Depression and anxiety in caregivers of patients with functional seizures.

OBJECTIVE: Contrary to patients, the psychological impact of functional seizures to caregivers has not been adequately investigated. This study aimed to evaluate the rates and determinants of depression and anxiety in caregivers of patients with functional seizures. METHODS: Patients with functional seizures and their caregivers completed surveys about demographic, disease-related, and psychosocial characteristics. Rates and determinants of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventory scores as dependent variables and patient and caregiver characteristics as independent variables. RESULTS: Twenty-nine patients (76% female, mean age of 37 years) and their caregivers (59% female, mean age of 43 years) were recruited. Symptoms of anxiety and/or depression were present in 96% of patients (96% depression, 92% anxiety) and 59% of caregivers (52% depression, 50% anxiety). Specifically, 31% of caregivers manifested mild depression, 14% moderate depression, and 7% severe depression, whereas 48% were not depressed. Similarly, 14% of caregivers manifested mild anxiety, 29% moderate anxiety, and 7% severe anxiety, whereas 50% were not anxious. Patient and caregiver depression levels strongly correlated (r = .73, p < .0001). The presence of anxiety and depression in the caregiver was associated with male patient gender (p = .02), patient depression level (p = .002), the caregiver being a parent or sibling (p = .02), and caregiver burden (p = .0009). SIGNIFICANCE: Caregivers of patients with functional seizures experience high rates of anxiety and depression, explained by specific demographic and psychosocial factors that could act as intervention targets.

Tissue-Based Thrombolysis for Wake-Up Stroke With Basilar Artery Occlusion: A Case Report.

Stroke from basilar artery occlusion is associated with a poor natural history with high rates of death and disability. Intravenous thrombolysis administered within 4.5 hours of last known well time improves the odds of a good neurological outcome after ischemic stroke, including in patients with basilar artery occlusion. Thrombectomy for basilar artery occlusion has had mixed outcomes. The WAKE-UP randomized clinical trial demonstrated that administration of intravenous thrombolysis can benefit select patients with wake-up strokes whose brain MRI shows restricted diffusion but no accompanying T2 FLAIR change. We report a case of a wake-up acute ischemic stroke presenting with acute vertigo followed by progressive brainstem dysfunction from a basilar artery occlusion. The patient was successfully treated with intravenous thrombolysis beyond 4.5 hours of last known well and symptom discovery time according to an MRI tissue-based approach resulting in partial recanalization of her basilar artery and recovery to near normal. This case suggests that hyperacute MRI can serve as a tissue clock to select patients with wake-up stroke for acute reperfusion therapy even if they do not meet standard trial inclusion criteria, including patients with basilar artery occlusion.

Translating Phenomenology of Psychogenic Nonepileptic Seizures Into Nosology: Insights From Patients' and Caregivers' Profiles.

BACKGROUND: Patients with psychogenic nonepileptic seizures (PNES) can be semiologically dichotomized into those with hyperkinetic and those with paucikinetic events. The objective of this study was to compare characteristics of patients with diverse phenomenology and their caregivers to evaluate for differences that could inform about disease nosology. METHODS: Patients and caregivers monitored at the Epilepsy Monitoring Unit completed surveys about sociodemographic and disease characteristics, treatment and health care utilization, physical and psychosocial impact, and epilepsy knowledge. Patients were classified into hyperkinetic versus paucikinetic based on their recorded events. Comparison of the 2 populations was performed using Student t test for continuous variables and Fischer exact test for categorical variables. RESULTS: Forty-three patients with Epilepsy Monitoring Unit confirmed PNES and 28 caregivers were enrolled. Patients with hyperkinetic events were more commonly non-White patients and necessitated greater caregiving time. Otherwise, no statistically significant differences were seen between the 2 semiologically diverse groups of patients and caregivers in their sociodemographic (age, sex, employment, income, marital, and education) and disease (age of onset, duration, seizures frequency) characteristics, treatment (number of antiseizure medications before diagnosis, side effects) and health care utilization (emergency room visits, hospitalizations, clinic visits), physical (injuries) and psychosocial (depression, anxiety, quality of life, stigma, burden) characteristics, nor in their knowledge about seizures. CONCLUSIONS: Hyperkinetic events were more frequently encountered in non-White patients and required more caregiving time. Further research is required to elucidate if phenomenological dichotomy of PNES can inform about their nosological basis, and if it can guide treatment and define prognosis.

