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A Susac-szindróma ritka, többszörös szervi érintettséggel járó kórkép, melyet encephalopathiából, a retinát ellátó artéria ágainak okklúziójából és halláscsökkenésből álló triász jellemez. Ritka előfordulása, fluktuáló lefolyása és a hosszabb-rövidebb ideig inkomplett klinikai kép miatt sokszor nem ismerik fel, pedig az időben megkezdett kezelés a prognózist kedvezően befolyásolja. Módszer: Közleményünkben egy beteg esetét ismertetjük, és összefoglaljuk a kórkép legfontosabb ismérveit, diagnosztikai és terápiás lehetőségeit. Eredmények: A 30 éves nőbeteg ismeretlen eredetű encephalopathia, napok alatt kialakuló személyiségváltozás, meglassult gondolkodás, indítékhiány miatt került a pszichiátriai, majd a neurológiai klinikánkra. A koponya MR-vizsgálata multiplex fehérállományi laesiókat, liquorvizsgálata emelkedett összfehérjét mutatott. Az anamnézisben szereplő ismétlődő kétoldali látászavar, halláscsökkenés és migrénes fejfájás az encephalopathiával együtt a fiatal nőbeteg esetében Susac-szindróma lehetőségét vetette fel. Az immunszerológiai vizsgálatok szisztémás kötőszöveti betegséget nem jeleztek, a thrombophilia irányában végzett vizsgálatok negatívak voltak. A fundoszkópia és a fluoreszcens angiográfia a retinaerek többszörös okklúzióját, az audiogram kétoldali típusos halláscsökkenést mutatott. A liquor vizsgálata a szindrómára jellemző összfehérje-emelkedést jelezte. A krónikus szteroidterápia a tünetek regresszióját eredményezte. Következtetések: Egy magyar eset ismertetésével célunk ráirányítani a figyelmet egy olyan ritka kórképre, melynél az interdiszciplináris gondolkodás a klinikai diagnózis alapvető része.

It is necessary to rethink, from time to time, the efficacy of various treatment methods and, consequently, their place in the curing of certain pathological conditions. History of the development of methods throws a light on the fact that it is not always a question to be solved that brings about research; but there are cases when a technique realized for a totally different purpose is being used as a therapeutic process. In autoimmune illnesses, the plasmapheresis therapy is not of recent origin; in spite of that, however, a number of experiences, collected in the treatment of illnesses having divergent pathological symptoms, is not sufficient in itself to establish effectiveness without random double-blind tests. Intervention trying to obtain results under any circumstances (heroic medicine) is to be avoided. When evaluating results in general, however, we must take into consideration the proportion of costs also (cost/benefit principle).

There is a lack of data on the impact on health related quality of life of peripheral neuropathic pain in Hungary. The main aims of the study were to assess the health related quality of life of non-diabetic PeNP patients identified in general practices through screening, and to assess the relationship between condition specific pain scores and health state utilities.Non-diabetic patients aged 30 years were recruited in 10 general practices in Hungary. At first, patients filled in the PainDETECT Questionnaire (PD-Q) and those who have achievedor =13 PD-Q score (unclear or possible neuropathic pain) were further assessed by the DN4 questionnaire. Patients with PD-Q score18 or DN4 score 4 were considered to have PeNP and they completed the EQ-5D health questionnaire.Among the 111 patients identified as non-diabetic PeNP patients the mean age was 62 (SD=14) years, 69% were women. Average EQ-5D score was 44% lower than the gender and age matched Hungarian norm (0.42 vs. 0.75, p0.001) and it worsened with increasing pain intensity. The pain/discomfort and anxiety/depression were the most affected EQ-5D dimensions. Strong relationship was demonstrated between the PD-Q and EQ- 5D score. Most of the PeNP patients (86%) were undiagnosed.Non-diabetic PeNP pain has a huge negative impact on health related quality of life. Although PeNP is a serious chronic condition, the disease burden is seriously underestimated, both on the level of individuals and society, due to the fact that patients are rarely identified.

Human fibroblast growth factor 21 (FGF21) is a regulator of lipid and glucose metabolism. It is expressed in skeletal muscle and may be a sensitive and specific marker for mitochondrial diseases and other neuromuscular disorders.Serum FGF21 levels were determined in 71 human samples. Thirty patients with mitochondrial disease, 16 patients with myotonic dystrophy type 1 (DM1), 5 patients with facioscapulohumeral dystrophy, and 20 healthy controls were enrolled. Results Serum FGF21 levels were significantly elevated in patients with progressive external ophthalmoplegia and DM1 compared with patients with facioscapulohumeral dystrophy, other types of mitochondrial diseases, and controls. In the mitochondrial disorder group, serum FGF21 levels were related to the number of ragged blue fibers. Significant insulin resistance was found in DM1 that might be responsible for FGF21 elevation. Conclusions FGF21 elevation may be associated with certain types of mitochondrial disease, and it is influenced by insulin resistance. Muscle Nerve 55: 564-569, 2017.

Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term 'epilepsy' which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level "A") as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient's compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.

BACKGROUND The Unified Dyskinesia Rating Scale (UDysRS) was published in 2008. It was designed to be simultaneous valid, reliable and sensitive to therapeutic changes. The Movement Disorder Society organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new UDysRS and its validation process into Hungarian. METHODS After the translation of UDysRS into Hungarian and back-translated into English, it was reviewed by the UDysRS translation administration team. Subsequent cognitive pretesting was conducted with ten patients. For the large field testing phase, the Hungarian official working draft version of UDysRS was tested with 256 patients with Parkinson's disease having dyskinesia. Confirmatory factor analyses (CFA) determined whether the factor structure for the valid Spanish UDysRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the Spanish-language version. RESULTS For the Hungarian UDysRS the CFI was 0.98. CONCLUSION The overall factor structure of the Hungarian version was consistent with that of the Spanish version based on the high CFIs for the UDysRS in the CFA; therefore, this version was designated as the Official Hungarian Version Of The UDysRS.

Parkinson's disease is a well known representent of the movement disorder group of neurological disorders. The diagnosis of Parkinson's disease is based on specific symptoms and signs of movement abnormalities. In addition to classic motor symptoms, Parkinson's disease has characteristic non-motor features, and some of these emerges the classic signs.The authors discuss characteristics and therapeutic interventions in Parkinson's disease related sleep disturbances.The authors reviewed and summarised literature data on sleep disorders in Parkinson's disease published in the PubMed database up to January 2015.Sleep problems are important non-motor complains (insomnia, hypersomnia, REM behaviour disorder, sleep apnea and restless legs syndrome). The neurodegenerative process of the brain-stem, the effect of symptoms of Parkinson's disease on sleep and concomitant sleep disorders constitute the background of the patient's complains.Appropriate diagnosis and therapy of the consequential or concomitant sleep disorders in Parkinson's disease will help to improve the patient's quality of life.

In the present review the recent developments in the definitions of neurocognitive disorders associated with Parkinson's disease are summarized including the possibilities for screening and treating. For a long time, the recognition of neurocognitive disorders associated in patients with Parkinson's disease was unsatisfactory due to the heterogeneity of definitions. The recently developed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) introduced the definitions of mild and major neurocognitive disorders instead of mild cognitive impairment and dementia. The new DSM-5 definitions are clinically well applicable; therefore, the validation of the most frequent screening tests (Mini-Mental State Examination; Addenbrooke's Cognitive Examination; Montreal Cognitive Assessment; Mattis Dementia Rating Scale) is warranted. Based on a Hungarian sample of 295 patients with Parkinson's disease, the cut-off scores having the best discriminative values are highly dependent on education years (Addenbrooke's Cognitive Examination: 0-8 years of education: 82.5 points, 9-12 years of education: 83.5 points, and ≥13 years of education: 84.5 points; Mini-Mental State Examination: 26.5-27.5-28.5 points, Montreal Cognitive Assessment: 23.5-24.5-24.5 points, Mattis Dementia Rating Scale: 138.5-139.5-139.5 points, respectively).

The aim of this study was to evaluate the long-term adverse effect (AE) profile of azathioprine (AZA) plus methylprednisolone combined immunosuppressive treatment in myasthenia gravis (MG) in a larger patient cohort. A prospective, open, observational study was conducted on 163 MG patients treated with combined immunosuppressive medication for a mean duration of 35.5 months (range 9-79 months). During the treatment course, AEs occurred in 61.4% of patients; 18% of these patients developed both steroid- and AZA-related AE, 15% had purely AZA-related AE and 67% had steroid-associated AEs. Severe AEs were encountered in only 6.7% of patients in whom treatment had to be discontinued. The clinical severity of MG at the start of the immunosuppressive treatment was positively correlated with the frequency and severity of AEs during the treatment, and patients with severe MG were found to be at higher risk of developing AEs during the combined immunosuppressive treatment. Combined immunosuppressive treatment of MG patients is well tolerated, and severe AEs requiring treatment cessation are rare. The incidence of steroid-related AEs is high during long-time therapy which underlines the importance of its combination with AZA. The probability of developing AEs seems to correlate with the severity of MG at the beginning of the treatment.

