Five-year stroke prognosis. Influence of post-stroke delirium and post-stroke dementia on mortality and disability (Research Study - Part of the PROPOLIS Study).

INTRODUCTION: With increasing life expectancy and the rising incidence of stroke in young adults, it is important to know the long-term prognosis of this condition. Post-stroke delirium and post-stroke dementia are common complications of stroke that negatively affect prognosis. The purpose of this study was to evaluate five-year mortality from stroke and to assess the influence of post-stroke delirium and post-stroke dementia on mortality and disability over the five-year period. METHODS: Consecutive patients admitted to the stroke unit for acute stroke or transient ischemic attacks were screened for in-hospital delirium. At the three- and twelve-month follow-up, the same patients underwent neurocognitive testing. Diagnoses of in-hospital delirium and dementia after three and twelve months based on DSM-5 criteria. Five years after stroke surviving patients were reevaluated. Outcome assessment included place of stay, current functional status assessed by the modified Rankin Scale (mRS), or death. RESULTS: At the five-years of follow-up, data were collected from 575 of 750 patients originally included in the study (76.67%). The mortality rate was 51.65%. In-hospital post-stroke delirium and post-stroke dementia diagnosed three and twelve months after stroke were independent risk factors for death and an increase in mRS score of ≥ 1 or ≥ 2 points. There was no significant association with institutionalization rate. CONCLUSIONS: More than half of post-stroke patients die within five years of follow-up. Post-stroke delirium and post-stroke dementia are associated with an increased risk of death and disability.

Network analysis of neuropsychiatric, cognitive, and functional complications of stroke: implications for novel treatment targets.

AIM: Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of poststroke complications using network analysis in diverse stroke samples. METHODS: Data from 2185 patients were sourced from member studies of STROKOG (Stroke and Cognition Consortium), an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items. RESULTS: Across cohorts, a single network of interrelated poststroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow-up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER [Cognition and Affect after Stroke: Prospective Evaluation of Risks] study: S = 9.72, P = 0.038; SSS [Sydney Stroke Study]: S = 13.56, P = 0.069). CONCLUSION: Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of poststroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.

Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment.

BACKGROUND: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. METHODS: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives. RESULTS: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. CONCLUSIONS: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD.

Transient cognitive impairment in the acute phase of stroke - prevalence, risk factors and influence on long-term prognosis in population of patients with stroke (research study - part of the PROPOLIS study).

BACKGROUND: Cognitive impairment is a common complication of the acute phase of stroke, which can be transient and resolve while still in the hospital. This study evaluated the prevalence and risk factors for transient cognitive impairment and their impact on long-term prognosis in a population of acute-phase stroke patients. METHODS: Consecutive patients admitted to a stroke unit with acute stroke or transient ischemic attack were screened twice for cognitive impairment using the parallel version of Montreal Cognitive Assessment: the first time between the first and third day and the second time between the fourth and seventh day of hospitalization. If the second test score increased by two or more points, transient cognitive impairment was diagnosed. Patients were scheduled for follow-up visits three and 12 months after stroke. Outcome assessment included place of discharge, current functional status, dementia, or death. RESULTS: Four hundred forty-seven patients were included in the study, 234 (52.35%) were diagnosed with transient cognitive impairment. Delirium was the only independent risk factor for transient cognitive impairment (OR 2.417, 95%CI 1.096-5.333, p = 0.029). In the analysis of effects on three- and twelve-month prognosis, patients with transient cognitive impairment had a lower risk of hospital or institution stay 3 months after stroke compared with patients with permanent cognitive impairment (OR 0.396, 95%CI 0.217-0.723, p = 0.003). There was no significant effect on mortality, disability or risk of dementia. CONCLUSIONS: Transient cognitive impairment, which often occurs in the acute phase of stroke, does not increase the risk of long-term complications.

Cognitive disorders in patients with chronic kidney disease: specificities of clinical assessment.

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients.

Headache Associated with Sexual Activity-A Narrative Review of Literature.

Headache associated with sexual activity (HAWSA) has accompanied humanity since ancient times. However, it is only since the 1970s that it has become the subject of more extensive and detailed scientific interest. The purpose of this review is to provide an overview of the development of the concept of HAWSA, its clinical presentation, etiopathogenesis, diagnosis and treatment especially from the research perspective of the last 20 years. Primary HAWSA is a benign condition, whose etiology is unknown; however, at the first occurrence of headache associated with sexual activity, it is necessary to exclude conditions that are usually immediately life-threatening. Migraine, hypnic headache or hemicrania continua have been reported to co-occur with HAWSA, but their common pathophysiologic basis is still unknown. Recent advances in the treatment of HAWSA include the introduction of topiramate, progesterone, and treatments such as greater occipital nerve injection, arterial embolization, and manual therapy. Whether these new therapeutic options will stand the test of time remains to be seen.