Depression and Anxiety in Adult Persons With Epilepsy and Their Caregivers: A Survey-Based Study at a Tertiary Care Center.

ABSTRACT: This study evaluated the rates of depression and anxiety and their determinants in adult persons with epilepsy and their caregivers. Both completed surveys about demographic, disease-related, and psychosocial characteristics. One hundred patients and caregivers participated. A mood disorder was present in 89% of patients and 56% of caregivers. In the univariate analysis, the presence of mood disorder in the patient was associated with being unmarried, unemployed, frequent hospitalizations, side effects from polypharmacy, patient stigma, patient quality of life, caregiver anxiety, and caregiver burden. In the multivariate analysis, medication side effects sustained as an important determinant. In the univariate analysis, the presence of mood disorder in the caregiver was associated with seizure frequency, patient anxiety, patient quality of life, caregiver stigma, and caregiver burden. In the multivariate analysis, patient anxiety level and caregiver burden sustained as important determinants. Adult persons with epilepsy and their caregivers experience high rates of mood disorders, explained by certain clinical factors.

DDESVSFS: A simple, rapid and comprehensive screening tool for the Differential Diagnosis of Epileptic Seizures VS Functional Seizures.

OBJECTIVE: Functional seizures (FS) are often misclassified as epileptic seizures (ES). This study aimed to create an easy to use but comprehensive screening tool to guide further evaluation of patients presenting with this diagnostic dilemma. MATERIALS AND METHODS: Demographic, clinical and diagnostic data were collected on patients admitted for video-EEG monitoring for clarification of their diagnosis. Upon discharge, patients were classified as having ES vs FS. Using the collected characteristics and video-EEG diagnosis, we created a multivariable logistic regression model to identify predictors of ES. Then, we trained an integer-coefficient model with the most frequently selected predictors, creating a pointing system coined DDESVSFS, with scores ranging from -17 to +8 points. RESULTS: 43 patients with FS and 165 patients with ES were recruited. In the final integer-coefficient model, 8 predictors were identified as significant in differentiating ES from FS: normal electroencephalogram (-3 points), predisposing factors for FS (-3 points), increased number of comorbidities (-3 points), semiology suggestive of FS (-4 points), increased seizure frequency (-4 points), longer disease duration (+3 points), antiepileptic polypharmacy (+2 points) and compliance with antiepileptic drugs (+3 points). Cumulative scores of ≤ -9 points carried <5% predictive value for ES, while cumulative scores of ≥ -1 points carried >95% predictive value. The model performed well (AUC: 0.923, sensitivity: 0.945, specificity: 0.698). CONCLUSIONS: We propose DDESVSFS as a simple, rapid and comprehensive prediction score for the Differential Diagnosis of Epileptic Seizures VS Functional Seizures. Large prospective studies are needed to evaluate its utility in clinical practice.

Mind the gap: health disparities in families living with epilepsy are significant and linked to socioeconomic status.

There is limited information on disparities of people with epilepsy (PWE) and, foremost, their caregivers. The objective of this study was to comprehensively compare between PWE and caregivers with low socioeconomic status (SES) and those with high SES for disparities in demographic and epilepsy characteristics, treatment and health care utilization, physical and psychosocial impact, and knowledge about epilepsy. PWE and caregivers completed surveys about the aforementioned outcomes during their epilepsy clinic visit or epilepsy monitoring unit admission. Associations were evaluated using SES as a binary independent variable and the patient and caregiver related outcomes as dependent variables. Thirty-eight patients with low SES and 88 patients with high SES were recruited. Patients with low SES were more commonly non-white, uninsured, unemployed, of lower educational attainment and living in larger households. They were more likely to visit the emergency room for their seizures, were more frequently on polypharmacy and experienced more AED adverse effects. They exhibited higher depression and anxiety levels and worse quality of life. Twenty-two caregivers with low SES and 66 caregivers of high SAS were recruited. Caregivers with low SES were more likely to be non-white and single. They manifested poorer knowledge about epilepsy. There are notable inequalities in demographic, treatment-related and health care utilization aspects of care of PWE, as well as in the psychosocial impact of their disease. Additional demographic and epilepsy knowledge-related disparities are recognized in caregivers of PWE. Identification of those disparities is a critical step in the creation of appropriate interventions to eliminate them.

Social aspects of life in patients with functional (psychogenic nonepileptic) seizures: An international study.

