2011, Vol 11, No 2
The search for inflammatory biomarkers of ischaemic stroke
AKTUALN NEUROL 2011, 11 (2), p. 106-110
ABSTRACT

The search for stroke biomarkers has been initiated several years ago. Commonly available and sensitive biomarkers of stroke are still not available for the early diagnosis of this disease as well as for monitoring of its treatment. The ideal stroke biomarker should be very specific to differentiate stroke from other clinically similar diseases like complicated migraine, transient ischaemic attack (TIA), multiple sclerosis or posticus paralysis. Moreover, its concentration in the blood should correlate with the concentration in the cerebrospinal fluid (CSF). Additionally it should be detectable shortly after stroke clinical signs appearance and should allow to differentiate between TIA and stroke or ischaemic stroke with haemorrhagic stroke. Good stroke biomarker should be also an useful indicator of effectiveness of stroke treatment. In this review we present potential inflammatory biomarkers tested in stroke and their experimental models. The most commonly analysed inflammatory biomarkers are C-reactive protein (CRP), interleukin 1, 6, 8, metalloproteinase 9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule (ICAM) and tumour necrosis factor-alpha (TNF-α). Currently available results suggest that there are a few potentially interesting inflammatory biomarkers of stroke but still further studies are necessary to confirm their usefulness in this field.

Keywords: ischaemic stroke, biomarkers, atherosclerosis, inflammation, cytokines
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Idiopathic hypertrophic pachymeningitis – case report
AKTUALN NEUROL 2011, 11 (2), p. 79-84
ABSTRACT

Idiopathic hypertrophic pachymeningitis (IHPM) is a rare disaster, with still unknown aetiopathogenesis. There are above 100 described cases of IHPM in the medical literature till 2010 year of which majority was reported in last 10 years. We would like to present a case of 52 years old woman admitted to Department of Neurology and Epileptology, Medical University of Lodz in August 2010. The disease was started with weakening of visual acuity in 2007 year in left eye. Because of this she was hospitalised in ophthalmology ward and after that at neurological ward, but the reason for weakening of visual acuity was unclear. She had had numerous CT scans of head, which were correct always. In May 2009 she was given an cardiostimulator because of cardiologic disease, which excluded ability to future MRI examination. In August 2009 she was diagnosed a total atrophy of left optical nerve and beginning of atrophy of right optical nerve.In February headaches change from occasional to every day pains. After she was admitted to hospital the CT scan of head showed cerebral haematoma. Although the existing symptoms of pressure to the right lateral ventricle with its displacement but she was not qualified to the operation by neurosurgeon. In August 2010 after another hospitalisation because lack of evolution of haematoma and increasing displacement she was transferred to the Neurosurgery Department. During the surgery stated thicker dura mater about 7 mm, which fragments were sent to pathomorphological examination. They showed changes of a fibrogranular nature. Many other laboratory test were made to discover cause of IHPM and they were negative, that proof the idiopathic hypertrophic pachymeningitis diagnosis.

Keywords: pachymeningitis hypertrophica, atrophia nervi opici, haematoma cerebral, headaches
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Role of VEGF, neurotrophic and proangiogenic factor in pathogenesis of Alzheimer’s disease
AKTUALN NEUROL 2011, 11 (2), p. 123-130
ABSTRACT

Currently, neurodegenerative disorders represent one of the most serious diseases the mankind is struggling with. An increased morbidity rate of Alzheimer’s disease seems to be associated with general population aging. Despite the fact that the intensive studies have been conducted in many research centres for several years, etiopathogenesis of Alzheimer’s disease is still not fully understood. Furthermore, there is no drug which could, at least, inhibit progress of this disease effectively. Vascular endothelial growth factor (VEGF) is well-characterized proangiogenic substance, essential for the formation of new blood vessels during embryogenesis as well as others pathological condition. Recently, a new role for VEGF as a neurotrophic factor has been emerged. In the developing nervous system, VEGF plays a pivotal role in neuronal proliferation and guidance of neuronal development process. As proangiogenic and neurotrophic factor, VEGF has been suggested to be involved in the pathogenesis of Alzheimer’s disease. In patients suffering from this disease patients abnormal regulation of VEGF expression have been reported. Moreover, an interaction between VEGF and b-amyloid has been evidenced in in vitro studies on cell cultures and in vivo studies conducted on transgenic lab animals. In consequence, these data have stimulated an increasing interest in assessing the therapeutic potential of VEGF pharmacological modulation in treatment of Alzheimer’s disease.

