2007, Vol 7, No 3
Epilepsy as a problem of the elderly
Aktualn Neurol 2007, 7 (3), p. 141-147

Epilepsy in the elderly differs from that in younger people. It is an important and increasingly common clinical problem. Old age is the most common time to develop seizures and around 25% of new cases of epilepsy occur in elderly people. In people of 70 years and above, the prevalence of epilepsy has been estimated two times more to compared with the general population. The epidemiological studies showed that the value of incidence and prevalence in elderly epilepsy are similar in many countries. About one-half of cases of epilepsy in elderly cannot be linked to an identifitable cause, in the rest – 33% cerebrovascular disturbances, 12% dementia. In the elderly partial epilepsy dominated on tonic-clonic seizures. In connection to elongation of average age of population in Poland the number of the elderly epilepsy will be increase. Especially of the number of ischemic stroke in connection with epilepsy is typical in this age. To realize of scale of this problem the author according to the generally accepted the value of prevalence and incidence of epilepsy estimates suitable accounts with reference to our country. 

Keywords: elderly epilepsy, epidemiological aspects, post-stroke epilepsy, differential diagnosis, therapy
SYMPOSIUM: KURU: 50 YEARS. Kuru: 50 years later
Aktualn Neurol 2007, 7 (3), p. 148-157

Kuru is that unique field of scientific research, in which practically everything what has been achieved, had been achieved due to personal research endeavor of Daniel Carleton Gajdusek (born in 1923), one of the greatest scientists of the XX century. In October 11-12th, John Collinge and Michael Alpers organized at the Royal Society, London, UK, a meeting “The end of kuru: 50 years of research into an extraordinary disease”. That meeting was attended by the last survivors of early kuru research, who pioneered their work in the fifties of the XX century to open a new field of “slow viruses of man”. The latter term has been introduced by Björn Sigurdsson, who developed Institute of Experimental Pathology, University of Iceland. The term “slow viruses” has been then replaced by the term “prions”. The kuru field has been already honoured by two Nobel prizes – to Dr. D.C. Gajdusek (1976 with Baruch Blumberg, born in 1925) and to Stanley B. Prusiner (1997, born in 1942) and contributed to the third – for Kurt Wüthrich (born in 1938) for “for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution”. One of those molecules was prion protein in 1996. 

Keywords: kuru, prions, neuropathology, amyloid plaques, D.C. Gajdusek
SYMPOSIUM: KURU: 50 YEARS. Transmissible spongiform encephalopathies or prion diseases – update 2007
Aktualn Neurol 2007, 7 (3), p. 158-187
Prion diseases or transmissible spongiform encephalopathies are a group of neurodegenerative disorders characterized by a widespread deposition in the central nervous system, and some other tissues, of the pathological isoform of the prion protein (PrPd; “d” from disease). TSEs include: 
1) kuru; 
2) Creutzfeldt-Jakob disease (CJD), the disease that occurs in four etiologically forms: 
• sporadic CJD (sCJD), 
• familial CJD (fCJD), 
• iatrogenic CJD (iCJD), 
• variant CJD (vCJD); 
3) Gerstmann-Sträussler-Scheinker disease (GSS); 
4) fatal familial insomnia (FFI). 
There are also several TSEs in animals: 
– scrapie – in sheep, goats and moufflons; 
– bovine spongiform encephalopathy (BSE) and bovine atypical spongiform encephalopathy (BASE) or mad cow disease; 
– BSE passaged to: 
• domestic cats (feline spongiform encephalopathy, FSE) and large cats (lion, tiger, cheetah, ocelot and puma) 
• antelopes (kudu, nyala, oryx), bison; 
– chronic wasting disease in mule deer and elk; 
– transmissible mink encephalopathy in ranch-reared mink. 
Historically, the eponimic names are also included: atactic type of CJD or Betty Brownell syndrome, CJD with a cortical blindness (Heidenhain type) and the panencephalopathic type (Tateishi). The amyotrophic type is not TSE but motor neuron disease with dementi. In 1996, a new variant CJD (now only vCJD) was discovered as a result of a passage from BSE to humans. 
Keywords: transmissible spongiform encephalopathies, prions, kuru, Creutzfeldt-Jakob disease, review
SYMPOSIUM: KURU: 50 YEARS. The role of PrPc protein in process of neural differentiation in vitro and neurogenesis
Aktualn Neurol 2007, 7 (3), p. 188-194

