2008, Vol 8, No 1
Narcolepsy – new possibilities of diagnosis and treatment
Aktualn Neurol 2008, 8 (1), p. 10-15
ABSTRACT

Narcolepsy is well known disease from many years. Its diagnosis in Poland is rarely in the contrary to western countries or United States where its frequency is estimated from 5 to 10 cases per 10 000 people. Narcolepsy is characterised by excessive and repetitive daytime sleepiness, catalepsy, sleep paralysis and hypnagogic hallucinations. In healthy people the sleep is beginning from non-REM phases, but in the narcoleptic patients is immediately beginning from the REM phase of sleep. The association of narcolepsy with HLA DR2 and recently with HLA DQB1*0602 has been found. In humans, the hypocretin deficiency in the cerebrospinal fluid and a loss of the hypocretin neurons in the brain hypothalamus post mortem has been found. The prostaglandin D2 takes part in the process of sleep, which are synthetised in the human brain by the synthetase of prostaglandins. Many years ago in the treatment of narcolepsy were used amphetamine or ephedrine. Broughton et al. in 1988 year start with modafinil in the treatment of narcolepsy with very good results. Recently were trials of narcolepsy with GABA derivates, for example Xyrem, unfortunately this drug posses very dangerous side effect. The catalepsy was treated with tricyclic antidepressants, for example imipramine, clomipramine, amitryptiline or fluoxetine.

Keywords: narcolepsy, catalepsy, REM sleep, hypocretins, treatment
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SYMPOSIUM: MULTIPLE SCLEROSIS. Chemokines and their receptors in experimental autoimmune inflammation in the CNS
Aktualn Neurol 2008, 8 (1), p. 16-24
ABSTRACT

Chemokines are a family of small alkaline proteins with molecular weight of 6 to 14 kDa. Depending on physiological activities they can be divided into two groups, homeostatic (constitutive) and inflammatory. Homeostatic chemokines (e.g., CCL19, CCL21, CCL25, CCL27, CXCL12 and CXCL13) are usually constitutively expressed in the specific microenvironments of lymphoid organs and peripheral tissues. In contrast, inflammatory chemokines (e.g., CCL1, CCL2, CCL11, CCL17 and CCL22) are involved in development of inflammation. Their expression is induced by another inflammatory cytokines such as IL-1β or TNF. Chemokines act on various types of target cells through rhodopsin like G protein-coupled receptors. The main function of chemokines is induction of directed chemotaxis of different types of target cells. Moreover, they regulate inflammatory process and differentiation of immunological cells. Physiologically, chemokines constitutively expressed in the central nervous system (CNS) can initiate multipotential progenitor cells and neurons migration during the development of the brain as well as they can act as a trophic factors for neurons. The close correlation between the expression of chemokines and the influx of inflammatory cells to the CNS during an animal model of multiple sclerosis (MS) – experimental autoimmune encephalomyelitis (EAE) was observed. The mRNA expression of chemokines CCL2, CCL3, CCL4, CCL5, CCL7 and CXCL10 as well as chemokine receptors CCR2, CCR5, CCR8, CXCR2, CXCR3, CXCR4 andCX3CR1 in the CNS of animals with EAE was increased. These data suggest that chemokines and their receptors may be involved in the pathogenesis of autoimmune neuroinflammation, including MS. 

Keywords: experimental autoimmune brain inflammation, multiple sclerosis, chemokines, chemokine receptors, autoimmunity
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SYMPOSIUM: MULTIPLE SCLEROSIS. Mechanisms of neurodegeneration and its markers in multiple sclerosis
Aktualn Neurol 2008, 8 (1), p. 25-32
ABSTRACT

