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Objectives: Transient ischemic attack (TIA) is a neurological emergency and a precursor of ischemic stroke. ABCD2 and ABCD3I scores predict stroke after TIA, and clinicians use preclinical, clinical, and radiological parameters for calculating these scores. Our study aimed to investigate the efficacy of peripheral blood markers in predicting 90-day and long-term stroke risk after TIA. Methods: This retrospective study was conducted in Kastamonu Training and Research Hospital between January 2015 and November 2022. The demographic data of 99 patients who applied with the diagnosis of TIA and peripheral blood markers at the time of first admission to the hospital were used in the study. These parameters was evaluated in 90-day and long-term (> 12 months) stroke after TIAs. Results: Of the 99 patients in our study, 59% (n = 58) were male. The mean age of the patients was 70 ± 13 years. ABCD2 (age, blood pressure, clinical features, duration of symptoms, and presence of diabetes mellitus) and ABCD3I (age, blood pressure, clinical features, duration of symptoms, presence of diabetes mellitus, dual TIA, and ipsilatheral carotis stenosis) scores and C-reactive protein (CRP) were statistically significant in predicting 90-day stroke. ABCD2 and ABCD3I were not effective in predicting long-term stroke. In addition, CRP, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) parameters were statistically significant in long-term stroke. CRP (AUC=793, sensitivity = 82%, and specificity = 81%) values were higher than ABCD2 (AUC = 779, sensitivity = 73%, and specificity = 76%) and ABCD3I (AUC = 755, sensitivity = 82%, and specificity = 70%) scores in predicting 90-day stroke. Conclusions: Our study showed that ABCD2, ABCD3I, and CRP effectively predict 90-day stroke after TIA. Furthermore, CRP was more effective than ABCD2 and ABCD3I scores in predicting 90-day stroke after TIA. CRP, NLR, PLR, and SII also effectively predicted long-term stroke after TIA. [ABSTRACT FROM AUTHOR]

Shuxia Qian, Xiaoling Zhang, Yanping Wang Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of ChinaCorrespondence: Xiaoling Zhang; Yanping Wang, Department of Neurology, The Second Affiliated Hospital of Jiaxing University, No. 1518 the North Road Around the City, Jiaxing, 314000, People’s Republic of China, Email Zhangxiaoling_1966@126.com; ypwang93@163.comIntroduction: Patients with acute isolated vertigo have a high risk for developing cerebral infarction (CI). Risk stratification for cerebral infarction in patients with acute isolated vertigo is critical for early treatment and preventative therapy. In the present study, we aim to characterize the diagnostic value of serum adiponectin (APN) combined with ABCD2 scoring in determining cerebral infarction risk.Methods: Patients with acute isolated vertigo admitted to the emergency room were recruited. Diagnosis of cerebral infarction was performed using diffusion-weighted MRI (DWI-MRI) and T2WI and T2Flair imaging. Blood was collected for analysis of APN levels using enzyme-linked immunosorbent assay (ELISA). Multivariate analysis was used to analyze diabetes, hypertension, serum APN, and ABCD2 in association with CI.Results: Compared to non-CI patients (n = 185), patients with CI (n = 68) demonstrated significantly lower serum APN levels (p < 0.001) and higher ABCD2 score (p < 0.001). A strong negative correlation was found between serum APN levels and ABCD2 scores. Multivariate analysis and ROC analysis suggested that low serum APN and high ABCD2 are strong predictors of CI in patients with acute isolated vertigo. Notably, the combination of APN and ABCD2 had a much stronger predictive sensitivity and specificity.Conclusion: Our analysis suggests that the combination of serum APN and ABCD2 analyses offers a significantly improved prediction sensitivity and specificity for CI among patients with acute and isolated vertigo, which supports the potential use of this new marker in clinics.Keywords: acute isolated vertigo, adiponectin, ABCD2, cerebral infarction

Background: Patients with initial transient ischaemic attack (TIA) subsequently have a higher risk of recurrent TIA or acute ischemic stroke (AIS). The role of scoring intracranial arterial calcification (IAC) in predicting the prevalence of stroke remains unclear. We aim to evaluate if radiological CT calcium score measuring IAC burden could predict future ischemic events in a cohort of TIA patients.Methods: We studied consecutive patients from July 2014 to December 2015 who presented with first episode of TIA. All patients had noncontrasted CT or CT-angiogram of the brain on admission. CT calcium score (cm3) was quantified by measuring calcium deposition in the bilateral internal carotid arteries, middle cerebral arteries, and vertebrobasilar system. Patients were followed up for 2 years and ischemic events for either recurrent TIA or AIS were recorded. We compared patients in terms of clinical profile at presentation and CT calcium score using appropriate univariate and multivariable analyses.Results: Of 156 TIA patients studied, 22% (n = 35) had recurrent TIA or AIS within 2 years of follow-up. On univariate analyses, recurrent TIA/AIS was associated with gender (OR 0.61; 95%CI 0.40-0.95; P = .038), hypertension (mean difference 2.49; 95%CI 1.08-5.75; P = .030) and higher CT calcium score (mean difference 0.84 95%CI 0.16-1.52 P = .016). On multivariable logistic regression, a higher CT calcium score was significantly associated with recurrent TIA/AIS (adjusted OR 1.25 95%CI 1.01-1.55 P = .042).Conclusions: In TIA patients, higher IAC burden by measurement of a quantitative CT calcium score may be associated with recurrent ischemic events. [ABSTRACT FROM AUTHOR]

