2013, Vol 13, No 2
Topiramate – review of selected papers
AKTUALN NEUROL 2013, 13 (2), p. 88–95
ABSTRACT

Epilepsy is one of the most wide spread and serious paroxysmal disorders as well as 30% cases of resistant epilepsy. Topiramate (TPM) is one of many drugs of the second generation. Topiramate, a sulfonatesubstituted derivative of the monosacharide D-fructose, has been associated with a broad spectrum of antiepileptic activity. The precise mechanism of TPM is unknown, is considered that TPM produce antiepileptic effects through enhancement of GABA-erge activity, inhibition of kainate/AMAP glutamate receptors, inhibition of voltage- sensitivite sodium and calcium channel, increases in potasium conductance and inhibition of carbonic anhydrase. Oral TPM is rapidly absorbed in patients with epilepsy with a relative bioavailability of near 80%. In many clinical trials, appeareddosages (i.e. 200 mg b.d.) of topiramate as monotherapy or adjunctive therapy were effective in reducing the frequency of seizures in patients with primary generalised tonic-clonic seizures, partial seizures. The cost-utility analysis included direct medical and social services cost in the UK, TPM was predicted to be cost-effective relative to standard treatment with valproic acid in adults with generalised or unclassified epilepsy cross a range of thresholds for the cost per quality-adjusted life-year (QALY) gained as was preferred over lamotrigine. However, in adults with partial epilepsy, lamotrigine appeared to be cost-effective relative to standard treatment with carbamazepine over gabapentin and topiramate. Treatment with topiramate is commonly associated with adverse events, among others especially with weight-loss and cognitive dysfunction. The carbonic anhydrase inhibitory effects of TPM may result in metabolic acidosis, renal calculi and hypohidrosis.

Keywords: epilepsy, topiramate, pharmacokinetic properties, therapeutic efficacy, adverse events
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Pharmacogenetic determinants of drug resistance in epilepsy
AKTUALN NEUROL 2013, 13 (2), p. 96–102
ABSTRACT

Epilepsy is one of the most common CNS disorders occurring in approximately 1% of the world population. It is characterized by the occurrence of recurrent attacks of varying symptomatology. It is estimated that 30% of patients, despite the appropriate antiepileptic treatment, still experiencing seizures. In this case we are dealing with so-called the phenomenon of drug resistance. In Poland, this problem concerns about 100–120 thousand patients. Predisposing factors for epilepsy include: onset of symptoms before 1 year of age, high frequency of seizures before treatment and structural changes of the brain, including cortical malformations. Uncontrolled seizures affect the patients quality of life, increasing the risk of injury, affecting the physical well-being and psychosocial functioning.Despite knowing these presumable risk factors for epilepsy, it remains unknown why in the two patients with the same type of epilepsy or the same type of seizure, efficacy of antiepileptic drugs can be extremely different. Potential reasons for this may be genetic factors, changing the pharmacodynamic and pharmacokinetic attributes of antiepileptic drugs. Among these factors is mentioned genetically determined polymorphism of some microsomal enzymes (CYP2C9, CYP2C19), P-glycoprotein, a protein MRP (multidrug resistance-associated protein) and pharmacodynamic malfunction of GABA (GABAA) and ion channels. It seems that research on the mechanisms of drug resistance may lead to the introduction of new therapeutic strategies This article aims to show the impact of genetic factors to the lack of treatment efficacy in epilepsy.

Keywords: pharmacogenetics, drug-resistant epilepsy, cytochrome P450, drug transporter proteins, single nucleotide polymorphism – SNP
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Challenges for treatment of dementia in Alzheimer’s disease
AKTUALN NEUROL 2013, 13 (2), p. 103–108
ABSTRACT

The prevalence of dementia is reaching epidemic proportions globally. Alzheimer’s disease (AD) is one of the main causes of dementia. In the absence of a causal cure for AD, symptomatic treatment play a key role in management the disease. After proper diagnosis of AD patients should be offered the opportunity to benefit from non-pharmacological and pharmacological therapies. Cholinesterase inhibitors (rivastigmine, donepezil, galantamine) and the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine are currently widely approved for the treatment of AD. These drugs can offer benefits in three main affected areas: activities of daily living, behaviour and cognition. Several guidelines recommend treatment with cholinesterase inhibitors at the time of diagnosis of AD, taking into account expected therapeutic benefits and potential safety issues. These drugs should be used longitudinally withgood tolerated maximum daily dose. Memantine is approved for the treatment of moderate to severe AD. Cholinesterase inhibitors can also delay the onset if the decrease and the severity of behavioural and psychotic symptoms in AD. Currently, there is insufficient evidence to support the use of other agents than cholinesterase inhibitors and memantine in the treatment or prevention of AD.

