Background
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by
NOTCH3
gene ...mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL.
Methods
Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities.
Results
128 patients (mean age 56.3 ± 12.4 years) were included. A
NOTCH3
mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity.
Conclusions
A careful familial history collection and neuroradiological assessment can identify patients in whom
NOTCH3
genetic testing has a higher yield.
To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.
Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. ...Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale NIHSS ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale mRS ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death.
Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio OR 1.68, 95% confidence interval CI 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007).
Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.
Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. ...Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient’s clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.
BACKGROUND AND PURPOSE:Both obstructive sleep apnea (OSA) and cardiac organ damage have a crucial role in acute ischemic stroke. Our aim is to explore the relationship between OSA and cardiac organ ...damage in acute stroke patients.
METHODS:A total of 130 consecutive patients with acute ischemic stroke were enrolled. Patients underwent full multichannel 24-h polysomnography for evaluation of OSA and echocardiography to evaluate left ventricle (LV) mass index (LV mass/BSA, LV mass/height), thickness of interventricular septum (IVS) and posterior wall (LVPW), LV ejection fraction and left atrium enlargement. Information on occurrence of arterial hypertension and its treatment before stroke was obtained from patients’ history.
RESULTS:61.9% (70) of patients, mostly men (67.1%), with acute stroke had OSA (AHI > 10). Patients with acute stroke and OSA showed a significant increase (P < 0.05) of LV mass index, IVS and LVPW thickness and a significant left atrial enlargement as compared with patients without OSA. LV ejection fraction was not significantly different in stroke patients with and without OSA and was within normal limits. No relationship was found among cardiac alterations, occurrence of OSA and history of hypertension.
CONCLUSION:Acute stroke patients with OSA had higher LV mass and showed greater left atrial enlargement than patients without OSA. This study confirms the high prevalence of OSA in stroke patients, suggesting also an association between OSA and cardiac target organ damage. Our finding of structural LV abnormalities in acute stroke patients with OSA suggests a potential role of OSA as contributing factor in determining both cerebrovascular and cardiac damage, even in absence of clear link with a history of blood pressure elevation.
Purpose
To report the results of carotid artery stenting (CAS) in symptomatic
patients (stroke/transient ischemic attack) after recent percutaneous
transluminal coronary angioplasty (PTCA) for acute ...coronary syndrome
(ACS).
Methods
Between January 2009 and July 2011, 28 consecutive patients (18 women; mean
age 66 years, range 42–82) underwent protected CAS for symptomatic
carotid stenosis following recent PTCA that included bare or drug-eluting
stents requiring uninterrupted dual antiplatelet therapy. Primary technical
success, neurological complications, major adverse cardiovascular events,
and death were evaluated at 30 days and over midterm follow-up.
Results
Technical success was 96%; 1 patient suffered a nonfatal major stroke
(3.5% 30-day stroke rate) during the procedure. During a median
21.6-month follow-up, 4 (14%) patients died of myocardial infarction
(all diabetic smokers with ejection fractions <40%), but there
were no new neurological events. Estimated survival was 89.3% at 2
years. Further coronary interventions were performed in 2 diabetic patients
with a body mass index >34 kg/m2.
Conclusion
This preliminary experience demonstrated that CAS is a reasonable, safe, and
effective treatment for patients with symptomatic carotid artery stenosis
who were recently treated with coronary stents requiring uninterrupted dual
antiplatelet therapy.
Multiple deletions of mitochondrial DNA (mtDNA) are associated with different mitochondrial disorders inherited as autosomal dominant and recessive traits. Causative mutations have been found in five ...genes, mainly involved in mtDNA replication and stability. They include
POLG1
, the gene encoding the catalytic subunit of mtDNA polymerase (polγ),
POLG2
encoding its accessory subunit,
ANT1
coding the adenine nucleotide translocator and
PEO1
which codes for Twinkle, the mitochondrial helicase. Finally
OPA1
missense mutations are involved in phenotypes presenting optic atrophy as a major feature.
To define the relative contribution of
POLG1, POLG2, ANT1
and
PEO1
genes to the mtDNA multiple deletion syndromes, we analysed them in a cohort of 67 probands showing accumulation of multiple mtDNA deletions in muscle. The patients were predominantly affected with a mitochondrial myopathy with or without progressive external ophthalmoplegia (PEO). Genetic analysis revealed that 1)
PEO1
has a major role in determining familial PEO, since it accounts for 26.8 % of familial cases, followed by
ANT1
(14.6 %) and
POLG1
(9.8 %); 2) no mutations in any of the known genes were found in 53.7 % of probands of this series. Six novel missense mutations contributing to the mutational load of
PEO1
gene (p.R334P, p.W315S, p. S426N, p.W474S, p.F478I, p.E479K) were associated with an adult onset PEO phenotype.
Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease due to mutations involving loss or ...gain of a cysteine residue in the NOTCH3 gene. A cluster of mutations around exons 3 and 4 was originally reported. Identification of pathogenic mutation is important for diagnostic confirmation of the disease, however genetic counselling and testing of relatives at risk is critical in mutation carriers. Methods Mutation analysis of the NOTCH3 gene was performed through direct sequencing in 140 patients with clinical suspicion of CADASIL. Patients underwent genetic counselling pre and post testing. The 2–23 exons containing all EGF-like domains were screened. Results 14 familial forms of the disease have been identified with 14 different causative mutations in exons 2, 3, 4, 5, 7, 10, 14, 19, 20 and 22 of the NOTCH3 gene; no pathogenetic mutations have been identified in exons 6 and 8; several genetic variations both in coding as well as in intronic regions were identified too. Conclusions Our data confirm the importance of screening the whole EGF-like domains region of NOTCH3 gene for the molecular diagnosis of CADASIL among the Italian population too. Moreover genetic variants different from loss or gain of a cysteine residue are identified and presented.
Statins, due to their well-established pleiotropic effects, have noteworthy benefits in stroke prevention. Despite this, a significant proportion of high-risk patients still do not receive the ...recommended therapeutic regimens, and many others discontinue treatment after being started on them. The causes of non-adherence to current guidelines are multifactorial, and depend on both physicians and patients. The aim of this study is to identify the factors influencing statin prescription at Stroke Unit (SU) discharge.
This study included 12,750 patients enrolled on the web-based Lombardia Stroke Registry (LRS) from July 2009 to April 2012 and discharged alive, with a diagnosis of ischemic stroke or transient ischemic attack (TIA) and without contra-indication to statin therapy. By logistic regression analysis and classification trees, we evaluated the impact of demographic data, risk factors, tPA treatment, in-hospital procedures and complications on statin prescription rate at discharge.
We observed a slight increase in statins prescription during the study period (from 39.1 to 43.9%). Lower age, lower stroke severity and prestroke disability, the presence of atherothrombotic/lacunar risk factors, a diagnosis of non-cardioembolic stroke, tPA treatment, the absence of in-hospital complications, with the sole exception of hypertensive fits and hyperglycemia, were the patient-related predictors of adherence to guidelines by physicians. Overall, dyslipidemia appears as the leading factor, while TOAST classification does not reach statistical significance.
In our region, Lombardia, adherence to guidelines in statin prescription at Stroke Unit discharge is very different from international goals. The presence of dyslipidemia remains the main factor influencing statin prescription, while the presence of well-defined atherosclerotic etiopathogenesis of stroke does not enhance statin prescription. Some uncertainties about the risk/benefit of statin therapy in stroke etiology subtypes (cardioembolism, other or undetermined causes) may partially justify the underuse of statin in ischemic stroke. The differences that exist between current international guidelines may prevent a more widespread use of statin and should be clarified in a consensus.
Mitochondrial disorders are human genetic diseases with extremely variable clinical and genetic features. To better define them, we made a genotype-phenotype correlation in a series of 207 affected ...patients, and we examined most of them with six laboratory examinations (serum CK and basal lactate levels, EMG, cardiac and EEG studies, neuroradiology). We found that, depending on the genetic abnormality, hyperckemia occurs most often with either chronic progressive external ophthalmoplegia (CPEO) and ptosis or with limb weakness. Myopathic EMGs are more common than limb weakness, except in patients with A8344G mutations. Peripheral neuropathy, when present, is always axonal. About 80% of patients with A3243G and A8344G mutations have high basal lactate levels, whereas pure CPEO is never associated with increased lactate levels. Cardiac abnormalities mostly consist of conduction defects. Abnormalities on CT or MRI of the brain are relatively common in A3243G mutations independently of the clinical phenotype. Patients with multiple mtDNA deletions are somehow "protected" against the development of abnormalities with any of the tests. We conclude that, despite the phenotypic heterogeneity of mitochondrial disorders, correlation of clinical features and laboratory findings may give the clinician important clues to the genetic defect, allowing earlier diagnosis and counselling.
Histochemical, biochemical and immunologic analysis of cytochrome c oxidase (COX) in skeletal muscle, heart and kidney during human fetal development was performed. COX histochemical activity was ...present only in few muscle fibres from the 11th to the 20th week of gestation. At the same developmental stage intrafusal muscle fibres, heart and kidney already showed strong activity. At the 28th week of gestation muscular COX activity was present in about 90% of the fibres. Tissue biochemical analysis confirmed these histochemical findings. Histochemical and biochemical findings compared to the immunocytochemical results and ELISA indicate that COX activity parallels the progressive synthesis of the enzyme in each tissue.
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