Even though increasing evidence indicates the importance of peroxisomal lipid metabolism in regulating biological and pathological events, its involvement in cartilage development has not been well studied. Here, we identified the importance of peroxisomal function, particularly the functional integrity of ABCD2, in the pathogenesis of osteoarthritis (OA). Knockdown of ABCD2 in OA chondrocytes induced the accumulation of very long chain fatty acids (VLCFAs) and apoptotic cell death. Moreover, knockdown of ABCD2 altered profiles of miRNAs that affect the expression level of ACSL4, a known direct regulator of lipid metabolism. Suppression of ACSL4 in human chondrocytes‐induced VLCFA accumulation, MMP‐13 expression, and apoptotic cell death. In vivo morph‐down of the ACSL4 homologue in zebrafish resulted in significant defects in cartilage development and in vivo knockdown of ACSL4 in cartilage tissue of an OA model mice promoted severe cartilage degradation. In summary, to the best of our knowledge, this is the first report suggesting that the regulatory network among peroxisomal ABCD2:ACSL4:VLCFA serves as a novel regulator of cartilage homeostasis, and these data may provide novel insights into the role of peroxisomal fatty acid metabolism in pathogenesis of human OA. Significance of the study: Our study indicates that peroxisomal dysfunction is closely related to OA pathogenesis. Particularly, the functional integrity of ABCD2 may play an important role in OA pathogenesis via the accumulation of VLCFAs and stimulation of apoptotic death through altering profiles of miRNAs that target ACSL4. Our findings suggest that targeting the regulatory network among the peroxisomal ABCD2:ACSL4:VLCFA axis may provide a new potential therapeutic strategy for OA pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Vertigo or dizziness is a common occurrence, but it remains a challenging symptom when encountered in the emergency department (ED). A diagnostic score for stroke with high accuracy is therefore required.Methods: A single-center observational study (498 patients) was conducted. The predictor variables were derived from a multivariate logistic regression analysis with Akaike information criterion. The outcome was the occurrence of stroke. We evaluated the utility of a new diagnostic score (TriAGe+) and compared it with the ABCD2 score.Results: The cohorts included 498 patients (147 with stroke [29.4%]). Eight variables were included: triggers, atrial fibrillation, male gender, blood pressure ≥140/90 mm Hg, brainstem or cerebellar dysfunction, focal weakness or speech impairment, dizziness, and no history of vertigo or dizziness or labyrinth or vestibular disease. We derived the TriAGe+ score from these variables. In the cohort, the prevalence of stroke increased significantly using the diagnostic score: 5.9% for a score of 0-4; 9.1% for 5-7; 24.7% for 8-9; and 57.3% for 10-17. At a cutoff value of 10 points, the sensitivity of the score was 77.5%, the specificity was 72.1%, and the positive likelihood ratio was 3.2. When the cutoff was defined as 5 points, the score obtained a high sensitivity (96.6%) with a good negative likelihood ratio (.15). The new score outperformed the ABCD2 score for the occurrence of stroke (C statistic, .818 versus .726; P < .001).Conclusions: The TriAGe+ score can identify the occurrence of stroke in patients with vertigo or dizziness presenting to the ED. [ABSTRACT FROM AUTHOR]

Cerebrovascular attack (CVA) and transient ischemic attack (TIA) are major causes of emergency department visits around the globe. A significant number of these patients may experience repeat attacks if left untreated. Several risk stratifying scoring systems have been developed in recent years to point out the high risk patients. ABCD2 is based on age, blood pressure, clinical status, diabetes mellitus, and duration of symptoms and is used commonly for this purpose. In this study, we were to enhance its sensitivity and specificity with the addition of another criterion namely atrial fibrillation and making ABCD2-F. A prospective study in two hospitals was performed and 138 patients diagnosed with TIA/CVA were enrolled. Demographic, clinical, and paraclinical data of all patients were registered. All patients were followed for three months for any sign or symptom of a recurrent ischemic attack. Recurrent ischemic attacks happened in 9.4% of the patients. None of the criteria of ABCD2-F was associated with higher chance of ischemic attacks. Similarly, ABCD2-F was not different between patients with or without repeat cerebral ischemia. The addition of atrial fibrillation to ABCD2 did not enhance the accuracy of this scoring system to detect patients high risk for repeat cerebral ischemia. More studies in the future to improve sensitivity and specificity of this test are warranted.