Current view on post-stroke dementia.

Dementia is one of the leading complications after stroke affecting about one third of survivors. Prevalence of post-stroke dementia (PSD) differs between studies due to variability in methodology, characteristics of included patients, type of stroke, diagnostic tools used to identify patients with dementia, or time when the assessment was performed. Patients diagnosed with PSD are at higher risk of mortality, disability, and institutionalization. Aetiology of PSD may include mixed overlapping processes such as vascular brain pathology or Alzheimer's disease. Several risk factors have been found to increase PSD incidence, involving demographics, vascular factors, stroke characteristics, abnormalities on neuroimaging, and stroke complications. However, the influence of some other factors still remains unclear. PSD may coexist with other neuropsychiatric disorders and its association with post-stroke depression seems to be the most significant. There is a strong need for further research on possible genetic, biological, and inflammatory biomarkers. Also, there are no unambiguously efficacious methods of management. Continuing to address these issues will help to find more effective interventions directly targeting prevention and treatment of PSD in the future.

Case report on novel mutation in SPAST gene in Polish family with spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia is a large group of degenerative, neurological disorders characterized by progressive lower limb spasticity and weakness. The disease was investigated precisely but still clinicians often make incorrect or late diagnosis. Our aim was to investigate the genetic background and clinical phenotype of spastic paraplegia in large Polish family. CASE PRESENTATION: A 37 years old woman presented with 4-year history of walking difficulties. On neurological examination, she had signs of upper motor lesion in lower extremities. She denied sphincter dysfunction and her cognition was normal. Her family history was positive for individuals with gait problems. The initial diagnosis was familial spastic paraplegia. Genetic testing identified a novel mutation in SPAST gene. All available family members were examined and had genetic testing. The same mutation in SPAST gene was identified in other affected family members. All patients caring the mutation presented with different phenotypes. CONCLUSION: This study presents a family with spastic paraplegia due to a novel mutation c.1390G>T(p.Glu464Term) in SPAST gene. Affected individuals showed a range of phenotypes that varied in their severity. This case report demonstrates, the signs of hereditary spastic paraplegia can be often misdiagnosed with other diseases. Therefore genetic testing should always be considered in patients with lower limb spasticity and positive family history in order to help to establish the correct diagnosis.

Poststroke Delirium Clinical Motor Subtypes: The PRospective Observational POLIsh Study (PROPOLIS).

OBJECTIVE: Although delirium is the most common neurobehavioral complication after stroke, its motor subtypes-hypoactive, hyperactive, mixed, and none-as well as their risk factors are not well characterized. Motor subtypes influence recognition and prognosis of delirium in hospitalized patients. METHODS: The aim of this prospective study was to assess the frequency of poststroke delirium subtypes and to describe their predictive models. Consecutive patients with stroke were screened for delirium with the Confusion Assessment Method for the Intensive Care Unit. Delirium was diagnosed according to DSM-5 criteria, and subtypes were classified with the Delirium Motor Subtype Scale-4. Baseline demographic characteristics, biochemistry, stroke-related data, medications, neurological deficits, and premorbid cognitive and functional impairments were assessed. RESULTS: Out of 750 patients (mean age, 71.75 years [SD=13.13]), 203 (27.07%) had delirium: 85 (11.34%) were hypoactive, 77 (10.27%) were mixed hypoactive-hyperactive, 31 (4.13%) were hyperactive, and 10 (1.33%) had an unspecified type. Cognitive impairment at the time of hospital admission and spatial neglect, among other factors, were identified as the best predictors for all motor delirium subtypes. CONCLUSIONS: Screening for poststroke delirium is important because the hypoactive subtype bears the worst prognosis and is misdiagnosed the most compared with other subtypes. All identified factors for the predictive models of delirium subtypes are routinely assessed during hospital admission. Their occurrence in patients with stroke should alert the treating physician to the high risk for a particular delirium subtype.

Prevalence of the apolipoprotein E ε4 allele in amyloid ß positive subjects across the spectrum of Alzheimer's disease.

INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid ß (Aß) pathology. METHODS: We included 3451 Aß+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. RESULTS: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aß+ cognitively normal and Aß+ mild cognitive impairment (P < .05) but not in Aß+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. DISCUSSION: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aß pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

[Anxiety and depressive symptoms in epilepsy in the context of defense mechanisms and electrodermal activity]. / Objawy leku i depresji w padaczce w kontekscie mechanizmów obronnych i aktywnosci elektrodermalnej.

