A Case Report of Pseudotumor Cerebri Syndrome with a Huge Retroperitoneal Cyst.

Background: Aside from primary pseudotumor cerebri syndrome (PTCS) with an unknown etiology (i.e., idiopathic intracranial hypertension), which typically occurs in association with obesity, several conditions including cerebral venous abnormalities, drug use, and hormonal imbalance may be a secondary cause of PTCS. However, a focal space-occupying lesion outside of the brain as a cause of PTCS has rarely been reported. Case Presentation: A previously healthy 34-year-old man presented with blurred vision for three weeks. The patient had a three-month preceding history of worsening headache. On admission, he was hypertensive (160/90 mmHg) and underweight with a body mass index of 18.4 kg/m2. Fundus examination documented papilledema in both eyes. Neurological examination was unremarkable except for mild nuchal rigidity, and results of routine serologic testing were normal. Gadolinium-enhanced brain magnetic resonance imaging revealed bilateral posterior scleral flattening, suggesting intracranial hypertension. There was no other abnormal brain parenchymal lesion or meningeal enhancement. Cerebrospinal fluid (CSF) assay showed a markedly increased opening pressure (30.0 cmH2O) with normal CSF composition. A tentative diagnosis of PTCS was made based on ophthalmological, neuroradiological, and laboratory findings. During differential diagnosis, abdomen computed tomography demonstrated a huge benign cystic lesion (14.7 × 10.6 × 16.4 cm) in the right retroperitoneal space, which originated from the mesentery and resulted in hydronephrosis and renovascular hypertension due to external compression of the right kidney. Other evaluations were unremarkable. After successful surgical removal of the cyst, clinical symptoms such as headache, blurred vision, and papilledema on fundus examination were markedly improved, and blood pressure was normalized during the three-month follow-up period. Conclusions: A large retroperitoneal cyst that can increase intra-abdominal pressure could be a rare cause of PTCS. Therefore, meticulous evaluation is warranted for patients with PTCS, especially those without known risk factors.

Frequency, management, and outcomes of early neurologic deterioration due to stroke progression or recurrence.

OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Uncommon cause of trigeminal neuritis and central nervous system involvement by herpes labialis: a case report.

BACKGROUND: Trigeminal neuropathy is characterized by numbness in the region innervated by the trigeminal nerves, with or without neuropathic weakness in the muscles of mastication. Trigeminal neuritis is a form of trigeminal neuropathy in which the lesion is caused by an inflammation. Herein, we report a patient with trigeminal neuritis due to central nervous system (CNS) involvement of herpes labialis (HL) infection, which was successfully treated with anti-viral and anti-inflammatory agents. CASE PRESENTATION: A young healthy female presented with numbness in the left hemiface for two weeks. She had a preceding typical HL infection on left facial lip one week before the sensory symptom onset. Brain magnetic resonance imaging revealed high signal intensities and asymmetrical thickening with enhancement along the cisternal segment of the left trigeminal nerve. Additionally, brain MR angiography showed multifocal stenoses in the M1 segment of the middle cerebral artery and the cavernous portion of the internal carotid artery. Cerebrospinal fluid (CSF) examination showed mild pleocytosis with normal protein level, glucose ratio, but CSF polymerase chain reaction assay for specific anti-viral antibodies including herpes simplex virus was negative, and CSF culture also did not identify a specific pathogen. The results of serologic testing including tumor markers and autoimmune markers were all unremarkable. A tentative diagnosis of trigeminal neuritis as a complication of HL involving the CNS was made considering the clinical, neuroradiological, and laboratory findings of the patient. Therefore, the patient was treated with intravenous methylprednisolone and acyclovir for 10 days. After the treatments, her sensory disturbance was markedly improved. Brain MRI at the 3-month follow-up also demonstrated improvement of previously identified high signal intensity lesions and multifocal intracerebral artery stenoses. CONCLUSION: HL is usually a self-limiting, benign disease without complications, but rarely presents as trigeminal neuritis due to CNS involvement. Therefore, meticulous evaluation may be necessary if trigeminal neuritis or CNS involving symptoms occur after HL.

Stroke of Other Determined Etiology: Results From the Nationwide Multicenter Stroke Registry.

BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

BACKGROUND: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. METHODS AND FINDINGS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. CONCLUSIONS: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

d-dimer Level as a Predictor of Recurrent Stroke in Patients With Embolic Stroke of Undetermined Source.

Background and Purpose: This study aimed to investigate the value of d-dimer levels in predicting recurrent stroke in patients with embolic stroke of undetermined source. We also evaluated the underlying causes of recurrent stroke according to d-dimer levels. Methods: A total of 1431 patients with undetermined source were enrolled in this study and divided into quartiles according to their baseline plasma d-dimer levels. The primary outcome measure was the occurrence of recurrent stroke (ischemic or hemorrhagic) in the year following the stroke event. Results: The risk of recurrent stroke increased significantly with the increasing d-dimer quartile (log-rank P=0.001). Patients in the higher d-dimer quartiles had a higher probability of recurrent embolic stroke because of covert atrial fibrillation, hidden malignancy, or undetermined sources. Most recurrent strokes in Q3 and Q4 were embolic but not in Q1 or Q2. Multivariate analysis revealed that patients in Q3 and Q4 had a significantly increased risk of recurrent stroke compared with those in Q1 (hazard ratio, 3.12 [95% CI, 1.07−9.07], P=0.036; hazard ratio, 7.29 [95% CI, 2.59−20.52], P<0.001, respectively; Ptrend<0.001). Binary analyses showed a significant association between a high d-dimer level above normal range and the risk of recurrent stroke (hazard ratio, 2.48 [95% CI, 1.31−4.70], P=0.005). In subgroup analyses, a high d-dimer level was associated with a significantly higher risk of recurrent stroke in men than in women (P=0.039). Conclusions: Our findings suggest that d-dimer levels can be a useful risk assessment biomarker for predicting recurrent stroke, especially embolic ischemic stroke, in patients with undetermined source.

Association of pretreatment pontine infarction with extremely poor outcome after endovascular thrombectomy in acute basilar artery occlusion.

BACKGROUND: The association between pretreatment brain stem infarction and thrombectomy outcomes remains to be elucidated in patients with acute basilar artery occlusion (BAO). We aimed to assess the association between pretreatment pontine infarction and extremely poor outcome in patients who underwent endovascular thrombectomy due to acute BAO. METHODS: We retrospectively reviewed data from a stroke database to identify patients with acute BAO who underwent thrombectomy between January 2011 and August 2019. Patient characteristics, pretreatment diffusion-weighted imaging (DWI) data, and outcomes were evaluated. The largest infarct core was expressed as the percentage of infarct core area in each brain stem region on the DWI slice displaying the largest lesion. Extremely poor outcome was defined as a 90-day modified Rankin Scale score of 5 or 6. RESULTS: A total of 113 patients were included, 37 of whom had extremely poor outcome. Among the 15 patients with extensive pontine infarction (largest pontine infarct core of ≥70%), 93.3% had extremely poor outcome. Multivariate logistic regression analysis revealed that the following variables were independent predictors of extremely poor outcome: extensive pontine infarction (adjusted OR 22.494; 95% CI 2.335 to 216.689; p=0.007), posterior circulation ASPECTS on DWI (adjusted OR per 1-point decrease 1.744; 95% CI 1.197 to 2.541; p=0.004), age (adjusted OR per 1-year increase 1.067; 95% CI 1.009 to 1.128; p=0.023), and baseline NIHSS (adjusted OR per 1-point increase 1.105; 95% CI 1.004 to 1.216; p=0.040). CONCLUSION: Our results showed that a large pontine infarct core of ≥70% on pretreatment DWI was strongly associated with extremely poor outcome among patients treated with endovascular thrombectomy for acute BAO.

Clinical warning signs of life-threatening hematochezia in neurosurgical patients with long-term bed rest: Three cases report.