Keywords: Alzheimer’s disease, b-amyloid, treatment of AD, transgenic models, vascular endothelial growth factor (VEGF)
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Hyperleptinaemia in patients with acute ischaemic stroke
AKTUALN NEUROL 2011, 11 (2), p. 115-122
ABSTRACT

Background: Leptin is an adipocytokine with potentially anti-atherogenic and anti-inflammatory effect. Leptin is a proof that adipose tissue is not only a store of energy but it is the reservoir of very important for human body hormones too. Aim: The aim of this study was to evaluate the leptin level in patients with acute ischaemic stroke and estimate correlation between leptin and risk factors of vascular diseases. Material and methods: To the study we qualified 72 patients with acute ischaemic stroke and 29 referents without CNS diseases, matched with age and gender. In all subjects we examined lipid pattern, blood glucose level, blood pressure, BMI and central fat markers – WC (waist circumference) and WHR (waist to hip ratio). In all patients we diagnosed the presence of metabolic syndrome, according to NCEP and IDF. Leptin level was measured by an enzyme linked immunosorbent assay. In every patient we evaluated CIMT and presence of arteriosclerosis. In stroke group we estimated the neurological deficit according to NIHSS, in I and VII day of hospitalisation. Results: The leptin level was higher in stroke group. Hyperleptinaemia is more often present in patients with abdominal obesity (p<0.001), enlarged CIMT (p<0.01), present of arteriosclerosis (p<0.05) and in subjects with metabolic syndrome (p<0.01). There is no independent association between increased leptin concentrations and glucose levels, presence of hypertension, level of TG and HDL. In patients with worse neurological status (higher NIHSS) we observed higher leptin levels. Conclusions: High leptin level can have an important role in pathogenesis of ischaemic stroke, for example by influence on arteriosclerosis. Identification the role of leptin in the pathogenesis of cerebrovascular diseases can improve the prophylaxis of ischaemic stroke.

Keywords: leptin, ischaemic stroke, CIMT, obese, metabolic syndrome
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Hemicraniectomy and hypothermia in the treatment of ischaemic stroke
AKTUALN NEUROL 2011, 11 (2), p. 111-114
ABSTRACT

Stroke constitutes the third cause of deaths and the most frequent cause of disability of patients above 40 years old. The malignant middle cerebral artery infarction is associated with high mortality when standard treatment is applied, so the new methods of treatment are searched. Apart from pharmacological treatment the surgical treatment and hypothermia are recommended lately. Hemicraniectomy is a surgical method of treatment where a part of cranium is removed what decreases the intracranial pressure. The analysis of three European randomised clinical trials suggests that hemicraniectomy performed within 48 hours after stroke significantly reduced mortality and improved functional outcome in patients after a surgical decompression. Hypothermia is a condition in which body temperature drops below 35.0°C. It is suggested that only mild hypothermia can give the neuroprotective effect. It means that the temperature of the body should be hold between 34-32°C. Some clinical trials showed that mild hypothermia used during 72 hours after stroke can reduce mortality up to 44%. In the last decade some randomised clinical trials have shown that hemicraniectomy and mild hypothermia are effective in the malignant middle cerebral artery (MCA) territory infarction and significantly reduce mortality and disability in patients with brain oedema. There is however not enough data so far and more randomised controlled clinical trials are needed to confirm the efficacy of those methods of stroke treatment.

Keywords: hemicraniectomy, hypothermia, stroke, malignant middle cerebral artery infarction, stroke treatment
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Medulloblastoma – heterogeneous histopathology
AKTUALN NEUROL 2011, 11 (2), p. 96-99
ABSTRACT

Medulloblastoma is the most common paediatric brain tumour. It is a malignant embryonal tumour of the cerebellum with predominantly neuronal differentiation and tendency to metastasises via CSF pathways. The WHO classification of CNS tumours (2007) distinguishes classic medulloblastoma and four variants: desmoplastic/nodular (D/N), medulloblastoma with extensive nodularity (MBEN), anaplastic medulloblastoma and large cell medulloblastoma. Classic medulloblastoma consists of sheets of small cells with prominent nucleus and scant cytoplasm. Neoplastic cells of classic medulloblastoma might be elongated with oval nuclei and display moderate nuclear pleomorphism. Some classic tumours contain Homer Wright rosettes or palisades. The main histopathological features of D/N medulloblastoma and MBEN are nodules of differentiated neurocytic cells and internodular desmoplasia. Anaplasia in medulloblastoma is defined as marked nuclear pleomorphism, cell molding, cell wrapping, high mitotic activity and apoptosis. The large cell medulloblastoma contains groups of large cells with round nuclei with a single nucleolus. Because of the rarity of the pure large cell medulloblastoma and mixture of large cell and anaplastic phenotypes in some medulloblastoma, it is suggested to combine the two variants into a single category of large cell/anaplastic medulloblastoma. MBENs and D/N medulloblastomas in infants have better prognosis than classic tumours. Large cell/anaplastic medulloblastomas are more aggressive tumours.

