Browsing by Author "Pavlović, Aleksandra (7003808508)"

Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy leading to recurrent strokes and vascular dementia in young and middleaged patients. The diagnosis of CADASIL is based on typical clinical presentation and characteristic magnetic resonance imaging (MRI) changes, and has to be confirmed by biopsy of the sural nerve, muscle and skin, as well as by genetic analysis. Mutations within the Notch3 gene were identified as the underlying genetic defect in CADASIL. Case outline The clinical manifestations of the first presented patient with migraine from the age of thirteen, stroke without vascular risk factors and stepwise progression of vascular dementia comprising the typical clinical picture of CADASIL, were confirmed after seven years with pathological verification. The second presented case did not satisfy the clinical criteria for CADASIL. His stroke was considered to be related with vascular risk factors - diabetes mellitus and hypertension. The aetiological diagnosis was established only when his brother without vascular risk factors presented with similar clinical manifestations. Conclusion Until the development of the new neuroimaging techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a rare disorder. However, the increasing number of CADASIL families has been identified throughout the world showing that this entity is usually underdiagnosed. This article presents three patients from two Serbian families with clinical suspicion of CADASIL verified by pathologic examination.

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In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation. © 2011 Springer-Verlag.

In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation. © 2011 Springer-Verlag.

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing. © 2017 The Author(s).

Introduction. Tolosa-Hunt syndrome (THS) is a rare entity, characterized by unilateral orbital pain associated with paresis of one or more of the oculomotor cranial nerves and caused by a granulomatous inflammation in the cavernous sinus, superior orbital fissure or orbit. The low prevalence of THS with a broad spectrum of other disorders that could cause painful ophtalmoplegia resulted in a stricter diagnostic criteria of THS in the latest edition of the International Classification of Headache Disorders. Current criteria require demonstration of granuloma by magnetic resonance imaging or biopsy. The diagnosis could be difficult and the initiation of treatment delayed due to a high variablity of clinical presentation of TSH. Reducing the number of patients that, based on clinical presentation, could be classified as having THS, but do not fullfil all diagnostic criteria further complicates establishing of correct diagnosis. Case report. Hereby we presented eight patients diagnosed with and treated for THS. Inspite the exclusion of other causes of painful ophtalmoplegia, granuloma could not be demonstrated in a half of patients. Clinical presentation of THS in patients with and without shown granuloma, did not significantly differ concerning headache characteristics (localization, intensity, quality, duration preceding cranial nerve palsy, response to steroids), the affected cranial nerve, disease course and response to the treatment, as well as types of diagnostic procedures that were performed in ruling out other diseases from the extensive differential diagnosis of painful ophthalmoplegia. Conclusion. There is no significant difference between the THS patients with and without demonstrated granuloma. © 2017, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Transcranial sonography (TCS) appeared to be a promising marker associated with depression: hypo/anechogenicity of the brainstem raphe (BR) was found in 50–70 % of patients with unipolar depression, in 40–60 % of depressed patients with Parkinson’s disease (PD), but also in 8–28 % of healthy controls. Our study included 120 consecutive PD outpatients. Abnormal BR echogenicity was found in 51 (43 %), while normal findings were present in 67 PD patients (57 %). Patients with abnormal BR echogenicity had higher scores on the Montgomery–Asberg Depression Rating Scale (MADRS) items of apparent sadness (p = 0.03), reported sadness (p = 0.01), and pessimistic thoughts (p = 0.049), when compared to those with normal BR. In the second part of the study, previously suggested cut-off value at 14/15 on the MADRS was used to dichotomize patients into depressed (dPD) (46 patients; 39 %) and non-depressed PD patients (ndPD) (72 patients; 61 %). Abnormal TCS BR findings were obtained in 27 dPD (58.7 %) and in only 24 ndPD patients (33.3 %) (p = 0.007): the risk that PD patients with the TCS BR abnormality would display depressive symptoms was about 3.5 times higher when compared to PD patients with intact BR, controlling for the effect of motor difficulties (cross-odds ratio; OR = 3.48). Therefore, at least in a subgroup of dPD patients, TCS of the midbrain midline structure may potentially be a useful tool for depressive symptoms prediction. © 2015, Springer-Verlag Berlin Heidelberg.

Transcranial sonography (TCS) appeared to be a promising marker associated with depression: hypo/anechogenicity of the brainstem raphe (BR) was found in 50–70 % of patients with unipolar depression, in 40–60 % of depressed patients with Parkinson’s disease (PD), but also in 8–28 % of healthy controls. Our study included 120 consecutive PD outpatients. Abnormal BR echogenicity was found in 51 (43 %), while normal findings were present in 67 PD patients (57 %). Patients with abnormal BR echogenicity had higher scores on the Montgomery–Asberg Depression Rating Scale (MADRS) items of apparent sadness (p = 0.03), reported sadness (p = 0.01), and pessimistic thoughts (p = 0.049), when compared to those with normal BR. In the second part of the study, previously suggested cut-off value at 14/15 on the MADRS was used to dichotomize patients into depressed (dPD) (46 patients; 39 %) and non-depressed PD patients (ndPD) (72 patients; 61 %). Abnormal TCS BR findings were obtained in 27 dPD (58.7 %) and in only 24 ndPD patients (33.3 %) (p = 0.007): the risk that PD patients with the TCS BR abnormality would display depressive symptoms was about 3.5 times higher when compared to PD patients with intact BR, controlling for the effect of motor difficulties (cross-odds ratio; OR = 3.48). Therefore, at least in a subgroup of dPD patients, TCS of the midbrain midline structure may potentially be a useful tool for depressive symptoms prediction. © 2015, Springer-Verlag Berlin Heidelberg.

