Antonija Mišmaš

Assessment of prevalence and pathological response to orthostatic provocation in patients with multiple sclerosis.

OBJECTIVE The aim of this study was to determine the prevalence of pathologic response to orthostatic challenge in patients with relapsing remitting multiple sclerosis (RRMS) and the difference of the response in patients in relapse and remission. PATIENTS AND METHODS We included 112 RRMS patients; group 1 included 53 patients in a relapse and group 2, 59 patients in remission. The head up tilt table test was used to provoke an orthostatic reaction. RESULTS 71 (63%) patients (60.4% and 66% of relapse and remission subjects respectively) had a pathological response to orthostatic provocation. Syncope was found in 9 (17%) patients in group 1 compared to 22 (37.3%) in group 2 (p=0.014). Postural orthostatic tachycardia syndrome (POTS) was found in 17 (32%) patients in group 1 compared to 4 (6.8%) in group 2 (p=0.001). There was a significantly negative correlation between the Expanded Disability Status Scale (EDSS) and POTS (-0.201; p=0.034) and a positive correlation between the EDSS and syncope (0.190; p=0.044). CONCLUSION The prevalence of distinct types of orthostatic autonomic dysfunction in different phases of RRMS seems to be in direct correlation with the EDSS. Furthermore, certain autonomic dysfunctions of orthostasis, more specifically syncope and POTS, tend to be increased in remission and relapse respectively.

PPARγ and IL-6 - 174G>C gene variants in Croatian patients with ischemic stroke

AIM Etiology of ischemic stroke (IS) is multifactorial and includes interaction of genetic and environmental factors. Different genes, their polymorphisms, host susceptibility, and inflammation processes play a role in IS development. The aim of this study was to evaluate the effect of PPAR-γ and IL-6 gene variants on IS onset. MATERIAL AND METHODS A total of 301 subjects (144 males, 157 females) participated in the study, 114 patients with IS and 187 healthy controls. RESULTS Statistically significant predictors of IS were male gender (OR 7.13, 95% CI 2.92-17.39, p<0.001), hypertension (OR 7.82. 95% CI 2.53-24.19, p<0.001), lowered HDL cholesterol (OR 8.20, 95% CI 2.41-27.94, p=0.001), elevated C-reactive protein (OR 5.26, 95% CI 1.92-14.41) and IL-6 -174 GC (OR 2.44 95% CI 1.01-5.91, p=0.0048) genotype. Males, compared to females, had 7 times higher odds for stroke. IL6 -174G/C genotype increased the odds for IS for 2.4 times. PPARγ was not statistically significantly associated with stroke. CONCLUSION We can point to the IL-6 -174G>C polymorphisms as candidate gene marker and risk factor for the prediction of ischemic stroke.

Prevalence of genetic polymorphisms of CYP2C9 and VKORC1 - implications for warfarin management and outcome in Croatian patients with acute stroke.

BACKGROUND Data on the prevalence of CYP2C9 and VKORC1 genes and their influence on anticoagulant effect and warfarin dose in stroke patients are scarce. The aim of this study was to determine the occurrence and significance of these gene polymorphisms and to establish pharmacogenetic algorithm to estimate the dose of introduction. Also, the goal was to determine tailored safety and intensity of anticoagulation response depending on the allelic variants and their impact on the clinical outcome in acute stroke patients in Croatia. METHODS A total of 106 consented acute stroke patients were tested for CYP2C9 2, 3 and VKORC1 1173C>T gene polymorphisms. We estimated the dose of introduction and monitored anticoagulant effect obtained by INR values, time to reach stable dose, stable maintenance dose, time spent within the therapeutic/supratherapeutic INR range, occurrence of dosage side effects and clinical outcome depending on genotypes. RESULTS We found that 83% of stroke patients in our study were carriers of multiple allelic variants. The predicted initial dose correlated with the stable warfarin maintenance dose (p=0.0311) and we correctly estimated the dose for 81.5% of 61.3% of study patients who required higher/lower doses than average. Warfarin dosage complications were slightly more frequent among the carriers of CYP2C9 2, 3 compared to the carriers of VKORC1 1173T alleles (68. 9% versus 62.5%), but their occurrence did not affect the final clinical outcome. CONCLUSION Our data indicated rapid and safe anticoagulation achieved by using pharmacogenetically-predicted warfarin dose in high-risk acute stroke patients without increasing the risk of warfarin dosage complications in an elderly population.

Endovascular treatment of internal carotid artery pseudo-aneurysm presenting with epistaxis. A case report.

Recurrent epistaxis is a rare presentation of internal carotid artery C4/C5 segment pseudo-aneurysm rupture. We describe a case of a traumatic internal carotid artery pseudo-aneurysm with recurrent epistaxis as a leading symptom that was finally managed with endovascular treatment with stent-assisted coil placement. Clopidogrel and acetylsalicylic acid orally were introduced in the therapy for further stent thrombosis prevention and epistaxis did not recur on six-month follow-up. Endovascular treatment with stent-assisted coil placement seems to be a good method for pseudo-aneurysm treatment while keeping the lumen of the parent artery patent.

Onset of sweating depends on the type of reflex syncope

Reflex syncope is classified based on the efferent autonomic system as vasodepressant type, cardioinhibitory type and mixed type. We employed quantitative sweat testing to assess differences in sudomotor sympathetic activity in relation to the type of reflex syncope. In cardioinhibitory type sweating started in 7/9 patients after and in vasodepressor type in 11/12 patients before syncope. In mixed type sweating in 20 patients started before and in 10 after syncope. The onset of sweating correlated significantly with the onset of syncope symptoms. These results possibly reflect different onsets of emotional sweating.

Bilateral ptosis with wall-eyed bilateral internuclear ophthalmoplegia and vertical gaze paralysis

A 53-year-old patient presented in the neurological emergency department complaining of sudden onset of blurry vision, as well as difficulty opening his eyes. He had no previous medical history, and of significance was his body mass index of 48. Initial neurological examination showed binocular vertical double vision, bilateral ptosis with exotropia of the left eye, bilateral adduction deficit combined with abducting nystagmus (wall-eyed bilateral internuclear ophthalmoplegia, WEBINO) and vertical gaze paralysis. Bedside examination showed normal acuity and no visual field deficit. During the examination, patient quickly deteriorated, becoming comatose, tetraplegic, with unreactive pupils, anisocoria (right pupil wider) and ataxic breathing. After lowering his blood pressure from 260/160 to 160/90 mmHg, his condition improved to somnolence, dysarthria, bilateral ptosis, anisocoria with medium sized fixed pupils (R [ L), bilateral adduction deficit with abducting nystagmus and exotropia (more pronounced on the left eye), skew deviation (hypertropia of the left eye, presence of incyclotorsion was uncertain in the setting of bedside examination in emergency department) and vertical gaze paralysis (Fig. 1, Video 1). There was no compensating head tilt and no ocular counter-roll, while vertical VOR were absent. Urgent cerebral CT and CT angiography were normal, but MRI showed small areas of restricted diffusion in medial portions of both thalami, as well as in rostral part of mesencephalon (characteristic V sign absent) (Fig. 2), all consistent with acute infarction. Question: Occlusion of which artery is consistent with presented clinical and MRI features?