Keywords: dementia, Alzheimer’s disease, cholinesterase inhibitors, memantine
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The role of selected risk factors in the aetiology and the course of Alzheimer’s disease
AKTUALN NEUROL 2013, 13 (2), p. 109–118
ABSTRACT

Alzheimer’s disease (AD) is the most common form of dementia among elderly. It is a progressive, neurodegenerative disease. Morbidity of AD rises with age. Aetiology of AD is multifactorial and it compounds of genetics and environmental factors including general lifestyles, diet, physical activity smoking and alcohol abuse. It is believed that a diet similar in composition to the Mediterranean diet has a protective effect and promotes a long life in health. Hyperhomocysteinemia and a diet deficient in B12 is indirectly associated with AD. On the other hand, supplementation of vitamins C, E and folate in diet can be protective from AD. Both, obesity and undernutrition, can increase the risk of development of AD. The importance of correlation between vascular disease of the brain and dementia is undeniable. It is supported by the fact that appropriate diet, proper nutritional status, absence of diabetes, avoiding smoking and attention to physical activity play an important role not only in preventing cardiovascular diseases,but also the AD. Epidemiological studies suggest that the incidence of AD will continue to rise along with aging population, which will increase the amount of disable people due to AD impacting medical, cultural and economic aspects of the society. Therefore the role of individual factors should have been investigated still and prophylactic activities must have been introduced in the early age.

Keywords: Alzheimer’s disease, risk factors, diet, physical activity, addiction
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The genetic causes of mental retardation, which the neurologist may encounter in everyday practice
AKTUALN NEUROL 2013, 13 (2), p. 119–129
ABSTRACT

Mental retardation is defined as significantly lower than the average level of intellectual functioning in association with impairments in adapting, binding to changes in the central nervous system. Alternatively, such terms as mental stunting, reduced intellectual performance, mental retardation and intellectual disability, and more recently learning disorders, are used. In the 1990s there have been tremendous changes in terms of mental retardation by deviating from the traditional medical and biological concepts, according to which the impairment was treated as a state of irreversible and defining a low ceiling development. Mental retardation is not only biological disorder, but also the psychological state which occurs as a result of improper development process. The impact on this state are: the prenatal period (exposure to X-ray beam, the use of drugs by the mother during pregnancy, alcohol, cigarette smoke, drugs, viral and bacterial infections, immune factors), the perinatal period (shock to the newborn child, the brain damage, premature birth, asphyxia, iatrogenic mistakes) and postnatal period [a history of infectious diseases and complications of (measles and whooping cough), trauma (accidents), poisoning (e.g. lead) and food poisoning]. Classification of intellectual disability can be very different depending on the selected criteria. The most famous is a four stage classification of degrees: 1) light, 2) moderate, 3) a large and 4) deep retardation. As shown, genetic factors play a very important role in the causes of mental disability. Among the genetic factors that cause impairment are distinguished: changes in the number or structure of chromosomes, single-gene mutation, polygene and epigenetic heredity. More and more researchers focus on in-depth assessment of the role of genetic factors for these disorders. Not all of the factors has been discovered and thoroughly investigated, so further research is necessary. It is also clear that mental retardation, autism and epilepsy have a lot in common. Presented by us work presents some of the disease and their genetic causes.

Keywords: mental retardation, genetic factors, neurology, tuberous sclerosis, Rett syndrome, Angelman syndrome, Prader-Willi syndrome, Smith-Lemli-Opitz syndrome, mental retardation associated with fragile X chromosome, Duchenne muscular dystrophy
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December insolation and ultraviolet B radiation are associated with multiple sclerosis mortality in Poland
AKTUALN NEUROL 2013, 13 (2), p. 130–135
ABSTRACT

