Osman Sinanović

Post-stroke dementia – a comprehensive review

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.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common and best known monogenic small vessel disease. Here, we review the clinical, neuroimaging, neuropathological, genetic, and therapeutic aspects based on the most relevant articles published between 1994 and 2016 and on the personal experience of the authors, all directly involved in CADASIL research and care. We conclude with some suggestions that may help in the clinical practice and management of these patients.

Depression, Anxiety and Somatization in Women with War Missing Family Members

Introduction: During the war circumstances, women and children are exposed to multiple traumatic experiences, one of which is an violent disappearance of a family member. Goal: The aim of this research was to establish the presence of symptoms of depression, anxiety and somatization in women in Bosnia and Herzegovina who have sought their war missing family members for 15 to 18 years. Subjects and Methods: The research was based on a sample of 120 women with war missing family member and 40 women without a war missing family member as a control group. For assessment of depression, anxiety and symptoms of somatization the self-rating Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), Somatic Symptoms Index (SSI) questionnaire and a general questionnaire on the sociodemographic data and data on war missing family members were used. Results: A significantly higher intensity of symptoms of depression (p<0.001), anxiety (p<0.001) and somatization (p = 0.013) was present in women with, in comparison to women without a missing family member. In comparison of the kinship with the missing family members, statistically significantly higher intensity of symptoms of depression, anxiety and somatization was in women with a missing child (p<0.001) in comparison to other missing family members. Conclusion: A prolonged period of seeking, waiting and uncertainty of what happened in the war with the missing family member presents for those women a prolonged suffering manifested through depression, anxiety and symptoms of somatization.

Short-term postnatal quality of life in women with previous Misgav Ladach caesarean section compared to Pfannenstiel–Dorffler caesarean section method

Objective. To examine whether short-term postnatal health-related quality of life differed among women after different methods of cesarean sections. Methods. One hundred forty-five women were evaluated with previous CS (85 by Misgav Ladach and 60 by Pfannenstiel–Dörffler). Short-time quality of life was measured using the Croatian version of Short Form Health Survey (SF – 36). Short-term postoperative recovery was assessed using two criteria: febrile morbidity and degree of pain. Incidence of peritoneal adhesions was assigned using Bristow scoring system. Results. Four weeks after delivery women with previous Misgav Ladach cesarean section significantly scored higher on the bodily pain (72.4 vs. 56.7, p < 0.05), social functioning (71.5 vs. 60.4, p < 0.05), and the vitality (61.7 vs. 50.3, p < 0.05) subscales. These differences disappeared in the second assessment (12-weeks postpartum) except in the bodily pain (74.7 vs. 61.2, p < 0.05) subscale. There was a significant trend toward a higher requirement for postoperative analgesics in the Pfannenstiel–Dörfler group (doses: 5.4 vs. 8.7, p < 0.05; hours: 17.9 vs. 23.3, p < 0.05), and they had a significantly higher rate of febrile morbidity than the Misgav Ladach group (5.7 vs. 9.4%, p < 0.05). Hospitalization time was reduced in the Misgav Ladach group (4.2 vs. 7.3, p < 0.05). The incidence of adhesions was significantly lower in patients who had undergone a previous operation using the original Misgav Ladach method (0.47 vs. 0.77, p < 0.05). Conclusion. Misgav Ladach cesarean section method might lead to better short-time quality of life resulting in reducing postoperative complications compared to Pfannenstiel–Dörfler cesarean section method.

gErSTmANN'S SyNdrOmE iN ACuTE STrOkE PATiENTS

Objective: Gerstmann in 1924. observed in a few patients a concomitant impairment in discriminating their own fingers, writing by hand, distinguishing left from right and performing calculations. He claimed that this tetrad of symptoms constituted a syndromal entity, assigned it to a lesion of the dominant parietal lobe. Since than, Gerstmann`s syndrome (GS) was enigma for neuropsychologists. The aim of this study was to analyze frequency and clinical features of GS among acute stroke patients. Patients and methods: We prospectively analyzed 194 acute stroke patients (average age 65±11.06 years, male 113 (58.2%), female 81 (41.8%) hospitalized at department of Neurology, University Clinical Center tuzla, during the six mounths in 2010. For clinical assessment of agraphia, alexia and acalculia we used Minessota test for differential diagnosis of aphasia’s. Results: Among these acute stroke patients, 59 (30.40%) had alexia, agraphia and acalculia or different combinations of these disorders. two patients (3.4%) had agraphia and acalculia associated with other part of tetrad of GS: fi nger agnosia and left-right disorientation. they both where men, right handed, and cranial computed tomography scan showed ischemic lesion in the left parietal and left temporoparietal lobe. Conclusion: Gerstmann`s syndrome is rare clinical entity, and has the high value in localization and the lesion is mainly localized to angular gyrus of the dominant hemisphere.

