Gordana Tomic

Increased total homocysteine level is associated with clinical status and severity of white matter changes in symptomatic patients with subcortical small vessel disease

OBJECTIVE Elevated plasma total homocysteine (tHcy) is an independent risk factor for ischemic stroke and has been linked to cerebral small vessel disease (SVD), in particular. Controversy persists as to whether increased tHcy is associated with functional status and cognitive decline in these patients. METHODS Plasma tHcy, MTHFR polymorphism, vascular risk factors, functional and cognitive status and severity of lesions on MRI, assessed with the Age-Related White Matter Changes (ARWMC) visual grading scale, were analyzed in 95 patients with SVD and 41 healthy control subjects. RESULTS Plasma tHcy levels were higher in patients with SVD (14.4±5.0 μmol/L) compared to healthy SVD-free controls (8.9±3.9 μmol/L). In SVD patients, tHcy levels strongly correlated with cognitive status (age-adjusted risk 5.8, 95% CI 1.3-25.3, p=0.015), functional status (age-adjusted risk 3.2, 95% CI 1.2-8.8, p=0.022) and severity of MRI lesions (age-adjusted risk 1.2, 95% CI 1.1-1.4; p=0.004). Only total ARWMC score was independently associated with increased tHcy levels (OR 1.2, 95%CI 1.1-1.4, p=0.004). Independent predictors of WMC occurrence were tHcy levels (OR 1.2, 95%CI 1.1-1.3, p=0.003) and mRS score (OR 2.2, 95%CI 1.2-4.1, p=0.017). CONCLUSIONS In patients with cerebral SVD there is a positive association of increased plasma tHcy levels with clinical status and severity of WMC.

Baseline Predictors of Cognitive Decline in Patients with Cerebral Small Vessel Disease

INTRODUCTION Cerebral small vessel disease (SVD) is a common cause of cognitive impairment and vascular dementia. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION In patients with SVD, independent predictors of VCI were baseline severity of WMH and total number of lacunar infarcts.

Baseline characteristic of patients presenting with lacunar stroke and cerebral small vessel disease may predict future development of depression

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.

Speech and language disorders secondary to diffuse subcortical vascular lesions: Neurolinguistic and acoustic analysis. A case report

BACKGROUND AND PURPOSE Subcortical white matter (WM) plays an important role in speech production and language processing. Most frequently, cerebral WM lesions are secondary to small vessel disease in patients with vascular risk factors. We report the case of a 53-year-old man with history of hypertension and ischemic subcortical lesions, who presented with speech difficulties and mild cognitive impairment. METHODS Language and cognitive assessment included Boston Diagnostic Aphasia Examination, Boston Naming Test, Rey Auditory-Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Scale for Evaluation of Perceptive Characteristics of Voice and Speech, and Multidimensional Evaluation of Speech and Voice. RESULTS Brain MRI showed ischemic WM lesions and lacunar infarcts in the brainstem and right cerebellum. Cognitive testing revealed mild cognitive impairment, predominantly affecting attention and executive functions. Speech and language analysis demonstrated dysarthria, dysphonia with hypophonia, and imprecise articulation, as well as short rushes of speech, palilalia and mild subcortical dysphasia. CONCLUSIONS Neurolinguistic and acoustic analysis in patients with ischemic WM lesions can provide additional information in the understanding of language and speech disturbances, and can assist in patient management.

What are the differences between younger and older patients with symptomatic small vessel disease

OBJECTIVE Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age. PATIENTS AND METHODS Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35-55 years) and older (>56 years) patients. RESULTS In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5-5.5; p=0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3-2.5; p=0.0001) and cognitive (χ(2) 13.94; p=0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0-1.18; p=0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p<0.0001). CONCLUSION In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged ≤55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.

Increased risk of cognitive impairment and more severe brain lesions in hypertensive compared to non-hypertensive patients with cerebral small vessel disease

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.

[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)--three case reports from Serbia].

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 middle-aged 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.

Plasma homocysteine levels and cognitive status in patients with ischemic cerebrovascular disease

Background and aims: Hyperhomocysteinemia is an important and independent risk factor for vascular disease, including stroke. The relationship between plasma homocysteine levels and cognitive status in patients with different types of ischemic cerebrovascular disease has been explored. Methods: Plasma homocysteine levels were determined in 95 patients with ischemic cerebrovascular disease. All patients underwent vascular RF assessment, neuropsychological testing and brain MRI scanning. Total Age Related White Matter Changes (ARWMC) scale score was obtained. Score on modified Rankin scale (mRS) was determined in all patients. Results: Group comprised 55 (57.9%) men, 40 women (42.1%), mean age 55.6±14.9 years. Mean group homocysteine level was 14.3±5.03 μmol/L. Univariate analysis showed that higher homocysteine levels were associated with an increased risk of cognitive decline (OR 1.14; 95% CI 1.04–1.25, p=0.005), higher score on mRS (OR 1.1; 95% CI 1.01–1.21, p=0.050), and higher ARWMC total score (OR 1.14; 95% CI 1.04–1.25, p=0.006). In multivariate model, higher homocysteine levels were independently associated with an increased risk of cognitive decline (OR 2.71; 95% CI 1.12–6.54, p=0.026). Conclusions: There is an association between higher plasma homocysteine levels and cognitive decline in patients with ischemic cerebrovascular disease.

Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia

BACKGROUND/AIM Spasmodic dysphonia (DS) is a disabling speech disturbance appearing as the consequence of dystonic vocal folds contraction. Its intermittent appearance in the laryngeal muscles causes vocal function discontinuation. The quality of life of these patients is significantly disturbed. Surgical and a medical therapy appear to be inadequate and unsuccessful ones of no steady improvement. It is the botulinum toxin therapy that proved to be highly efficacious one, with the established improvement in 80-100% of patients. The aim of our study was to evaluate the efficacy of botulinum toxin therapy in patients with SD and to show our preliminary results. METHODS The study included 10 patients with adductor spasmodic dysphonia. After diagnostic procedures, botulinum toxin was applied either in one or both vocal folds, in doses of 12-16 units each. In our study we applied indirect technique originally developed by Hocevar and Pirtosek. Perceptive voice and speech analysis was performed prior to and after the instillation of botuline toxin as per structured Scale of pathological characteristics of voice and speech appearing in the spasmodic dysphonia. RESULTS The majority of our patients experienced both subjective improvement and the improvement in the terms of the quality of life, Voice Henolicap Index--(VHI) that was rated as rather significant one (t = 3.562; p = 0.006). CONCLUSION Regardless unquestionable improvement of definite phonation, further function restitution requires individual vocal therapy and psychotherapy. Vocal therapy includes structural vocal techniques which reduce degree of vocal tension and rapid changes in the power and the height of voice. Further investigations are necessary for the scope of the definition of a standardized therapeutically procedure for spasmodic dysphonia treatment which comprises multidisciplinary approach in diagnosis, therapy and treatment efficacy evaluation.