After it was reported that increased tissue iron concentrations were associated with increased echogenicity of the substantia nigra (SN) obtained with transcranial sonography (TCS) in animal and postmortem studies, our goal was to use this method in a disorder characterized with iron accumulation in human brain tissue. Therefore, magnetic resonance imaging (MRI) and TCS were conducted in 5 unrelated patients with pantothenate kinase-associated neurodegeneration (PKAN), caused by PANK2 mutations. All patients had an eye of the tiger sign. Hypointense lesions on the T2-weighted MRI images were restricted to the globus pallidus (GP) and SN. TCS also revealed bilateral hyperechogenicity restricted to the LN and SN, with normal DTV values. Both TCS and MRI studies in PKAN patients are in accordance with the pathological findings that accumulation of iron, even in advanced cases, is restricted to the GP and SN, suggesting selective involvement of these structures. © Springer-Verlag 2011.

After it was reported that increased tissue iron concentrations were associated with increased echogenicity of the substantia nigra (SN) obtained with transcranial sonography (TCS) in animal and postmortem studies, our goal was to use this method in a disorder characterized with iron accumulation in human brain tissue. Therefore, magnetic resonance imaging (MRI) and TCS were conducted in 5 unrelated patients with pantothenate kinase-associated neurodegeneration (PKAN), caused by PANK2 mutations. All patients had an eye of the tiger sign. Hypointense lesions on the T2-weighted MRI images were restricted to the globus pallidus (GP) and SN. TCS also revealed bilateral hyperechogenicity restricted to the LN and SN, with normal DTV values. Both TCS and MRI studies in PKAN patients are in accordance with the pathological findings that accumulation of iron, even in advanced cases, is restricted to the GP and SN, suggesting selective involvement of these structures. © Springer-Verlag 2011.

Objectives: The aim of this study was to search for possible differences in the findings of transcranial sonography (TCS) between groups of patients with glucocerebrosidase (GBA)-associated Parkinson's disease (PD) (4 patients with Gaucher disease type 1 and parkinsonism [GD+PD+] and 18 PD patients with heterozygous GBA mutations; [GBA+PD+]) and groups of 12 patients with Gaucher disease type 1 and no signs of parkinsonism (GD+PD-), 9 asymptomatic carriers of heterozygous GBA mutations (GBA+PD-), 32 sporadic PD patients (sPD), and 43 healthy controls. Results: In all groups of patients, except asymptomatic carriers of heterozygous GBA mutations (mean ± SD: 0.16 ± 0.03 cm2), the maximal areas of substantia nigra hyperechogenicity (aSN-max) was higher (GD+PD+: 0.28 ± 0.15 cm2; GD+PD-: 0.18 ± 0.06 cm2; GBA+PD+: 0.27 ± 0.06 cm2; sPD: 0.28 ± 0.10 cm2) when compared to controls (0.12 ± 0.08 cm2) (p = 0.001). In GBA-associated PD (GD+PD+ and GBA+PD+) and sPD, aSNmax values were very similar. Moderate or marked SN hyperechogenicity was present in 87.5% of sPD patients and in 83% of PD patients with heterozygous GBA mutations, but in only 11.6% of controls, and in 22.2% and 33.3% of patients from GBA+PD- and GD+PD- groups, respectively (p < 0.001). The prevalence of interrupted or missing echogenicity of the brainstem raphe differed between the groups (p = 0.046), while no difference was observed in the diameter of the third ventricle. Conclusions: TCS findings in GBA-associated PD were consistent to those of patients with sporadic PD. © 2013 Elsevier Ltd.

Objectives: The aim of this study was to search for possible differences in the findings of transcranial sonography (TCS) between groups of patients with glucocerebrosidase (GBA)-associated Parkinson's disease (PD) (4 patients with Gaucher disease type 1 and parkinsonism [GD+PD+] and 18 PD patients with heterozygous GBA mutations; [GBA+PD+]) and groups of 12 patients with Gaucher disease type 1 and no signs of parkinsonism (GD+PD-), 9 asymptomatic carriers of heterozygous GBA mutations (GBA+PD-), 32 sporadic PD patients (sPD), and 43 healthy controls. Results: In all groups of patients, except asymptomatic carriers of heterozygous GBA mutations (mean ± SD: 0.16 ± 0.03 cm2), the maximal areas of substantia nigra hyperechogenicity (aSN-max) was higher (GD+PD+: 0.28 ± 0.15 cm2; GD+PD-: 0.18 ± 0.06 cm2; GBA+PD+: 0.27 ± 0.06 cm2; sPD: 0.28 ± 0.10 cm2) when compared to controls (0.12 ± 0.08 cm2) (p = 0.001). In GBA-associated PD (GD+PD+ and GBA+PD+) and sPD, aSNmax values were very similar. Moderate or marked SN hyperechogenicity was present in 87.5% of sPD patients and in 83% of PD patients with heterozygous GBA mutations, but in only 11.6% of controls, and in 22.2% and 33.3% of patients from GBA+PD- and GD+PD- groups, respectively (p < 0.001). The prevalence of interrupted or missing echogenicity of the brainstem raphe differed between the groups (p = 0.046), while no difference was observed in the diameter of the third ventricle. Conclusions: TCS findings in GBA-associated PD were consistent to those of patients with sporadic PD. © 2013 Elsevier Ltd.

Vascular dementia (VaD) is the second most frequent dementia after Alzheimer's disease, and is diagnosed during lifetime in 20% of demented patients. Five-year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors for VaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step-by-step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class IIa recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer's disease dementia.