2013, Vol 13, No 4
Immunohistochemical identification methods of CD133+ cells in glioblastoma
AKTUALN NEUROL 2013, 13 (4), p. 253–257
ABSTRACT

Glioblastoma (GBM, WHO grade IV) is the most lethal type of brain tumours. Despite advances in radiotherapy, chemotherapy and surgical techniques, this tumour is still associated with a median overall survival of approximately 1 year. Histopathological features of GBM include nuclear atypia, foci of palisading necrosis, microvascular proliferation and robust mitotic activity. Glioblastoma is one of the best vascularized tumours in humansand its proliferation is hallmarked by a distinct proliferative vascular component. Studies of glioblastoma’s vascularization have cast some light on the role of non-endothelial cells in tumour neoangiogenesis. A characteristic feature of protein CD133 is its rapid down-regulation during cell differentiation, which makes it a unique cell surface marker for identification of stem cells in brain tissue. CD133+ tumour cells are located mainly in perivascular niches. CD133 positive cells were also found in blood vessels wall. The aim of this study was to optimize immunohistochemical staining method to facilitate identification of cells recognized by anti-CD133 antibody in paraffin- embedded glioblastoma tissue sections. In this study, several pretreatments, detection systems, dilution of antibody and time incubation were used. Immunohistochemical staining method in which autoclave, a buffer pH 9.0 and LSAB+System-HRP were used gave the best result.

Keywords: immunohistochemistry, CD133, glioblastoma, cancer stem cells, confocal microscopy
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Levetiracetam and therapy of epilepsy in specific clinical situations
AKTUALN NEUROL 2013, 13 (4), p. 258–266
ABSTRACT

Epilepsy is a chronic, frequently encountered neurological disease, demanding long-term treatment with antiepileptic drugs (AEDs). It involves high treatment expenses. Epilepsy is a complex pathophysiological process, the numerous and complex symptoms are the result of various disorders of the brain. In the treatment of epilepsy, there is no one standard way to proceed. The main and primary goal of epilepsy treatment is complete seizure control and getting the least side effects during treatment with antiepileptic drugs. It is vital that individual adjustment of the drug for each patient. The drug should be adapted to the type of seizure or seizure team, the frequency and severity of seizures. The emergence of a new generation of drugs gave them a certain advantage over the oldergeneration drugs. Levetiracetam is one of the antiepileptic drugs – the pharmacokinetic profile of levetiracetam has been evaluated in many populations. Overall, levetiracetam has a very favourable pharmacokinetic profile, with rapid absorption following oral administration, excellent bioavailability, quick achievement of steady-state concentrations, linear kinetics, minimal plasma protein binding and without important hepatic metabolism. The mechanism of actions is still unclear. It may be used as monotherapy in patients with newly diagnosed epilepsy, to treat seizures with focal onset with secondary generalization or without secondary generalization. Levetiracetam may also be used supplementary to other antiepileptic drugs in the treatment of seizures of focal onset with secondary generalization or without secondary generalization, myoclonic seizures or primary generalized tonic-clonic seizure. This medicine is very useful tool for clinicians.

Keywords: epilepsy, antiepileptic drugs, pathogenesis, epileptogenesis, levetiracetam, pharmacokinetics, treatment of epilepsy, pro-inflammatory cytokins, inflammation
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Increasing occurrence of multiple sclerosis in women is linked with cigarette smoking
AKTUALN NEUROL 2013, 13 (4), p. 267–274
ABSTRACT

Introduction: Reasons of increasing multiple sclerosis (MS) occurrence in women are unclear, although infection with Epstein-Barr virus and smoking were taken into consideration. The current study investigates relation between smoking and increasing occurrence of MS in women. Method: The female to male ratio (FMR) in smokers of the general population was correlated to FMR in 10 272 (M – 4367, F – 5905) MS patients, who died in the years 1982–2008 in Poland. The ratio of F:M in expected MS patients, who smoked cigarettes and died over 27 years, was also correlated to FMR in smoking general population. Data concerning deceased MS assemblage was received from the Central Statistical Office and information on prevalence of smoking was obtained from the Centre of Oncology in Warsaw. Correlation test by Pearson and linear regression test were used in the study. Results: Annual FMR in 10 272 MS patients was growing in Poland from 1.12 to 1.37 over the years 1982–2008; correlation coefficient r with calendar year was 0.548, p < 0.01. Significant correlation was found between the gender-specific smoking ratio in the general population and the sex-specific ratio in MS assemblage during 27 years: r = 0.595, p = 0.003. Strong correlation was ascertained between the F:M ratio in smoking general population and expected smokers with MS, who died over 3 decades; r = 0.882, p = 0.01-7. The result corresponded to close link between the F:M ratio in MS assemblage and in expected cohort of smokers with MS: r = 0.809, p = 0.01-5. Noteworthy was significant correlation of FMR in expected MS smokers with calendar year (1982–2008): r = 0.794, p < 0.001. Results indicate that the higher was the F:M ratio in cigarette smoking general population, the more increased was the F:M ratio in MS assemblage. Conclusions: The F:M ratio in MS calculated according to year of death increased significantly over 3 decades in Poland. The increasing occurrence of MS in women showed association with F:M smoking proportion in the general population. Growing occurrence of MS in women was at least in part linked with cigarette smoking.

