Clinical Neuroscience

[Calcium ion is a common denominator in the pathophysiological processes of amyotrophic lateral sclerosis]

PATAI Roland1, NÓGRÁDI Bernát2, MESZLÉNYI Valéria2, OBÁL Izabella3, ENGELHARDT József István3, SIKLÓS László1

JULY 30, 2017

Clinical Neuroscience - 2017;70(07-08)


[Amyotrophic lateral sclerosis (ALS), the most frequent motor neuron disease is characterized by progressive muscle weakness caused by the degeneration of the motor neurons in the spinal cord and motor cortex. However, according to the recent observations, ALS is a rather complex syndrome which frequently involves symptoms of cognitive impairment. Therefore, ALS cases can be interpreted in a clinico-pathological spectrum spanning from the classical ALS involving only the motor system to the fronto-temporal dementia. The progression of the disease, however, manifested in the degeneration of the upper and lower motor neurons, is based on the same complex pathobiology. The main elements of the pathomechanism, such as oxidative stress, excitotoxicity, immune/inflammatory processes and mitochondrial dysfunction are well described already, which operate in orchestrated way and amplify the deleterious effect of each other. It is assumed that calcium ions act as a catalyst in this interaction, hence each of the individual mechanisms has strong, positive and reciprocal calcium dependence thus may combine the individual pathological processes into a unified escalating mechanism of neuronal destruction. This review provides an overview of the role of calcium in connecting and amplifying the major mechanisms which lead to degeneration of the motor neurons in ALS. ]


  1. MTA Szegedi Biológiai Kutatóközpont, Biofizikai Intézet, Szeged
  2. A Szegedi Orvosbiológiai Kutatások Jövôjéért Alapítvány, Szeged
  3. Szegedi Tudományegyetem, Neurológiai Klinika, Szeged



Further articles in this publication

Clinical Neuroscience

[Guidelines for the treatment of traumatic brain injury - 2017]

BÜKI András, BARZÓ Pál, DEMETER Béla, KANIZSAI Péter, EZER Erzsébet, TÓTH Péter, HORVÁTH Péter, VARGA Csaba

[Traumatic brain injury (TBI) is recognized to be the main cause of death and disability in the first four decades representing a major socio-economical problem worldwide. Recent communications revealed a particularly worrying image about the quality of care for TBI in Hungary. For any improvement a systematic approach characterized by utilization of scientific evidence based guidelines forming the basis for close monitoring of the actual care are considered a prerequisite. In Hungary the first evidence based guidelines in the field of TBI have been issued by the National Society for Anesthesiology and Intensive Care more than two decades ago followed by joint guidelines of the Hungarian Neurosurgical Society and the Hungarian College of Neurosurgeons. These publications were primarily based on the work of the European Brain Injury Consortium as well as guidelines issued by the Brain Trauma Foundation. Recent renewal of the latter and a need to refresh the outdated national guidelines was met by a call from regulatory authorities to issue the updated version of the Hungarian TBI-guidelines. The present review is aimed to briefly summarize the most fundamental elements of the national head injury guidelines that would hopefully be officially issued in a far more detailed format soon.]

Clinical Neuroscience

[Valproate in the treatment of epilepsy and status epilepticus]

JANSZKY József, TÉNYI Dalma, BÓNÉ Beáta

[According to Hungarian guidelines, valproate - with the exception of infants and small children as well as fertile women - is the first drug of choice in generalized and unclassified epilepsies because it is effective in most seizure types and epilepsy syndromes. It is highly effective in juvenile myoclonic epilepsy. Even though it is not the first-line drug in focal epilepsies, if the first-line therapy is ineffective, it is a plausible alternative as second choice therapy, owing to its different mechanism of action. If the type of epilepsy can’t be surely established, valproate is the drug of choice, as it possesses the broadest-spectrum among antiepileptic drugs. After administration of benzodiazepines, intravenously applied valproate can be a first choice therapy in all types of status epilepticus, owing to its broad-spectrum and efficacy. Valproate is the first-choice therapy in patients with glioblastoma - independently of the seizure type -, as it is likely to improve the survival rate with 2-10 months and the effectivity of chemo- and radiotherapy. Valproate is generally not suggested for fertile women, but - as it is the most effective therapy in some epilepsy syndromes -, the patient has the right to choose valproate therapy, thus undertaking the elevated risk of developmental abnormalities, for higher safety regarding seizures. If only valproate therapy owns the ability to obtain seizure freedom, then stopping its administration is not suggested, but a low dosage has to be aimed (500-600 mg/day, but not more than 1000 mg/day): according to some studies, most idiopathic generalized epilepsies can be controlled by low valproate dosage. Stopping valproate therapy in case of an ongoing pregnancy is not suggested. ]

Clinical Neuroscience

Validation of the Hungarian version of the Test Your Memory

KOLOZSVÁRI Róbert László, KOVÁCS György Zoltán, SZŐLLŐSI József Gergő, HARSÁNYI Szilvia, FRECSKA Ede, ÉGERHÁZI Anikó