X-linked adrenoleukodystrophy (X- ALD) is a progressive neurometabolic disease caused by mutations/deletions in the Abcd1 gene. Similar mutations/deletions in the Abcd1 gene often result in diagonally opposing phenotypes of mild adrenomyeloneuropathy and severe neuroinflammatory cerebral adrenoleukodystrophy ( ALD), which suggests involvement of downstream modifier genes. We recently documented the first evidence of loss of AMP-activated protein kinase α1 ( AMPKα1) in ALD patient-derived cells. Here, we report the novel loss of AMPKα1 in postmortem brain white matter of patients with ALD phenotype. Pharmacological activation of AMPK can rescue the mitochondrial dysfunction and inhibit the pro-inflammatory response. The FDA approved anti-diabetic drug Metformin, a well-known AMPK activator, induces mitochondrial biogenesis and is documented for its anti-inflammatory role. We observed a dose-dependent activation of AMPKα1 in metformin-treated X- ALD patient-derived fibroblasts. Metformin also induced mitochondrial oxidative phosphorylation and ATP levels in X- ALD patient-derived fibroblasts. Metformin treatment decreased very long chain fatty acid levels and pro-inflammatory cytokine gene expressions in X- ALD patient-derived cells. Abcd2 [adrenoleukodystrophy protein-related protein] levels were increased in metformin-treated X- ALD patient-derived fibroblasts and Abcd1- KO mice primary mixed glial cells. Abcd2 induction was AMPKα1-dependent since metformin failed to induce Abcd2 levels in AMPKα1- KO mice-derived primary mixed glial cells. In vivo metformin (100 mg/Kg) in drinking water for 60 days induced Abcd2 levels and mitochondrial oxidative phosphorylation protein levels in the brain and spinal cord of Abcd1- KO mice. Taken together, these results provide proof-of-principle for therapeutic potential of metformin as a useful strategy for correcting the metabolic and inflammatory derangements in X- ALD by targeting AMPK. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to define the roles of ABCD² score as well as other diagnostic parameters such as the presence of AF, serum fibrinogen, D-dimer and CRP levels as diagnostic predictors to determine the risk of stroke in patients diagnosed with TIA. Materials and Methods: We performed a prospective study of 70 patients who were admitted to the emergency department at Ankara Training and Research Hospital with a diagnosis of TIA. Patients demographic data and vital signs were calculated and scores with ABCD². The blood samples for measuring CRP, D dimer and fibrinogen levels were collected. Patients were interviewed by telephone and stroke prognosis was learned after 3 months. Results: Dysphasia (45%) and weakness (40%) were the most common presenting symptom. 52.9% of patients had moderate risk, and 12.9% had high stroke recurrence risk. 14.3% of patients have had a stroke within 3 months. AF has been detected of 10% (n:7) of all the patients and five of the seven (71.4%) patients with AF developed stroke (p<0.05). Only the CRP was targeted as possible blood predictors of stroke recurrence in TIA (p=0.008). Conclusion: Our findings provide evidence that the ABCD² score may predict the recurrence of TIA and likelihood of having stroke after the diagnosis of TIA. Although the presence of AF, CRP, fibrinogen and D-dimer levels may be used in the diagnosis of stroke or TIA, combining the presence of AF and high-CRP levels can enhance the predictive value of ABCD? score to determine the risk of stroke. Giriş: İnme için en önemli risk faktörlerinden biri de geçici iskemik ataklardır (GİA). Bu çalışma ile ABCD? skoru, koagülasyon belirteçleri yanı sıra atriyal fibrilasyon (AF) varlığını kullanarak GİA hastalarında erken dönemde inme riskini hesaplanamak amaçlanmıştır. Materyal ve Metod: Ankara Eğitim ve Araştırma Hastanesi Acil Servise başvuran, GİA tanısı almış ve katılım için onam veren 70 ardışık hasta çalışmaya alındı. Hastaların anamnez, fizik muayene ve vital bulguları ile ABCD? skorları hesaplandı. Hastaların acil servis içinde tetkik ve tedavileri devam ederken CRP, fibrinojen, D-Dimer düzeyleri için kan alındı. Hastaların inme geçirip geçirmedikleri 3 ay sonra telefonla aranarak öğrenildi. Bulgular: Konuşma bozukluğu (%45) ve güç kaybı (%40) en sık saptanan semptomlardı. İnme gelişme riski hastaların %52.9' unda orta iken, %12.9'unda yüksek saptandı. 3 ay içinde hastaların %14.3' ünde inme gelişti. Hastaların tamamı ele alındığın %10 (n:7)' unda AF saptandı ve bu AF saptanan yedi hastanın beşinde (%71.4) inme gelişti (p<0.05). Serum belirteçlerinden sadece CRP markerının inme geçirme durumuyla ilişkisi bulundu. (p=0.008). Sonuç: Bulgularımız ABCD? skorlamasının GİA tanısı alanlarda; GİA tekrarı ve inme gelişme riski hakkında tahmin edilebilir kanıtlar sunduğu yönündedir. AF ve yüksek CRP, fibrinojen ve D-dimer seviyelerinin varlığı, inme veya GİA tanılarında kullanılabilmesine rağmen çalışmamızda sadece AF ve yüksek CRP seviyelerinin birlikteliğinin ABCD? skorunun prediktif değerini artırdığını göstermesine rağmen daha fazla çalışmalar ile bu bulguların teyid edilmesi gereklidir. [ABSTRACT FROM AUTHOR]

