Vocational outcome in cerebral venous thrombosis: Long-term follow-up study.

OBJECTIVES: Few studies have investigated long-term functional outcome in patients with cerebral venous thrombosis (CVT). We aimed to evaluate return to work (RTW) after CVT and its association with self-reported life satisfaction, quality of life, health, participation, fatigue, depression, and anxiety. METHODS: From hospital records, we identified all patients diagnosed with CVT in Sahlgrenska University Hospital between 1996 and 2016 and invited all survivors to a clinical follow-up visit >1 year after onset. Primary outcome was RTW within the follow-up period which was defined as ≥50% of gainful work or equivalent activity. Patients that were >62 years when they developed CVT were excluded. Cox regression analyses identified associated factors to RTW and Mann-Whitney U tests compared distributions of self-reported questionnaires on life satisfaction and health. RESULTS: Of 62 eligible and consenting patients (median age: 41.5 years (28.75-51.0); 61.3% female), 44 (71.0%) did RTW within the follow-up period (median 135 months, IQR 64-197). Median time to RTW was 7.0 months (IQR 1.4-12.7). Female sex (HR = 0.50, 95% CI = 0.25-0.99, P = .049) and parenchymal lesion detected during acute hospital stay (HR = 0.45, 95% CI = 0.24-0.82, P = .009) were significantly associated with no RTW. Patients with RTW reported significantly higher life satisfaction, quality of life, health, participation and lesser impact of fatigue, depression, and anxiety. CONCLUSIONS: Return to work after CVT is associated with higher life satisfaction, participation, and health. Parenchymal lesion in acute phase and female sex were associated with no RTW. Despite the young age of the patients, a significant portion did not regain working ability.

Comorbidities, Clinical Features, and Prognostic Implications of Cancer Patients with Cerebrovascular Disease.

PURPOSE: The objective of this study was to identify and describe the comorbidities, clinical features, and prognostic implications of cancer patients with cerebrovascular disease. MATERIALS AND METHODS: All patients with cerebrovascular disease (CVD) seen in the neuro-oncology unit at a cancer referral center from April 2010 to November 2016 were included; demographic, oncologic diagnosis, risk factors, and prognostic considerations were presented as well. RESULTS: We report on 256 patients with CVD and cancer, of whom 66% were women. The mean age at the time CVD occurred was 56 years. The most frequently associated malignancies were gynecologic (including breast cancer), hematologic, head and neck, and urologic. The men had more smoking and alcohol consumption history, hemorrhagic CVD, and urologic and hematologic malignancies. The women, besides gynecologic cancer, had more ischemic CVD. Thrombotic CVD, followed by embolic and hemorrhagic CVDs, was more frequent. A comorbid condition besides cancer was found in 71% of the patients. The most frequent clinical presentation was focal motor weakness, altered mental status, and aphasia. The 10-year mortality was 59%; higher rates were found in men, in those with hemorrhagic CVD, in tobacco users, and in those with altered mental status. CONCLUSIONS: Cancer is a well-known risk factor for stroke, which has been associated with a higher frequency in cancer. We found that ischemic stroke due to thrombosis and cardioembolism was more common, and gender, comorbidities, clinical presentation, and type of CVD, but not cancer type, were elements associated with prognosis.

Functional deficits induced by cortical microinfarcts.

Clinical studies have revealed a strong link between increased burden of cerebral microinfarcts and risk for cognitive impairment. Since the sum of tissue damage incurred by microinfarcts is a miniscule percentage of total brain volume, we hypothesized that microinfarcts disrupt brain function beyond the injury site visible to histological or radiological examination. We tested this idea using a mouse model of microinfarcts, where single penetrating vessels that supply mouse cortex were occluded by targeted photothrombosis. We found that in vivo structural and diffusion MRI reliably reported the acute microinfarct core, based on spatial co-registrations with post-mortem stains of neuronal viability. Consistent with our hypothesis, c-Fos assays for neuronal activity and in vivo imaging of single vessel hemodynamics both reported functional deficits in viable peri-lesional tissues beyond the microinfarct core. We estimated that the volume of tissue with functional deficit in cortex was at least 12-fold greater than the volume of the microinfarct core. Impaired hemodynamic responses in peri-lesional tissues persisted at least 14 days, and were attributed to lasting deficits in neuronal circuitry or neurovascular coupling. These data show how individually miniscule microinfarcts could contribute to broader brain dysfunction during vascular cognitive impairment and dementia.