RATIONALE: Patients with long term bed rest in intensive care unit after neurosurgery could experience splanchnic hypoperfusion. These patients have several other medical conditions that exacerbate splanchnic hypoperfusion during treatment and the splanchnic hypoperfusion could result in "stress-induced intestinal necrosis", which could cause massive hematochezia. We report here the experience of life-threatening hematochezia in 3 patients who underwent brain surgery in our institution. PATIENTS CONCERNS: One female patient (72-year-old) and 2 male patients (58- and 35-year-old) were admitted to our institution because of traumatic intracerebral hemorrhage, subarachnoid hemorrhage due to a ruptured anterior communicating artery, and subarachnoid hemorrhage with unknown cause respectively. All patients underwent emergency brain surgery for diagnosis and treatment. After surgery, they all experienced long-term bed rest in intensive care unit. Hematochezia occurred on postoperative day 15, 17, and 49, respectively. DIAGNOSES: All of the patients were assessed by abdomen/pelvis computed tomography and underwent a colonoscopy. INTERVENTIONS: The female patient underwent embolization through pelvic arteriography and epinephrine injection through colonoscopy, but a total colectomy and ileostomy was performed due to refractory hematochezia. 58-year-old male patient had a laparoscopic ileostomy for the bowel rest. The other patient underwent nil per os and conservative treatment for 2 weeks. OUTCOMES: The female patient was discharged without further treatment plan, 58-year-old male patient survived after laparoscopic ileostomy, while the other patient survived after 2 weeks of nil per os. LESSON: Abdominal symptoms, such as hematochezia, should be actively managed in neurosurgical patients who are undergoing long-term bed rest in an intensive care unit under physiologically stressful medical conditions.

Factors Influencing 1-Year Medication Adherence of Korean Ischemic Stroke Survivors.

BACKGROUND: Medication adherence is important for secondary stroke prevention. However, suboptimal adherence to medication among patients after stroke or transient ischemic attack is reportedly 30.9%. We assessed medication adherence of Korean stroke survivors within 1 year of acute ischemic stroke and identified factors that influence adherence. METHODS: We consecutively enrolled ischemic stroke survivors who visited the Department of Neurology of a university hospital from March 9 to June 15, 2016. Data were collected by face-to-face interviews using a structured questionnaire which assessed general characteristics, clinical characteristics, medication beliefs, social support, and depression. Medication adherence was measured using the 8-item Morisky Medication Adherence Scale. Multiple logistic regression was used to identify factors independently associated with medication adherence. RESULTS: Of the total 250 participants, 183 (73%) were in the optimal adherence group. Age (p = 0.035), smoking (p = 0.020), number of prescribed medicines (p = 0.037), frequency of daily doses (p = 0.040), and beliefs about medication (p < 0.001) were associated with medication adherence. Optimal medication adherence was associated with being a non-smoker (OR, 3.19; 95% CI, 1.29-7.87; p = 0.012), more prescribed medicines (OR, 1.27; 95% CI, 1.05-1.54; p = 0.014), less frequency of daily doses (OR, 0.37; 95% CI, 0.18-0.79; p = 0.010), and stronger beliefs about medication (OR, 1.09; 95% CI, 1.03-1.15; p = 0.004). CONCLUSION: To improve medication adherence of stroke survivors, post-stroke care should focus on bolstering patients' belief in the necessity of medication and encouraging lifestyle modifications, such as quitting smoking, as well as prescribing medicine with simple regimens.

Outcomes of endovascular treatment in acute ischemic stroke patients with current malignancy.

BACKGROUND AND PURPOSES: The role of endovascular recanalization in the treatment of cancer patients with acute stroke remains elusive. Our study aimed to investigate the clinical and imaging outcomes of endovascular recanalization treatment in patients with acute large vessel occlusion stroke who had active cancer. METHODS: We retrospectively reviewed the data from our stroke registry from January 2011 to September 2016 which was collected prospectively. Acute stroke patients with large artery occlusion in the anterior circulation who had active cancer were identified. Baseline clinical characteristics and postprocedural and long-term clinicoradiological outcomes were evaluated. A good outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. Outcomes were also compared with those of non-malignancy patients who had received endovascular therapy during the same period. RESULTS: A total of 378 ischemic stroke patients received endovascular treatment, of whom 27 (7.14 %) had current malignancy. In patients with current malignancy, a low baseline NIHSS score and male sex were associated with functional independency at 90 days. When comparing with non-malignancy patients, no significant differences in the proportions of patients with symptomatic intracranial hemorrhage (11.1% vs 16.2%, p = 0.60) and good functional outcome (37.0% vs 39.6%, p = 0.84) were found in the malignancy patients. CONCLUSION: Endovascular treatment might be a feasible therapeutic option for acute ischemic stroke patients with current malignancy when candidates are selected carefully because the outcomes were not differed. Future large-scale prospective studies are necessary.