The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis

Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, P = 0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P = 0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P = 0.017). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS.

Tamoxifen associated bilateral optic neuropathy.

Tamoxifen is a selective estrogen receptor modulator and its use in estrogen receptor positive breast cancer patients can significantly reduce breast cancer mortality [1]. The use of tamoxifen is associated with several ocular toxicities: keratopathy, cataract, optic neuritis, retinopathy and maculopathy [1]. These conditions are reported to be dosedependent and are reversible if the symptoms are recognized on time and tamoxifen treatment is stopped [1–4]. We report a case of severe unrecognized tamoxifen associated optic neuropathy resulting with optic atrophy.

Angiotensin-converting enzyme gene polymorphism in patients with multiple sclerosis from Bosnia and Herzegovina.

BACKGROUND Increased activity of angiotensin-converting enzyme (ACE) in the blood and cerebrospinal fluid of patients with multiple sclerosis (MS), and the inhibition of ACE in experimental autoimmune encephalomyelitis, suggested that ACE may play a role in the pathogenesis and progression of MS. We recently published the first report on the potential association of MS and ACE I/D polymorphism in Slovenian and Croatian patients with MS, in which it was shown that the DD genotype might contribute to a higher risk of developing MS in men. To confirm these findings in a similar ethnic population, we analyzed ACE I/D gene polymorphism in patients with MS from Bosnia and Herzegovina. SUBJECTS AND METHODS One hundred and seventy patients with MS and 170 healthy controls were genotyped by the polymerase chain reaction method. RESULTS There was no significant difference in the distribution of ACE I/D genotypes (p=0.783) or in the allelic frequencies (p=0.538) between patients with MS and control subjects. When patients with MS were stratified by sex, no statistically significant differences in allele or genotype distributions were observed. Finally, there was no indication of an impact of the ACE I/D genotype on disease course or severity. CONCLUSION The ACE I/D polymorphism is not a risk factor for development of MS, nor does it contribute to disease severity in this Bosnia and Herzegovina population.

Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)- PTSD Study

Abstract Background Posttraumatic stress disorder is characterized by an overactive noradrenergic system conferring core posttraumatic stress disorder symptoms such as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine oxidase A gene exonI/intronI region was investigated for the first time regarding its role in posttraumatic stress disorder risk and severity. Methods Monoamine oxidase A methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells in a total sample of N=652 (441 male) patients with current posttraumatic stress disorder, patients with remitted posttraumatic stress disorder, and healthy probands (comparison group) recruited at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. Posttraumatic stress disorder severity was measured by means of the Clinician-Administered Posttraumatic Stress Disorder Scale and its respective subscores representing distinct symptom clusters. Results In the male, but not the female sample, patients with current posttraumatic stress disorder displayed hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553, GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder patients and healthy probands. Symptom severity (Clinician-Administered Posttraumatic Stress Disorder Scale scores) in male patients with current posttraumatic stress disorder significantly correlated with monoamine oxidase A methylation. This applied particularly to symptom clusters related to reexperiencing of trauma (cluster B) and hyperarousal (cluster D). Conclusions The present findings suggest monoamine oxidase A gene hypermethylation, potentially resulting in enhanced noradrenergic signalling, as a disease status and severity marker of current posttraumatic stress disorder in males. If replicated, monoamine oxidase A hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of posttraumatic stress disorder guiding personalized treatment decisions on the use of antiadrenergic agents.

The Influence of Palliative Care on Quality of Life in Patients with Lung Cancer

Objective: Objective of this work is to determine influence of palliative care on the quality of life in patients with lung cancer. Subjects and Methods: Our study group included 40 patients, consecutively selected, which is determined by symptomatic treatment and hospitalized at the Department of Palliative Care of University Clinical Center Tuzla. The control group consisted of 40 patients who had a diagnosis of lung cancer treated at home by an authorized ambulance Health Center Tuzla. Tests in both groups were carried out using the test SF-36 scale for assessing quality of life in period of two weeks. Two-stage test was performed, initially, immediately after disease was diagnosed, and two weeks later. Results: All life quality parameters (general, physical and emotional) were better in second test, in patients who were situated in the department of palliative care (study group) (p<0.0001). In the area of physical health (physical function, physical limitations, pain, general health), in patients who have resided in the department of palliative care (study group), showed a statistically significant improvement in all the aspects (p<0.0001). In the study patients all aspects of mental health were statistically significantly improved after two weeks being in department (p<0.0001). Conclusion: Two weeks treatment of patients with lung cancer in the Department of Palliative Care significantly improve all general aspects of quality of life.