2007, Vol 7, No 4
Chemokines and their receptors in pathogenesis of multiple sclerosis
Aktualn Neurol 2007, 7 (4), p. 223-231
ABSTRACT

Chemokines are relatively recently characterized and growing fast family of low molecular weight cytokines, which stimulate migration of cells in vitro and in vivo. Together with adhesion molecules chemokines are involved in the complex process of migration of leukocytes outside of blood vessels. They also direct their migration within inflamed peripheral tissues. Chemokines are divided into four subfamilies. The main criterion of this division is the localization of pairs of cysteines in the NH2 region. The major chemokine subfamilies are CXC (α) and CC (β) chemokines. In CC subfamily the first cysteines are adjacent, in CXC group they are separated by a single aminoacid. The exemptions are lymphotactins α and β which posses only one pair of cysteines (C or γ subfamily) and fractalkine, in which the first cysteines are separated by three aminoacids (CX3C or δ subfamily). Functionally chemokines can be divided into proinflammatory and lymphoid. Chemokines influence their target cells through the specific seven transmembrane domain receptors. They are the important mediators of migration of inflammatory cells to the central nervous system (CNS) during different pathological processes that’s why they became the target of interest in the studies on multiple sclerosis (MS). Analysis of MS brains showed significantly increased expression of chemokines CCL4 and CCL5 at mRNA level. In the cerebrospinal fluid of MS patients during relapse increased level of chemokines CCL5, CXCL9 and CXCL10 was detected. Within chronic active demyelinating plaques in MS brains expression of CCR2, CCR3 and CCR5 was observed in macrophages and microglia.

Keywords: multiple sclerosis, chemokines, chemokine receptors, cell migration, autoimmune brain inflammation
DOWNLOAD ARTICLE (PDF)
Stem cells in Parkinson disease treatment
Aktualn Neurol 2007, 7 (4), p. 232-241
ABSTRACT

This review shows current progress in stem cell therapy of Parkinson disease. Article depicts strategies of stem cell therapy, discusses results of trials performed to treat Parkinson disease, describes experience of author in preparing cells for patients with Parkinson disease, and presents potential danger of stem cell therapy. Several strategies of stem cell therapies are presented. Strategies are divided in to: physiological, physiologically-biotechnological and biotechnological. Physiological strategy includes: use of neural stem cells, and Ratajczak concept. Plasticity (transdifferentiation), is considered as approach physiologically-biotechnological. Biotechnological strategy includes: cloning and reprogramming. Article shows opinions of authorities working on Parkinson disease stem cells therapy, briefly discusses trials of Hauser et al., Hegel et al., Brundin et al., Freed et al., and Olanow et al. Clues coming from these trials, for future use of stem cells derivatives, in the treatment of Parkinson disease are presented. Hints coming from works on Parkinson disease animals models, are also included. Moreover author presents his own experience in preparing cells potentially useful in Parkinson disease treatment, which is use of fibroblasts and neural stem cells. Finally possible dangerous consequences of stem cells therapy, such as risk of cancers development, are shown. Stem cell therapy appears as progressing, but in author opinion there is no final conclusion to say if it will work very efficiently or not. 

Keywords: stem cells, reprogramming, plasticity, differentiation, Parkinson disease
DOWNLOAD ARTICLE (PDF)
Osteoporosis occurrence in neurological diseases
Aktualn Neurol 2007, 7 (4), p. 242-245
ABSTRACT

Osteoporosis is generalized disease of the skeleton, characterized by low bone mineral density and disturbance of microarchitecture. Osteoporosis is a disease that appears in quite many people in Poland and there are many reasons for that. Many years ago osteoporosis was recognize as a disease of old people, but now it can reveal itself in every age and can lead to an increased susceptibility to fractures. There is a need to know how many factors can develop osteoporosis, for example genetic, environmental, dietetic or pharmacological. There are a lot of diseases, which might negatively effects bone mineral density. Osteoporosis mostly shows itself in those strictly connected with immobilization, such as stroke or spinal injury, and also in those with specific pharmacological treatment that negatively effects bone metabolism. And these disease are: epilepsy and sclerosis multiple. Osteoporosis is a big threat in many neurological diseases. It is vital to recognize diagnostic methods enabling to determine the bone metabolism, so as to prevent additional disorders. Taking into consideration a huge influence of everyday pharmacotherapy on bone metabolism, we are able to start diagnosis in an early stage and apply proper prophylactic.