Cerebrovascular attack (CVA) and transient ischemic attack (TIA) are major causes of emergency department visits around the globe. A significant number of these patients may experience repeat attacks if left untreated. Several risk stratifying scoring systems have been developed in recent years to point out the high risk patients. ABCD2 is based on age, blood pressure, clinical status, diabetes mellitus, and duration of symptoms and is used commonly for this purpose. In this study, we were to enhance its sensitivity and specificity with the addition of another criterion namely atrial fibrillation and making ABCD2-F. A prospective study in two hospitals was performed and 138 patients diagnosed with TIA/CVA were enrolled. Demographic, clinical, and paraclinical data of all patients were registered. All patients were followed for three months for any sign or symptom of a recurrent ischemic attack. Recurrent ischemic attacks happened in 9.4% of the patients. None of the criteria of ABCD2-F was associated with higher chance of ischemic attacks. Similarly, ABCD2-F was not different between patients with or without repeat cerebral ischemia. The addition of atrial fibrillation to ABCD2 did not enhance the accuracy of this scoring system to detect patients high risk for repeat cerebral ischemia. More studies in the future to improve sensitivity and specificity of this test are warranted. [ABSTRACT FROM AUTHOR]

Backgrounds: Diagnostics of a posterior circulation ischemia (POCI) in patients with acute vertigo is a challenging task. Recently, the combination of HINTS (Head Impulse, Nystagmus and Test of Skew) exam and ABCD2 has been recommended to identify stroke in these patients. Until now, studies regarding HINTS have mostly been tested on preselected patient groups and their results are only partially applicable to real clinical practice., Aims: To compare the sensitivity and specificity of HINTS and ABCD2 and their combination in unselected acutely dizzy patients in the emergency department (ED) toward posterior circulation stroke detection., Methods: A prospective cross-sectional monocentric study in ED patients with acute onset of dizziness lasting less than 72 h. Their clinical characteristics, HINTS, vascular risk factors, ABCD2 scores and neuroimaging data were analyzed., Results: 140 patients were recruited. Acute stroke was identified by MRI in 39 patients. All patients had central pattern nystagmus, skew deviation or further focal neurological finding. The age (≥60) and arterial hypertension clearly distinguished stroke and non-stroke group (p < 0001). The sensitivity of HINTS, ABCD2 and their combination in the unselected group was high (82,1 - 97,4%), but specificity low. After removing patients with inconclusive diagnosis, including transitory ischemic attack, specificity was much higher and comparable to previously published results., Conclusions: The sensitivity and specificity of HINTS in previously published studies may vary because of their selection criteria. Even though, our study was performed on the unselected patient cohort, combination of HINTS and ABCD2 remained highly sensitive in detecting POCI and outperformed each of these tests alone., Competing Interests: Conflict of interest No other interests to declare by any of the authors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and purpose The ABCD2 score can predict the early risk of stroke after transient ischaemic attack or minor stroke. However, there is no simple and practical assessment method for the long-term risks. Computed tomography ( CT) and transcranial Doppler ( TCD) findings were added to the ABCD2 score to build an ABCD2L2 score and whether the new scoring system could improve the predictive value of the ABCD2 score for the long-term risk of stroke was determined. Methods From January 2004 to December 2005, all patients with a definite diagnosis of transient ischaemic attack or minor stroke at the Prince of Wales Hospital were consecutively enrolled and followed up until August 2008. CT and TCD were performed. The areas under the curve were used to quantify the ABCD2 and ABCD2L2 scores and related items. Results All 481 patients completed the follow-up. The shortest follow-up time was 0.17 months (until death), the longest follow-up time was 55.60 months and the mean follow-up time was 40.3 ± 11.0 months. In total, 277 (57.6%) patients showed lesions on CT scans and 195 (40.6%) patients were found with intracranial large artery atherosclerosis. Further strokes occurred in 74 (15.4%) patients, including four (0.83%) patients who died of ischaemic stroke during the follow-up period. The area under the curve increased from 0.650 (0.586-0.715) for the ABCD2 score to 0.700 (0.637-0.764) for the ABCD2L2 score. Conclusion Adding CT and TCD results to the ABCD2 score to increase its predictability for long-term risk of stroke recurrence might be a meaningful exploration. [ABSTRACT FROM AUTHOR]