Depressive and anxiety disorders among people with epilepsy are more common than in general population and they are associated with less efficient emotion regulation and reduced quality of life. Unfortunately, these disorders are not always correctly diagnosed or treated. Some studies suggest that the electrodermal activity may serve as a marker for depression. AIM: The aim of the study was to measure and compare depressive and anxiety symptoms, defense mechanisms and electrodermal activity in response to cognitive stimulation in patients with epilepsy with the control group, and to test the correlations between symptoms of anxiety and depression, defense mechanisms and the electrodermal activity. MATERIALS AND METHODS: 64 patients diagnosed with epilepsy and 66 people from the control group were assessed with following psychological questionnaires: State-Trait Anxiety Inventory, Beck Depression Inventory, Defense Styles Questionnaire 40. MindLAB Set was used to measure electrodermal activity. RESULTS: The study showed that people with epilepsy tend to have increased levels of anxiety and depressive symptoms compared with the control group. Patients also tend to use neurotic defense mechanisms what may be associated with poorer emotion regulation. Electrodermal activity was lower among people with epilepsy after cognitive stimulation. There was no statistically significant correlation between electrodermal activity, anxiety and depressive symptoms. CONCLUSIONS: The results indicate the need for assessment of anxiety, depressive symptoms and types of defense mechanisms among patients with epilepsy, as appropriate psychotherapeutic and/or pharmacological intervention could significantly improve the quality of life of these patients.

Emotional Decoding Abilities Do Not Influence Neuropsychiatric Disturbances in Patients With Frontotemporal Dementia.

The ability to accurately recognize emotional information belongs to very important interpersonal communication skills in humans. Disturbance of emotional processing is present in behavioral variant of frontotemporal dementia (bvFTD), and the severity of pathological behavior may be linked to misunderstanding of other people's emotions. In our study, we examined hypothesis that patients with worse ability to decode emotions have more behavioral and psychopathological disturbances--the most challenging manifestations of dementia--than those who decode emotions better. We were not able to prove this hypothesis. The ability to decode emotions in patients with bvFTD did not influenced their behavior.

Knowns and Unknowns About Delirium in Stroke: A Review.

Delirium is a transient condition characterized by sudden and fluctuating disturbances in cognitive function. The condition can be considered a sign of the brain's vulnerability and diminished resilience to insult. Among the many clinical manifestations are cognitive, psychomotor, and sleep disturbances. Delirium is associated with longer hospital stays, worse functional outcomes, and higher mortality. Although up to 48% of patients who have had a stroke develop delirium, the condition has been studied much less in these patients than in general medicine, surgical, and intensive care patients. Coexisting neurologic deficits in patients with stroke limit the use of screening tools that are widely accepted in other populations. The variability of reported assessment methods highlights the need for delirium screening guidelines in stroke. Further, risk factors that are specific to stroke may play an important role in the etiology of delirium, along with such well-known factors as older age and infections. The delirium literature lacks data on differences in clinical manifestations and course in the various types of stroke. Here we review predisposing factors, diagnostic methods, and biomarkers of delirium in stroke and discuss aspects that need further research.

Mild Cognitive Impairment as a single sign of brain hemiatrophy in patient with Localized Scleroderma and Parry-Romberg Syndrome.

Neurologic involvement is well recognized in Systemic Scleroderma and increasingly reported in Localized Scleroderma. MRI brain abnormalities are often associated with symptoms such as seizures or headaches. In some cases they may be clinically silent. We describe a 23 years old female with head, trunk and limbs scleroderma who developed Parry-Romberg Syndrome. Brain MRI showed ipsilateral temporal lobe atrophy without any prominent neurologic symptoms. Neuropsychological examination revealed Mild Cognitive Impairment. During the 7 years of follow up we have noticed progression of face atrophy but no progression of brain atrophy. Cognitive functions have been stable. This case highlight that major MRI brain abnormalities in LS may occur with only subtle clinical manifestation such as Mild Cognitive Impairment.

PRospective Observational POLIsh Study on post-stroke delirium (PROPOLIS): methodology of hospital-based cohort study on delirium prevalence, predictors and diagnostic tools.

BACKGROUND: Between 10 % to 48 % of patients develop delirium in acute phase of stroke. Delirium determinants and its association with other neuropsychiatric disturbances in stroke are poorly understood. The wildly accepted predictive model of post-stroke delirium is still lacking. METHODS/DESIGN: This is a prospective, observational, single-center study in patients with acute phase of stroke. We aim to include 750 patients ≥18 years with acute stroke or transient ischemic attack admitted to the stroke unit within 48 hours after stroke onset. The goals of the study are: 1) to determine frequency of delirium and subsyndromal delirium in Polish stroke patients within 7 days after admission to the hospital; 2) to determine factors associated with incidence, severity and duration of delirium and subsyndromal delirium and to create a predictive model for post-stroke delirium; 3) to determine the association between delirium and its cognitive, psychiatric, behavioral and functional short and long-term consequences; 4) to validate scales used for delirium diagnosis in stroke population. Patients will be screened for delirium on daily basis. The diagnosis of delirium will be based on DSM-V criteria. Abbreviated version of Confusion Assessment Method and Confusion Assessment Method for the Intensive Care Unit will be used for delirium and sub-delirium screening. Severity of delirium symptoms will be assessed by Delirium Rating Scale Revised 98 and Cognitive Test for Delirium. Patients who survive will undergo extensive neuropsychological, neuropsychiatric and functional assessment 3 and 12 months after the stroke. DISCUSSION: This study is designed to provide information on clinical manifestation, diagnostic methods and determinants of delirium spectrum disorders in acute stroke phase and their short and long-term consequences. Collected information allow us to create a predictive model for post-stroke delirium.

