interval (CI), 74–80%) of prospective patients with either ES or DS, with a sensitivity of 74% and specificity of 84%. This accuracy was not significantly inferior than neurologists’ impression (84%, 95% CI: 80–88%) and the kappa between neurologists’ and the DSLS was 21% (95% CI: 1–41%). Only 3% of patients with DS were missed by both the fellows and our score (95% CI 0–11%). Significance The evidence-based DSLS establishes one method to reliably identify some patients with probable DS using clinical history. The DSLS supports and does not replace clinical decision making. While not all patients with DS can be identified by clinical history alone, these methods combined with clinical judgement could be used to identify patients who warrant further diagnostic assessment at a comprehensive epilepsy center.

Objective Psychogenic nonepileptic seizure (PNES) is a common diagnosis after evaluation of medication resistant or atypical seizures with video-electroencephalographic monitoring (VEM), but usually follows a long delay after the development of seizures, during which patients are treated for epilepsy. Therefore, more readily available diagnostic tools are needed for earlier identification of patients at risk for PNES. A tool based on patient-reported psychosocial history would be especially beneficial because it could be implemented in the outpatient clinic. Methods Based on the data from 1375 patients with VEM-confirmed diagnoses, we used logistic regression to compare the frequency of specific patient-reported historical events, demographic information, age of onset, and delay from first seizure until VEM in five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of this information to differentiate PNES only from ES only, we used multivariate piecewise-linear logistic regression trained using retrospective data from chart review and validated based on data from 246 prospective standardized interviews. Results The prospective area under the curve of our weighted multivariate piecewise-linear by-sex score was 73%, with the threshold that maximized overall retrospective accuracy resulting in a prospective sensitivity of 74% (95% CI: 70–79%) and prospective specificity of 71% (95% CI: 64–82%). The linear model and piecewise linear without an interaction term for sex had very similar performance statistics. In the multivariate piecewise-linear sex-split predictive model, the significant factors positively associated with ES were history of febrile seizures, current employment or active student status, history of traumatic brain injury (TBI), and longer delay from first seizure until VEM. The significant factors associated with PNES were female sex, older age of onset, mild TBI, and significant stressful events with sexual abuse, in particular, increasing the likelihood of PNES. Delays longer than 20 years, age of onset after 31 years for men, and age of onset after 40 years for women had no additional effect on the likelihood of PNES. Discussion Our promising results suggest that an objective score has the potential to serve as an early outpatient screening tool to identify patients with greater likelihood of PNES when considered in combination with other factors. In addition, our analysis suggests that sexual abuse, more than other psychological stressors including physical abuse, is more associated with PNES. There was a trend of increasing frequency of PNES for women during childbearing years and plateauing outside those years that was not observed in men.

SummaryObjective Low-cost evidence-based tools are needed to facilitate the early identification of patients with possible psychogenic nonepileptic seizures (PNES). Prior to accurate diagnosis, patients with PNES do not receive interventions that address the cause of their seizures and therefore incur high medical costs and disability due to an uncontrolled seizure disorder. Both seizures and comorbidities may contribute to this high cost. Methods Based on data from 1,365 adult patients with video-electroencephalography–confirmed diagnoses from a single center, we used logistic and Poisson regression to compare the total number of comorbidities, number of medications, and presence of specific comorbidities in five mutually exclusive groups of diagnoses: epileptic seizures (ES) only, PNES only, mixed PNES and ES, physiologic nonepileptic seizurelike events, and inconclusive monitoring. To determine the diagnostic utility of comorbid diagnoses and medication history to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and age, trained using a retrospective database and validated using a prospective database. Results Our model differentiated PNES only from ES only with a prospective accuracy of 78% (95% confidence interval =72–84%) and area under the curve of 79%. With a few exceptions, the number of comorbidities and medications was more predictive than a specific comorbidity. Comorbidities associated with PNES were asthma, chronic pain, and migraines (p < 0.01). Comorbidities associated with ES were diabetes mellitus and nonmetastatic neoplasm (p < 0.01). The population-level analysis suggested that patients with mixed PNES and ES may be a population distinct from patients with either condition alone. Significance An accurate patient-reported medical history and medication history can be useful when screening for possible PNES. Our prospectively validated and objective score may assist in the interpretation of the medication and medical history in the context of the seizure description and history.

A 28-year-old East African man with progressive visual impairment and keratitis presented with new symptoms including headache, nausea, disequilibrium, tinnitus, and right leg paresthesias. MRI showed bilateral retinal detachments and diffuse leptomeningeal enhancement (figure). Lumbar puncture showed lymphocytic pleocytosis and elevated protein. His clinical picture was consistent with Vogt-Koyanagi-Harada (VKH) disease: an autoimmune inflammatory disorder with ocular, auditory, skin, and neurologic involvement.1 VKH disease is more common in Asian, Middle Eastern, and Hispanic populations.1 Treatment includes early high-dose corticosteroids with prolonged taper over months.1,2 His symptoms improved following high-dose methylprednisolone.

Background: Poststroke dementia and cognitive impairment are associated with poor long-term outcomes after stroke. The contribution of genetic factors such as the presence of apolipoprotein (ApoE) ɛ4 allele and its association with cognitive impairment poststroke remains inconclusive, particularly in Middle Eastern regions. Objective: The aim of this study is to examine all correlates and potential predictors of cognitive impairment including self-awareness and regulation deficits in stroke patients and compare these functions with healthy older adults from a Middle Eastern population. Methods: A prospective stroke sample of 200 patients (case group) and 100 healthy aging individuals (control group) will be recruited from the largest medical complex in Bahrain. A neuropsychological battery of cognitive assessments (global, executive, and metacognition) will be conducted on all participants. Participants will be categorized into 4 subgroups (nonvascular cognitive impairment, vascular cognitive impairment with no dementia, vascular dementia, and mixed dementia) using standardized cognitive assessment scores and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, dementia criteria. Biomarkers will include ApoE genotype, soluble form of receptor for advanced glycation end products, neprilysin, beta-secretase 1, biochemistry, and hematology measurements. Results: The primary study outcome is to determine early risk factors for cognitive impairment after stroke in a Bahraini cohort. The study has received full ethical approval from the Bahrain Ministry of Health and from the affiliated university. Conclusions: With increasing stroke incidence rates in the Middle East, this research study will provide useful biological and epidemiological data for future development and planning of health policies and guidelines for stroke care within the Gulf region. [JMIR Res Protoc 2016;5(4):e223]