As a significant number of patients diagnosed with transient ischemic attack (TIA) at emergency department are at risk to develop TIA or cerebral vascular accident (CVA), several attempts have been made to figure out a predictive method to detect those at higher risk of such attacks. We aimed to evaluate the role of ABCD2 scoring which includes age, blood pressure, clinical symptoms, diabetes mellitus, and duration of symptoms in predicting short term outcome of the patients presenting with TIA. One hundred consecutive patients visited between 2009 and 2010 in Hazrat Rasoul Akram Hospital and diagnosed with TIA were enrolled and their ABCD2 scores were registered. The incidence of death, CVA, or TIA during the first week after the attack was recorded. Eleven patients suffered new TIA/CVA after 1 week. Sensitivity and specificity of ABCD2 score for predicting CVA/TIA at cut-off point of 4 were 72.7% and 52.8%, respectively. At the same cut-off point for ABCD2, positive and negative predictive values were 16% and 94 %, respectively. Our results show that although patients with ABCD2 score greater than 4 were more likely to develop recurrent TIA/CVA in short term, those with lesser score still harbour a considerable risk for TIA/CVA. Though ABCD2 as an easily applicable tool is very helpful in management of TIA patients at emergency department, but it should not be the only measure to rely on in our decision making.

Abstract: X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disorder characterized by the accumulation of very-long-chain fatty acids resulting from a β-oxidation defect. Oxidative stress and inflammation are also key components of the pathogenesis. X-ALD is caused by mutations in the ABCD1 gene, which encodes for a peroxisomal half ABC transporter predicted to participate in the entry of VLCFA-CoA into the peroxisome, the unique site of their β-oxidation. Two homologous peroxisomal ABC transporters, ABCD2 and ABCD3 have been proven to compensate for ABCD1 deficiency when overexpressed. Pharmacological induction of these target genes could therefore represent an alternative therapy for X-ALD patients. Since LXR activation was shown to repress ABCD2 expression, we investigated the effects of LXR antagonists in different cell lines. Cells were treated with GSK(17) (a LXR antagonist recently discovered from the GlaxoSmithKline compound collection), 22(S)-hydroxycholesterol (22S-HC, another LXR antagonist) and 22R-HC (an endogenous LXR agonist). We observed up-regulation of ABCD2, ABCD3 and CTNNB1 (the gene encoding for β-catenin, which was recently demonstrated to induce ABCD2 expression) in human HepG2 hepatoma cells and in X-ALD skin fibroblasts treated with LXR antagonists. Interestingly, induction in X-ALD fibroblasts was concomitant with a decrease in oxidative stress. Rats treated with 22S-HC showed hepatic induction of the 3 genes of interest. In human, we show by multiple tissue expression array that expression of ABCD2 appears to be inversely correlated with NR1H3 (LXRα) expression. Altogether, antagonists of LXR that are currently developed in the context of dyslipidemia may find another indication with X-ALD. [Copyright &y& Elsevier]

Abstract: The ‘accuracy’ of age, blood pressure, clinical features, duration and diabetes (ABCD2) scoring by non-stroke specialists referring patients to a daily Rapid Access Stroke Prevention (RASP) service is unclear, as is the accuracy of ABCD2 scoring by trainee residents. In this prospective study, referrals were classified as ‘confirmed TIAs’ if the stroke specialist confirmed a clinical diagnosis of possible, probable or definite TIA, and ‘non-TIAs’ if patients had a TIA mimic or completed stroke. ABCD2 scores from referring physicians were compared with scores by experienced stroke specialists and neurology/geriatric medicine residents at a daily RASP clinic; inter-observer agreement was examined. Data from 101 referrals were analysed (mean age=60.0years, 58% male). The median interval between referral and clinic assessment was 1day. Of 101 referrals, 52 (52%) were ‘non-TIAs’: 45 (86%) of 52 were ‘TIA mimics’ and 7 (14%) of 52 were completed strokes. There was only ‘fair’ agreement in total ABCD2 scoring between referring physicians and stroke specialists (κ =0.37). Agreement was ‘excellent’ between residents and stroke specialists (κ =0.91). Twenty of 29 patients scored as ‘moderate to high risk’ (score 4–6) by stroke specialists were scored ‘low risk’ (score 0–3) by referring physicians. ABCD2 scoring by referring doctors is frequently inaccurate, with a tendency to underestimate stroke risk. These findings emphasise the importance of urgent specialist assessment of suspected TIA patients, and that ABCD2 scores by non-stroke specialists cannot be relied upon in isolation to risk-stratify patients. Inter-observer agreement in ABCD2 scoring was ‘excellent’ between residents and stroke specialists, indicating short-term training may improve accuracy. [Copyright &y& Elsevier]

