Is the female sex associated with an increased risk for long-term cognitive decline after the first-ever lacunar stroke? Prospective study on small vessel disease cohort.

Background: Sex is a significant determinant of survival and functional outcome after stroke. Long-term cognitive outcome after acute lacunar stroke in the context of sex differences has been rarely reported. Methods: A cohort of small vessel disease (SVD) patients presenting with first-ever acute lacunar stroke and normal cognitive status has been evaluated 4 years after the qualifying event for the presence of cognitive impairment (CI) with a comprehensive neuropsychological battery. Differences in baseline clinical and neuroimaging characteristics were compared between sexes in relation to cognitive status. Results: A total of 124 female and 150 male patients were analyzed. No difference was detected between the groups regarding age (p = 0.932) or frequency of common vascular risk factors (p > 0.1 for all). At the baseline assessment, women had more disabilities compared to men with a mean modified Rankin scale (mRS) score of 2.5 (1.5 in men, p < 0.0001). Scores of white matter hyperintensities (WMH) of presumed vascular origin and a total number of lacunes of presumed vascular origin on brain MRI were higher in women compared to men (p < 0.0001 for all). As many as 64.6% of patients had CI of any severity on follow-up, women more frequently (77.4%) than men (54.0%; p < 0.0001). Univariate logistic regression analysis showed that female sex, higher NIHSS and mRS scores, presence of depression, and increasing WMH severity were associated with an increased risk for CI. Multivariate regression analysis indicated that only depression (OR 1.74, 95%CI 1.25-2.44; p = 0.001) and WMH severity (OR 1.10, 95%CI 1.03-1.17; p = 0.004) were independently associated with the CI. Conclusion: At the long-term follow-up, women lacunar stroke survivors, compared to men, more frequently had CI in the presence of more severe vascular brain lesions, but this association was dependent on the occurrence of depression and severity of WMH, and could not be explained by differences in common vascular risk factors.

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.

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

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.

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.

Dysarthria and mutism.

Dysarthria is a speech disorder associated with impairments of intelligibility, smoothness, loudness, and clarity of articulations. Dysarthria involves disability of reproducing various physical, tonal, and sound features of speech sounds in oral speech; unintelligible and slurred articulation with swallowing of sounds is characteristic. Articulatory movements and speech are slow, patients complain to the sensations of a 'thick' tongue and 'porridge' in the mouth. Patients'phrases are constructed correctly, vocabulary is not affected, and the grammatical structure of words is preserved. Reading, writing, internal speech, and understanding of speech are unaffected. Several types of dysarthria have been described on the basis of the lesion locations. Dysarthria can be associated with lacunar syndromes as well. Mutism represents a condition when patient cannot speak and answer the questions, but remains conscious and is able to produce written speech.

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.

[Incompetence of internal jugular vein valve in patients with transient global amnesia].

BACKGROUND/AIM: Transient global amnesia (TGA) could be related to acute ischemic disturbances in mesial parts of temporal lobes, which are important for memory. Incompetence of internal jugular vein (IJV) valve with venous congestion causes venous microthrombosis of hippocampus. The aim of this study was to investigate the frequency of IJV valve incompetence, as well as other hemodynamic and structural properties of cerebral circulation in TGA patients. METHODS: IJV valve competence was investigated in 40 TGA patients and 30 persons of the control group (matched by age and sex), as well as detection of microembolic signals and detection of right to left cardiopulmonal shunt, cerebral vasomotor reactivity and echocardiography by color triplex ultrasonography and transcranial doppler. RESULTS: A significant difference in frequency of IJV valve incompetence was found between the TGA patients and the control persons (55% TGA vs. 30% controls; p < 0.001). We did not find a significant structural (plaques frequency) or hemodynamic (flow velocity, pulsatility index) differences on arteries of the neck and cerebral arteries between the TGA patients and the controls, except for the increased pulsatility index on the basilar artery (40% TGA vs. 16.6% controls; p < 0.01) and decreased vasomotor reactivity in TGA patients (50% TGA vs 26.6% controls;p < 0.001). Microembolic signals were detected very rarely (17.5% TGA patients vs. 13.3% controls; p > 0.05), as well as right to left cardiopulmonal shunt (15% TGA vs. 16.6% controls; p > 0.05), indicating that embolism was not important for pathogenesis of TGA. Transesophageal echocardiography confirmed it, because only one TGA patient had a potent foramen ovale. CONCLUSION: We found a significantly increased frequency of IJV incompetence in the TGA patients, which confirmed the role of vein drainage disturbances in pathogenesis of TGA.

[Specific features of general anesthesia in stomatology for disabled people].

INTRODUCTION: People who have either developed or acquired disability are the patients with special needs. They often require general anesthesia for stomatological interventions. These patients often develop a complex disorder which interferes with a successful collaboration. General anesthesia should be adapted to the kind and length of intervention, to the physical condition of the patient and to the fact that majority of these interventions are performed under the "one day surgery" circumstances. The patient's preoperative preparation is of great importance. The anesthetics initially used and those to maintain anesthesia must be short-lived with minimal side-effects. The "gold standard" for the airway protection is the application of nasally placed endotracheal tubes, but the airway can also be protected by orally placed endotracheal tubes as well as by armored version of laryngeal mask airway during minor interventions. In the postoperative period patients are given analgetics and other necessary symptomatic therapy. The patient can be released no sooner than/four hours after the end of the operation. CONCLUSION: An appropriate preoperative preparation and the selection of the adequate kind of general anesthesia result in a reduced number of complications in this particular group of patients.

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.

[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.

[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.

[Executive functions in young patients with unipolar depression].

Neuropsychological deficits associated with unipolar depression are seen in a broad range of cognitive domains. Executive deficits may be prominent in depression. Investigation of executive functions in younger adult patients with unipolar depression has been the focus of our study. Twenty-two consecutively depressive inpatients (24-36 years) and 21 healthy control subjects, matched on age, gender, education and verbal IQ were included in the study. Neuropsychological tests for executive functions were applied to all subjects. Unipolar young depressives showed significantly reduced number of completed categories and more trials for completion of the first category on Wisconsin Card Sorting Test (WCST). No difference of tasks assessing the short-term memory, total errors on WCST, perseverative and non-perseverative errors, and of both phonemic and semantic conditions of verbal fluency was found between groups. The results suggested that unipolar depressives had specific cognitive style characterized by "negative cognitive set" (stronger negative reaction to negative feedback) and by failure to use negative feedback to improve their performance.

[Postoperative nausea and vomiting]. / Postoperativna muka i povracanje.

INTRODUCTION: Postoperative nausea and vomiting (PONV) and pain are the most common complaints following anesthesia and surgery, and due to negative emotional impact on patients, they cause prolonged postoperative recovery. The incidence of PONV is 20-30% during the first 24 h after anesthesia. Both peripheral and central mechanisms are involved in control of emesis. FACTORS: Many factors associated with anesthesia and surgery may affect PONV: patient's age and sex, history of PONV after pervious anesthesia, administration of antiemetics prior to operation, type and duration of operation, type of premedication, induction agent, maintenance agent, reversal of muscle relaxation, treatment of postoperative pain and movement of patients. ANTAGONISTS OF 5-HYDROXYTRYPTAMINE-3 (5-HT3) RECEPTORS: Ondansetron is a competitive serotonin type 3 receptor antagonist important in prevention of PONV. However, if 5-HT 3 receptor antagonists are effective against nausea and vomiting after a variety of anesthetic and surgical procedures, then at last we may have the key to the mechanism of PONV. Prophylaxis with a combination of antiemetic drugs is more effective in prevention of PONV.