Keywords: multiple sclerosis, gender ratio, smoking, prevention
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Stroke in the form of artery of Percheron syndrome. Case report
AKTUALN NEUROL 2013, 13 (4), p. 275–278
ABSTRACT

The artery of Percheron is a rare anatomical variant in which the medial parts of both thalami and the medial part of mesencephalon are supplied by branches of a common trunk deriving from the proximal section of one of the posterior cerebral arteries. The artery was given its name after her discoverer, who was the first to describe this anatomic variant in 1966. According to his classification in human brain there are four types of arterial supply of thalami and the artery of Percheron is the variant IIb. Pathologic process involving artery of Percheron (in most cases in course of small vessels disease or cardiogenic embolism) may lead to stroke giving typical triad of symptoms: abnormal vertical eye movements, memory and consciousness disturbances. Sudden onset of these symptoms may suggest the basilar artery syndrome, but prognosis in Percheron’s artery syndrome is more favourable. In our paper we present a case of a patient with bilateral thalami stroke probably due to cardiogenic embolism of the artery of Percheron.

Keywords: artery of Percheron, consciousness disturbance, eye movement disturbance, thalami stroke, stroke
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Traumatic damage of cervical arteries with a particular consideration of vertebral arteries: characteristics of diagnostic therapeutic process
AKTUALN NEUROL 2013, 13 (4), p. 279–286
ABSTRACT

Vertebral artery dissection is a disease that occurs rarely, but binding, however, with serious consequences. It is estimated that this is one of the most common causes of ischemic stroke in people under 45 years of age. The diagnosis of vertebral artery damage is easier when the patient shows signs of the occurrence of neck injury (e.g. cut injuries). However, the dissection of the vessel may also be a result of the so-called blunt trauma to the mechanism of “whip” for example, during an accident or during application of the abdominal pressure. Initially there is a rupture of the arterial intima, followed by the detachment and the formation of thrombus. This leads to the formation of thrombus or narrowing the lumen closure resulting in a clinical cerebral ischemia and neurological symptoms. Thrombus formation in the so-called misrepresent the artery can also be a source of embolic material. In case of suspicion of vertebral artery dissection are important: monitoring the neurological status of the patient and careful diagnosis of vascular. The aim of this study was to present the current state of knowledge about the causes of damage to the vertebral arteries, characteristic of the symptoms, diagnostic options and treatments and negotiations. It is believed that early diagnosis of arterial dissection and application of treatment increases the chance of survival and the patient avoid permanent neurological complications.

Keywords: cervical and vertebral dissection, neck injury, ultrasonography, thrombus, stroke
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Pharmacotherapy of cognitive dysfunctions in Alzheimer’s disease: current strategies and experimental therapies
AKTUALN NEUROL 2013, 13 (4), p. 287–294
ABSTRACT

Currently available methods of pharmacological treatment of cognitive dysfunction related to Alzheimer’s disease (AD) are based on augmentation of cholinergic neurotransmission (by inhibiting activity of cholinesterases) or modulation of glutamatergic transmission (by acting on NMDA receptor). Both classes of drug exhibit clinically significant (though modest) symptomatic improvement not only considering cognition but also behaviour and activities of daily living. Whether or not they modify natural course of the disease, is not clearly confirmed by result of rigorously planned clinical trials and is currently considered unlikely. With the development of genetic and molecular studies on the pathogenesis of AD novel treatment targets emerged recently, importantly these based on amyloid cascade hypothesis and τ protein phosphorylation. Unfortunately, the so far undertaken clinical trials yielded disappointing results, either proving not be effective or showing unfavourable side effects profile. The most commonlyproposed explanations of these failures include starting trials too late during the disease process and/or insufficiently specific strategies of patients’ selection resulting in inclusion of subjects suffering from other than AD cognitive dysfunctions. Biomarkers of disease-specific process are currently leading answer to the experienced trials failures as they are starting to be routinely used in novel studies.