Hyperfibrinogenemia predicts long-term risk of death after ischemic stroke.

In stroke patients higher levels of plasma fibrinogen are associated with increased risk of unfavourable functional outcome and short-term mortality. The aim of our study was to determine the relationship between plasma fibrinogen level and long-term risk of death in ischemic stroke patients. Seven hundred thirty six patients (median age 71; 47.1% men) admitted to the stroke unit within 24 h after stroke were included. Plasma fibrinogen level was measured on day 1 of hospitalisation. Hyperfibrinogenemia was defined as plasma fibrinogen concentration >3.5 g/L. The maximal follow-up period was 84 months. Hyperfibrinogenemia was found in 25.0% of patients. On multivariate logistic regression analysis, after adjustment for age, stroke severity, atrial fibrillation, smoking, white blood cell count, fever, in-hospital pneumonia and hyperglycemia, hyperfibrinogenemia was associated with increased case fatality (HR 1.71, 95% CI 1.29-2.26, P < 0.01). Hyperfibrinogenemia predicts the long-term risk of death in ischemic stroke patients.

The FGA Thr312Ala polymorphism and risk of intracerebral haemorrhage in Polish and Greek populations.

BACKGROUND AND PURPOSE: Spontaneous intracerebral haemorrhage (ICH) is the most fatal form of stroke with the highest morbidity and disability rate of all stroke types. Recent data suggest that the genetic background has a sizeable and mostly undiscovered effect on the brain haemorrhage risk. Since the coagulation system is crucial to ICH pathology, we studied the significance of the FGA Thr312Ala polymorphism in two European populations. MATERIALS AND METHODS: We genotyped 550 and 224 controls as well as 261 and 242 stroke patients in Polish and Greek populations, respectively. The ICH diagnosis was confirmed by computed tomography. The FGA Thr312Ala polymorphism was analysed using real-time polymorphism chain reaction. RESULTS: Both crude and multivariable regression analyses showed that the studied polymorphism is a protective factor in the Polish population under the dominant and additive models of inheritance. Those results did not replicate in the Greek population. The meta-analysis of results from the Polish and the Greek populations proved that FGA Thr312Ala polymorphism affects the risk of ICH in the dominant model of inheritance. CONCLUSIONS: The FGA Thr312Ala polymorphism affects a risk for ICH in the Polish but not in the Greek population. An advanced meta-analysis of well-designed studies with a significant number of cases might provide useful information of novel polymorphisms, including the FGA Thr312Ala polymorphism, and their role in ICH pathology.

Prevalence of poststroke anxiety and its associations with global cognitive impairment: An individual participant data analysis.

BACKGROUND AND PURPOSE: Anxiety is frequent after stroke; however, little is known about its determinants. This study aims to assess the prevalence and correlates of post stroke anxiety (PSA) within 3-6 months following ischemic stroke. METHODS: Three cohort studies from the STROKOG consortium were involved. Demographic and clinical data were standardized. PSA and PSD were assessed using inventories. The criteria for post-stroke cognitive impairment (PSCI) were at least one cognitive domain impaired if applicable, or a Montreal Cognitive Assessment (MoCA) score. Descriptive analyses were conducted to ascertain the prevalence of anxiety. Comparisons between anxious and non-anxious patients in the total sample were made using χ2 and t-tests. A two-step individual participant data (IPD) meta-analysis was employed to identify factors associated with PSA. RESULTS: 584 patients were included. The total prevalence of PSA was 35 % (95%CI = [31.23;38.97]) and ranged from 27 % to 45 % across cohorts. In the total sample, there was a higher proportion of females in the anxiety group than the non-anxiety group (χ2 = 19.62; p < 0.001). Anxious patients had lower education, (χ2 = 6.59; p = 0.03), higher stroke severity (t = 2.77; p = 0.002), and higher rates of PSD (χ2 = 118.09; p < 0.001), and PSCI (χ2 = 23.81, p < 0.001). The analysis demonstrates that the odds of presenting with PSA is larger in patients with PSCI (OR = 1.84, 95%CI = [1.14; 2.91]). CONCLUSIONS: Anxiety is frequent after stroke, especially in females, and is associated with depression and cognitive impairment.