Ultrasound Findings Disclose the Mutual Impact of Vertebrobasilar Dolichoectasia and Vertebral Artery Hypoplasia.

OBJECTIVES: Vertebrobasilar dolichoectasia (VBD) and vertebral artery hypoplasia (VAH) are known predisposing factors of posterior circulation stokes. These vascular conditions have unique hemodynamic patterns in neuroimaging studies; however, they have been presented as a single entity in some reports. The aim of this retrospective study was to clarify the relationship between these conditions with regard to ultrasound (US) findings. METHODS: A total of 465 patients with strokes were recruited. Brain magnetic resonance imaging of vertebrobasilar arteries and differences in extracranial side-to-side vertebral artery (VA) flow were recorded by US and compared in groups. RESULTS: The mean age of the 465 patients ± SD was 67.23 ± 12.13 years; 296 were men. The prevalence of VBD was 13.5% (n = 63), and 10.8% (n = 50) of the patients had coexisting VAH and VBD. These patients also had the highest prevalence of posterior circulation strokes (58% [n = 29]). A cutoff value of 55.65 mL/min and a ratio discrepancy of 5.28 (group median) for the side-to-side extracranial VA flow volume as detected by conventional US were also observed in the patients with both VAH and VBD. CONCLUSIONS: Our study revealed a higher prevalence of posterior circulation strokes in the patients with both VBD and VAH. Chronic asymmetric hemodynamic shear force in extracranial VAs leading to deformity of the vertebrobasilar system may explain our observations. Accordingly, the blood flow volume and the ratio difference could potentially be used to detect patients at risk of VBD and reduce stroke risk factors.

CHA2 DS2 -VASc scores for outcome prediction in acute ischaemic stroke.

BACKGROUND: The CHADS2 and CHA2 DS2 -VASc scores are clinical risk stratification instruments that are used clinically to assess the risk of stroke in patients with atrial fibrillation (AF). The aim of this study was to evaluate whether the prestroke CHADS2 and CHA2 DS2 -VASc scores could be useful for predicting infarction severity and long-term outcomes in patients with acute ischaemic stroke. MATERIALS AND METHODS: This prospective study included all 1494 patients who had acute ischaemic stroke without haemorrhagic transformation which was evidenced with magnetic resonance (MR) imaging during hospitalization. Total infarction volume and arterial stenosis score were calculated based on MR imaging. National Institutes of Health Stroke Scale scores (NIHSSs) were obtained at admission and discharge by board-certified neurologists. The clinical outcomes were defined as composite endpoints of restroke and mortality and were recorded with the mean follow-up period of 37.5 months. RESULTS: There were 195 (13.1%) patients with AF. The patients with AF had significantly higher median CHADS2 and CHA2 DS2 -VASc scores than the patients without AF (P < .001). Patients with higher CHADS2 and CHA2 DS2 -VASc scores had significantly higher total infarction volume, arterial stenosis score and NIHSS scores at discharge and poorer clinical outcomes. After adjusting for age, gender and AF, only CHA2 DS2 -VASc scores could predict both restroke and composite endpoints. CONCLUSIONS: Prestroke CHA2 DS2 -VASc scores appear to have better clinical value for predicting the severity of infarction and long-term clinical outcomes in acute ischaemic stroke patients with and without AF.

Change in Activities of Daily Living in the Year Following a Stroke: A Latent Growth Curve Analysis.

BACKGROUND: Early prediction of future functional capability is crucial for stroke survivors' care management. OBJECTIVES: The purposes of this study were to test the trajectory of change across time in activities of daily living (ADLs) and to determine whether the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours poststroke, gender, and age predict ADLs at 1, 3, 6, and 12 months poststroke. METHODS: A prospective cohort design was used. Baseline characteristics and neurological deficits were measured in 1,021 stroke survivors. The 13-item NIHSS was used to examine neurological status within 24 hours poststroke. ADLs were measured with the Barthel index at 1, 3, 6, and 12 months poststroke. A latent growth curve model was used to analyze how the dynamic changes in ADLs were related to NIHSS score, gender, and age. RESULTS: The latent growth curve model analyses revealed that, as the time following a stroke increases, survivors tend to gradually improve with regard to ADLs. In addition, lower levels of initial ADLs were associated with higher growth in ADLs over time. However, after 6 months poststroke, further gains in ADLs slowed. Based on further analysis, the findings indicate that a lower NIHSS score, being male, and a young age at time of stroke were associated with higher initial levels of ADLs. Having a higher NIHSS score, being female, and a young age at time of stroke predicted an increase in ADLs over time. DISCUSSION: To promote ADLs of stroke patients, NIHSS score at admission, gender, and age should be included as important predictors of stroke care management. The results highlight that the rehabilitation of stroke patients should be focused more on ADLs at 1-6 months poststroke.