Emodin from Polygonum multiflorum ameliorates oxidative toxicity in HT22 cells and deficits in photothrombotic ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of diseases associated with aging. Emodin, an active component from Polygonum multiflorum Thunb., provides benefits for brain disturbances induced by severe cerebral injury. AIM OF THE STUDY: We investigated the neuroprotective effect of emodin from Polygonum multiflorum Thunb. against glutamate-induced oxidative toxicity and cerebral ischemia. MATERIALS AND METHODS: For examination of neuroprotective effects of emodin, cell viability, cytotoxicity, flow cytometry, and Western blot were performed in HT22 cells and infarct volume, behavioral tests and Western blot in a mouse model of photothrombotic ischemic stroke. RESULTS: Pretreatment with emodin resulted in significantly reduced glutamate-induced apoptotic cell death in HT22 cells. However, blocking of phosphatidylinositol-3 kinase (PI3K) activity with LY294002 resulted in significantly inhibited cell survival by emodin. Exposure of glutamate-treated cells to emodin induced an increase in the level of Bcl-2 expression, whereas the expression of Bax and active caspase-3 proteins was significantly reduced. In addition, treatment with emodin resulted in increased phosphorylation of Akt and cAMP response element binding protein (CREB), and expression of mature brain-derived neurotrophic factor (BDNF). This expression by emodin was also significantly inhibited by blocking of PI3K activity. In a photothrombotic ischemic stroke model, treatment with emodin resulted in significantly reduced infarct volume and improved motor function. We confirmed the critical role of the expression levels of Bcl-2/Bax, active caspase-3, phosphorylated (p)Akt, p-CREB, and mature BDNF for potent neuroprotective effects of emodin in cerebral ischemia. CONCLUSIONS: These results suggest that emodin may afford a significant neuroprotective effect against glutamate-induced apoptosis through activation of the PI3K/Akt signaling pathway, and subsequently enhance behavioral function in cerebral ischemia.

Long-term outcome after cerebral venous thrombosis: analysis of functional and vocational outcome, residual symptoms, and adverse events in 161 patients.

Cerebral venous thrombosis (CVT) affects mainly working-aged individuals. Functional recovery after CVT is generally considered good with about 3/4 of patients achieving short-term independence. However, vascular events, long-term functional outcome, and employment after CVT remain poorly investigated. We identified consecutive adult CVT patients treated at the Helsinki University Hospital (1987-2013) and invited them to a follow-up visit. Each clinical examination was combined with interview. We also recorded recurrent venous thromboembolism (VTE) and hemorrhagic events during follow-up and antithrombotic medication use. A modified Rankin Scale (mRS) served to assess functional outcome. Logistic regression served to identify independent factors associated with unemployment and functional recovery. Of the 195 patients identified, 21 died, 9 declined to participate, and 4 were excluded from the study. Thus, 161 patients (106 women) underwent an examination after a median of 39 months (interquartile range 14-95). VTE (one of which was CVT) occurred in 9 (6%) patients, and severe hemorrhagic events in 10 (6%). Functional outcome was good, with 84% scoring 0-1 on the mRS; 42% reported residual symptoms. Altogether, 91 (57%) patients were employed. After adjusting for age and sex, a National Institutes of Health Stroke Scale score>2 at admission and low education level, associated with both unfavorable functional outcome and unemployment. Long-term functional outcome after CVT may appear good if measured with mRS, but patients often have residual symptoms and are frequently unable to return to their previous work.

Reversal of intraoperative arterial thrombosis with a fibrinolytic agent when treating large and giant partially thrombosed aneurysms of the middle cerebral artery.

OBJECTIVE: Thrombosis of the cerebral arteries is one of the complications of microsurgical operations for partially thrombosed intracranial aneurysms. The object of this study was to assess the frequency of intraoperative arterial thrombosis (IAT) during microsurgical treatment of large and giant partially thrombosed aneurysms of the middle cerebral artery (MCA) and also to assess the efficacy of the treatment of this complication. MATERIALS: The authors analyzed a consecutive series of 53 patients who underwent surgery for partially thrombosed aneurysms of the MCA at the Burdenko Neurosurgical Institute between January 2005 and September 2014. Thirty-two patients had large aneurysms (15-25 mm) and 21 had giant aneurysms (> 25 mm). Clipping of aneurysms was performed in 47 patients, trapping was performed in 3, and wrapping was performed in 3. RESULTS: IAT was diagnosed in 10 patients (18.9%). The authors describe a technique for IAT reversal involving the injection of modified human recombinant prourokinase (mr-proUK). Of the 7 patients who underwent injection of mr-proUK in the thrombosed artery, 5 (71.4%) were discharged without any change in neurological status, 1 (14.3%) experienced moderate deterioration (modified Rankin Scale [mRS] score of 2), and 1 (14.3%) experienced severe deterioration (mRS score of 4). Among the 3 patients who had complications and did not receive an injection of mr-proUK, 2 experienced severe deterioration (mRS score of 3 and 4) and 1 had moderate deterioration (mRS score of 2). CONCLUSIONS: The primary risk factor of thrombectomy with temporary trapping is thrombosis in the MCA branches. The injection of a fibrinolytic agent into thrombosed MCA branches is an effective method for the treatment of IAT.