PURPOSE: To explore various social aspects of life (i.e., employment, education, and driving) in a large sample of patients with functional seizures (FS) living in seven countries from four continents. METHODS: In this retrospective study, we investigated adult patients with FS, who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We studied the social aspects of life in the whole cohort. Then, we compared the social aspects of life between different world regions. RESULTS: Four hundred and forty patients were included (241 from Iran, 56 from Qatar, 52 from France, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia). One hundred and twenty six people (30%) had college education, 142 (33%) were employed, and 101 (28%) drove a motor vehicle in their routine daily lives. People with FS and college education were more likely to report a history of sexual abuse compared with those with a lower education. Patients with no loss of responsiveness with their FS were more likely to be employed. Male patients and patients without aura were more likely to drive a motor vehicle in their routine daily lives. None of the social characteristics of the patients with FS showed significant differences among the two large culturally different groups (Muslim nations vs. Christian nations). CONCLUSION: It appears that patients with FS across cultures have significant problems in their social aspects of life.

Ischemic stroke in COVID-19: An urgent need for early identification and management.

OBJECTIVE: In the setting of the Coronavirus Disease 2019 (COVID-19) global pandemic caused by SARS-CoV-2, a potential association of this disease with stroke has been suggested. We aimed to describe the characteristics of patients who were admitted with COVID-19 and had an acute ischemic stroke (AIS). METHODS: This is a case series of PCR-confirmed COVID-19 patients with ischemic stroke admitted to an academic health system in metropolitan Atlanta, Georgia (USA) between March 24th, 2020 and July 17th, 2020. Demographic, clinical, and radiographic characteristics were described. RESULTS: Of 396 ischemic stroke patients admitted during this study period, 13 (2.5%) were also diagnosed with COVID-19. The mean age of patients was 61.6 ± 10.8 years, 10 (76.9%) male, 8 (61.5%) were Black Americans, mean time from last normal was 4.97 ± 5.1 days, and only one received acute reperfusion therapy. All 13 patients had at least one stroke-associated co-morbidity. The predominant pattern of ischemic stroke was embolic with 4 explained by atrial fibrillation. COVID-19 patients had a significantly higher rate of cryptogenic stroke than non-COVID-19 patients during the study period (69% vs 17%, p = 0.0001). CONCLUSIONS: In our case series, ischemic stroke affected COVID-19 patients with traditional stroke risk factors at an age typically seen in non-COVID populations, and mainly affecting males and Black Americans. We observed a predominantly embolic pattern of stroke with a higher than expected rate of cryptogenic strokes, a prolonged median time to presentation and symptom recognition limiting the use of acute reperfusion treatments. These results highlight the need for increased community awareness, early identification, and management of AIS in COVID-19 patients.

Marital status in patients with functional (psychogenic nonepileptic) seizures: An international study.

PURPOSE: The study aimed to investigate the marital status in a cohort of patients with functional seizures from seven countries in four continents. Factors associated with marital status were also explored. METHODS: Adult patients with functional seizures who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE) were retrospectively identified. Marital status was assessed in the whole cohort. RESULTS: Four hundred thirty-two patients were included (241 from Iran, 52 from France, 48 from Qatar, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia); 302 were women and 130 were men. One hundred fifty (35%) subjects were single, 245 (57%) were married, and 37 (8%) were separated (31 divorced, 7%; 6 widowed, 1%). Auras with functional seizures were less frequently reported by single people in comparison with that by married patients (54% vs. 61%) [odds ratio (OR) = 0.58]. Separated people compared with those who were married less often had auras with their functional seizures (27% vs. 61%; OR = 0.26) and more often reported a history of sexual abuse (49% vs. 12%; OR = 6.14). CONCLUSION: The marital status has significant associations with the semiology of functional seizures. A history of sexual abuse is significantly associated with being separated and should be inquired and tackled appropriately during the management process of patients with functional seizures.

Stigma in psychogenic nonepileptic seizures.