Keywords: osteoporosis, spinal injury, stroke, SM, epilepsy
DOWNLOAD ARTICLE (PDF)
Mechanism of action of cytostatic drugs used in neurology
Aktualn Neurol 2007, 7 (4), p. 246-253
ABSTRACT

The aim of this review is the presentation of molecular mechanisms of action of cytostatic drugs used in the therapy of neurological disorders, mostly of multiple sclerosis (MS). From many years cytostatics like mitoxantrone, cyclophosphamide, cladribine and methotrexate were used in the MS clinical trials. So far only mitoxantrone has been approved by FDA for the treatment of progressive MS. The other cytostatics are still studied in clinical trials, the main problem with their approval for human therapy are their numerous side effects. So far those drugs are mostly used in oncology and haematology where the usage of this type of drugs is better justified. Now there are many studies leading to better understanding of mechanisms of action of cytostatics at the cellular and subcellular level. Mitoxantrone induces apoptosis and reduce the population of inflammatory cells capable to initiate demyelination in the central nervous system (CNS). At the molecular level mitoxantrone damages genome of inflammatory cells by inhibition of activity of topoisomerase II (TOP II) or direct interaction with DNA structure. Cyclophosphamide is a cytostatic acting mainly on dividing cells, in which it alkylates DNA and interferes with replication and cell apoptosis. Methotrexate inhibits activity of dehydrofolate reductase what leads to disturbance of replication and blocks phase S of the cell cycle in leukocytes. Cladribine is an antagonist of transcription. The detailed analysis of these mechanisms may lead to diminishing of the level of their side effects and to increase of their therapeutic potential, also in neurological therapy. 

Keywords: cytostatics, mitoxantrone, cyclophosphamide, methotrexate, cladribine, multiple sclerosis
DOWNLOAD ARTICLE (PDF)
Analysis of visual evoked potential in patients with clinically isolated syndrome
Aktualn Neurol 2007, 7 (4), p. 259-262
ABSTRACT

Background and objective: Visual evoked potential (VEP) is an essential element of the diagnostic process of multiple sclerosis. It proves substantially useful in the diagnosis of clinically silent demyelinization lesions of a visual tract. The purpose of the study is the analysis of VEP in patients with diagnosed clinically isolated syndrome – CIS. Material and methods: The study involved 77 patients with diagnosed CIS at the age range from 17 to 54 years old. VEP was performed both with pattern-reversal checkboard and flesh stimulation. Results: Mean values in both tests, were within normal. Abnormal result of VEP was obtained in 24 patients. P100 values exceeded the normal range in 21 cases (27.27%) in reversal test (in 6 patients bilaterally) and in 12 cases (15.58%) in flesh test (in 5 patients bilateral). Description: Presence of abnormal VEP was observed in 31% of examined cases, including 10 cases of retrobulbar optic neuritis in the past. Our results confirm earlier studies on the frequency of occurrence of abnormal VEP values in an early stage of MS. Further observations shall allow assessment of the function of VEP testing in identification of patients at a high risk of clinically definite multiple sclerosis (CDMS). 

Keywords: visual evoked potential (VEP), clinically isolated syndrome (CIS), multiple sclerosis, pattern-reversal checkboard, flesh stimulation
DOWNLOAD ARTICLE (PDF)
Hyperlipidemia and platelet activation markers in patients after ischemic stroke
Aktualn Neurol 2007, 7 (4), p. 263-269
ABSTRACT

Background: Platelet hyperactivity and coagulation readiness are additional predictors increasing risk of vascular events. The association between hyperlipidemia, excessive platelets activation and reactivity may be clinically significant because of increasing risk of ischemic stroke. Aim: The aim of our study was to investigate the influence of hyperlipidemia on platelet activation markers (platelet P-selectin, leukocyte-platelet aggregates) in patients after ischemic stroke. Methods: The study group consist of 41 patients after ischemic stroke (>3 months) confirmed by CT. We assessed platelet P-selectin and leukocyte-platelet aggregates in hyperlipidemic (HL, n=21), normolipidemic (NL, n=20) group and 20 healthy subjects served as controls using monoclonal antibodies anti-CD61, anti-CD62 and anti-CD45 on flow cytometer. We also assessed MPV and fibrinogen level. Results: We observed the highest percentage of platelets CD62P+ in HL and it was significantly higher compared to NL (p<0,05) and control group (p=0,005). The fibrinogen serum concentration was significantly higher in HL and NL in comparison with control group (p<0,001). There were no significant differences in the percentage of leukocyte-platelet aggregates and MPV between study group. Conclusion: We observed the risk of thrombosis in the shape of the increase of fibrinogen serum concentration in all patients after ischemic stroke. What’s more we noticed that the platelet activation is more intensive in patients with hiperlipidemia.