Neurodegeneration is a very important process in the pathology of multiple sclerosis (MS). However, mechanisms leading to neurodegeneration in MS are still poorly understood. One of the most probable mechanisms triggering damage of the neuron is apoptosis induced by calcium-dependent enzymes. This review presents the mechanism of calcium overload of neuronal cell and also describes the direct and indirect mechanisms of neurodegeneration. Direct mechanism of neurodegeneration is induced by infiltration of the central nervous system (CNS) by immune cells like T-cells and macrophages and their direct damaging interactions with neurons. Many particular molecules like TRAIL, CD95, TNF-α, TNF-β on immune cells, and CD95/Fas/Apo-1, TNFR1, TNFR2, DR3/Wd1-1/Tramp, DR4/TRAIL-R1, DR5/TRAIL-R2/TRICK/Killer and DR6 on the CNS cells are involved in this process. The direct mechanism of neurodegeneration may be also induced by ROS (reactive oxygen species) and NO (nitric oxide) produced by macrophages and microglia in inflammatory foci. Indirect, secondary mechanism of neurodegeneration is mainly induced by primary demyelination. Furthermore, this paper describes in details the current knowledge about the possible markers of neurodegeneration in MS like neurofilaments; anti-neurofilaments antibodies; tubulin, actin and anti-tubulin, anti-actin antibodies; tau i fosfo-tau proteins; 24S-hydroxycholesterol (24S-ChOH); apolipoprotein E (ApoE); amyloid precursor protein (APP); N-acetylaspartate (NAA); 14-3-3 protein; neuron-specific enolase (NSE); and S100B (S100 calcium binding protein B).

Keywords: neurodegeneration, neuronal loss, brain atrophy, multiple sclerosis, neurodegeneration markers
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SYMPOSIUM: MULTIPLE SCLEROSIS. The role of regulatory T cells (Tregs) in experimental autoimmune inflammation in the CNS
Aktualn Neurol 2008, 8 (1), p. 33-38
ABSTRACT

Regulation of the immune response to foreign antigens may develop at the central or peripheral level of the immune system. One of the crucial players of this process is regulatory T cell (Tregs). There are two hypotheses explaining the mechanism of the interactions between regulatory T cells and effector lymphocytes during the immune response. The first one suggests that Tregs inhibit proliferation of effector cells through the direct contact. It is also suggested that this interaction may be indirect and mediated by cytokines. Regulatory T cells are identified by expression of CD4, CD25 and Foxp3 markers. Our knowledge on the involvement of Tregs in the pathogenesis of multiple sclerosis (MS) and its animal model EAE (experimental autoimmune encephalomyelitis) is still unsufficient. Obtained results suggest that naturally occurring CD4(+)CD25(+) Tregs play an important role in the prevention and/or inhibition of the chronic pathological process in the brain during EAE. It was shown that passive transfer to donor of regulatory T cells may prevent or treat an ongoing EAE. In IL-10 knock-out mice, induced Tregs are not able to ameliorate this disease indicating the crucial role of IL-10 in induction of suppression by regulatory lymphocytes. Tregs are also partially responsible for the beneficial effect of glatiramer in EAE treatment. These observations confirm that regulatory T cells may be potentially used in the therapy of multiple sclerosis and other diseases of similar pathogenesis.

Keywords: regulatory lymphocytes, Treg, experimental autoimmune encephalomyelitis, multiple sclerosis, autoimmunity
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Stem cells in neurology
Aktualn Neurol 2008, 8 (1), p. 39-48
ABSTRACT

Human brain is a very complex biological system considering its cytoarchitecture, neuronal network, localisation of functional regions and integration. Until second half of the XX century it was believed that CNS is deprived of regenerative processes. At present there are many studies that confirm constant formation of new neurones in the human brain. However, this process of cell exchange is far less effective in comparison with the regeneration and functional renewal of other tissues of our organism. In the following article we present current data on local neurogenesis in the adult brain. There are at least 3 regions of CNS where cell proliferation takes place: subventricular zone – SVZ, subgranular zone – SGZ and posterior periventricular area – PPv. It has been estimated that single radial glial cell, which is the progenitor of cells residing in the aforementioned regions of the brain, would be enough to form 4×10(7) of new brains. Other tissues of our organism could become another source of stem cells for brain regeneration. This solution is tempting when we consider a theory of peripheral blood stem cells that reside in different organ niches. Injured tissue produces higher amounts of chemokines such as SDF-1 or LIF that causes increased migration of stem cells towards the “calling-for-help” organ. The last part of the article presents the progress that has been made in regeneration therapies of certain neurological disorders: cerebral stroke, Parkinson’s disease, multiple sclerosis, spinal cord injuries, amyotrophic lateral sclerosis, Huntigton’s disease and Alzheimer’s disease. 