[Akinetic mutism due to fulminant multilocular cerebral venous thrombosis, including the vein of Galen]. / Akinetischer Mutismus bei fulminanter multilokulärer Sinus- und Venenthrombose einschließlich der Vena Galeni.

Cerebral venous thrombosis may present with multifaceted symptoms and therefore be difficult to diagnose. Only few evidence-based data exist with respect to therapy and prognosis, especially concerning the deep cerebral venous system. A thrombosis of the vein of Galen is deemed to have a poorer prognosis. Our case report describes the local combined neuro-interventional therapy as an individual attempt to cure a patient with a fulminant disease course.

Impacts of perinatal induced photothrombotic stroke on sensorimotor performance in adult rats.

Perinatal ischemic stroke is a leading cerebrovascular disorder occurring in infants around the time of birth associated with long term comorbidities including motor, cognitive and behavioral deficits. We sought to determine the impact of perinatal induced stroke on locomotion, behavior and motor function in rats. A photothrombotic model of ischemic stroke was used in rat at postnatal day 7. Presently, we induced two lesions of different extents, to assess the consequences of stroke on motor function, locomotion and possible correlations to morphological changes. Behavioral tests sensitive to sensorimotor changes were used; locomotion expressed as distance moved in the open field was monitored and histological changes were also assessed. Outcomes depicted two kinds of lesions of different shapes and sizes, relative to laser illumination. Motor performance of rats submitted to stroke was poor when compared to controls; a difference in motor performance was also noted between rats with small and large lesions. Correlations were observed between: motor performance and exposition time; volume ratio and exposition time; and in the rotarod between motor performance and volume ratio. Outcomes demonstrate that photothrombotic cerebral ischemic stroke induced in early postnatal period and tested in adulthood, indeed influenced functional performance governed by the affected brain regions.

Predictors of quality of life in pediatric survivors of arterial ischemic stroke and cerebral sinovenous thrombosis.

Predictors of quality of life can define potentially modifiable factors to increase favorable outcomes after pediatric stroke. Quality of life was measured using the Centre for Health Promotion's Quality of Life Profile (CHP-QOL) in 112 children surviving arterial ischemic stroke or cerebral sinovenous thrombosis at mean 3 years after stroke. Overall quality of life was poor in 17.8% children despite mean scores (3.52) in the "adequate" range. Quality of life related to school and play was most problematic and that related to physical and home environment was least problematic. Female gender, cerebral sinovenous thrombosis stroke, and older age at testing predicted reduced overall and domain-specific quality of life (P < .05), whereas neurological outcome and family socioeconomic status did not. Cognitive/behavioral deficit and low Verbal IQ adversely affected socialization and quality of life, especially among older children and females. Altered cognition/behavior has a major impact on quality of life after pediatric stroke. Implementation of ameliorative strategies warrants further study.

Long-term sequelae after cerebral venous thrombosis in functionally independent patients.

BACKGROUND: The majority of survivors of cerebral venous thrombosis (CVT) regain functional independence, but it is unclear whether these patients experience long-term sequelae. The aim of this case-control study was to assess: (1) frequency of headache, fatigue, depression, and concentration impairment; and (2) impact of these sequelae on daily life and employment in patients with CVT who are functionally independent. METHODS: We included 44 patients with CVT older than 15 years diagnosed between January 1997 and July 2006 who were functionally independent (modified Rankin scale score

[Cerebral venous thrombosis: long-term functional and cognitive outcome in 16 patients]. / Thrombose veineuse cérébrale: étude du devenir fonctionnel et cognitif de 16 cas.