Using the in vivo enzyme protection-enzyme inhibition method, we visualized the distribution of the intraventricularly and cisternally (cisterna magna) injected ambenonium chloride (Am) bound reversibly to the extracellular acetylcholinesterase enzyme (AChE) in the rabbit brain in order to describe the extracellular flow pathways from the cerebrospinal fluid (CSF). We found that the distribution of Am-protected AChE (indicating the Am itself) is similar to tracers having no intracerebral binding sites. The topographical distribution after both ways of application indicates a preferential penetration of Am into the limbic structures of the cerebral hemispheres in a predictable topographic sequence starting from the corticoid areas, allo- and periallo cortices followed by the mesocortical regions and then, in a limited extent, to the isocortex. The lentiform nuclei and the central part of diencephalic halves are inaccessible to Am. The hierarchic order in the sequence of diffusion from the CSF into the hemispheric subpial regions and the distribution pattern of Am resemble the stereotypic topographic expansion pattern and the predominantly limbic distribution of neurofibrillary tangles (NFTs) in Alzheimer's disease and related conditions.

Neurology is currently recognized as an independent clinical and academic specialty in Hungary, but the early history of Hungarian neurology was intertwined with the development of internal medicine and psychiatry. Up to the end of the 19th century, neurologic patients were mostly treated at internal medicine departments.

Leber's hereditary optic neuropathy (LHON) is associated with point mutations in the mitochondrial DNA (mtDNA), coding for a mitochondrial respiratory chain complex I subunit. It is characterized by bilateral, usually sequential, optic neuropathy and may co-occur with multiple sclerosis-like white matter lesions. Despite repeated clinical reports including MRI and histopathological examination of the visual system, neuropathological descriptions of LHON associated with multiple sclerosis-like syndrome are lacking. We present here the case of a female patient with a point mutation at nucleotide position T14484C, who suffered from relapsing episodes of visual loss of both eyes and consecutively developed Hashimoto thyroiditis as well as widespread demyelinating CNS lesions outside the visual system. She died of bronchopneumonia at the age of 44 years, after a disease duration of 19 years, with progressive deterioration, epileptic seizures and immobility. Immunohistochemical analysis on formalin-fixed and paraffin-embedded tissue reveals a spectrum of neuropathological changes, including actively and inactively demyelinating plaques in the white matter and optic nerve, vacuolation and cystic necrosis with CD8-positive T cells in the frontal lobe, axonal damage, and vacuolation of white matter. Tissue destruction is associated with upregulation of mitochondrial manganese superoxide dismutase within the lesions and an increase in the expression of inducible nitric oxide synthase within macrophages and microglia. This variable phenotype of extraoptic LHON disease suggests that mtDNA mutations may affect the nervous system on a common metabolic basis and occasionally may aggravate or initiate autoimmune pathology.

In the advanced Parkison's disease (PD) the late complications of levodopa therapy have to be considered: motor and/or non-motor fluctuations with or without disturbing dyskinesias. The non-motor fluctuations often influence the quality of life (QoL) in a much more negative way compared with the motor symptoms. In the treatment of advanced PD there are several device-aided methods - deep brain stimulation, apomorphine pump, levodopa/carbidopa intestinal gel (LCIG) - to improve the symptoms, the QoL, sometimes even in an individual, tailored custom form. The LCIG therapy was introduced in Hungary in 2011. Here we summarize the data of our patients: we have tested almost 60 patients and in 43 cases we have started this treatment. We analyze the duration of illness, levodopa therapy, motor and non-motor fluctuation of patients and present our experiences with the test phase and the chronic LCIG therapy via PEG/PEJ implantation. We paid attention to the surgery and device - depending side effects. Our experiences are similar to the international data. In patients selection ,,the right treatment, to the right patient, in the right time" is of importance.

Introduction. Among the nonmotor features of Parkinson’s disease (PD), cognitive impairment is one of the most troublesome problems. New diagnostic criteria for mild and major neurocognitive disorder (NCD) in PD were established by Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). The aim of our study was to establish the diagnostic accuracy of widely used screening tests for NCD in PD.Methods. Within the scope of our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrooke’s Cognitive Examination (ACE), Mattis Dementia Rating Scale (MDRS), Mini Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA)) in 370 PD patients without depression.Results. MoCA and ACE feature the finest diagnostic accuracy for detecting mild cognitive disorder in PD (DSM-5) at the cut-off scores of 23.5 and 83.5 points, respectively. The diagnostic accuracy of these tests was 0.859 (95% CI: 0.818–0.894, MoCA) and 0.820 (95% CI: 0.774–0.859, ACE). In the detection of major NCD (DSM-5), MoCA and MDRS tests exhibited the best diagnostic accuracy at the cut-off scores of 20.5 and 132.5 points, respectively. The diagnostic accuracy of these tests was 0.863 (95% CI: 0.823–0.897, MoCA) and 0.830 (95% CI: 0.785–0.869, MDRS).Conclusion. Our study demonstrated that the MoCA may be the most suitable test for detecting mild and major NCD in PD.