Keywords: stem cells, progenitor cells, neurogenesis, cell therapy, nervous system
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Atypical course of sporadic form of Creutzfeldt-Jakob disease
Aktualn Neurol 2008, 8 (1), p. 49-55
ABSTRACT

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative condition caused by prions. In literature there are distinguished four forms of CJD: sporadic (sCJD), familial, iatrogenic and variant (vCJD). Current diagnostic criteria of these forms, basing on clinical symptoms of this disease, allow to distinguish probable and possible CJD. Unquestionable diagnosis can be established only after the patient’s death on the basis of characteristic neuropathological picture. Intravitally, in CJD diagnosis the result of anatomopathological examination can be taken into consideration (cerebral biopsy, palatine tonsils). A case has been presented of a 53-year-old female in whom basically the only clinical symptom (for 45 days) was psychogenic blindness followed by coma. Then, she survived eight months in a vegetative state. The clinical symptoms of the disease fulfilled the criteria of variant CJD but neuropathological examination revealed sCJD. The establishing of the diagnosis in the case of CJD usually takes weeks and even months and the diagnosis of vCJD results in epidemiological and thus economic complication. The presented case was an atypical course of sCJD. Authors wanted to emphasize that sCJD starts not always with the onset of dementia but that it is possible that it starts with psychotic symptoms.

Keywords: Creutzfeldt-Jakob disease, laboratory tests, MRI, diagnosed alive, sCJD
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Myositis ossificans progressiva
Aktualn Neurol 2008, 8 (1), p. 56-61
ABSTRACT

Fibrodysplasia ossificans progressiva is uncommon genetic disease of connective tissue characterized by congenital defects already in newborns. Clinical symptoms of that disease develop usually in the beginning of human life. The disease was displaying forms of big pain swellings. At first, the focus was to treat it like a benign tumour. Later, those swellings started to change in calcinosis. We report of the case 30-year-old woman, who was born with congenital defects characterized by distort of the fingers and feet. That disease was started in 4-5 year of old. The process of ossification walked progressively. The sharp worsening of health occurred after injury (fall of the bike). Diagnoses of downloading stretch the muscle and biopsy of muscle was performed. The diagnosis of the disease was early in 6 years of old and the treatment with etidronate sodium was unsuccessful on natural course of the disease.

Keywords: calcinosis, fibrodysplasia ossificans progressiva, pathogenesis, clinical course, proof of treatment
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Globoid cell leucodystrophy – disease with many faces?
Aktualn Neurol 2008, 8 (1), p. 62-65
ABSTRACT

Krabbe disease (globoid cell leukodystrophy) is a progressive, autosomal recessive inherited disorder affecting peripheral and central nervous system. This disease is associated with mutation in GALC gene and its locus has been mapped to chromosome 14q31. GALC gene code lysosomal hydrolytic enzyme galactocerebroside β-galactosidase (galactosylceramidase) which is crucial for degradation of galactolipids mostly: galactosylsphingosine (psychosine) and galactosylceramide (a major sphingolipid in the white matter of the central nervous system). This enzyme activity is required for correct metabolism of myelin. Krabbe disease is unique among the lipid storage diseases because there is no increase of lipid in the brain except within specialized microglia/macrophage cells described as globoid cells. Typically, the disease occurs among infants (90-95%), but rarer late-onset forms also exist. The disease may be subdivided into four types: infantile form with onset within the first six months, child form presenting between 6 months and 3 years, juvenile form presenting between 3 and 10 years and the rarest adult form with onset after 10 years. The diagnosis of Krabbe disease is based on clinical findings and confirmation of galactocerebroside β-galactosidase deficiency. We have found two families: first with child-onset and second with adult-onset disease. To our knowledge, it is the first observation of patient with adult form of Krabbe disease in Poland. We suggest that the founder effect in Polish population took place during Swedish Deluge.

Keywords: globoid cell leukodystrophy, Krabbe disease, galactocerebroside β-galactosidase, GALC, lateonset forms
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