Keywords: medulloblastoma, classification, histopathological variants, embryonal tumours, PNET
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Genetics of childhood medulloblastoma
AKTUALN NEUROL 2011, 11 (2), p. 85-90
ABSTRACT

Medulloblastoma is the most common type of embryonal tumour in paediatric population. This entity represents up to 4% of all intracranial neoplasms in the whole population and 20-25% of all brain tumours in children. The majority of tumours is located within vermis and fourth ventricle. Due to its frequency, histological aggressiveness, and unfavourable outcome, the treatment of children with medulloblastoma is a great clinical problem. According to the newest achievements of molecular biology, the significant heterogeneity of this tumour was confirmed. The most frequent types of molecular abnormalities detected in medulloblastoma were SHH and WNT pathways activation, MYC amplification and isochromosome i17q presence. Recently, on the basis of modern molecular analyses comprising gene expression profiling, several molecular subtypes of that tumour were described. Among them there were two subgroups connected with SHH and WNT pathways activation. SHH type medulloblastomas showed frequent CTNNB1 gene mutations and monosomy of chromosome 6. The PTCH and SUFU mutations accompanied by loss of chromosome 9 were identified in WNT type. Remaining subgroups distinguished on the basis of transcriptome analyses were not so clearly characterized and their number varied in particular molecular studies. This paper is a review of the latest data describing molecular background of medulloblastoma.

Keywords: children, expression, medulloblastoma, prognosis, genetic profiling
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Molecular characteristics of cancer stem cells and progenitors in medulloblastoma
AKTUALN NEUROL 2011, 11 (2), p. 91-95
ABSTRACT

Medulloblastoma is the most common type of embryonal tumours in paediatric population. Recently, on the basis of modern molecular analyses comprising gene expression profiling several molecular subtypes of that tumour were described. One of the conclusions from such studies is plausible different cellular origin of medulloblastoma with various molecular profiles. Up to now two main origins of precursors were proposed for this type of tumour, external granule layer (EGL) and cerebellar ventricular zone (CVZ). Recently other structures containing such cells (white matter of the cerebellum, rhombic lip, Bergmann glia) were also identified. Neural stem cells and/or progenitors existing within those regions have capacity to self-renew, multilineage differentiation and tendency to neurosphere formation. Molecular alterations of precursor cells can transform them into tumour stem cells (TSC). TSC, like normal stem cells frequently expresses CD133 protein, what was observed also in medulloblastoma. Moreover, CD133-negative cells without neurosphere- like formation were also detected. Expression of ATOH1 gene was proposed for identification of this type of cells. Among other markers of TSC in medulloblastoma, expression of FUT4, CXCR4, NGFR, CALB1, OTX2, SOX2 and SOX9 genes was mentioned. Proper identification of tumour stem cells and progenitor cells in this high grade tumour may become useful for individualizing of the therapy in children with medulloblastoma.

Keywords: children, medulloblastoma, progenitors, stem cells, treatment
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Th17 cells in pathogenesis of experimental model of multiple sclerosis
AKTUALN NEUROL 2011, 11 (2), p. 100-105
ABSTRACT

Th17 cells are quite recently discovered subpopulation of T helper lymphocytes, characterized by the production of IL-17 (IL-17). Research on these lymphocytes gives new light on the pathogenesis of multiple sclerosis (MS) and its experimental model (EAE). These lymphocytes have a high similarity to Th1 cells and naïve T CD4+ differentiate into Th17 phenotype under the influence of a specific set of cytokines. Formation of murine Th17 cells is induced by cytokines TGF-β and IL-6 or IL-21. Th17 cells produce various chemokines, including IL-17A/F, IL-21 and IL-22. It has been documented that the neutralization of IL-17 reduces the symptoms of the disease in an animal model of MS. The main mediator of central nervous system (CNS) pathology induced by Th17 cells is IL-17A. One of the best characterized function of IL-17A is the induction of the production of neutrophilic CXC ELR+ chemokines: CXCL1 and CXCL2. Moreover, Th17 cells can promote the development of EAE by activation of neutrophils within the bone marrow, which in consequences leads to the mobilization of immature monocytes into the bloodstream and the development of inflammation in the CNS. A growing number of data from the studies on MS and EAE confirms a major role of Th17 lymphocytes in the pathogenesis of this disease. Understanding the exact role of these cells requires further studies, since their results may be useful in developing new therapies for MS.

Keywords: Th17 cells, interleukin 17, multiple sclerosis, experimental autoimmune encephalomyelitis, chemokines
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