Evolution of acute "black hole" lesions in patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: Gadolinium-enhanced T1-weighted lesions are a well-established marker of areas with acute inflammatory activity. A majority of these gadolinium-enhanced T1 lesions are isointense relative to the surrounding white matter, but 20-40% of such active lesions will evolve during one year into areas of low signal ("black hole"). This study sought to characterize evolution of "black hole" lesions in patients with relapsing-remitting multiple sclerosis (MS) using the magnetic resonance imaging (MRI), which measures active lesions via the count of new or enlarged T2 and gadolinium-enhanced T1-weighted lesions. MATERIALS AND METHODS: This was a prospective, observational case-series study which utilized pre- and post-gadolinium contrast T1-weighted and Proton density MRI scans. Twenty-nine patients (8 males and 21 females) with average age of 38.86 ± 6.58 years and disease duration of 5.75 ± 7.00 years were used to analyze 196 acute demyelinating plaques detected on MRI images during the 24-month follow-up of post-gadolinium signal intensity enhancement of MS plaques. RESULTS: Significant difference in black hole development was found between the shapes of acute and chronic "black holes". Ring-shaped and patchy plaques were 4.09 (1.87-8.91) times more likely and 1.49 (0.71-3.12) times less likely to develop an acute "black holes" than homogeneous plaques, respectively. Acute plaques with higher lesion-to-CSF SI ratio and larger surface area showed a greater tendency to develop into acute and chronic "black holes". CONCLUSIONS: The value of lesion-to-CSF SI ratio and surface area were found as the predictors of the "black hole" formation.

Dehydroepiandrosterone (DHEA): Pharmacological Effects and Potential Therapeutic Application.

Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates, which is predominantly synthesized in the adrenal cortex. A characteristic curve of growth and decline of its synthesis during life was observed, together with the corresponding formation of its sulphate ester (DHEAS). High levels of plasma circulating DHEA are suggested as a marker of human longevity, and various pathophysiological conditions lead to a decreased DHEA level, including adrenal insufficiency, severe systemic diseases, acute stress, and anorexia. More recent studies have established the importance of DHEA in the central nervous system (CNS). A specific intranuclear receptor for DHEA has not yet been identified; however, highly specific membrane receptors have been detected in endothelial cells, the heart, kidney, liver, and the brain. Research shows that DHEA and DHEAS, as well as their metabolites, have a wide range of effects on numerous organs and organ systems, which places them in the group of potential pharmacological agents useful in various clinical entities. Their action as neurosteroids is especially interesting due to potential neuroprotective, pro-cognitive, anxiolytic, and antidepressant effects. Evidence from clinical studies supports the use of DHEA in hypoadrenal individuals and in treating depression and associated cognitive disorders. However, there is also an increasing trend of recreational DHEA misuse in healthy people, as it is classified as a dietary supplement in some countries. This article aims to provide a critical review regarding the biological and pharmacological effects of DHEA, its mechanism of action, and potential therapeutic use, especially in CNS disorders.

Risk Factors Related to Falling in Patients after Stroke.

BACKGROUND: The aim of this study was to identify the risk factors associated with falling in post stroke patients. METHODS: This retrospective case-control study included 561 neurology patients hospitalized for a stroke and divided into two groups: falling patients and non-falling patients. They referred to the Special Hospital for Cerebrovascular Diseases "Sveti Sava" in Belgrade, Serbia, from 2018-2019. Logistic regression analysis was applied to examine socio-economic factors associated with predictors of unmet healthcare needs. RESULTS: A significant difference was seen in the length of hospitalization of falling patients compared to the non-falling (P<0.001). We established statistically significant differences in mental status (P<0.001), sensibility (P=0.016), depressed mood (P<0.001), early (P=0.001) and medium insomnia (P=0.042), psychomotor slowness (P=0.030), somatic anxiety (P=0.044) and memory (P<0.001). CONCLUSION: Cerebrovascular disease distribution and the degree of neurological deficit primarily altered mental status, which could be recognized as one of the more important predictors for falling after stroke. The identification of risk factors may be a first step toward the design of intervention programs for preventing a future fall among hospitalized stroke patients.

