Browsing by Author "Pavlovic, Aleksandra M. (7003808508)"

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable cause of stroke and vascular dementia in adults. We present a family from Serbia presenting with stroke and depression in the lack of vascular risk factors, with brain MRI indicating CADASIL. A novel NOTCH3 Gly89Cys mutation was located in exon 3. This report illustrates that in the setting of a positive family history with typical clinical and MRI features, even with an atypical form of pedigree, a high suspicion of CADASIL should lead to genetic testing. © 2013 Belgian Neurological Society.

The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe. © 2013 Springer-Verlag Berlin Heidelberg.

The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe. © 2013 Springer-Verlag Berlin Heidelberg.

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease caused by conformational alteration of the ubiquitous prion protein. Sporadic CJD appears to progress faster if the basal ganglia are shown to be affected on magnetic resonance imaging. Transcranial B-mode sonography (TCS) enables visualization of differences in tissue echogenicity, which can be associated with changes in the cerebral metabolism of various metals. These metabolic changes are considered 1 of the potential mechanisms of the brain damage in CJD; TCS hyperechogenicity may reflect changes in metal homeostasis in CJD. We report a 63-year-old woman who presented with typical sporadic CJD. One month after she fell ill, a magnetic resonance imaging scan of her brain showed diffuse cortical but no obvious basal ganglia involvement. However, TCS revealed moderate hyperechogenicity of both lentiform nuclei. The patient's disease progressed quickly and she died 2 months later. TCS may show basal ganglia alteration early in the disease course of patients with quickly progressing CJD, thus aiding in premortem diagnosis. © 2014 by Lippincott Williams and Wilkins.

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease caused by conformational alteration of the ubiquitous prion protein. Sporadic CJD appears to progress faster if the basal ganglia are shown to be affected on magnetic resonance imaging. Transcranial B-mode sonography (TCS) enables visualization of differences in tissue echogenicity, which can be associated with changes in the cerebral metabolism of various metals. These metabolic changes are considered 1 of the potential mechanisms of the brain damage in CJD; TCS hyperechogenicity may reflect changes in metal homeostasis in CJD. We report a 63-year-old woman who presented with typical sporadic CJD. One month after she fell ill, a magnetic resonance imaging scan of her brain showed diffuse cortical but no obvious basal ganglia involvement. However, TCS revealed moderate hyperechogenicity of both lentiform nuclei. The patient's disease progressed quickly and she died 2 months later. TCS may show basal ganglia alteration early in the disease course of patients with quickly progressing CJD, thus aiding in premortem diagnosis. © 2014 by Lippincott Williams and Wilkins.

Objective Cerebral small vessel disease (SVD) is associated with late-onset depression and increases the risk for depression after stroke. We aimed to investigate baseline predictors of depression after long-term follow-up in patients with SVD, initially presenting with first-ever lacunar stroke, free of depression and cognitive impairment. Methods A total of 294 patients with SVD were evaluated 3-5 years after the qualifying event. We analyzed baseline demographic data, vascular risk factors, functional status expressed as a score on modified Rankin Scale (mRS), cognitive status, presence of depression, total number of lacunar infarcts and severity of white matter hyperintensities (WMH) on MRI with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. Results On follow-up, depression was registered in 117 (39.8%) SVD patients. At the baseline, patients with depression compared with non-depressed were older (64.4 vs 60.9 years; p = 0.007), had higher mRS score (2.8 ± 0.7 vs 1.5 ± 0.7; p < 0.0001) and had more severe lesions on MRI scales (p < 0.0001 for all parameters). On follow-up, depressed patients more frequently exhibited cognitive decline (75.2% depressed vs 56.5% non-depressed; p = 0.003). No difference was detected in risk factor frequency between groups. Multivariate Cox regression analysis adjusted by age and gender revealed independent predictors of depression: baseline mRS >2 (HR 2.17, 95%CI 1.74-2.72; p < 0.0001) and tARWMC (HR 1.05, 95%CI 1.02-1.09; p = 0.005), and cognitive decline on follow-up (HR 1.80, 95%CI 1.12-2.89; p = 0.015). Conclusions Baseline functional status and severity of WMH and development of cognitive decline predict the occurence of late-onset depression in patients with SVD. Copyright © 2015 John Wiley & Sons, Ltd.