Background Parkinson's disease (PD) is a neurodegenerative disorder mainly marked by selective degeneration of dopaminergic neurons that leads to disabling motor and cognitive impairment. This condition is less widely appreciated as a disease associated with a substantial variety of pain syndromes, although the prevalence of pain is relatively high. Repeated painful stimulation of peripheral nerves can cause pain ‘wind-up’ if the frequency of the stimulation is adequate and specifically stimulates the afferent C-fibres. We presumed that in case of PD, pain or pain severeness might be frequently caused by the aggravation of the ‘wind-up’ phenomenon due to any central or peripheral lesions or functional alterations. Methods To test for this hypothesis, we compared three groups (patients with left- and right-dominant PD and control subjects) using functional magnetic resonance imaging and thermally induced pain. Results Patient showed higher average ‘wind-up’ scores, compared to the healthy subjects, with lower values on the more affected sides compared to the less affected ones. In group level comparisons, patients had higher activation during ‘wind-up’ compared to control subjects in two main areas; these were the posterior division of cingulate gyrus and the precuneus cortex. In case of patients, further analyses showed that applied heat pain on the less affected side elicited higher activation in the supramarginal and postcentral gyri. Conclusions These differences may arise from the deficiency in the efferent information, as well as the alterations in the central processing. It is highly likely that both processes contribute to this phenomenon simultaneously.

Objective Myotonic dystrophy type 1 (DM1) is a common adulthood muscular dystrophy, characterized by muscle wasting, myotonia, and multisystemic manifestations. The phenomenon of involuntary muscle contraction during myotonia offers a unique possibility of investigating brain motor functions. This study explores cortical involvement during grip myotonia in DM1. Materials and methods Sixteen DM1 patients were enrolled in the study. Eight patients had apparent grip myotonia, while eight patients did not (control subjects). All patients underwent functional MRI grip task examination twice: prior a warm-up procedure (myotonia was elicited in patients with apparent grip myotonia) and after a warm-up procedure (myotonia was attenuated in patients with apparent grip myotonia). No myotonia was elicited during either examination in patients without apparent grip myotonia. Cerebral blood oxygen level-dependent (BOLD) signals were compared both between groups with and without apparent myotonia, and between pre- and post-warm-up sessions. Results Significantly higher BOLD signal was found during myotonia phase in patients with apparent grip myotonia compared to corresponding non-myotonia phase of patients without apparent grip myotonia in the supplementary motor area and in the dorsal anterior cingulate cortex. Significant differences in BOLD signal levels of very similar pattern were detected between prewarm-up session myotonia phase and post-warm-up session myotonia absent phase in the group of patients with apparent grip myotonia. Conclusion We showed that myotonia is related to cortical function in high-order motor control areas. This cortical involvement is most likely to represent action of inhibitory circuits intending motor termination.

Background and aims: The aim of the present study was to measure the test-retest validity of Parkinson’s Disease Sleep Scale 2nd version (PDSS-2) on PD patients with stable medication and motor symptoms over the period of 4 weeks. Methods: The subject population consisted of 92 PD patients. Besides PDSS-2, Unified PD rating scale, Montgomery-Asberg Depression Rating Scale and EQ-5D were assessed at baseline and 4 weeks later. Results: The total score of PDSS-2 decreased from 19.06 ± 10.78 points to 18.00 ± 9.34 points (p > 0.05). For the total score of PDSS-2 the Intra-class and Lin’s Concordance Correlation Coefficients were 0.782 and 0.799. The average difference between the baseline and follow-up total PDSS-2 scores was −1.06 points with the 95% confidence interval of −7.96 and +5.84 points. Conclusions: Our data supports that the items and the total score of PDSS-2 have acceptable test-retest reliability over a four week period on patients with stable PD symptoms and pharmacological therapy.

Background Our goal was to identify brain structures responsible for pain-related autonomic changes by the correlation of simultaneously acquired functional magnetic resonance imaging (fMRI) and electrocardiogram (ECG) data. Methods Eighteen healthy men (age: 22.89 ± 1.96) were involved. Painful sensation was evoked by heat. Simultaneously recorded brain fMRI and ECG data during pain were compared to data acquired during a non-painful heat sensation. From the ECG data, time- and frequency domain parameters of heart rate variability (HRV) were extracted. Results We found that: (1) among the common elements of both pain network and central autonomic network (CAN) only the medial prefrontal frontal cortex (MPFC) showed significant correlation with HRV; (2) the parasympathetic response to the painful stimuli showed a positive, while the sympathetic response a negative association with pain related BOLD-signal change observed in MPFC; (3) time domain parameters of HRV were negatively associated with MPFC activation. Conclusions The novelty of our study—compared to previous ECG–fMRI studies—is that we used pain as stimulus and investigated both frequency- and time-domain parameters of HRV. Compared to other stimuli used in earlier studies to activate the CAN, pain sensation can be standardized easier and might allow us to better understand the functional organization of CAN. The results of the current ECG–fMRI study may have direct clinical relevance in understanding the pathomechanisms of several clinical conditions. Perspective There are some simultaneous ECG–fMRI and ECG–Positron Emission Tomography (PET) studies, but limited information is available about the pain-related brain function–HRV relations. The novelty of our study is that we used pain as stimulus to activate the central autonomic network and investigated both frequency- and time-domain parameters of HRV.

Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearman’s rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lin’s Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the “disturbed sleep” domain of PDSS-2 showed high correlation with “sleep problems” item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with “daytime sleepiness” item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation.

Tardive syndromes associated with dopamine-receptor blocking agents have heterogeneous appearance. The treatment of tardive dyskinesia, dystonia, myoclonus, tourettism, tremor and akathisia is challenging for both psychiatrists and neurologists. Lack of randomized and controlled examinations for many routinely applied clinical therapeutic options make the development of clinical guidelines difficult. The present review article summarizes the available evidence for the treatment of tardive syndromes. According to the treatment guideline published by the American Academy of Neurology in 2013, the usage of clonazepam, ginkgo biloba, amantadine and tetrabenazine has enough evidence to draw conclusions. Although lowering or stopping the eliciting agent, changing to atypical antipsychotics, and adding anticholinergics are widely used techniques, there are no convincing controlled studies available to support their efficacy. The usage of Vitamin E, levetiracetam, propranolol, botulinum toxin and deep brain stimulation may be promising treatment options in the future.

The aim of this longitudinal study was to investigate changes of migraine-related brain white matter hyperintensities 3 years after an initial study. Baseline quantitative magnetic resonance imaging (MRI) studies of migraine patients with hemispheric white matter hyperintensities performed in 2009 demonstrated signs of tissue damage within the hyperintensities. The hyperintensities appeared most frequently in the deep white matter of the frontal lobe with a similar average hyperintensity size in all hemispheric lobes. Since in this patient group the repeated migraine attacks were the only known risk factors for the development of white matter hyperintensities, the remeasurements of migraineurs after a 3-year long follow-up may show changes in the status of these structural abnormalities as the effects of the repeated headaches.The same patient group was reinvestigated in 2012 using the same MRI scanner and acquisition protocol. MR measurements were performed on a 3.0-Tesla clinical MRI scanner. Beyond the routine T1-, T2-weighted, and fluid-attenuated inversion recovery imaging, diffusion and perfusion-weighted imaging, proton magnetic resonance spectroscopy, and T1 and T2 relaxation time measurements were also performed. Findings of the baseline and follow-up studies were compared with each other.The follow-up proton magnetic resonance spectroscopy studies of white matter hyperintensities showed significantly decreased N-acetyl-aspartate (median values 8.133 vs 7.153 mmol/L, P=.009) and creatine/phosphocreatine (median values 4.970 vs 4.641 mmol/L, P=.015) concentrations compared to the baseline, indicating a more severe axonal loss and glial hypocellularity with decreased intracellular energy production. The diffusion values, the T1 and T2 relaxation times, and the cerebral blood flow and volume measurements presented only mild changes between the studies. The number (median values 21 vs 25, P.001) and volume (median values 0.896 vs 1.140 mL, P.001) of hyperintensities were significantly higher in the follow-up study. No changes were found in the hemispheric and lobar distribution of hyperintensities. An increase in the hyperintensity size of preexisting lesions was much more common than a decrease (median values 14 vs 5, P=.004). A higher number of newly developed hyperintensities were detected than disappeared ones (130 vs 22), and most of them were small (.034 mL). Small white matter hyperintensities in patients with a low migraine attack frequency had a higher chance to disappear than large white matter hyperintensities or white matter hyperintensities in patients with a high attack frequency (coefficient: -0.517, P=.034).This longitudinal MRI study found clinically silent brain white matter hyperintensities to be predominantly progressive in nature. The absence of a control group precludes definitive conclusions about the nature of these changes or if their degree is beyond normal aging.

Objective Vitamin D plays an important role in brain development and functioning. Low levels of vitamin D have been described in several psychiatric and neurologic conditions including autism spectrum disorder. Alexithymia that shows high comorbidity with autism is also present in the general population as well as hypovitaminosis D. Methods Here we assessed the relation between alexithymia as measured by the Toronto Alexithymia Scale-20 and vitamin D level in healthy young adults. Results We found an inverse correlation between the levels of alexithymia and vitamin D. Discussion These data suggest the association between disturbed emotional processing and low levels of vitamin D to be present in young healthy subjects.