As a significant number of patients diagnosed with transient ischemic attack (TIA) at emergency department are at risk to develop TIA or cerebral vascular accident (CVA), several attempts have been made to figure out a predictive method to detect those at higher risk of such attacks. We aimed to evaluate the role of ABCD² scoring which includes age, blood pressure, clinical symptoms, diabetes mellitus, and duration of symptoms in predicting short term outcome of the patients presenting with TIA. One hundred consecutive patients visited between 2009 and 2010 in Hazrat Rasoul Akram Hospital and diagnosed with TIA were enrolled and their ABCD² scores were registered. The incidence of death, CVA, or TIA during the first week after the attack was recorded. Eleven patients suffered new TIA/CVA after 1 week. Sensitivity and specificity of ABCD² score for predicting CVA/TIA at cut-off point of 4 were 72.7% and 52.8%, respectively. At the same cut-off point for ABCD², positive and negative predictive values were 16% and 94 %, respectively. Our results show that although patients with ABCD² score greater than 4 were more likely to develop recurrent TIA/CVA in short term, those with lesser score still harbour a considerable risk for TIA/CVA. Though ABCD² as an easily applicable tool is very helpful in management of TIA patients at emergency department, but it should not be the only measure to rely on in our decision making. [ABSTRACT FROM AUTHOR]

Abstract: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene. Accumulation of very long chain fatty acids (VLCFA) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity are the hallmark of the disease. Overexpression of ABCD2 gene, the closest homolog of ABCD1, has been shown to compensate for ABCD1, thus correcting the VLCFA derangement. The accumulation of VLCFA leads to a neuroinflammatory disease process associated with demyelination of the cerebral white matter. The present study underlines the importance of caffeic acid phenethyl ester (CAPE) in inducing the expression of ABCD2 (ALDRP), and normalizing the peroxisomal β-oxidation as well as the levels of saturated and monounsaturated VLCFAs in cultured human skin fibroblasts of X-ALD patients. The expression of ELOVL1, the single elongase catalyzing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1), was also reduced by CAPE treatment. Importantly, CAPE upregulated Abcd2 expression and peroxisomal β-oxidation and lowered the VLCFA levels in Abcd1-deficient U87 astrocytes and B12 oligodendrocytes. In addition, using Abcd1/Abcd2-silenced mouse primary astrocytes we examined the effects of CAPE in VLCFA-induced inflammatory response. CAPE treatment decreased the inflammatory response as the expression of inducible nitric oxide synthase, inflammatory cytokine, and activation of NF-κB in Abcd1/Abcd2-silenced mouse primary astrocytes was reduced. The observations indicate that CAPE corrects both the metabolic disease of VLCFA as well as secondary inflammatory disease; therefore, it may be a potential drug candidate to be tested for X-ALD therapy in humans. [Copyright &y& Elsevier]

Background and purpose Early recurrent strokes lead to extended hospitalization and high number of complications. We investigated three stroke scores, the Essen Stroke Risk Score (ESRS), the ABCD² and the Recurrence Risk Estimator at 90 days (RRE-90) for their prognostic value to predict early recurrent stroke, death and progressive stroke. Methods Clinical and radiological data from 1727 consecutive patients with ischaemic stroke, being admitted to the stroke unit, were evaluated retrospectively. Predictive value of stroke scores was tested for early recurrence within 7 days, death and progressive stroke expressed as observational risk and area under the receiver operator curve ( AUROC). Results Early recurrent stroke occurred in 56 patients (3.2%), 40 patients (2.3%) died within the first 7 days and 125 patients (7.2%) had a progressive stroke. ESRS was not predictive for early recurrence, death or progressive stroke. ABCD² score was predictive for death ( P < 0.01; χ²; AUROC, 0.65; 0.58-0.72), and progressive stroke ( P < 0.001; χ²; AUROC, 0.70; 0.66-0.74). RRE-90 predicted early recurrent stroke ( P < 0.001; χ²; AUROC, 0.65; 0.58-0.73), early death ( P < 0.001; χ²; AUROC, 0.72; 0.66-0.78) and progressive stroke ( P < 0.001; χ²; AUROC, 0.66; 0.61-0.71). Conclusions RRE-90 bears high potential to not only predict early recurrence but also death and progression after ischaemic stroke. ABCD² appears to be useful to predict risk of death and progression. These findings have relevant clinical implications for early triage of patients being admitted to stroke units. [ABSTRACT FROM AUTHOR]