Keywords: hyperlipidemia, ischemic stroke, P-selectin, leukocyte-platelets aggregates, fibrinogen
DOWNLOAD ARTICLE (PDF)
Neuropsychological assessment of early and long-term outcome after operative treatment in patients with bleeding from anterior or posterior communicating artery aneurysms
Aktualn Neurol 2007, 7 (4), p. 270-276
ABSTRACT

Introduction: The aim of the paper was to assess a character, magnitude and dynamism of neuropsychological disorders in patients operated on for intracranial aneurysms located either on anterior communicating or posterior communicating arteries. We attempted to establish the usefulness of the Hunt and Hess grading as a predictor of subsequent postoperative neuropsychological disorders. Material and methods: To this study 82 patients with SAH from a single aneurysm located either on the anterior or posterior communicating arteries were enrolled. Directly before surgery the patients were assessed according to Hunt and Hess grading and only those assigned to grades I, II and III were taken into consideration. Neurological outcome of all these patients a discharge was described as good (GOS 4-5). The neuropsychological tests were carried out first about three weeks after the surgery and again six months later. Results: Compared to average results found in the population, our patients displayed decreased scores in the range of all functions examined with Wechsler Intelligence Scale. This was particularly true in patients Hunt and Hess grade III. Neuropsychological tests six months after the surgery confirmed apparent dynamics of the changes, particularly in the non-verbal tests. Conclusions: Hunt and Hess grading proved to be of satisfying prognostic value for future neuropsychological disorders. As a rule, Hunt and Hess grade I and II patients achieved better results in neuropsychological tests then those grade III. The only exception was noted in the case of the factor of the susceptibility to distraction, where the results were below average in all patients, both directly and six months after the surgery. 

Keywords: subarachnoid hemorrhage, intracranial aneurysm, neuropsychological evaluation, Hunt and Hess grade, Wechsler Intelligence Scale
DOWNLOAD ARTICLE (PDF)
Buccal cavity hemineglect syndrome
Aktualn Neurol 2007, 7 (4), p. 277-281
ABSTRACT

Background and purpose: Hemineglect is a group of behavioural symptoms in a person with right hemispheric (mostly vascular) lesion. The aim of the study was to determine whether there are, besides other hemineglect syndrome symptoms, signs of buccal hemineglect syndrome in patients with right hemispheric stroke lesion. Material and methods: The reference population comprised 20 patients (12 female and 8 male), aged 51-78 years after right hemispheric stroke. Control group consisted of 20 age and sex matched people after left hemispheric stroke. They had no speech disturbances in a degree making verbal contact or fulfilling protocol specific tests impossible. Patients with multiple stroke history, pseudobulbar syndrome, buccofacial apraxia, mental impairment, dementia and severe facial nerve paresis were excluded. All patients were examined after the acute phase of stroke. Motor deficit was assessed using neurological examination and was based on National Institute of Health Stroke Scale. Evaluation of spatial hemineglect was done using visual, motor tests and perception tests (reading, writing and body image tests). Anosognosia was assessed using specially selected test procedures. Evaluating buccal hemineglect we performed: chewing and swallowing organs examination with extinction assessment, exploration of taste, exploration of swallowing to check for dribbling, choking, stasis of the saliva or food in a mouth cavity. Results: Buccal hemineglect was usually concomitant with other hemineglect symptoms resulting from the lesion of the right hemisphere. Clinical signs associated with this condition consisted of: impaired swallowing (food retention, food debris in the left side of buccal cavity, drooling from the left angle of the mouth and choking), taste and sensory disturbances in the left hemibuccal space. These disturbances were incorrectly diagnosed initially. Conclusions: Buccal hemineglect is frequent phenomenon in subjects with other hemineglect syndrome symptoms. Proper rehabilitation can reduce the number of complications and greatly improve the neglected functions. 

Keywords: hemineglect syndrome, buccal hemineglect, clinical features, diagnosis, treatment
DOWNLOAD ARTICLE (PDF)
Cognitive and behavioural disorders after carbon monoxide intoxication – case report
Aktualn Neurol 2007, 7 (4), p. 254-258
ABSTRACT

Carbon monoxide (CO) is a highly toxic, odorless, nonirritating gas. The most common cause of its exposure are faulty combustion heating systems and fires. CO competes with oxygen in the blood, binding to haemoglobin in place of it (the affinity of CO to haemoglobin is approximately 200 times greater than that of oxygen). Secondary hypoxia leads to damage of multiple organs especially those with high oxygen utilization such as the central nervous system. A case of a 26-year-old woman with prolonged deep cognitive impairment, which occurred after an accidental carbon monoxide intoxication, is presented. A course of over 2-year neuropsychological rehabilitation of the patient is thoroughly described by the authors and its positive effects are emphasized. In spite of all prophylactic measures carbon monoxide poisoning still remains a significant clinical issue. CO intoxication may produce a wide spectrum of neurological, emotional and cognitive disorders. Neuropsychological rehabilitation is an effective method of treatment of cognitive impairment after carbon monoxide intoxication. Positive effects of a systematic rehabilitation are observed even several years after poisoning. 

Keywords: carbon monoxide, intoxication, cognitive impairment, behavioural disorders, rehabilitation
DOWNLOAD ARTICLE (PDF)