Extracranial and Intracranial Ultrasonographic Findings in Posterior Circulation Infarction.

OBJECTIVES: Patients with posterior circulation infarction are at higher risk of early recurrent stroke, especially those with vertebrobasilar stenosis or hypoplasia. The clinical presentations of this condition vary over a broad range, making diagnosis and treatment a challenge. Hemodynamic changes and stenosis detected by ultrasonography (US) are sensitive and important indicators for further evaluation. In this study, we correlated extracranial and intracranial US characteristics with brain magnetic resonance imaging (MRI) in patients with posterior circulation infarction. METHODS: Inpatients with acute ischemic stroke who received both MRI and US were enrolled. Baseline characters, underlying disorders, the ischemic territory, and vascular stenosis on MRI were recorded. Series of US data, including flow volume, diameter, mean velocity, and pulsatility index, were analyzed. Patients with new infarction over the medulla, pons, midbrain, or cerebellum were enrolled as the posterior circulation infarction group. Patients with pure anterior circulation infarction were also enrolled. RESULTS: A total of 210 patients with anterior circulation infarction (mean age ± SD, 66.24 ± 12.88 years) and 143 with posterior circulation infarction (mean age, 65.82 ± 11.39 years) were enrolled. Significant higher frequencies of vertebral artery hypoplasia and decreased intracranial vertebrobasilar velocity in the posterior circulation infarction group (44.75% and 64.33%, respectively) were documented (P < .0001; P = .035). Ischemic lesion distributions were correlated with vertebral artery hypoplasia (55.56 %) and low vertebral and basilar artery velocities (44.44% and 25.53%), as documented by US. A low vertebrobasilar velocity was highly correlated with MRI-documented vascular stenosis (53.06%). CONCLUSIONS: Vertebral artery hypoplasia and a low velocity in the intracranial vertebrobasilar system on US might change the treatment of patients with posterior circulation infarction for primary and secondary prevention.

Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients.

BACKGROUND: We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. METHODS: From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. RESULTS: Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. CONCLUSIONS: Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Derivation and validation of a discharge disposition predicting model after acute stroke.

BACKGROUND: Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. METHODS: We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. RESULTS: Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). CONCLUSIONS: The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

Exploration of the Molecular Mechanism by Which Caveolin-1 Regulates Changes in Blood-Brain Barrier Permeability Leading to Eosinophilic Meningoencephalitis.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigated pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4/MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

FDG PET/CT Demonstrated Unilateral Striatum Hypometabolism in a Case of Advanced Nasopharyngeal Cancer.

ABSTRACT: A 79-year-old man with nasopharyngeal cancer (NPC) presented with diplopia symptom and a history of diabetes mellitus was referred for an FDG PET/CT scan to determine the pretreatment staging. The FDG PET/CT scan revealed NPC with skull base invasion and decreased FDG uptake at the left striatum. A review of his clinical history and a brain MRI conducted 5 months ago confirmed a previous diagnosis of left hyperglycemic hemichorea. In this NPC patient with inadequate blood sugar control, unilateral striatum hypometabolism may persist for up to 5 months after the initial clinical symptoms.

Complicated acute motor axonal neuropathy with delayed acute respiratory distress syndrome and rapidly progressive glomerulonephritis: a case report.

PURPOSE: Acute motor axonal neuropathy (AMAN), a variant of Guillain Barre syndrome (GBS), is frequently induced by the antecedent infection of some atypical pathogen, such as Campylobacter jejuni, Mycoplasma pneumonia and some virus. It is generally accepted that corticosteroids and immunosuppressants are not recommended in patients with GBS including AMAN. However, if systemic autoimmune reaction developed, the principle of management might be changed. CASE REPORT: We report a young man who rapidly developed acute motor axonal neuropathy. Although plasma exchange had been given, the violent immunological reaction was unable to be controlled, prolonged leukemoid reaction and high level of autoimmunological titers, including C-reactive protein (CRP), rheumatoid factor (Rf), and antineutrophil cytoplasmic autoantibody (ANCA) persisted. Consequently, two months later, this patient developed acute respiratory distress syndrome (ARDS) and type 3 of rapidly progressive glomerulonephritis (RPGN) with rapid decline of renal function until immunosuppressants were given. CONCLUSION: AMAN combined with the violent systemic autoimmune reaction strongly indicated an uneven disease course and implied that only standard plasmapheresis is not sufficient and corticosteroids with immunosuppressant should be added in early stage.