Background: The role of environmental factors (EF) determining the occurrence of multiple sclerosis (SM) is the subject of current investigations. Objective: To establish association between duration of insolation along with intensity of ultraviolet B (UVB) radiation and mortality rates for SM in Poland. Method: The study was based on assemblage of 2172 SM persons (M – 878, F – 1294) who died in Poland in the years 2004–2008. Regional previous duration of insolation was measured in hours, intensity of UVB radiation was monitored in minimal erythema dose units (MED), ozone concentration in the ground layer of atmosphere was recorded in μg/m3. Measurements of insolation, UVB radiation and ozone concentration were performed at provincial stations and territorial sites of the State Environmental Monitoring. EF were correlated to provincial crude mortality rates (CMR) for MS. Correlational test by Pearson was used in the study. Demographic data were obtained from the Central Statistical Office, information on EF was received from the Institute of Meteorology and the Institute of Environmental Protection. Results: Annual, average, crude MR for MS per 100,000 inhabitants in Poland was 1.12 (SD 0.14). In northern part it amounted to 1.20 (SD 0.18) and in southern part reached 1.03 (SD 0.11). Significant inverse correlation was found between previous minimal duration of insolation in December and CMR for SM in the country: r = -0.518, p = 0.044. Borderline significance of inverse correlation was established between minimal intensity of UVB radiation in December and crude death rates for SM in Poland: r = -0.478, p = 0.060. CMR for SM in northern Poland was accompanied not only by lower UVB radiation level, but also by slower spring increase and autumn faster decrease of radiation. No significant correlation was ascertained between the ground atmospheric ozone concentration or the annual number of days with ozone concentration above 120 μg/m3 and MS mortality rates. Conclusion: Inverse association was found between previous December insolation, UVB radiation level and mortality for SM in Poland. No correlation was ascertained between mortality and the part ozone concentration in the ground layer of the atmosphere.

Keywords: sclerosis multiplex, mortality, insolation, ultraviolet B radiation, prevention, Poland
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Implementation of computer programs in neuropsychological rehabilitation of cognitive impairment in SM patients
AKTUALN NEUROL 2013, 13 (2), p. 136–144
ABSTRACT

In the clinical picture of sclerosis multiplex (SM) the neurological functioning of patients is affected, besides the neurological symptoms, by neuropsychological symptoms, which include emotional disturbances, cognitive dysfunction, and personality factors. Memory, attention or executive functions disturbances affect reduction of adaptability, which play a key role in the quality of life of patients. Prevalence studies using large, community and clinical samples indicate that roughly 45–60% of patients with SM are cognitively impaired. Cognitive disorders with mobility disabilities may hinder daily functioning, often they become obstacle to take life tasks, so there is a need to develop new and effective rehabilitation programs for this group of patients. Neuropsychological rehabilitation of patients with SM is covered by the various types of impacts, especially reduction of cognitive deficits as much as possible. There is increasingly use of computer programs to cognitive trainings in neuropsychologist work.The basis for this type of impact is evidence of neuroplastic changes in people with SM. The greatest therapeutic effects are achieved through the cooperation of an interdisciplinary team, including neurologist, psychiatrist, neuropsychologist and physiotherapist. Obtaining such assistance by patients with SM still remains difficult in Poland. An example illustrating the effective usage of neuropsychological rehabilitation with the help of computer programs is a case study of a patient with SM.

Keywords: neuropsychological rehabilitation, sclerosis multiplex, cognitive impairment, depression, neuroplasticity
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The attempts to use stem cells in the therapy of selected disorders of the nervous system.
AKTUALN NEUROL 2013, 13 (2), p. 145–156
ABSTRACT

Until the second half of the twentieth century there was a view that central nervous system, after its evolution, was unable to any further regeneration. Moreover, it was said that neurogenesis (the development of nerve tissues) of an adult (postnatal) did not exist. However, in the course of time, some findings indicated that the process of new neurons was continuously formed in mature brains of primates as well as human beings. A breakthrough discovery of active, proliferating neural stem cells existing in a fully developed brain has given grave possibilitiesto modern neuroscience. The process of neurogenesis among adults is an extraordinary phenomenon. It plays an important role in a few processes. There is also evidence that neurogenesis may help answer the hippocampus to stress and prevent any onset of depression. Nowadays, it is identified to be three areas in the adult mammalian brain where processes of cell proliferation take place. These areas are: subventricular zone (SVZ), subgranular zone (SGZ) and posterior periventricular area (PPv). By excessive formating new tissues circulatory system is the opposite to the nervous system. Although the latter is the complex biological system with its cytostructure, neural network, the location of the functional centers and its integration it has a poor ability to regeneration. Because of the complexity of the central nervous system a few disorders can be distinguished such as: multiple sclerosis, ischemic stroke, Alzheimer’s disease, Parkinson’s disease or brain tumors. At present stem cells are matters of interest to scientists. Not only are stem cells being observed by researchers but also they are to be conducted studies on. The end result of these findings could be primarily usable for CNS regenerative therapies.

Keywords: neurogenesis, stem cells, central nervous system, regeneration, stem cell isolation
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