Association between Anxiety and Functional Outcomes in Patients with Stroke: A 1-Year Longitudinal Study.

OBJECTIVE: Anxiety is one of the most common complications in patients with stroke, but studies on its relationship to functional outcomes are limited and controversial. We investigated the association between post-stroke anxiety (PSA) and a 1-year trajectory of functional outcome. METHODS: A total of 423 patients were recruited within 2 weeks after a stroke (acute phase) during hospitalization. Of them, 306 (72.3%) completed follow-up examinations 1 year thereafter (chronic phase). Anxiety was evaluated using the Hospital Anxiety and Depression Scale-Anxiety subscale, and functional outcomes were measured using the National Institutes of Health Stroke Scale for stroke severity, the Barthel Index for activities of daily living (ADL), and the Mini-Mental State Examination for cognitive function at 2 weeks and 1 year. A range of demographic and clinical covariates were considered. The cross-sectional and longitudinal associations between PSA and functional outcomes were investigated. RESULTS: PSA at the acute phase was not associated with functional outcomes at the cross-sectional point, but predicted worsening of outcome on stroke severity and ADL 1 year after stroke. PSA at the chronic phase was cross-sectionally associated with poor functional outcomes in all three measures. All associations were independent of potential covariates. CONCLUSION: Screening for anxiety is recommended even during the acute phase of stroke, considering its independent detrimental effect on functional prognosis. Screening for anxiety during the chronic phase is also encouraged, as this may reflect the functional status of stroke.

A longitudinal study of the associations of BDNF genotype and methylation with poststroke anxiety.

BACKGROUND: Although the precise etiology of poststroke anxiety (PSA) has yet to be fully elucidated, it is known that brain-derived neurotrophic factor (BDNF) is important for neural plasticity and long-term potentiation, associated with the pathophysiology of anxiety. The expression of BDNF is regulated by epigenetic and genetic profiles. Thus, we investigated the association between BDNF methylation status and PSA at 2 weeks and 1 year after stroke while accounting for interactions with the BDNF Val66Met polymorphism. METHODS: The baseline sample comprised 286 patients who were assessed at 2 weeks after stroke; of these patients, 222 (78%) were followed up with at 1 year after stroke. The presence of PSA was determined using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), and the effects of BDNF methylation status and polymorphisms on PSA status were assessed with multivariate logistic regression models. RESULTS: The prevalence of PSA was slightly lower (27 [9.4%]) at baseline, and 35 (15.8%) patients were identified as having PSA at the 1-year follow-up. Stroke patients with a higher average methylation status were more likely to have PSA at 1 year. The BDNF Val66Met polymorphism was not independently associated with PSA during either the acute or chronic phase after stroke, but there was a significant interactive effect between BDNF methylation and genotype on PSA at 2 weeks. CONCLUSIONS: In this study, BDNF methylation in combination with the met/met BDNF polymorphism (Val66Met polymorphism) was associated with PSA. These findings may help identify patients at higher risk for PSA.

Predictors and impact of hemorrhagic transformations after endovascular thrombectomy in patients with acute large vessel occlusions.

BACKGROUND: Predictors and impact of hemorrhagic transformation (HT) after thrombectomy remain to be elucidated. OBJECTIVE: To investigate the independent predictors and impact of each hemorrhagic infarction (HI) and parenchymal hematoma (PH) after thrombectomy in patients with acute stroke due to intracranial large vessel occlusion (LVO). MATERIALS AND METHODS: We retrospectively reviewed data from 400 patients with acute LVO who underwent thrombectomy. Logistic regression analyses were performed to determine independent predictors of HI and PH on post-treatment CT scans. Associations between HT and poor outcome (modified Rankin Scalescore ≥3) at 90 days were analyzed. RESULTS: HT was observed in 98 patients (62 HIs (15.5%) and 36 PHs (9%)). Independent predictors of HI were male sex, atrial fibrillation, and time from symptom onset to groin puncture. Hyperlipidemia (OR=0.221, 95% CI 0.064 to 0.767, P=0.017) and successful reperfusion (OR=0.246, 95% CI 0.093 to 0.651, P=0.005) were independently associated with a lower chance of PH, while hypertension (OR=2.260, 95% CI 1.014 to 5.035, P=0.046) and longer procedure duration (OR=1.046, 95% CI 1.016 to 1.077, P=0.003) were independently associated with a higher chance of PH. Only PH (OR=10.154, 95% CI 3.260 to 31.632, P<0.001) was an independent predictor of poor outcome. CONCLUSIONS: PH is independently associated with poor outcome, whereas HI does not predict outcome after thrombectomy in patients with acute LVO. Our findings suggest that rapid and successful reperfusion is essential to prevent PH in patients undergoing thrombectomy for acute LVO. In addition, our study suggests that hyperlipidemia is associated with a lower risk of PH in such patients.