INTRODUCTION: Although the prognosis of cerebral venous thrombosis (CVT) is better than previously reported, long-term behavioral and cognitive sequelae have not been systematically investigated. OBJECTIVE: The aim of this study was to evaluate the long-term functional and cognitive outcome in CVT patients. METHODS: We included all patients admitted to the Neurology department of the Amiens university hospital between January 1997 and December 2002 with the diagnosis of CVT. Outcome between April and June 2003 was evaluated. Patients with cognitive complaints or impaired, MMSE were assessed using a standardized neuropsychological battery and behavioral disorder assessment. RESULTS: Among the 26 patients fulfilling inclusion criteria, 16agreed to participate and formed the study population (13 women; median age: 46.8years). The median follow-up was 34.5months. Functional ability assessed using the modified Rankin Scale (mRk) was relatively spared (mRk=0; n=6; mRk=1; n=6; mRk=2; n=4). Ten patients with cognitive complaints underwent a detailed neuropsychological assessment: it revealed deficits of long-term memory and executive functions. CONCLUSIONS: Despite relatively good functional long-term outcome, our results indicate that CVT patients suffer from long-term memory deficit and moderate executive dysfunction. Such a pattern is close to that observed in arterial stroke although less severe and this warrants a larger study.

Risk factors for pediatric stroke: consequences for therapy and quality of life.

A retrospective population-based study was conducted to calculate incidence of pediatric stroke, detect risk factors, determine long term outcome and to optimize therapy. Patients (age: >1 month and <19 years) with stroke in Vorarlberg, Austria, from 1984-2005 were investigated. Outcome was evaluated in terms of neurological deficits, neuropsychological measures, and quality of life. Consequences on therapy were established according to current guidelines. Twenty-two children, median age 6 years (range, 0.9-14) years, 16 ischemic and 6 hemorrhagic stroke, correspond to an incidence of 1.96 and 0.74/100.000 child-years, respectively. No child died; one had a recurrent stroke. Twenty children (12 boys) were included after a median time of 3.7 years (range, 0.4-18). Risk factors were vasculopathy (17/20; 85%), lipometabolic disorders (17/20; 85%), and prothrombotic abnormality (10/20; 50%). Three children had no risk factor; four children had a reduced quality of life. The study led to therapeutic consequences in 13 of 20 children (65%): aspirin (5/20; 25%), folic acid in (3/20; 15%), and rehabilitative therapy (9/20; 45%). Most children with pediatric stroke have more than one risk factor, mainly vasculopathies or elevation of lipoprotein(a). Overall outcome is determined solely by neurological deficits and is positively influenced by good quality of life.

Functional outcome after severe cerebral venous thrombosis.

Severe cerebral venous thrombosis (CVT) is a rare cerebrovascular condition which in the more severe cases warrants intensive care treatment. While the outcome in the majority of uncomplicated CVT cases is good, it may be fatal in more affected patients. We provide long-term functional and quality of life (QOL) outcome data in the form of a retrospective analysis of 10 patients admitted to a neurological ICU with severe CVT. Outcome measures used were the modified Rankin Scale, the 36-item Short Form Health Survey, and the Psychological General Well-Being index. The mortality rate was 50% but 4 out 5 survivors had a good functional outcome with normal QOL despite a very severe clinical course. This finding justifies extensive life-sustaining therapy as the prognosis even of severe cases may be good if the acute phase is survived.

Speed of motor re-learning after experimental stroke depends on prior skill.

Many motor rehabilitation therapies are based on principles of motor learning. Motor learning depends on preliminary knowledge of the trained and other (similar) skills. This study sought to investigate the influence of prior skill knowledge on re-learning of a precision reaching skill after a cortical lesion in rat. One group of animals recovered a previously known skill (skill training, followed by stroke and re-learning training, TST, n = 8). A second group learned the skill for the first time after stroke (ST, n = 6). A control group received prolonged training without stroke (n = 6). Unilateral partial motor cortex lesions were induced photothrombotically after identifying the forelimb representation using epidural stimulation mapping. In TST animals, re-learning after stroke was slower than learning before stroke (post hoc repeated measures ANOVA P = 0.039) and learning in the control group (P = 0.033). De novo learning after stroke (ST group) was not different from healthy learning. These findings show that skill learning can be performed if the motor cortex is partially lesioned; re-learning of a skill after stroke is slowed by prior knowledge of the skill. It remains to be tested in humans whether task novelty positively influences rehabilitation therapy.

Relationship between changes in rat behavior and integral biochemical indexes determined by laser correlation spectroscopy after photothrombosis of the prefrontal cortex.

Experiments on rats showed that Noopept improved retention and retrieval of conditioned passive avoidance response after phototrombosis of the prefrontal cortex (a procedure impairing retention of memory traces). The impairment of mnesic functions was accompanied by changes in integral biochemical indexes of the plasma determined by laser correlation spectroscopy. Treatment of behavioral disorders with Noopepet normalized biochemical indexes.