We describe a case of an 18-years-old boy with GTS, who developed severe, continuous, disabling tics after an arbitrary and abrupt withdrawal of haloperidol, tiapride and clonazepam therapy. This exacerbation considered as tics status lasted for weeks despite of intravenous re-administration of these drugs and interfered with sleeping; therefore, propofol and midazolam sedation, and later relaxation with artificial ventilation were applied for an immediate relief. Changing the medication to olanzapine and levetiracetam in parallel to sedation was effective to improve the motor symptoms to the baseline level. As far as the authors are aware, our case is the first published tics status case lasting for weeks and requiring sedation, intubation, and relaxation.

The metal ion chelator cuprizone (bis(cyclohexanone)oxalyldihydrazone) is an effective agent for inducing experimental demyelination in rodents. The current work was undertaken to assess whether this demyelination was a result of the ability of cuprizone to sequester metal ions thereby leading to a reduction of tissue concentrations of essential trace metals. After cuprizone administration, demyelination in mouse brain was followed using biochemical techniques and it was shown that mice fed cuprizone for 49 days had reduced blood concentrations of copper, zinc and iron but that the brain contents of these cations were not decreased. Also, that loss of carbonic anhydrase activity (CAII)(a zinc metalloenzyme) in cuprizone fed mice could not be prevented by the feeding of a zinc supplemented diet. Indeed, zinc supplementation itself had an deletrious effect on kidney CA11 activity. The findings are discussed in relation to possible roles for CA in the CNS and kidney.

JC virus (JCV), a human polyomavirus, is the agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV exists in four main genotypes in the USA. Type 1, including subtypes Type 1A and Type 1B, makes up about 64% of strains in the USA and is thought to be of European origin. Type 2 is found in Asia, and Type 3 in Africa. A fourth type is found only in the USA. In general, these genotypes differ in 1-2.5% of their DNA sequence. Thirty MS patients and 30 paired controls from Budapest were studied. The clinical course of MS was mainly secondary progressive, and patients were stable at the time of testing. Most of the controls were relatives of the probands: a spouse, parent, or child. Overall, 25 of 60 (42%) of the urines tested positive for JCV by PCR. These included 13 of 30 MS patients, and 12 of 30 controls. Genotyping in the VP1 gene showed all 25 JCV strains to be Type 1. Among the MS patients, seven were Type 1A and six were Type 1B. Among the controls, nine were Type 1A and three were Type 1B. In five pairs of MS patients and controls, both were positive for JCV by PCR. Two of these were husband/wife pairs of which one pair was matched for subtype (both Type 1A), and the other was not. Two of them were mother/daughter pairs, and both were matched for subtype (both Type 1B). These findings demonstrate that JCV Type 1 predominates among Hungarians, and suggest that parent/child pairs can be used to trace JCV transmission within the MS family.

Objectives Vitamin D is important in normal brain development. In animals low vitamin D level is associated with brain morphological alterations including enlargement of the brain. Whether a similar association exists in humans is unknown. Here we investigated the relationship between vitamin D and total intracranial volume as well as total volume of the cortical grey and cerebral white matter and that of the ventricles in young healthy women. Methods To assess volumes we applied semi-automatic user-independent MR volumetry. For the vitamin D measurements automated electrochemiluminescence immunoassay was used. Results We found a significant negative correlation between vitamin D and total intracranial volume as well as total cortical grey and cerebral white matter volumes. Discussion This association may reflect a trait-like relationship between vitamin D and brain size possibly determined in early development.

Most people are left-hemisphere dominant for language. However the neuroanatomy of language lateralization is not fully understood. By combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we studied whether language lateralization is associated with cerebral white-matter (WM) microstructure. Sixteen healthy, left-handed women aged 20-25 were included in the study. Left-handers were targeted in order to increase the chances of involving subjects with atypical language lateralization. Language lateralization was determined by fMRI using a verbal fluency paradigm. Tract-based spatial statistics analysis of DTI data was applied to test for WM microstructural correlates of language lateralization across the whole brain. Fractional anisotropy and mean diffusivity were used as indicators of WM microstructural organization. Right-hemispheric language dominance was associated with reduced microstructural integrity of the left superior longitudinal fasciculus and left-sided parietal lobe WM. In left-handed women, reduced integrity of the left-sided language related tracts may be closely linked to the development of right hemispheric language dominance. Our results may offer new insights into language lateralization and structure-function relationships in human language system.

Epilepsy is one of the most common neurological diseases usually demanding long term treatment. The prime goal of therapy is to achieve seizure freedom with avoidance of side effects. Precise diagnosis is fundamental selecting the proper antiepileptic drug(s). In addition of wide-spectrum antiepileptics, selective syndrome-specific antiepileptic drugs are available. Pharmacological features of the new antiepileptics allow more personalized clinical use. Aim of this paper is to provide a comprehensive pragmatic review of therapeutic possibilities and recommendations currently accessible in Hungary.