The Impact of Tumor Necrosis Factor-α and Interleukin-1ß Levels and Polymorphisms on Long-Term Stroke Outcomes.

BACKGROUND: The accuracy of predictions regarding disability that sets in after stroke could be improved by using blood biomarker measurements. This study aimed to investigate the roles of serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß concentrations and polymorphisms in stroke outcomes. METHODS: In total, 286 patients were evaluated at the time of admission and at 2 weeks after stroke, and 222 of these patients (78%) were followed up for 1 year to evaluate the consequences of stroke during both the acute and chronic stages. Stroke outcomes were dichotomized into good and poor using the modified Rankin Scale. RESULTS: The association of TNF-α and IL-1ß concentrations and their corresponding genotypes with stroke outcomes was investigated using multivariate logistic regression. Higher TNF-α levels were associated with poor outcomes 1 year after stroke in the presence of the -850T and -308A alleles, and IL-1ß levels were associated with poor 1-year stroke outcomes in the presence of the -511T and +3953T alleles. No such associations were found at 2 weeks after stroke. CONCLUSIONS: These data provide evidence that serum TNF-α and IL-1ß concentrations are related to poor long-term outcomes after stroke in the presence of particular alleles.

Associations of Tumor Necrosis Factor-α and Interleukin-1ß Levels and Polymorphisms with Post-Stroke Depression.

OBJECTIVE: Proinflammatory cytokines have been implicated in the pathophysiology of post-stroke depression (PSD), and their production levels are influenced by the transcriptional activity of genetic polymorphisms. The present study aimed to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the serum on the risk of PSD while taking into account the TNF-α -850C/T and -308G/A polymorphisms and the IL-1ß -511C/T and +3953C/T polymorphisms. METHODS: A total of 286 patients were evaluated at 2 weeks post stroke and 222 (78%) of these patients were followed up 1 year later. Depressive (major or minor) disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria during both examinations; evaluations of cytokine concentrations and polymorphisms and demographic and clinical covariates were performed at 2 weeks. The effects of TNF-α and IL-1ß concentrations and genotypes on PSD status were investigated using multivariate logistic regression models. RESULTS: Higher TNF-α levels were associated with PSD at 2 weeks in the presence of the -850T allele with a significant interaction term; higher IL-1ß levels were associated with PSD at 2 weeks in the presence of the -511T allele with a borderline significant interaction term and with any +3953C/T polymorphism without a significant interaction term. No associations were found with PSD at 1 year. CONCLUSIONS: These findings indicate the important roles that TNF-α and IL-1ß serum levels play regarding the risk of PSD, particularly during the acute phase of stroke and in patients with genetic susceptibility.

Genetic Polymorphisms rs699947, rs1570360, and rs3025039 on the VEGF Gene Are Correlated with Extracranial Internal Carotid Artery Stenosis and Ischemic Stroke.

Extracranial internal carotid artery (ECICA) stenosis is a modifiable risk factor of ischemic stroke. VEGF plays a crucial role in the maintenance of endothelial integrity and physiological function. This study was designed to assess the correlations of VEGF polymorphisms with ECICA stenosis in ischemic stroke and to explore the relationships between these polymorphisms and different biochemical parameters. This study included a total of 650 ischemic stroke patients, 232 with ECICA stenosis while 418 had no ECICA stenosis as assessed by magnetic resonance angiography. Three SNPs in the VEGF gene, rs699947, rs1570360, and rs3025039, were assessed by real-time PCR coupled with melting curve analysis. Serum samples were analyzed for biochemical parameters in an automated clinical chemistry analyzer in the Laboratory Medicine Department. The CA and CA+AA (A allele bearing) genotype frequencies of the rs699947 polymorphism (AOR=1.46 and 1.47, respectively) and the GA genotype frequency of the rs1570360 polymorphism (AOR=7.33) showed a significant association with ECICA stenosis. However, the haplotype frequencies of C-A-A, T-A-C, and T-A-A (rs302503-rs1570360-rs699947) were significantly different between patients who experienced stroke with and stroke without ECICA stenosis. We found that the total homocysteine (tHcy) levels of stroke patients with ECICA stenosis with rs1570360 and rs699947 SNPs were significantly different compared to the wild-type reference genotype. In conclusion, VEGF rs699947 and rs3025039 polymorphisms were associated with increased risk of stroke, while rs1570360 and rs699947 were associated with stroke and ECICA stenosis.