Cerebral small vessel disease (SVD) is a common cause of cognitive impairment and vascular dementia. We aimed to investigate predictors of cognitive decline in patients with SVD who initially presented with first-ever small subcortical stroke of lacunar type but had normal cognitive status. A total of 294 patients with SVD were evaluated 3-5 years after initial presentation. We analyzed baseline demographic data, vascular risk factors, functional status expressed as score on modified Rankin Scale, total number of lacunar infarcts, and severity of white matter hyperintensities (WMH) on magnetic resonance imaging with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. At follow-up, vascular cognitive impairment (VCI) on any type was detected in 188 (63.9%) of SVD patients, with 65 (22.1%) meeting criteria for vascular dementia and 123 (41.8%) presenting with cognitive impairment not dementia. Patients with VCI were older (64.4 ± 10.3 in VCI versus 58.6 ± 10.5 years in non-VCI; p < 0.0001) at the time of initial clinical presentation and more frequently male (57.9% VCI versus 46.2% non-VCI; p = 0.052). No difference was noted in frequency of vascular risk factors in VCI versus non-VCI cases. Multivariate logistic regression analysis adjusted by age and gender identified overall severity of WMH (tARWMC HR 1.42, 95% CI 1.01-2.00; p0.043) and total number of lacunar infarcts (HR 3.06, 95% CI 1.71-5.50, p < 0.001) as independent predictors of cognitive decline. In patients with SVD, independent predictors of VCI were baseline severity of WMH and total number of lacunar infarcts. © 2014-IOS Press and the authors.

Cerebral small vessel disease (SVD) is a common cause of cognitive impairment and vascular dementia. We aimed to investigate predictors of cognitive decline in patients with SVD who initially presented with first-ever small subcortical stroke of lacunar type but had normal cognitive status. A total of 294 patients with SVD were evaluated 3-5 years after initial presentation. We analyzed baseline demographic data, vascular risk factors, functional status expressed as score on modified Rankin Scale, total number of lacunar infarcts, and severity of white matter hyperintensities (WMH) on magnetic resonance imaging with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. At follow-up, vascular cognitive impairment (VCI) on any type was detected in 188 (63.9%) of SVD patients, with 65 (22.1%) meeting criteria for vascular dementia and 123 (41.8%) presenting with cognitive impairment not dementia. Patients with VCI were older (64.4 ± 10.3 in VCI versus 58.6 ± 10.5 years in non-VCI; p < 0.0001) at the time of initial clinical presentation and more frequently male (57.9% VCI versus 46.2% non-VCI; p = 0.052). No difference was noted in frequency of vascular risk factors in VCI versus non-VCI cases. Multivariate logistic regression analysis adjusted by age and gender identified overall severity of WMH (tARWMC HR 1.42, 95% CI 1.01-2.00; p0.043) and total number of lacunar infarcts (HR 3.06, 95% CI 1.71-5.50, p < 0.001) as independent predictors of cognitive decline. In patients with SVD, independent predictors of VCI were baseline severity of WMH and total number of lacunar infarcts. © 2014-IOS Press and the authors.

Objectives: Structural changes and metabolic stress have been reported on diffusion-weighted magnetic resonance imaging in the cornu ammonis 1 area of the hippocampus in patients with transient global amnesia (TGA), but a consensus on pathogenesis is still lacking. The aim of our study was to perform a comprehensive ultrasound analysis of the cerebrovascular circulation in our population of patients with TGA. Methods: One hundred patients with TGA and 50 age- and sex-matched control participants underwent ultrasound examinations of the cervicocranial circulation. Results: The most significant risk factor for TGA was arterial hypertension (P <.01). There were no significant atherosclerotic lesions on the large arteries of the neck (mean internal carotid artery stenosis ± SD, 28.7% ± 11.7%) or on the large intracerebral arteries (good structural and hemodynamic status; P >.05). Rarely detected microembolic signals or a right-left cardiopulmonary shunt excluded an emboligenic mechanism of TGA (P >.05). The internal jugular vein valves were incompetent in 54% of patients with TGA, and this condition was associated with an increased risk of TGA (odds ratio, 4.16; 95% confidence interval, 1.91–9.04). The mean values of the breath holding index and pulsatility index, as parameters of small-vessel function, were within normal ranges and without differences between the TGA and control groups (P >.05). Conclusions: Our ultrasound examination did not detect significant structural atherosclerotic changes of cervicocranial arteries, and an emboligenic mechanism was excluded. Only a significant rise of blood pressure in TGA and significant valvular insufficiency of the internal jugular vein were established. New research should clarify whether these simultaneous functional circulatory changes have relevance for metabolic stress in the cornu ammonis of the hippocampus. © 2017 by the American Institute of Ultrasound in Medicine