Background: The newly proposed transient ischemic attack (TIA) definition demands for MRI exclusion of infarction. Due to limited resources other tools than MRI predicting tissue infarction would be valuable. We hypothesized that ABCD2 risk score is a valid screening tool for diffusion-weighted imaging (DWI) lesions. Methods: TIA patients were prospectively enrolled in an observational MRI study to receive acute and follow-up stroke MRI. ABCD2 scores were calculated, and sociodemographics and risk factors were recorded. Results: One hundred and thirty-two TIA patients were enrolled over nine months. Five patients were excluded due to different diagnosis. Forty-five of the 127 remaining patients showed acute ischemic lesions on DWI. Median ABCD2 scores for DWI-negative and -positive patients were 4 and 5, respectively. Ordinal, trichotomized and dichotomized ABCD2 were significantly associated to DWI. Univariate analysis of single score items and other risk factors demonstrated unilateral weakness, duration of symptoms and smoking as predictive for DWI restrictions. In multivariate analysis unilateral weakness remained significant. Conclusions: High-risk ABCD2 score due to the impact of hemiparesis is associated with the occurrence of DWI lesions but is still not accurate enough for a reliable differentiation of cerebrovascular events with and without MRI lesions. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective. The purpose of this systematic review with meta-analysis is to determine the predictive value of the ABCD2 at 7 and 90 days across three strata of risk.Background. The risk of stroke after transient ischaemic attack (TIA) is significant. The ABCD2 clinical prediction rule is designed to predict early risk of stroke after TIA. A number of independent validation studies have been conducted since the rule was derived.Methods. A systematic literature search was conducted to identify studies that validated the ABCD2. The derived rule was used as a predictive model and applied to subsequent validation studies. Comparisons were made between observed and predicted number of strokes stratified by risk group: low (0–3 points), moderate (4–5 points) and high (6–7 points). Pooled results are presented as risk ratios (RRs) with 95% confidence intervals (CIs), in terms of over-prediction (RR > 1) or under-prediction (RR < 1) of stroke at 7 and 90 days.Results. We include 16 validation studies. Fourteen studies report 7-day stroke risk (n = 6282, 388 strokes). The ABCD2 rule correctly predicts occurrence of stroke at 7 days across all three risk strata: low [RR 0.86, 95% CI (0.47–1.58), I2 = 16%], moderate [RR 0.99, 95% CI (0.67–1.47), I2 = 68%] and high [RR 0.84, 95% CI (0.6–1.19), I2 = 46%]. Eleven studies report 90-day stroke risk (n = 6304). There is a non-significant trend towards over-prediction of stroke in all risk categories at 90 days. There are 426 strokes observed in contrast to a predicted 626 strokes. As the trichotomized ABCD2 score increases, the risk of stroke increases (P < 0.01). There is no evidence of publication bias in these studies (P > 0.05).Conclusion. The ABCD2 is a useful CPR, particularly in relation to 7-day risk of stroke. [ABSTRACT FROM AUTHOR]

The new definition and risk stratification for transient ischemic attack (TIA) have clear implications for the urgency of evaluation and treatment. The optimal antithrombotic treatment for TIA is being intensively studied. New guidelines for prevention of non-cardioembolic stroke in patients with stroke or TIA recommend the use of antiplatelet agents rather than oral anticoagulation. New antiplatelet drugs are being used in cardiovascular patients, and their role in cerebrovascular patients is being studied. The impact of genetic CYP2C19 polymorphisms is becoming clarified in cardiovascular patients and it is likely these polymorphisms will affect the management of cerebrovascular patients. The results of trials of clopidogrel plus aspirin in patients with lacunar strokes and acute TIAs are forthcoming. The results of CLOSURE I, a study of a patent foramen ovale device closure trial for cryptogenic stroke or TIA, showed no differences in stroke or TIA at 2 years. [ABSTRACT FROM AUTHOR]

Stroke management in the UK has only moved to the forefront of medicine in the recent past. Stroke is the third most common cause of death after heart disease and cancer and has an estimated total cost to the economy of approximately £9 billion per year. Almost 20% of ischaemic strokes are cardioembolic in origin and potentially treatable. With the publication of the National Stroke Strategy in 2007 and the establishment of hyper acute stroke units, the NHS hopes to deliver a world class service for the treatment of strokes. [ABSTRACT FROM AUTHOR]