Concerns regarding the projected prevalence of Alzheimer’s disease (AD) over the next several decades have stimulated a need for the detection of AD in its earliest stages. A self-administered cognitive test (Test Your Memory, TYM) is designed as a short, cognitive screening tool for the detection of AD. Our aim was to validate the Hungarian version of the Test Your Memory (TYM-HUN) test for the detection of AD. The TYM-HUN was applied in case of individuals aged 60 years or more, 50 patients with AD and 50 healthy controls were recruited into the study. We compared the diagnostic utility of the Hungarian version of the TYM in AD with that of the Mini-Mental State Examination (MMSE). The sensitivity and specificity of the TYM-HUN in the detection of Alzheimer’s disease were determined. The patients with AD scored an average of 15.5/30 on the MMSE and 20.3/50 on the TYM-HUN. The average score achieved by the members of the healthy control group was 27.3/30 on the MMSE and 42.7/50 on the TYM. The total TYM-HUN scores significantly correlated with the MMSE scores (Spearman’s rho, r=0.8830; p<0.001). Multivariate logistic regression model demonstrated that a one-point increase in the TYM score reduced the probability of having AD by 36%. The optimal cut-off score on the TYM-HUN was 35/36 along with 94% sensitivity and 94% specificity for the detection of AD. The TYM has a much wider scoring range than the MMSE and is also a suitable screening tool for memory problems, furthermore, it fulfils the requirements of being a short cognitive test for the non-specialists. The TYM-HUN is useful for the detection of Alzheimer’s disease and can be applied as a screening test in Hungarian memory clinics as well as in primary care settings.

Clinical Neuroscience

[Is second-line immunomodulatory treatment effective in multiple sclerosis?]


[Purpose - Natalizumab is the first evidence based monoclonal antibody, which was launched for treatment in relapsing remitting multiple sclerosis in Hungary in 2010. Standardized follow-up is required to use it. Our aim was to evaluate the efficacy and to monitor the safety of natalizumab treatment by using an electronic database established for MS registry. Clinical activity was measured by annual relapse rates, functional status of patients measured by EDSS and MFSC. Radiological activity was evaluated by standard MRI protocol. Data, results of MS patients and side effects of natalizumab treatment were recorded in iMed software. Results - 31 patients started the natalizumab treatment after 6.5±5.8 years from the onset of MS. The efficacy of treatment was evaluated after a mean of 67 (min: 14 max: 128) infusions in December 2016. The drop-out rate was low, due to the presence of neutralising antibodies in one case, pregnancy in two cases and development of malignant disease in one case which was not related to the natalizumab treatment. The treatment was well tolerated with excellent compliance without serious side effects. The annual relapse rate reduced from a mean of 1.7 to 0.03 (p<0.000001) in the first 12 months of treatment compared to the pretreatment 12 month activity, and it stayed at low level during the whole follow up. EDSS was stable or improved with an exception of two cases. In 23 subjects (77%) lack of new/enlarging T2 lesions and lack of gadolineum-enhancing lesions on MRI were observed. 18 patients (60%) had no evidence of disease activity (NEDA-3). PASAT test improved in most of the cases. Conclusion - The natalizumab therapy was very effective in all cases including those patients who had active disease under the previous immunomodulatory treatment.]

Clinical Neuroscience

[Systemic thrombolysis after the administration of idarucizumab in acute ischemic stroke]


[Introduction - Expanding indications have resulted in an increasing number of patients taking novel oral anticoagulants, posing a major treatment dilemma in acute ischemic stroke. Case presentation - We present a successful intravenous thrombolysis in a dabigatran-treated patient with acute ischemic stroke after the administration of idarucizumab. Discussion - According to current guidelines, systemic thrombolysis is contraindicated under treatment with novel oral anticoagulants (taken within 48 hours). In this scenario, idarucizumab offers a solution by reversing the anticoagulant effect of dabigatran. Conclusion - Although there have only been case reports published so far, the dabigatran-antidote idarucizumab seems to give new therapeutic opportunities in the treatment of acute ischemic stroke.]

