The Differences in the Cellular and Plasma Antioxidative Capacity Between Transient and Defined Focal Brain Ischemia: Does it Suggest Supporting Time-Dependent Neuroprotection Therapy?

There are many opened questions about the precocious role of oxidative stress in the physiopathology of the early stage of transitory ischemic attack (TIA) and defined focal brain ischemia, as well as about its correlation with clinical severity, short-lasting and clinical outcome prediction in these conditions. The study evaluates the values of glutathione (GSH), glutathione peroxidase, and superoxide dismutase (SOD) in hemolysates and total thiol content (-SH), advanced oxidation protein products (AOPP), SOD, and malondialdehyde (MDA) in plasma, in TIA and stroke patients in the early stage of their neurological onset. The results are interpreted in view of the potential relationship between tested parameters and clinical severity and clinical outcome prediction. Better hemolysates' and total antioxidant profile with higher values of AOPP were observed in TIA compared to stroke patients (p < 0.05). The stroke patients with initially better clinical presentation showed better antioxidant profile with lower values of AOPP (p < 0.05). In TIA patients, this was observed for GSH, -SH content, and AOPP (p < 0.05), which correlated with a short risk for stroke occurrence in this group (p < 0.01). Beyond MDA values, all tested parameters showed correlation with clinical outcome in stroke patients (p < 0.05). The measurement of oxidative stress in TIA and stroke patients would be important for identifying patients' subgroups which might receive supporting therapy providing better neurological recovery and clinical outcome. That approach might give us an additional view of a short-lasting risk of stroke occurrence after TIA, and its clinical outcome and prognosis.

Diagnostic value of neurophysiological tests in the diagnosis of brain death--do we need changes in national guidelines?

For a final diagnosis of brain death one needs particular proof that the brain has fully stopped functioning. In this respect, diagnostic tests need to be used to confirm the clinical findings. Since in different countries there are various national guidelines for the determination of brain death, the aim of this study is to point to the diagnostic value of electroencephalography (EEG) and evoked potentials (EP) in verifying brain death. The need is emphasized for the two methods to be used in combination, and, accordingly, for the current national guidelines to be changed in our country and also in other countries round the world.

Identification of clinical and paraclinical findings predictive for headache occurrence during spontaneous subarachnoid hemorrhage.

OBJECTIVES: Headache is recognized as the main but unwarranted symptom of subarachnoid hemorrhage (SAH). There are no enough findings identified as predictive for headache occurrence in SAH. We evaluated the clinical and paraclinical factors predictive for headache occurrence in SAH. PATIENTS AND METHODS: We retrospectively analyzed medical records of 431 consecutive non traumatic SAH patients (264 females and 167 males), ages from 19 to 91 years, presenting with headache (70.3%) and without headache (29.7%) during period of 11years. RESULTS: Among all tested parameters, as negative predictors for headache occurrence were recognized: patients' ages (OR 0.97 [95%CI: 0.96-0.99], p=0.025), persistence of coagulation abnormality (OR 0.23 [95%CI: 0.08-0.67], p=0.006), atrial fibrilation (OR 0.23 [95%CI: 0.09-0.59], p=0.002), chronic renal failure (OR 0.26 [95%CI: 0.09-0.76], p=0.014) and more diseases (OR 0.11 [95%CI: 0.04-0.32], p<0.0001), as higher clinical score (OR 0.94 [95%CI: 0.90-0.99], p=0.018) including positive neurological findings (OR 0.34 [95%CI: 0.21-0.55], p<0.001) and loss of consciousness (OR 0.22 [95%CI: 0.12-0.39], p<0.001) at the SAH onset, while the complaint of neck stiffness was identified as its positive predictor (OR 1.93 [95%CI: 1.19-3.10], p=0.007). CONCLUSIONS: Although diagnosis based solely on clinical presentation is not reliable and speculative, our findings could provide physicians with evidence to consider SAH not only in conditions of its headache occurrence but also in those with headache absence.

Slower EEG alpha generation, synchronization and "flow"-possible biomarkers of cognitive impairment and neuropathology of minor stroke.

BACKGROUND: We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. METHODS: We included 10 patients with right middle cerebral artery (MCA) ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS), whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and MoCA memory index (MoCA-MIS). The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8), and corresponding lateral posterior (P3, P4, T5, T6) electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (αAVG), the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure), the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs). Statistical analysis was done using a Kruskal-Wallis ANOVA with a post-hoc Mann-Whitney U two-tailed test, and Spearman's correlation. RESULTS: We demonstrated transient cognitive impairment alongside a slower alpha frequency (αAVG) in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra-hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered "alpha flow", indicating the sustained augmentation of inter-hemispheric interactions. Although the stroke induced slower alpha was a transient phenomenon, the increased alpha intra-hemispheric synchronization, overlying the ipsi-lesional hemisphere, the increased alpha F3-F4 inter-hemispheric synchronization, the delayed alpha waves, and the newly established inter-hemispheric "alpha flow" within the frontal cortex, remained as a permanent consequence of the minor stroke. This newly established frontal inter-hemispheric "alpha flow" represented a permanent consequence of the "hidden" stroke neuropathology, despite the fact that cognitive impairment has been returned to the control values. All the detected permanent changes at the EEG level with no cognitive impairment after a minor stroke could be a way for the brain to compensate for the lesion and restore the lost function. DISCUSSION: Our study indicates slower EEG alpha generation, synchronization and "flow" as potential biomarkers of cognitive impairment onset and/or compensatory post-stroke re-organizational processes.

Hospitalizations due to spontaneous intracerebral hemorrhage in the region of Nis (Serbia): 11-year time-series analysis.