Abstract: The gene mutated in X-linked adrenoleukodystrophy (X-ALD) codes for the HsABCD1 protein, also named ALDP, which is a member of the superfamily of ATP-binding cassette (ABC) transporters and required for fatty acid transport across the peroxisomal membrane. Although a defective HsABCD1 results in the accumulation of very long-chain fatty acids in plasma of X-ALD patients, there is still no direct biochemical evidence that HsABCD1 actually transports very long-chain fatty acids. We used the yeast Saccharomyces cerevisiae to study the transport of fatty acids across the peroxisomal membrane. Our earlier work showed that in yeast the uptake of fatty acids into peroxisomes may occur via two routes, either as (1.) free fatty acid or as (2.) acyl-CoA ester. The latter route involves the two peroxisomal half-ABC transporters, Pxa1p and Pxa2p, which form a heterodimeric complex in the peroxisomal membrane. We here report that the phenotype of the pxa1/pxa2Δ yeast mutant, i.e. impaired growth on oleate containing medium and deficient oxidation of oleic acid, cannot only be partially rescued by human ABCD1, but also by human ABCD2 (ALDRP), which indicates that HsABCD1 and HsABCD2 can both function as homodimers. Fatty acid oxidation studies in the pxa1/pxa2Δ mutant transformed with either HsABCD1 or HsABCD2 revealed clear differences suggesting that HsABCD1 and HsABCD2 have distinct substrate specificities. Indeed, full rescue of beta-oxidation activity in cells expressing human ABCD2 was observed with C22:0 and different unsaturated very long-chain fatty acids including C24:6 and especially C22:6 whereas in cells expressing HsABCD1 rescue of beta-oxidation activity was best with C24:0 and C26:0 as substrates. [Copyright &y& Elsevier]

drenoleukodystrophy (ALD) is an X-linked disorder affecting primarily the white matter of the central nervous system occasionally accompanied by adrenal insufficiency. Despite the discovery of the causative gene, ABCD1, no clear genotype-phenotype correlations have been established. Association studies based on single nucleotide polymorphisms (SNPs) identified by comprehensive resequencing of genes related to ABCD1 may reveal genes modifying ALD phenotypes. We analyzed 40 Japanese patients with ALD. ABCD1 and ABCD2 were analyzed using a newly developed microarray-based resequencing system. ABCD3 and ABCD4 were analyzed by direct nucleotide sequence analysis. Replication studies were conducted on an independent French ALD cohort with extreme phenotypes. All the mutations of ABCD1 were identified, and there was no correlation between the genotypes and phenotypes of ALD. SNPs identified by the comprehensive resequencing of ABCD2, ABCD3, and ABCD4 were used for association studies. There were no significant associations between these SNPs and ALD phenotypes, except for the five SNPs of ABCD4, which are in complete disequilibrium in the Japanese population. These five SNPs were significantly less frequently represented in patients with adrenomyeloneuropathy (AMN) than in controls in the Japanese population ( p = 0.0468), whereas there were no significant differences in patients with childhood cerebral ALD (CCALD). The replication study employing these five SNPs on an independent French ALD cohort, however, showed no significant associations with CCALD or pure AMN. This study showed that ABCD2, ABCD3, and ABCD4 are less likely the disease-modifying genes, necessitating further studies to identify genes modifying ALD phenotypes. [ABSTRACT FROM AUTHOR]

Mutations in the ABCD1 gene cause the clinical spectrum of the neurometabolic disorder X-linked adrenoleukodystrophy/adrenomyeloneuropathy (X-ALD/AMN). Currently, the most efficient therapeutic opportunity for patients with the cerebral form of X-ALD is hematopoietic stem cell transplantation and possibly gene therapy of autologous hematopoietic stem cells. Both treatments, however, are only accessible to a subset of X-ALD patients, mainly because of the lack of markers that can predict the onset of cerebral demyelination. Moreover, for female or male X-ALD patients with AMN, currently only unsatisfying therapeutic opportunities are available. Thus, this review focuses on current and urgently needed future pharmacological therapies. The treatment of adrenal and gonadal insufficiency is well established, whereas applications of immunomodulatory and immunosuppressive drugs have failed to prevent progression of cerebral neuroinflammation. The use of Lorenzo's oil and the inefficacy of lovastatin to normalize very-long-chain fatty acids in clinical trials as well as currently experimental and therefore possible future therapeutic strategies are reviewed. The latter include pharmacological gene therapy mediated by targeted upregulation of ABCD2, the closest homolog of ABCD1, antioxidative drug treatment, small molecule histone deacetylase inhibitors such as butyrates and valproic acid, and other neuroprotective attempts. [ABSTRACT FROM AUTHOR]