Keywords: dementia, cognitive dysfunction, cholinesterase inhibitors, memantine, immunotherapy
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Pharmacotherapy of behavioural disorders associated with dementia
AKTUALN NEUROL 2013, 13 (4), p. 295–301
ABSTRACT

Pharmacotherapy of behavioural and psychological symptoms of dementia (BPSD) has been studied in numerous clinical trials. Their results, however, are inconclusive and do not allow simple recommendations applicable for majority of patients. Antipsychotics (including atypicals) has been proved effective for agitation and aggression, with doubtful effectiveness against delusions and hallucinations. Moreover, their efficacy is counterbalanced by safety concerns that include cerebrovascular events and related mortality. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are similarly to antipsychotics effective for agitation and psychosis; this is encouraging for their wider use considering their better safety profile. Other drugs, including antiepileptics and benzodiazepines, are poorly studied to date and both their effectiveness and safety are questionable. Hierarchical clinical management of BPSD is recommended for routine practice. In this model psychotropics are allowed only after careful diagnostic process (including exclusion of delirium) and employment of non-pharmacologic interventions coupled with optimal use of cholinesterase inhibitors and/or memantine.

Keywords: dementia, behavioural disturbances, pharmacotherapy, atypical antipsychotics, selective serotonin reuptake inhibitors
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Non-pharmacological strategies of behavioural symptoms associated with dementia management
AKTUALN NEUROL 2013, 13 (4), p. 302–307
ABSTRACT

Behavioural and psychological symptoms of dementia (BPSD) are common among demented patients and constitute a serious problem not only because of additional care-related issues and increased caregivers’ burden, but also due to considerable consequences for the patients, including faster progression of cognitive disorder, increased care need and earlier institutionalization, risk of falls and injuries as well as increased mortality. Commonly used drugs (antipsychotics, antidepressants, antiepileptic) have limited efficacy and tolerability. Moreover, antipsychotics use in dementia has been linked to increased risk of cerebrovascular events (like stroke and myocardial infarct) and premature mortality. Non-pharmacological interventions have been proposed as an alternative to drug use. Their efficacy, although also limited, is not inferior to drugs while the risk of side effects is minimal as compared to any drug. Four different theoretical models (genetic-biological, behavioural, stress hypersensitivity and frustrated needs) are used for the development of different management approaches. The resulting, clinically confirmed methods include sensory interventions, structured activities and social activities potentialization.The commonly used behavioural methods, although popular, are surprisingly insufficiently examined in clinical trials. Wider use of non-pharmacological methods for dementia (including BPSD) is compromised by mental barriers of health professionals (including beliefs and habits), low level of knowledge among professionals and caregivers as well as barriers related to health care system and costs of care.

Keywords: dementia, behavioural symptoms, non-pharmacological interventions, stress, needs
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Diagnosis and management of dementia with Lewy bodies: current recommendations and unsolved issues
AKTUALN NEUROL 2013, 13 (4), p. 308–313
ABSTRACT

Dementia with Lewy bodies is considered to be the second most common, after Alzheimer’s disease, cause of primarily degenerative dementias. Dementia with Lewy bodies, despite being quite common (according to epidemiological and clinicopathological studies), is still relatively rarely diagnosed in general practice. Wrong diagnoses of Alzheimer’s and Parkinson’s diseases are the commonest diagnostic errors, psychosis (usually attributed solely to aging process) being an alternative. Incorrect diagnosis results in ineffective treatment, and because of hypersensitivity to even small doses of antipsychotic drugs in DLB cases, treatment often could be extremely dangerous. Differential diagnosis includes differentiation with other primarily neurodegenerative dementias, including the closest phenotypically – Alzheimer’s disease with parkinsonism and dementia in Parkinson’s disease. Differentiation and giving of the correct diagnosis facilitates the use of clinical diagnostic criteria and additional tests. The most important issue is finding the characteristic clinical picture of psychiatric and neurologicalpresentation and the sequence of the onset of dementia and parkinsonism. Optimal improvement in majority of patients is possible with correct diagnosis and the use of strategies from the border of neurology and psychiatry. Cholinesterase inhibitors are mainstream treatment option for cognitive dysfunction (also some behavioural improvement, psychosis included, might be achieved) while levodopa is used for motor symptoms control. Antipsychotics must be used very cautiously and the first-line choice is currently quetiapine. An important issue is the treatment of coexisting REM-sleep disorder and autonomic dysfunction.

Keywords: dementia, Lewy bodies, diagnostic criteria, screening questionnaire, treatment
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