BACKGROUND: The study of seasonal variability of intracerebral hemorrhage (ICH) occurrence may contribute to a better understanding of the nature of this disease and open up new perspectives in its prevention. The aim of this study was to test seasonal patterns in the number of admissions of ICH patients and determine which months have maximal and minimal number of admissions. METHODS: The main data source for this study was a hospital-based registry at the Clinic of Neurology in Nis, Serbia. During the studied period (1997-2007) a total of 1569 ICH patients were registered. Time series, consisting of the monthly number of hospitalized patients, for the 128 months of the study duration, has been successfully modeled using the multiplicative Auto Regressive Integrated Moving Average (ARIMA) model. RESULTS: Using the maximum likelihood method, utilizing Melrad's algorithm, the parameters of this ARIMA model have been calculated: constant (estimate 12.068, p<0.001), auto regressive-AR(1) (estimate 0.866, p<0.001), moving average-MA(1) (estimate 0.775, p<0.001), seasonal moving average-SMA(12) (estimate -0.198, p=0.036). ARIMA modeling has been successful and showed that there is a clear seasonal pattern in the data analyzed. CONCLUSION: Based on the seasonal multiplicative ARIMA model and the seasonal time series decomposition, we showed that, in the period covered by the study, the peak of admissions occurred in March, and the trough of admissions was found in August.

Weekly variation of hospital admissions for stroke in Nis (Serbia).

OBJECTIVES: Weekly variability in stroke occurrence could be related to the change in behaviors of patients or medical personnel that occur during certain periods of the week. The aim of the present study was to examine the weekly variation in hospital admissions for stroke in Nis (Serbia), as well as to investigate how the demographic factors influenced these changes. PATIENTS AND METHODS: The main data source for this study was the Nis Stroke Registry. During the study period (1996-2007) a total of 9675 stroke patients were registered. According to stroke subtypes, all registered patients were divided into three groups: patients with subarachnoid hemorrhage (SAH) (438 or 4.5%), patients with intracerebral hemorrhage (ICH) (1576 or 16.3%) and patients with ischemic stroke (IS) (6946 or 71.8%). Analyses were conducted separately for SAH, ICH and IS. Each stroke type was stratified by gender, age group and education level. RESULTS: We have showed that there is a significant weekly variability in the number of SAH (p=0.028) and IS (p<0.001) admissions, with the minimum number of admissions on Sundays (39.27 and 14.04% less than expected), and the maximum one on Tuesdays (21.46% more than expected) and Wednesdays (10.96% more than expected), respectively. We have also registered more SAH (p=0.015) and IS (p<0.001) admissions on weekdays than on weekend days. CONCLUSION: Results of this hospital-based study confirm that there is a pattern in the variation of the number of stroke admissions on the weekly level. Reasons for the weekly variation of hospital admissions for stroke cannot be determined from the present study.

[Total antioxidant blood capacity in patients with type 2 diabetes mellitus and distal symmetrical polyneuropathy].

BACKGROUND/AIM: Reduced systemic antioxidant defence is considerd to play an important mediating role in pathogenesis of diabetic neuropathy. The aim of this study was to evaluate if the total antioxidant blood capacity (TAC) is reduced in patients with type 2 diabetes mellitus (DM) and diabetic distal symmetrical polyneuropathy (DDSP) and to correlate this antioxidant capacity with the degree of peripheral nerve dysfunction. METHODS: This study involved 100 patients with type 2 DM and signs of DDSP, as well as the control group of 50 healthy subjects. The evaluation of DDSP was based on physical examination and nerve conduction studies. The degree of peripheral nerve dysfunction was estimated by scoring and analysing sensory and motor nerve conduction parameters (distal latency and amplitude of evoked potential, conduction velocity). Laboratory analyses involved blood glucose and HbA1C levels, as well as plasma TAC. RESULTS: Blood glucose and HbA1C level was significantly higher in the patients than in the control group (p < 0.0001). The TAC was depleted in the diabetic group and the depletion was statistically significant (p < 0.0001). There was no significant correlation between the TAC and the serum glucose level, TAC and HbA1C level as well as between TAC and the duration of DM. There was no significant correlation between TAC and peripheral nerve conduction parameters. CONCLUSION: Total antioxidant blood capacity is reduced in patients with DDSP, but it does not correlate with blood sugar level, with the duration of DM or with the degree of functional nerve damage. These results show a reduced systemic antioxidant defence in patients with type 2 DM and DDSP. However, it is still unclear to what extent the oxidative stress is a contributing factor or leading cause of diabetic neuropathy, suggesting that further studies are necessary.

[Intravascular lymphoma of the central nervous system]. / Intravaskularni limfom centralnog nervnog sistima.

Intravascular lymphomatosis is an uncommon lymphoproliferative disorder characterised by intravascular distribution of neoplastic lymphoid cells (B- or T-lymphocites), what leads to occlusion of small vessels and causes signs and symptoms of disorder. Its initial predilection sites are the brain or the skin, and hematopoetic organs are usually spared. The signs and symptoms of the disorder are attributed to vascular occlusion. Clinical course is fatal, besides therapy. In our case disorder has started with partial epileptic seizures with secundar generalisation, and after that with motor aphasia, right hemiparesis, urinary incontinence and cognitive changes. She was hospitalized for several times, completely investigated, but with no conclusion. Seven months after apperance of symptoms, she died. And diagnosis was determined at autopsy. A myriad of neurological and systemic manifestations are putting us in an unequal position with this fatal disease. Early diagnosis can increase survival and decrease intensity of symptoms. So every new case is important as warning that we must not forget about this disease.