The phenomena of neural differentiation in vitro and neurogenesis in vivo involve a numerous cellular proteins to create the differentiation signaling pathways. The role of the cellular isoform of prion protein PrPc – a product of the PRNP gene, seems also to be connected with a process of neural differentiation. The primary investigations in this field revealed increase of PRNP gene expression during both neurogenesis and neural differentiation in vitro; however, the majority of results were obtained with the use of animal models or cancer-derived cell lines. The latest experiments using neural stem/progenitor cells as an experimental models, seem to confirm the previous results, suggesting participation of PrPc in a neural differentiation. On the basis of the further analyses, PrPc appears to be a part of differentiation signaling pathways. Moreover, PrPc activity may contribute to acquire and maintain the functions specific for neurons. Surprisingly, the prion protein-deficient cells are still able to differentiate into neurons, although the process of differentiation is delayed. The controversy nevertheless persists about expression of PRNP gene during glial cells differentiation that is reflected in inconsistent published results, beginning with hypothesis postulating the importance of “astrocytic” PrPc for neural differentiation, ending with data presenting no PrPc expression in glial lineage. Studying the literature data does not allow to create the uniform PRNP expression pattern during neural differentiation. It rather seems to be an individual feature, which should be considered in the broader context of particular cell type and the specificity of metabolic processes accompanying neural differentiation in vitro or neurogenesis in vivo

Keywords: PrPc, PRNP, neural differentiation, neurogenesis, neuronal lineage, glial lineage
Natalizumab: a new way of multiple sclerosis therapy
Aktualn Neurol 2007, 7 (3), p. 195-201

Natalizumab (Tysabri®) is the first approved for therapy, commertially available selective antagonist of integrins. Integrins are glycoproteins belonging to adhesion molecules family, which play an important role in the process of cell adhesion. Natalizumab binds to α4 chain of integrins α4β1 and α4β7 present on the surface of almost all subpopulations of leukocytes. Blockade of interaction between integrin and its ligand prevents leukocyte transmigration through endothelium to the tissue site of inflammation. The clinical efficacy of natalizumab in remitting-relapsing MS was analyzed in two multicenter, randomized and placebo controlled third phase clinical trials: AFFIRM (Natalizumab Safety and Efficacy in RR-MS) and SENTINEL [Safety and Efficacy of Natalizumab in Combination with Avonex (IFN-β-1α) in Patients with MS). In AFFIRM trial natalizumab was evaluated in monotherapy, in SENTINEL study as add on therapy to IFN-β-1α. Both trials confirmed that natalizumab is beneficial in all analyzed endpoints. There was statistically significant decrease of relapse number and the risk of the disease progression. There was also beneficial influence of natalizumab therapy on the central nervous system (CNS) MRI parameters. After two years of therapy the number of gadolinium-enhanced MS plaques, as well as the number of the new and enlarging hyperintensive T2 plaques, was decreased. Because of the rare but serious side effect (progressive multifocal leukoencephalopathy, PML) the registration of natalizumab was suspended in June 2004. Detailed analysis of the results of both third phase clinical trials led to reapproval of natalizumab to therapy in June 2006. The strict criteria of patients’ inclusion to natalizumab therapy were established to minimize the risk of the serious side effects. 

Keywords: natalizumab, multiple sclerosis, immunomodulation treatment, adhesive molecules, integrines
Diabetic neuropathy in children and adult with type I diabetes – diagnosis and management
Aktualn Neurol 2007, 7 (3), p. 202-209

Diabetic neuropathy is one of the most common and serious complications of diabetes both type I and type II. In type I diabetes mellitus neuropathy usually assumes form of a distal symmetric polyneuropathy (DPN) and/or a diabetic autonomic neuropathy (DAN). Other forms as acute sensory neuropathy, cranial neuropathy, truncal radiculoneuropathy or proximal motor neuropathy are present sporadically in patients with type I diabetes. Damage to nerves in the abnormal environment of diabetes mellitus leads to diabetic neuropathy. There are three hypotheses that explain the pathogenetic mechanism of polyneuropathy: metabolic, vascular and immunological. Many diabetic patients have demonstrable abnormalities of autonomic function without any evidence of clinical disease. Tests of autonomic function and tests of conduction velocity in peripheral nerves are assumed to be a measure of neurological state and may be important methods of assessing therapy of diabetic complications. Control of hyperglycaemia is the basis of the adequate management. α-liponic acid is used due to some evidences suggesting the role of free radicals in pathogenesis diabetic neuropathy. Antiepileptics and antidepressants inhibiting selective norepinephrine and serotonin reuptake are administered for pain control in symptomatic management. 

Keywords: type I diabetes mellitus, diabetic neuropathy, peripheral neuropathy, autonomic neuropathy, diagnosis of neuropathy, management of neuropathy