OBJECTIVE: There is scarce literature on stigma in families living with psychogenic nonepileptic seizures (PNES). Using a cohort of patients with epileptic seizures (ES) and their caregivers as controls, we aimed to quantify the level of patient and caregiver stigma in PNES and identify associations of patient and caregiver characteristics with it. METHODS: Patients with PNES and ES and their caregivers completed surveys about demographic, clinical, and psychosocial characteristics. Multivariate regression analysis was used to identify correlates of patient and caregiver stigma. RESULTS: Forty-three patients with PNES and 165 patients with ES were recruited. Compared with patients with ES, patients with PNES had shorter disease duration, higher seizure frequency, normal diagnostic data, poorer psychosocial health, and fewer antiseizure medications (ASMs). A total of 76.5% of patients with PNES and 59.5% of patients with ES felt stigmatized. Patient stigma level was higher in patients with PNES compared with those with ES, and it was negatively associated with patient quality of life (QOL). Additionally, 28 caregivers of patients with PNES and 99 caregivers of patients with ES were recruited. There were no significant demographic, caregiving, or psychosocial differences between the two caregiver cohorts. Seventy-two percent of caregivers of patients with PNES and 47% of caregivers of patients with ES felt stigmatized. Caregiver stigma level was also higher in caregivers of patients with PNES compared with caregivers of patients with ES, and it was negatively associated with patient QOL and positively associated with patient and caregiver anxiety. CONCLUSION: Compared with those with ES, patients and caregivers living with PNES experience stigma more frequently and to a higher extent. Patient QOL emerges as a consistent correlate of that stigma.

Caregiver burden in psychogenic non-epileptic seizures.

OBJECTIVE: Caregiver burden in psychogenic non-epileptic seizures (PNES) is an important but understudied reality. The objective of this exploratory study was to quantify caregiver burden in PNES and to identify the patient and caregiver characteristics associated with it. METHODS: PNES patients and their identified caregivers completed surveys about demographic, disease related and psychosocial characteristics during their Epilepsy Monitoring Unit (EMU) admission. Associations were evaluated using the Zarit Caregiver Burden Inventory (ZCBI) score as an independent variable and the patient and caregiver related characteristics as dependent variables. RESULTS: 43 patients and 28 caregivers were recruited. The patients were on average 36 years old, single women, unemployed, with some college education. They suffered from PNES on average for 8 years, having approximately 20 seizures per month, and were previously maintained on ≥ 2 antiseizure medications. Most caregivers were first degree relatives with a mean age of 43 years, married employed women of higher educational attainment, typically cohabitating with the patients. Caregiver burden was within the mild-moderate range (ZCBI mean score 28). The burden appeared higher in caregivers of male patients. Patient quality of life, depression and medication side effects were associated with that burden. Additionally, caregiver stigma, depression and anxiety emerged as potential contributors. In the multivariate analysis, patient quality of life and caregiver depression stood out as the most robust factors. CONCLUSION: There is substantial caregiver burden in PNES. It is associated with both the patient and the caregiver psychosocial well-being in a reciprocal relationship.

Socioeconomic disparities in patients with psychogenic nonepileptic seizures and their caregivers.

OBJECTIVE: There is no information on disparities of patients with psychogenic nonepileptic seizures (PNES) and their caregivers. The objective of this exploratory study is to compare patients with PNES and caregivers with low socioeconomic status (SES) with those of high SES for disparities in healthcare use, seizures, medication adverse effects, psychosocial impact, and knowledge about epilepsy. METHODS: Patients with PNES and caregivers completed surveys about the aforementioned outcomes during their Epilepsy Monitoring Unit (EMU) admission. Associations were evaluated using SES as a binary independent variable and the patient- and caregiver-related outcomes as dependent variables. RESULTS: Forty-three patients and 28 caregivers were recruited. The majority of patients were on average 36 years old, single women, unemployed, with some college education. The majority had PNES for 8 years averaging 20 seizures per month and were maintained on ≥2 antiepileptic drugs (AEDs) prior to their EMU admission. Most caregivers were first-degree relatives with a mean age of 43 years, married employed women of higher educational attainment, typically cohabitating with the patients. Low SES patients showed poorer knowledge about epilepsy (p < 0.0001) and higher anxiety levels (p = 0.03). Conversely, high SES patients demonstrated poorer social functioning (p = 0.04). High SES caregivers showed higher caregiving burden (p = 0.01). CONCLUSION: There are noteworthy disparities in patients with PNES of different SES and their caregivers. Identification of those disparities is a critical step in the creation of appropriate interventions to address them.

Clinical characteristics of functional (psychogenic nonepileptic) seizures: An international retrospective study.