Spinal cord stimulation has become an established clinical option for treatment of refractory chronic pain and angina pectoris, but its precise mechanism of action is unclear. We investigated the effect of spinal cord stimulation (SCS) on heart rate variability (HRV) and evaluating its influence on the sympathetic/parasympathetic balance in chronic pain. MATERIALS AND PURPOSE: Seven patients (three men, four women) with SCS due to chronic pain were included. The SCS was programmed in three different ways: (i) to stimulate at an amplitude known to generate paresthesias (ON-state), (ii) at a subliminal level (SUB state), or (iii) switched off (OFF-state). HRV analysis was based on 5-min segments of the consecutive normal RR intervals and was performed with custom software (Kubios HRV Analysis).The mean heart rate was higher in ON state compared to SUB state (p = 0.018) and the high-frequency component of the HRV was lower in ON compared to OFF period (p = 0.043). Other HRV parameters values did not significantly differ during the three tested periods.Spinal cord stimulation in chronic pain seems to be accompanied by reduced parasympathetic tone, unlike SCS in angina pectoris where previous studies found a reduced cardiac sympathetic tone. Our study might lead to understand the mechanism of action of SCS We investigated a relatively small number of patients, which is the main limitation of our study. Thus, further studies with larger number of patients are required for validation of our results.

Data on disease burden of multiple sclerosis from Eastern-Central Europe are very limited. Our aim was to explore the quality of life, resource utilisation and costs of ambulating patients with multiple sclerosis in Hungary.Cross-sectional questionnaire survey was performed in two outpatient neurology centres in 2009. Clinical history, health care utilisation in the past 12 months were surveyed, the Expanded Disability Status Scale and the EQ-5D questionnaires were applied. Cost calculation was conducted from the societal perspective.Sixty-eight patients (female 70.6%) aged 38.0 (SD 9.1) with disease duration of 7.8 (SD 6.7) years were involved. Fifty-five (80.9%) had relapsing-remitting form and 52 (76.5%) were taking immunomodulatory drug. The average scores were: Expanded Disability Status Scale 1.9 (SD 1.7), EQ-5D 0.67 (SD 0.28). Mean total cost amounted to 10 902 Euros/patient/year (direct medical 67%, direct nonmedical 13%, indirect costs 20%). Drugs, disability pension and informal care were the highest cost items. Costs of mild (Expanded Disability Status Scale 0-3.5) and moderate (Expanded Disability Status Scale 4.0-6.5) disease were 9 218 and 17 634 Euros/patient/year respectively (p0.01), that is lower than results from Western European countries.Our study provides current inputs for policy making and contributes to understanding variation of cost-of-illness of multiple sclerosis in Europe.

Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination and neurodegeneration in the central nervous system. Until recently, disease-modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya®) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from ten Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients., peer-reviewed

It has been reported that multiple sclerosis has four different neuropathological subtypes, and two of them (type III and IV) are characterized by primary oligodendrocyte loss. However, the exact pathomechanism that lead to oligodendrocyte apoptosis in human demyelinating diseases is still elusive. The copper chelator cuprizone induces primary oligodendrocyte apoptosis and consequent demyelination in well defined areas of the mouse brain. Nevertheless, the precise subcellular events that result in oligodendrocyte cell death in the cuprizone model are still unknown. We aimed to study the ultrastructural alterations that might induce oligodendrocyte apoptosis in the cuprizone experimental demyelination model.C57BL/6 mice were given cuprizone for two, 21 and 35 days to induce demyelination to investigate early pathological events, and different stages of demyelination. In addition, mice were given cuprizone for 35 days and were allowed to recover for two or 14 days to study early and late remyelination. After the cuprizone treatment, mice were sacrificed and the corpus callosum, the superior cerebellar peduncle, the optic nerve and the sciatic nerve were studied by electron microscopy.The ultrastructural analysis revealed that cuprizone induced oligodendrocyte apoptosis is accompanied by the formation of giant mitochondria in the affected cells in the corpus callosum and in the superior cerebellar peduncle. Apoptosis of the myelin producing cells was present through the whole cuprizone challenge. Severe demyelination occurred after three weeks of cuprizone administration associated with massive macrophage infiltration and astrocytosis of the demyelinated areas. Axons and neurons remained unaffected.The formation of giant mitochondria in myelin producing oligodendrocytes is the first pathological sign in the cuprizone experimental demyelination. Mitochondrium pathology in the cuprizone challenge might serve as a useful model to study the pathomechanism of multiple sclerosis subtypes (III and IV) characterized by primary oligodendrocyte degeneration.

Apoliporotein A5 (APOA5), a member of the apolipoprotein family, plays a key regulatory role in triglyceride (TG) metabolism. Even though the exact biochemical background of its mechanism is not yet fully understood, diseases associated with this particular gene highlighted its key role in the metabolism of triglycerides in humans. Naturally occurring functional variants of the gene and their natural major haplotypes are known to associate with moderately elevated triglyceride levels, and are also known to confer risk or protection for major polygenic diseases, like coronary heart disease, stroke, or metabolic syndrome. On the other hand, case reports and even robust resequencing studies verified APOA5 mutations as underlying genetic defects behind extreme hypertriglyceridemic phenotype. Soon after the recognition of the first cases, there were indications which suggest the existence of less frequent genetic variants which, in combination with the common allelic variants of the gene, can define haplotypes that are associated with substantial triglyceride level increase. In addition, it became evident, that there are rare mutations of the APOA5 gene which can be associated with specific complex phenotypes and different types of hyperlipoproteinemia, which includes extremely high triglyceride levels with multiple organ pathology. These rare mutations may cause inheritable hypertriglyceridemia, but they presented at a low frequency and could not be captured by standard genotyping array screenings. The identification of new mutations still relies on the direct sequencing of APOA5 gene of patients with hypertriglyceridemia with an unusual pattern, individually or in huge resequencing studies.

Based on our previous survey on the capacities of neurological services and on the predictable changes in the neurologist workforce in Hungary, we present a proposal for the organization of the structure of neurological services in the future. We discuss the diagnostic groups treated by neurologists, the neurological services and their progressive organization. Using the current capacities as baseline, we propose patient groups to be treated by neurologists in the future, and the levels of services. Based on the tendencies seen in the last years we suggest to consider to allocate acute stroke services exclusively to stroke units in neurological departments, and we identify a few other diagnostic groups where neurology should have a larger share in patient care. We define three levels for inpatient care: university departments, regional/county hospitals, city hospitals. Instead of minimum criteria we assign outpatient and inpatient standards that are functional from the economic point of view as well. University departments cover all areas of neurological services, have a function in graduate and postgraduate training, and on a regional basis they participate in professional quality assurance activities at the county and city hospital levels, and would have a more independent role in residency training. As far as patient care is concerned, the task of the regional/county hospitals would be similar to that of university departments - without the exclusively university functions. A general neurological service would be offered at the city hospital level - the representation of all subspecialties of neurology is not required. Neurorehabilitation would be organized at special units of neurological wards at the city hospital level, at independent neurorehabilitation wards in regional/county hospitals, and also as an outpatient service offered at the patients' home. The most significant organizational change would affect the outpatient neurological services. In addition to the special outpatient units associated with university departments and regional/county hospitals, the general neurological outpatient services would be organized as private practices, similarly to the current system of general practitioners, where the individual practices contract independently with the health insurance fund. Their task would be a general neurological service offered 30 hours per week, and also basic, screening neurophysiological and neurosonological examinations, with proper equipment and trained assistance. A transformation in residency training and a change in financing is needed for this plan to fulfill.

The background of feeding associated and metabolic diseases is not sufficiently understood yet. Since gustatory alterations may be of particular significance in the above illnesses, in the present experiments, cerebral activation was detected by fMRI in twelve obese patients and twelve, age and gender matched healthy subjects. The gustatory stimulus solutions were delivered via intraorally positioned polyvinyl tubes. Each session consisted of three runs. Sucrose was used as a pleasant; quinine HCl as an aversive; and a high-calorie, vanilla flavored nourishment solution as a complex taste of high palatability. In each run, only one taste was used as a stimulus. During all runs, distilled water served as a neutral stimulus. Group analysis was made by using the FSL software package. The taste stimuli elicited characteristic and distinct activity changes of the two groups. In contrast to the controls, in the obese patients, stronger activation was detected in various cortical (anterior cingulate cortex, insular and opercular cortices, orbitofrontal cortex) and subcortical (amygdala, nucleus accumbens, putamen and pallidum) structures in case of all three stimuli. The present examinations elucidated differential activation of various brain structures to pleasant and unpleasant gustatory stimuli in obese patients compared to control subjects. These taste alterations are supposed to be of particular significance in obesity, and our findings may contribute to develop better strategies for prevention and effective therapies in the future.

Neuronal activity regulates expression of phenotype-specific genes, including galanin, which coexists with choline acetyltransferase in septal and basal forebrain neurons. Transections of the fornix and the diagonal band alter galanin expression in septohippocampal neurons attributed to a deficit in target-derived trophic factors. The present study demonstrates that tetrodotoxin-induced blockade of neuronal activity fully mimicked the effect of axotomy (transection of the septohippocampal fibers) in the neurons of the nucleus of the diagonal band, and caused a dramatic, although temporary, up-regulation of galanin immunoreactivity and galanin mRNA without significant alteration in choline acetyltransferase expression. This finding suggests that in the septohippocampal cholinergic system perturbance of electrical activity alone can lead to temporary up-regulation of galanin expression, previously attributed exclusively to a "lesion effect."

Brain tissues from 6 patients with concentric sclerosis (Balo) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.