Proteasome serves as pivotal regulator in Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis.

Proteasome primarily degrades the unneeded or damaged proteins by proteolysis. Disruption of the brain barrier and its resulting meningoencephalitis caused by Angiostrongylus cantonensis are important pathological events in non-permissive hosts. In this study, the results showed upregulated proteasome during A. cantonensis infection. Occludin degradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. Moreover, confocal immunoflourescence microscopy showed that occludin was co-localized with MMP-9. The infected-mice were treated with proteasomal activity inhibitor MG132 by 1.5 and 3.0 mg/kg/day, which resulted in significantly reduced protein levels of phosphorylated IκBα (P<0.05) compared with the untreated control. The phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) showed similar result. In addition, MMP-9 activity and occludin degradation were reduced because of MG132 treatment. These results suggested that the proteasome in A. cantonensis infection degraded phosphorylated IκBα, modulated phosphorylated NF-κB, and then regulated the activation of MMP-9 and occludin degradation. Proteasome alterations were presented in eosinophilic meningitis of BALB/c mice and may contribute to the pathophysiology of eosinophilic meningitis by increasing occludin degradation. This molecule would serve as pivotal regulator in A. cantonensis-induced eosinophilic meningoencephalitis.

A new avenue for treating neuronal diseases: Ceftriaxone, an old antibiotic demonstrating behavioral neuronal effects.

Several neurodegenerative disorders, namely Parkinson's disease dementia, dementia with Lewy bodies, and Alzheimer's disease, share common pathophysiological features, such as (1) cognitive deficits, (2) glutamatergic hyperactivity-related excitotoxicity, and (3) deposition of α-synuclein (α-syn) and ß-amyloid (Aß). Ceftriaxone (CEF) is a well-tested and safe drug that has been used as an antibiotic for several decades. Recent studies have demonstrated the following effects of CEF: (1) increasing glutamate transporter-1 expression and glutamate reuptake and suppressing excitotoxicity, (2) binding well with α-syn and inhibition of α-syn polymerization, (3) modulating expression of genes related to Aß metabolism, and (4) enhancing neurogenesis and recovery of neuronal density. In addition, our data revealed that CEF ameliorates seizure and abnormal neuronal firing in the brain. These results suggest the potential of CEF in treating neuronal disorders. This paper addresses the effects and pharmacology of CEF.

Resveratrol relieves Angiostrongylus cantonensis - Induced meningoencephalitis by activating sirtuin-1.

Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice. Moreover, resveratrol treatment significantly reduced eosinophil counts, p65, Interferon-γ, interleukin (IL)-5, IL-33, and tumor necrosis factor-α levels, matrix metalloproteinase-9 activity, claudin-5 degradation, and blood-brain barrier permeability. By contrast, the anti-inflammatory factor IL-10 was significantly increased in resveratrol-treated mice. Resveratrol treatment was partially beneficial in controlling the pathological processes of angiostrongyliasis meningoencephalitis. The results demonstrate the neuroprotective and anti-inflammatory effects of resveratrol against Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis in mice. Treatment with sirtuin-1 agonist was given within a therapeutic window after A. cantonensis infection.

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry.

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160-200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11-1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76-8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI.

Familial paroxysmal nonkinesigenic dyskinesia: clinical and genetic analysis of a Taiwanese family.

Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder in autosomal dominant inheritance. The clinical features and genetic findings of PNKD, rarely described in the Asians, were mostly delineated from European families. The present study characterized the clinical and genetic findings of a Taiwanese PNKD family. The clinical features of our five patients in successive three generations included onset age less than 10 years, attack duration between 3 min and 4h, and a variety of aura symptoms. The attacks were provoked not by sudden action but by emotional stress, caffeine, fatigue, heavy exercise and sleep deprivation. Sleep could abolish or diminish the attack and the attacks responded well to clonazepam. Sequencing the whole coding region of PNKD/MR-1 gene identified a heterozygous c.20 C>T (p.Ala7Val) mutation which was clearly segregated in the five affected patients. Comparing our patients with previously reported 18 families with PNKD/MR-1 mutations, the majority of the patients exhibited quite similar manifestations in attack patterns and precipitating factors. The recurrent conservative mutations in different ethnicities indicate importance in the pathogenesis of PNKD.