Effects of interleukin-6, interleukin-18, and statin use, evaluated at acute stroke, on post-stroke depression during 1-year follow-up.

Proinflammatory cytokines are associated with the development of post-stroke depression (PSD). Statins are thought to possess anti-inflammatory properties but their interactions with cytokines regarding the risk of PSD have yet to be investigated. Thus, the present study aimed to determine whether interleukin (IL)-6 and IL-18 were associated with the development of depression at 2 weeks and 1year after stroke using a longitudinal post-stroke cohort. Furthermore, this study examined the potential interactions between statin use and cytokines on PSD. For this study, 286 patients were evaluated 2 weeks after stroke and 222 patients were followed-up 1year later. Depression was diagnosed using criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and then categorized into no PSD or any PSD, which included diagnoses of both major and minor depression. The effects of IL-6 and IL-18 on PSD as well as their interaction with a statin at both examination time-points were investigated using a multivariate logistic regression model. Higher IL-6 and IL-18 levels were independently associated with depressive disorders within 2 weeks and at 1year after stroke. When stratified by statin use, these significant associations were more evident in patients who did not use a statin. Furthermore, there was a significant interaction between statin use and IL-6 on the presence of a depressive disorder at 1year. The present findings support the cytokine hypothesis of PSD and indicate that the preventive effects of statin use against PSD may be mediated by its interactions with IL-6.

The reemergence of long-term potentiation in aged Alzheimer's disease mouse model.

Mouse models of Alzheimer's disease (AD) have been developed to study the pathophysiology of amyloid ß protein (Aß) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6-7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14-19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons.

18F-FDG PET/CT imaging factors that predict ischaemic stroke in cancer patients.

PURPOSE: 18F-FDG PET/CT can acquire both anatomical and functional images in a single session. We investigated which factors of 18F-FDG PET/CT imaging have potential as biomarkers for an increased risk of ischaemic stroke in cancer patients. METHODS: From among cancer patients presenting with various neurological symptoms and hemiparesis, 134 were selected as eligible for this retrospective analysis. A new infarct lesion on brain MRI within 1 year of FDG PET/CT defined future ischaemic stroke. The target-to-background ratio (TBR) of each arterial segment was used to define arterial inflammation on PET imaging. Abdominal obesity was defined in terms of the area and proportion of visceral adipose tissue (VAT), subcutaneous adipose tissue and total adipose tissue (TAT) on a single CT slice at the umbilical level. RESULTS: Ischaemic stroke confirmed by MRI occurred in 30 patients. Patients with stroke had higher TBRs in the carotid arteries and abdominal aorta (P < 0.001) and a higher VAT proportion (P = 0.021) and TAT proportion (P = 0.041) than patients without stroke. Multiple logistic regression analysis showed that TBRs of the carotid arteries and abdominal aorta, VAT and TAT proportions, and the presence of a metabolically active tumour were significantly associated with future ischaemic stroke. Combining PET and CT variables improved the power for predicting future ischaemic stroke. CONCLUSION: Our findings suggest that arterial FDG uptake and hypermetabolic malignancy on PET and the VAT proportion on CT could be independent predictors of future ischaemic stroke in patients with cancer and could identify those patients who would benefit from medical treatment.

Infliximab ameliorates AD-associated object recognition memory impairment.

Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of Aß oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of Aß oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-α, visual recognition memory impaired by pre-administered Aß oligomers dramatically improved and the detrimental Aß effect on mAChR-LTD was annulled. Taken together, these findings suggest that Aß-induced inflammation is mediated through TNF-α signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits.