2012, Vol 12, No 1
Alternative methods in the treatment of epilepsy
AKTUALN NEUROL 2012, 12 (1), p. 13-17
ABSTRACT

In spite of introduction of new generations of antiepileptic drugs, management of drug resistant epilepsy is still an unsolved issue. Therefore, we need an entirely new approach to the problem of lack of desired therapeutic effect in epilepsy, particularly when consecutive multidrug regimen proves ineffective. As some children respond favourably to ketogenic diet, the author suggests its use in adult patients too. Furthermore, legitimacy of this therapeutic modality has been confirmed by rigorous trials performed in this age group. Spectrum of possible applications of immunoglobulins in medicine, including neurology, is expanding continuously. Formerly, immunoglobulins were recommended in children with chronic epilepsy and concomitant immune deficit. Reduction of seizure frequency of after administration of immunoglobulins has been observed. Research has also focused on calcium channel blockers, as they may play a role in the pathogenesis of some types of seizures. Verapamil as added drug may also reduce the severity of seizures. Other blockers do not have such properties, but possible effects of vinpocetine are noteworthy. Statins are another important group of drugs contributing to reduction of seizures, particularly atorvastatin. Its antiepileptic effect is independent of cholesterol level reduction.As an adjuvant drug, it is often recommended in the elderly. To sum up, in properly managed drug resistant epilepsy, implementation of one of these treatment options should be considered.

Keywords: drug-resistant epilepsy, ketogenic diet, immunoglobulins, calcium channel blockers, statin
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Sylwia Janiak, Monika Kołodziejska
AKTUALN NEUROL 2012, 12 (1), p. 18-21
ABSTRACT

Epilepsy is one of the most frequent and oldest-known neurological disorders. While most people with epilepsy lead a normal life, their expected lifespan is 2-10 years shorter than that of their peers in general population, depending on epilepsy type. Mortality rate among persons with epilepsy is twice as high as in healthy people. Sometimes, they suffer sudden death from unclear reasons (sudden unexpected death in epilepsy, SUDEP). In most cases, SUDEP affects people aged 20-40. Most common causes of death in adults with epilepsy include: ischaemic heart disease, cerebral vascular disease, malignancy, respiratory tract infections, trauma and suicide. They account for nearly 80% of all deaths. Patients often die from causes which have led to the development of their epilepsy. Mortality rate in children with epilepsy may be even 90-fold higher than in their non-epileptic peers. Reliability of epidemiologic data concerning SUDEP is limited due to poor reporting of such cases and small number of post-mortem exams performed in these patients. In view of the relatively large population of patients with epilepsy, SUDEP becomes an important medical problem. Data have raised much interest among epileptologists and encouraged studies searching for causes, potential risk factors and possible preventive measures. This paper reviews the SUDEP phenomenon, possible risk factors, pathomechanisms associated therewith and available preventive strategies.

Keywords: epilepsy, sudden unexpected death in epilepsy (SUDEP), clinical criteria, risk factors, post-mortem exam
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Whether somatosensory evoked potentials can be a prognostic indicator in patients with immunomodulating therapies of multiple sclerosis?
AKTUALN NEUROL 2012, 12 (1), p. 22-25
ABSTRACT

Background: Based on clinical studies published to date, it is assumed that immunomodulation therapy (DMT) is effective in the treatment of relapsing-remitting form of multiple sclerosis. The aim of this study was an analysis of predictive value of somatosensory evoked potentials (SEP) in patients treated for two years with interferon (INF β-1a, IFN β-1b) and glatiramer acetate (GA). Material and methods: The study included 106 patients (35 men, 71 women, aged 18-54 years) diagnosed with multiple sclerosis, undergoing an at-least 2-years’ DMT treatment (IFN β-1a, IFN β-1b, GA). Results: Before treatment, normal SEP response was noticed in 37 patients (35%) and abnormal values – in 69 patients (65%). In the study group, 32 patients (30.1%) had a relapse during follow-up. In this group 6 patients had baseline normal SEP value, and others had abnormal SEP value. At the end of DMT, in normal baseline SEP group, the disease progression (defined as progression at least 1 point in EDSS scale) was seen in 8 patients, while in abnormal SEP group – in 18 patients. Conclusions: In patients with baseline abnormal SEP, relapses during DMT therapy were more frequent than in those with normal SEP.

Keywords: visual evoked potential (VEP), multiple sclerosis, immunomodulating therapy (DMT), demyelinating lesions, magnetic resonance
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Predictive value of visual evoked potential in immunomodulating therapy of multiple sclerosis
AKTUALN NEUROL 2012, 12 (1), p. 26-29
ABSTRACT

Background: Visual evoked potential is an essential element of the diagnosis of multiple sclerosis. It is useful in the detection of asymptomatic demyelinating lesions. The aim of this study was to determine, whether VEP, apart from its diagnostic role, can also be a predictor of responsiveness to immunomodulating therapy (DMT). Material and methods: The study recruited 110 patients (35 men, 75 women, aged 18-54 years) diagnosed with multiple sclerosis, subjected to an at least 2-years’ DMT treatment (IFN β-1a, IFN β-1b, GA). Results: In this group, 32 patients (29%) had a relapse during observation period. Normal baseline VEP was documented in 8 patients and an abnormal VEP – in the remaining 24. After 2-years’ treatment in the normal VEP group, disease progression was seen in 7 patients, 3 of whom had also new lesions in their MRI scans. In the abnormal VEP group, disease progression was seen in 22 patients, 12 of whom had new demyelinating lesions in their MRI scans. Conclusions: In DMT-treated group, clinical and radiological disease progression was more common in patients with abnormal baseline VEP compared with those with normal baseline VEP.

Keywords: visual evoked potential (VEP), multiple sclerosis, immunomodulating therapy (DMT), magnetic resonance
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Monoclonal antibodies in disease-modifying treatment of relapsing-remitting subtype of multiple sclerosis – current status and future perspectives
AKTUALN NEUROL 2012, 12 (1), p. 30-39
ABSTRACT

Recent studies indicate that relapsing-remitting subtype is the most common form of multiple sclerosis in Poland and that monoclonal antibodies appear to be an important option for patients not responding to first-line therapy with interferon beta or glatiramer acetate. The aim of such an immunomodulating therapy is to arrest progression of disease at its early phase, when inflammation predominates over neurodegeneration, i.e. at the time when chances for a therapeutic success are maximal, at least in theory. Currently available monoclonal antibodies, e.g. natalizumab, daclizumab, alemtuzumab and rituximab which inhibit immune cells, significantly reduce the size and number of lesions visualized by magnetic resonance imaging. Furthermore, by decreasing severity and frequency of relapses, they have a favourable effect on the patients’ clinical condition. The only exception is ustekinumab, which proved ineffective in this setting.Decision to start second-line drugs – in SM this means monoclonal antibodies – should be based on the patient’s general condition and coexisting diseases. In Poland only one antibody – natalizumab (Tysabri) has been registered in this indication, while the others are currently at the phase of clinical trials. Recently published data indicate that sometimes their use (natalizumab, rituximab) may have serious adverse effects, particularly development of progressive multifocal leukoencephalopathy. Use of alemtuzumab is associated with a high risk of autoimmune disorders, mainly of the thyroid. The aim of this article is a review of currently published clinical trials concerning the effectiveness of monoclonal antibodies in the treatment of relapsing-remitting subtype of multiple sclerosis, with a special emphasis on their adverse effects.

Keywords: multiple sclerosis, epidemiology, monoclonal antibody, natalizumab, daclizumab, alemtuzumab, rituximab, ustekinumab, therapeutic efficacy, side effects
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Incidence of dyskinesias in levodopa-treated Parkinson’s disease
AKTUALN NEUROL 2012, 12 (1), p. 40-43
ABSTRACT

The aim of this study was to assess the incidence of dyskinesias during long-term treatment of Parkinson’s disease with levodopa. Material and methods: Analysis encompassed 103 patients with Parkinson’s disease (54 with and 49 without dyskinesias) of similar age (64.37±6.94 vs. 64.94±6.81 years). Their clinical and neurological status was assessed using the Hoehn-Yahr scale, Unified Parkinson’s Disease Rating Scale (UPDRS), Mini-Mental State Examination (MMSE). Each patient has had a CT scan to assess brain atrophy and angiogenic lesions. Risk factors included in the analysis were: hypertension, hypercholesterolaemia, ischaemic heart disease and diabetes. Results: Dyskinesia more frequently developed in persons with hypertension, ischaemic heart disease, hypercholesterolaemia or diabetes. Furthermore, they presented more frequently cortical atrophy in their CT scans as compared with the control group (25 vs. 8). Levodopa doses were higher in patients with dyskinesias (1013.43±260.61 vs 877.55±216.46 mg) and duration of treatment was on the average 2 years longer than in the control group. Performance status as assessed by Hoehn-Yahr and UPDRS rating systems was similar in both groups. Conclusions: Our study indicates that in patients with Parkinson’s disease dyskinesias develop mostly in cases of more advanced neurodegenerative process, associated with longer duration of symptoms and use of higher doses of levodopa. This correlated with higher prevalence of additional risk factors in this group of patients.

Keywords: Parkinson’s disease, dyskinesias, levodopa, computed tomography, risk factors
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Nestin immunoexpression in pilocytic astrocytoma and glioblastoma
AKTUALN NEUROL 2012, 12 (1), p. 44-49
ABSTRACT

Pilocytic astrocytoma and glioblastoma are both primary glial tumours of the central nervous system with entirely different histological malignancy grades. One of their features is vascular proliferation, which in the case of glioblastoma is a hallmark of malignancy but not in the case of pilocytic astrocytoma. While vascular proliferations in both tumours usually differ in microscopic appearance, they may be quite difficult to discriminate in a sparse biopsy material and also in a pilocytic astrocytoma with increased proliferation index. Independent studies of glioblastoma have shed some light on the role of non-endothelial cells in tumour neoangiogenesis. These cells originate from neoplastic, nestin immunoreactive stem cells. Expression of this protein has been noticed in grade II-IV astrocytic tumours and in primary grade I glial tumours (e.g. pilocytic astrocytoma). The aim of this study was to assess nestin expression in tumour cells and in blood vessels of tumours at differing grades of malignancy, using immunohistochemical staining and confocal laser microscopy. In our material, nestin was expressed in the cytoplasm of most glioblastoma cells and isolated cells of pilocytic astocytoma.Cytoplasmic immunoexpression of nestin was also detected in cells lining single blood vessels and vascular proliferations. Results of this study suggest that nestin should not be used as the only marker used to differentiate malignant from benign vascular proliferation in CNS tumours.

Keywords: nestin, pilocytic astrocytoma, glioblastoma, microvascular proliferation, cancer stem cells
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Role of melatonin in pathophysiology and therapy of migraine
AKTUALN NEUROL 2012, 12 (1), p. 50-56
ABSTRACT

Migraine is one of the most common neurological disorders. In Poland, approximately 4 million individuals suffer from migraine headaches. A migraine headache may last 4-72 hours, is throbbing, moderate to severe in intensity, usually unilateral and is associated with nausea, vomiting, and hypersensitivity to light and sound. Lack of biological markers and inter-individual variations result in problems with correct diagnosis. Pathophysiological basis of migraine remains unclear, but recent research including neuroimaging and genetic studies, has significantly advanced our understanding of migraine pathophysiology. Since over 30 years, there is ongoing research on the role of melatonin – hormone enabling adaptation of the organism to cyclic changes in environmental conditions – in the pathophysiology of migraine. Experimental studies revealed manifold associations between secretion of melatonin and migraine, but this correlation has not been clearly determined. Several studies confirmed altered secretion of melatonin in patients with migraine. Available data assessing melatonin profile in persons with migraine depend on nature of headache (episodic or chronic) and temporal relationship of sampling to headache attack (ictal or interictal). Currently, there are only few reports concerning attempts at using melatonin in the treatment of migraine. Largescale, multicentre trials are necessary to define principles of use of melatonin in the treatment of migraine.

Keywords: migraine, melatonin, migraine pathophysiology, headache, pineal gland
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RETRACTED - The role of non-coding RNA in nervous system pathology
AKTUALN NEUROL 2012, 12 (1), p. 57-64
ABSTRACT

Besides proteins and low-molecular-weight regulators, non-coding RNA (ncRNA) plays an important regulatory role in nervous system function. Recent studies revealed that this is an important mechanism regulating expression of cellular genetic information. Number of ncRNA molecules discovered to date is increasing continuously, while the exact role of most of them is still poorly understood. ncRNA plays a crucial role in nervous system development and function, both in normal and in pathological conditions. Enormous potential of ncRNA-based control of central nervous system function is evidenced by multitude of processes where their contribution has been demonstrated. These include mechanisms of synaptic plasticity, learning, memory, and reaction to stress. Defective ncRNA biosynthesis results in development of several neurodegenerative, neurodevelopmental and neuropsychiatric disorders. As long as their role remains obscure, it will be impossible to elucidate complex intracellular processes going on in nervous system cells. Recently, interest of scientific community focused on microRNA (miRNA). These small, endogenous, non-coding molecules participate in several biological processes, e.g. proliferation, angiogenesis, cell differentiation or apoptosis. Nearly 70% of human miRNA discovered to date are located in the brain. As estimated, they control expression of about 50% of genes, and affect almost all metabolic pathways. Therefore, they appear a perfect target of research when looking for novel therapies for central nervous system diseases.

Keywords: non-coding RNA, microRNA, biogenesis of microRNA, regulation of gene expression, central nervous system, role of ncRNA in neurological diseases
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Application of magnetic field and visible light in the treatment of low back pain and sciatic neuralgia
AKTUALN NEUROL 2012, 12 (1), p. 65-68
ABSTRACT

Background and aim of the study: Sciatic neuralgia, ischialgia (Latin: ischias) is the syndrome of signs resulting from compression on spinal radices L4, L5 or S1, which form the sciatic nerve. Therapeutic approach in the treatment of these condition changes considerably and selected physiotherapeutic techniques are used increasingly often. Recently, we see an increasing number of publications concerning application of low frequency magnetic fields in medicine. Wide range of indications and possible practical uses provides a promising framework for their clinical applications. Material and method: Forty-seven patients with a diagnosis of sciatic neuralgia caused by degeneration of intervertebral disc were included in the study. Patients were divided into 3 groups treated by magnetotherapy, magnetostimulation or magnetoledtherapy in order to compare their efficacy. Subjective assessment of severity of pain was performed using the VAS scale. Additionally, a questionnaire was used, assessing frequency of analgesic medication. Quality of life was evaluated using the EuroQoL scale. Each patient underwent the Lasègue test during his/her physical examination. Results: Our results revealed a significant reduction of pain as expressed by VAS scale (p<0.01), considerably reduced consumption of analgesic medication and improved quality of life as expressed by EuroQoL score (p<0.01) after application of low frequency magnetic fields. Conclusions: Treatment with magnetic fields, independent of implemented technique of delivery, resulted in reduction of pain, improved quality of life and reduced demand for analgesic medication. No significant advantage of any one of the methods analysed in relation to results obtained has been observed.

Keywords: physiotherapy, treatment, physical medicine, magnetic fields, sciatic neuralgia
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