The impact of betaplus program on patient treatment satisfaction with interferon beta-1b in multiple sclerosis: Multicentric cross-sectional survey in the western Balkan countries.

BACKGROUND: Long-term treatment adherence to disease-modifying drugs (DMDs) may have significant impact on clinical outcomes in multiple sclerosis (MS). It has been recently emphasized that low treatment satisfaction (TS) may be an important factor for achieving high rates of treatment adherence. Interferon (IFN) beta-1b was the first DMD approved for the treatment of MS. The aims of our study were to assess TS in subjects with relapsing-remitting (RR) MS treated with IFN beta-1b in Serbia, Montenegro and the Republika Srpska, Bosnia and Herzegovina (B&H), and additionally, to evaluate the impact of patient support program on TS and adherence. METHODS: This is a cross-sectional survey performed in order to examine TS and adherence with IFN beta-1b in seven MS centers across three countries (Serbia, Montenegro and B&H). Included in the study were 296 adult patients with RRMS treated with IFN beta-1b for at least 6 months. They were invited to complete the Treatment Satisfaction Questionnaire for Medication (TSQM). Additional two treatment adherence questions were also asked. Patient support program (Betaplus®) was available exclusively for patients in Serbia and not for those in Montenegro and the Republika Srpska, B&H. In order to assess the potential impact of this program on TSQM, we combined two groups of patients from Montenegro and B&H and compared their results with those from patients in Serbia. Statistical analysis includes multivariable linear regression analysis in order to assess the differences between three MS patients groups in terms of the TSQM scores, adjusted for potential confounders. For the evaluation of the effects of Betaplus® program, multivariable logistic regression was used, controlling for the same confounding factors. RESULTS: Each of the TSQM summary scores in all three countries implicated high level of patients' satisfaction. There was statistically significant group difference on the Effectiveness summary score (p=0.001) and the Side effects summary score (p=0.006) between the group of subjects from Serbia and the combined group of subjects from Montenegro and B&H, in favor of the former cohort. There was statistically significant group difference neither on the Convenience summary score nor on the Overall satisfaction summary score. Results of adjusted logistic regression analysis based on the availability of patient support program (dependent variable) implicate that it had the most significant impact on the Effectiveness summary score (p=0.008). According to the correlation coefficients in the total patient cohort, all TSMQ summary scores except Effectiveness significantly correlated with the decreased adherence (Side effects: p=0.037; Convenience: p=0.016; Overall satisfaction: p=0.046). CONCLUSION: TS with IFN beta-1b was high in our MS patients. Additionally, these results have demonstrated that patient support program have significant impact on TS with IFN beta-1b in the Balkan cohort of RRMS patients.

Renin-angiotensin system gene polymorphisms as risk factors for multiple sclerosis.

The components of renin-angiotensin system, such as angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II receptor type 1 and 2 (AT1R and AT2R), are expressed in the central nervous system and leukocytes and proposed to be involved in the inflammation and pathogenesis of multiple sclerosis (MS). ACE I/D, AT1R 1166A/C and AT2R -1332A/G are functional polymorphisms associated with phenotypes of diverse chronic inflammatory diseases. The aim of this study was to investigate the association between ACE I/D, AT1R 1166A/C and AT2R -1332A/G gene polymorphisms and MS in Serbian population. A total of 470 MS patients and 478 controls participated in the study. Allele-specific polymerase chain reaction (PCR) was performed for genotyping of the ACE polymorphism. The AT1R and AT2R genotyping was done by duplex PCR and restriction fragment length polymorphism analysis. Both ACE homozygotes, II and DD, were significantly overrepresented in MS patients, compared to controls (χ(2) test p=0.03). Neither genotype nor allele frequencies of AT1R 1166A/C polymorphism were significantly different between patients and controls. Significant overrepresentation of AT2R -1332 AA genotype in female patients, compared to female controls, was detected (OR=1.67, 95%CI=1.13-2.49, χ(2) test p=0.01), suggesting that this genotype could be a gender-specific genetic risk factor for MS.