PURPOSE: We conducted a multicenter international cross-cultural comparative study to investigate clinical semiology and predisposing factors of functional seizures in a large cohort of patients living in different countries around the world. We hypothesized that semiology and predisposing factors of functional seizures differ between various world regions. METHODS: We conducted this retrospective observational study in adults with functional seizures admitted to epilepsy centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We assessed and compared the demographic and clinical seizure characteristics of these patients, according to the patients' reports and review of the ictal recordings during video-electroencephalogram (EEG) monitoring. RESULTS: Five hundred nine patients were included (270 from Iran, 74 from Qatar, 63 from France, 43 from the USA, 22 from Egypt, 20 from UAE, and 17 from Georgia). Although all major manifestations of functional seizures (e.g., aura, loss of responsiveness, generalized motor seizures, ictal injury) were seen in all world regions, seizure semiology differed significantly across countries. Auras, ictal urinary incontinence, and ictal injury were more commonly reported by the American patients than patients from other world regions, whereas loss of responsiveness and generalized motor seizures were more frequently observed in the Iranian and American patients than the European and Arab patients. CONCLUSION: Semiology of functional seizures seems to vary across various regions of the world; socioeconomic, cultural, ethnic, and religious differences may play an essential role in the modulation of functional seizures semiology across different nations and cultures.

Obstructive Lung Disease and Obstructive Sleep Apnea (OLDOSA) cohort study: 10-year assessment.

STUDY OBJECTIVES: Asthma, chronic obstructive pulmonary disease (COPD), and obstructive sleep apnea (OSA) are very prevalent disorders. Their coexistence in the same individual has an unclear effect on natural history and long-term outcomes. METHODS: The OLDOSA (Obstructive Lung Disease and Obstructive Sleep Apnea) cohort enrolled 4,980 veterans with an acute hospitalization and in whom asthma, COPD, OSA, overlapping conditions, or none of these disorders at baseline had been diagnosed. Pulmonary function, polysomnography, positive airway pressure (PAP) recommendations and adherence, and vital status were collected and analyzed. Various proportional hazards models were built for patients with OSA to test the effect of PAP therapy on survival. RESULTS: Ten-year all-cause cumulative mortality rate was 52.8%; median time to death was 2.7 years. In nonoverlapping asthma, OSA and COPD, mortality rates were 54.2%, 60.4%, and 63.0%, respectively. The overlap syndromes had the following mortality: COPD-OSA 53.2%, asthma-COPD 62.1%, asthma-OSA 63.5%, and triple overlap asthma-COPD-OSA 67.8%. In patients with OSA not on PAP therapy, after adjustment for age, comorbidities, and lung function, risk of death was 1.34 (1.05-1.71) times higher than those undergoing treatment. Similarly, in patients with OSA nonadherent to PAP therapy the adjusted risk of death was 1.78 (1.13-2.82) times higher versus those using it at least 70% of nights and more than 4 hours nightly. CONCLUSIONS: In this large longitudinal cohort of hospitalized veterans with high comorbid burden, asthma, COPD, OSA and their overlap syndromes had very high long-term mortality. In patients with OSA, PAP initiation and superior therapeutic adherence were associated with significantly better survival.

Neuropathologically defined subtypes of Alzheimer's disease differ significantly from neurofibrillary tangle-predominant dementia.

Alzheimer's disease (AD) can be classified based on the relative density of neurofibrillary tangles (NFTs) in the hippocampus and association cortices into three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic-predominant AD (LP AD). AD subtypes not only have pathologic, but also demographic, clinical, and genetic differences. Neurofibrillary tangle-predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic structures, shares this feature with LP AD raising the possibility that NFTD is a variant of AD. The objective criteria for pathologic diagnosis of NFTD are not available. A goal of this study was to design a mathematical algorithm that could diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and association cortices, analogous to that used to subtype AD. Moreover, we aimed to compare pathologic, demographic, clinical, and genetic features of NFTD (n = 18) with LP AD (n = 19), as well as the other AD subtypes, typical AD (n = 52) and HpSp AD (n = 17). Using digital microscopy, we confirmed that burden of phospho-tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT densities and showed expected patterns across AD subtypes. HpSp AD had the highest and LP AD had the lowest burden of cortical CP13 and Ab39 immunoreactivity. On the other hand, cortical ß-amyloid burden did not significantly differ between AD subtypes. Semi-quantitative assessment of SPs in the basal ganglia did show HpSp AD to have significantly more frequent presence of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP AD, NFTD had an older age at disease onset and shorter disease duration, as well as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as well as CP13, Ab39, and Aß immunoreactivities were very low in the frontal cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1 genotype frequency was high (~70 %) in NFTD and LP AD, and similar to typical AD, while APOE ε4 carrier state was low in NFTD. While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.