All articles in the issue

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[The role of alfacalcidol in the prevention of osteopenia following renal transplantation]


[AIM - The aim of this prospective study was the long-term evaluation of the effect of calcium and alfacalcidol treatment on calcium metabolism in patients with renal transplantation. METHODS - Patients were divided in two groups. Patients in Group 1 (n=159) received calcium substitution, while patients in Group 2 (n=81) were treated with alfacalcidol. Serum Ca, P, Mg, alkaline phosphatase (AP) and PTH levels were determined before and after transplantation regularly for three years. Femur neck and lumbar vertebral bone mineral densities (BMD) were measured at the same time after transplantation. RESULTS - After transplantation the mean serum calcium level significantly increased, while the mean serum phosphate level significantly decreased in both groups. After the operation the PTH levels decreased in both groups and it was found to be more pronounced in the alfacalcidol group.The majority of patients had osteopenia in the follow-up period. Between the third month and the third year after transplantation, BMD increased by 9.4% in Group1, and decreased by 4% in Group 2 at the lumbar spine. At 3 years the mean BMD value at the femoral neck was increased by 6.5% in Group 1, and by 6.7% in Group 2, compared to the 3-month values.The change in BMD was only significant at the lumbar spine, in Group 1 (p=0.019). During the follow-up period osteonecrosis was diagnosed in 6 patients in Group 1 and in 9 cases in Group 2. CONCLUSION - Alfacalcidol treatment decreased secondary hyperparathyroidism more rapidly and effectively, which was also indicated by the more pronounced decrease of serum PTH levels. During the 3 years follow-up period, BMD increased in both groups except for the lumbar spine in Group 2, however, the majority of the patients still had osteopenia.The study could not demonstrate a superiority of alfacalcidol over calcium supplementation in the prevention of posttransplantational osteopenia.]


[Calcium supplementation and the risk of cardiovascular disease - Real apprehension or picking the spin?]


[Some data shows that calcium supplementation, a basic intervention for treating osteoporosis in postmenopausal women, may increase the risk of atherosclerotic vascular disease. Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. However, the deposition of calcium into the vascular wall is due to an active mechanism, involving such genes and proteins which play role in bone metabolism. In this work the data about the cardiovascular side effect of calcium supplementation are reviewed. Also, I demonstrate studies with the conclusions that calcium supplements with or without vitamin D do not increase the risk of cardiovascular events, especially that of myocardial infarction.]


[Osteoporotic patient’s use of prescription drugs - pilot study]


[BACKGROUND - In Hungary, the number of the highest mortality hip fractures is between 12 000-15 000 per year. The cost of treating hip fractures is several times higher than that of preventive medical therapy. Thus, the compliance of patients with osteoporosis is of great importance. METHODS - Using the informatical database of St. András Rheumatology Hospital at Héviz, we collected one year’s prescription drugs for osteoporosis and compared them with the number of drugs obtained by the patients, determined from National Health Insurance data. RESULTS - In general, the patients obtained 75% of prescription drugs. From the 4354 boxes of prescribed antiporotics, 3637 contained bisphosphonate (not considering vitamin D and calcium). Within this group, 88% of combination preparations were obtained, which is a greater ratio than that of non-combination bisphosphonates (84%). CONCLUSIONS - On the basis of our results, we posit that prescription of a combination preparation somewhat improves the patients’ compliance. The low concordance of vitamin D and calcium preparations is worrying.]

Clinical Neuroscience

[The role of β-amyloid and mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease]


[Alzheimer’s disease is the most common form of dementia in mid- and late life. The 7-10% of the population over 65 and the 50-60% of the population over 85 are affected by this disease. On the contrary of its prevalence the pathogenesis of the disease is not well defined and there is no effective neuroprotective therapeutic agent. Three predominant neuropathological features of the Alzheimer’s disease brain are intracellular neurofibrillary tangles consisting mainly of the hyperphosphorylated protein t; the extracellular amyloid deposits (neuritic plaques) consisting of amyloid b peptide; and the extensive neuronal cell loss in the hippocampus and in portions of the cerebral cortex. The possible reason of the extensive neuronal cell loss can be the mitochondrial dysfunction observed in Alzheimer’s disease. Beyond the unclarified pathogenesis the causality of these characteristic neuropathologic phenomena are still unknown. In this study we would like to deal with two actual hypotheses, with the amyloid cascade and with the mitochondrial cascade hypotheses. We try to give an overview of these two hypotheses and to depict their interrelationship.]


[The role of calcium in the chemoprevention of colorectal cancer]


[One of the most exciting research areas of the past decade has concerned the chemoprevention of colorectal cancer (CRC). Numerous clinical studies have been conducted on the preventive role of NSAIDs, high fibre intake, selenium, phytooestrogens, hormone replacement therapy, antioxidants, COX-inhibitors, folic acid and calcium, however, their results are controversial. Among the suggested chemopreventive agents, the preventive role of calcium is supported by the strongest evidence.This paper aims to review the available facts on the role of calcium. Recent studies suggest that appropriate calcium intake may partially counterbalance the effect of the genes that contribute to the development of CRC. Experimental data show that calcium directly influences the expression of several genes involved in tumorigenesis and that it is also involved in a number of signalling pathways that control cell proliferation, differentiation and apoptosis.These effects mostly arise through the activation of the calcium sensing receptor. The main goal of this review is to draw attention to the established chemopreventive role of calcium in CRC. Published data suggest that a lifelong daily calcium intake between 1200 to 1500 mg (even 2000 mg in high risk groups) would significantly decrease the incidence of CRC by inhibition of tumorigenesis.]