Posterior reversible encephalopathy syndrome--A case report.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is characterized by the following symptoms: seizures, impaired consciousness and/or vision, vomiting, nausea, and focal neurological signs. Diagnostic imaging includes examination by magnetic resonance (MR) and computed tomography (CT), where brain edema is visualized bilaterally and symmetrically, predominantly posteriorly, parietally, and occipitally. CASE REPORT: We presented a 73-year-old patient with the years-long medical history of hypertension and renal insufficiency, who developed PRES with the symptomatology of the rear cranium. CT and MR verified changes in the white matter involving all lobes on both sides of the brain. After a two-week treatment (antihypertensive, hypolipemic and rehydration therapy) clinical improvement with no complications occurred, with complete resolution of changes in the white matter observed on CT and MR. CONCLUSION: PRES is a reversible syndrome in which the symptoms withdraw after several days to several weeks if early diagnosis is made and appropriate treatment started without delay.

Bilateral hippocampal infarction and amnesia: A case report.

INTRODUCTION: The hippocampus along with other structures of the medial temporal lobe plays an important role in the process of learning and memory consolidation. Bilateral hippocampal lesions lead to persistent anterograde amnesia while unilateral damage results in milder, content-specific forms of amnesia. Hippocampus may be affected by an acute or chronic pathologic process from a wide spectrum of neurological disorders. CASE REPORT: A 61-year-old female patient with a long history of hypertension, glucose intolerance, hypercholesterolemia and depression was hospitalized for acute anterograde amnesia, which led to repeated excessive drug taking. By further examinations that included laboratory tests, electroencephalography, Doppler sonography of intra- and extracranial vessels and neurovisualization methods [multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) of the brain] bilateral hippocampal ischemia that occurred at different times was detected. Cognitive and neuropsychological evaluation revealed an isolated severe damage of episodic memory with the inability of retention of new information which persisted at the control examination three months later. The assumed mechanism of occurrence of ischemia in this case could be arterioarterial embolism. CONCLUSION: Although ischemic stroke is one of the most common neurological diseases, ischemic stroke of the hippocampus is rare, the isolated bilateral presentation with clinical signs of severe amnestic syndrome in particular. Timely recognition and modern therapeutic approach could have a favorable impact on the recovery from severe neurological, cognitive deficit. It could be suggested that in patients with the clinical image of acute anterograde amnesia and vascular risk factors the MSCT examination of the brain with computed tomography perfusion and angiography is performed immediately upon hospitalization.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

INTRODUCTION: Fast and precise diagnostics of the disease from the large group of adult leukoencephalopathy is difficult but responsible job, because the outcome of the disease is very often determined by its name. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by the mutation of Notch 3 gene on chromosome locus 19p13. Beside the brain arterioles being the main disease targets, extracerebral small blood vessels are affected by the pathological process. Clinically present signs are recurrent ischemic strokes and vascular dementia. CADASIL in its progressive form shows a distinctive pattern of pathological changes on MRI of endocranium. The diagnosis is confirmed by the presence of granular osmiophilic material (GOM) in histopathological skin biopsies. CASE REPORTS: Two young adult patients manifested ischemic strokes of unknown etiology, cognitive deterioration, migraine and psychopathological phenomenology. MRI of endocranium pointed on CADASIL. Ultrastructural examination of skin biopsy proved the presence of GOM in the basal lamina and near smooth muscle cells of arteriole dermis leading to CADASIL diagnosis. The presence of GOM in histopathological preparation is 100% specific for CADASIL. The patients were not searched for mutation in Notch 3 gene on chromosome 19, because some other leukoencephalopathy was disregarded. CONCLUSION: Suggestive clinical picture, distinctive finding of endocranium MRI, the presence of GOM by ultrastructural examination of histopathological skin biopsies are sufficient to confirm CADASIL diagnosis.