Objectives: Structural changes and metabolic stress have been reported on diffusion-weighted magnetic resonance imaging in the cornu ammonis 1 area of the hippocampus in patients with transient global amnesia (TGA), but a consensus on pathogenesis is still lacking. The aim of our study was to perform a comprehensive ultrasound analysis of the cerebrovascular circulation in our population of patients with TGA. Methods: One hundred patients with TGA and 50 age- and sex-matched control participants underwent ultrasound examinations of the cervicocranial circulation. Results: The most significant risk factor for TGA was arterial hypertension (P <.01). There were no significant atherosclerotic lesions on the large arteries of the neck (mean internal carotid artery stenosis ± SD, 28.7% ± 11.7%) or on the large intracerebral arteries (good structural and hemodynamic status; P >.05). Rarely detected microembolic signals or a right-left cardiopulmonary shunt excluded an emboligenic mechanism of TGA (P >.05). The internal jugular vein valves were incompetent in 54% of patients with TGA, and this condition was associated with an increased risk of TGA (odds ratio, 4.16; 95% confidence interval, 1.91–9.04). The mean values of the breath holding index and pulsatility index, as parameters of small-vessel function, were within normal ranges and without differences between the TGA and control groups (P >.05). Conclusions: Our ultrasound examination did not detect significant structural atherosclerotic changes of cervicocranial arteries, and an emboligenic mechanism was excluded. Only a significant rise of blood pressure in TGA and significant valvular insufficiency of the internal jugular vein were established. New research should clarify whether these simultaneous functional circulatory changes have relevance for metabolic stress in the cornu ammonis of the hippocampus. © 2017 by the American Institute of Ultrasound in Medicine

Although cerebral small vessel disease (SVD) is traditionally associated with aging and hypertension (HT), there are patients exhibiting sporadic SVD, free of HT. We aimed to investigate the differences in clinical and neuroradiological presentation in SVD patients in reference to the presence of HT as a risk factor (RF). Vascular RF, cognitive and functional status were evaluated in a cohort of 424 patients. Patients were classified in two groups based on the presence of HT. Severity of vascular lesions was assessed using 1.5 T magnetic resonance imaging with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular (PV) and deep subcortical (DS) scores. No difference between groups in age and sex distribution was noted. In univariate analysis, HT was associated with vascular cognitive impairment (vCI) (OR 2.30, 1.53-3.45, P < 0.0001), functional status (OR 1.47, 1.11-1.95, P = 0.007), depression (OR 2.13, 1.23-3.70, P = 0.007), tARWMC (OR 1.10, 1.05-1.16 95% CI, P < 0.0001), Fazekas PV score (OR 1.34, 1.08-1.67 95% CI, P = 0.008), Fazekas DS score (OR 1.95, 1.44-2.63 95% CI, P < 0.0001) and total number of lacunes (OR 1.10, 1.02-1.18 95% CI, P = 0.009). Multivariate logistic regression analysis indicated that HT was an independent RF for vCI (OR 1.74, 1.09-2.76 95% CI, P = 0.020) and higher Fazekas DS score (OR 1.57, 1.11-2.22 95% CI, P = 0.011). The Kaplan-Meier curve of estimates of survival of SVD patients without vCI revealed a higher proportion of patients with HT progressing to vCI over time when compared to HT-free cases. In patients with sporadic SVD, HT is a contributing factor to worse clinical outcomes and neuroradiological presentation. ©2018 Wiley Periodicals, Inc.

New therapeutic strategies under development aim to improve recanalization rates and clinical outcomes after ischemic stroke. One such approach is ultrasound (US)- enhanced thrombolysis, or sonothrombolysis, which can improve thrombolytic drug actions and even intrinsic fibrinolysis. Although the mechanisms are not fully understood, it is postulated that thrombolysis enhancement is related to nonthermal mechanical effects of US. Recent results indicate that US with or without microbubbles may be effective in clot lysis of ischemic stroke even without additional thrombolytic drugs. Sonothrombolysis is a promising tool for treating acute ischemic stroke, but its efficacy, safety, and technical details have not been elucidated and proved yet in stroke treatment. © 2013 by the American Institute of Ultrasound in Medicine.

New therapeutic strategies under development aim to improve recanalization rates and clinical outcomes after ischemic stroke. One such approach is ultrasound (US)- enhanced thrombolysis, or sonothrombolysis, which can improve thrombolytic drug actions and even intrinsic fibrinolysis. Although the mechanisms are not fully understood, it is postulated that thrombolysis enhancement is related to nonthermal mechanical effects of US. Recent results indicate that US with or without microbubbles may be effective in clot lysis of ischemic stroke even without additional thrombolytic drugs. Sonothrombolysis is a promising tool for treating acute ischemic stroke, but its efficacy, safety, and technical details have not been elucidated and proved yet in stroke treatment. © 2013 by the American Institute of Ultrasound in Medicine.