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Middle cerebral artery occlusion (MCAO) models show substantial variability in outcome, introducing uncertainties in the evaluation of treatment effects. Early outcome predictors would be essential for prognostic purposes and variability control. We aimed to compare apparent diffusion coefficient (ADC) MRI data obtained during MCAO and shortly after reperfusion for their potentials in acute-phase outcome prediction. Fifty-nine male rats underwent a 45-min MCAO. Outcome was defined in three ways: 21-day survival; 24 h midline-shift and neurological scores. Animals were divided into two groups: rats surviving 21 days after MCAO (survival group, n = 46) and rats dying prematurely (non-survival/NS group, n = 13). At reperfusion, NS group showed considerably larger lesion volume and lower mean ADC of the initial lesion site (p –6), while NS group showed a mixed pattern. At reperfusion, lesion volume and mean ADC of the initial lesion site were significantly associated with 24 h midline-shift and neurological scores. Diffusion MRI performed soon after reperfusion has a great impact in early-phase outcome prediction, and it works better than the measurement during occlusion.

A variant of benign paroxysmal positional vertigo (BPPV) involves the subjective report of vertigo without the coinciding nystagmus. This presentation includes truncal retropulsion when sitting up from the ipsilesional provocative test (ie, Dix-Hallpike), which we term type 2 BPPV. The primary objective of this study is to prospectively determine the prevalence and describe the clinical course of type 2 BPPV. We offer a theoretical explanation for the absence of nystagmus.Prospective, observational study carried out in 2 tertiary hospitals. One hundred eighty patients (134 women, 46 men) met the inclusion criteria and were included between January 10, 2018, and October 30, 2019. Efficacy of physical therapy maneuvers was determined at 1-week follow-up. Three-dimensional reconstructions of the planes of the semicircular canal cupula from histological preparations are offered as evidence for the theoretical explanation.One-third of the patients met the criteria for type 2 BPPV; the remainder had typical posterior or horizontal semicircular canal involvement. Symptoms from type 2 BPPV were longer in duration yet responded favorably to physical therapy maneuvers. Upon repeat testing, 19 patients treated for posterior canalithiasis developed a slight, persistent positional downbeat nystagmus in the Dix-Hallpike position that we propose as evidence the otoconia entered the short arm of the posterior semicircular canal.Our data and 3-dimensional rendering suggest the report of vertigo, yet absent nystagmus in type 2 BPPV is from otoconia aligning with the gravitoinertial vector during provocative testing that precludes cupular stimulation. Type 2 BPPV appears to be a common and treatable form of vertigo.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A372).

Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN.We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well.MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment.Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.A multifokális motoros neuropathia (MMN) ritka, immunmediált progresszív betegség, ami kizárólag a motoros idegeket érinti. Habár számos tanulmány leírta az oxidatív stressz szerepét a perifériás neuropathiákban, MMN-ben még nem vizsgálták ennek a patomechamizmusnak a szerepét.Tanulmányunkban prospektíven meg­ha­tá­roztuk 10 beteg L-arginin-, valamint szimmetrikus és aszimmetrikus dimetil-arginin- (SDMA- és ADMA-) szintjét, melyek az L-arginin/NO útvonal résztvevői, és szerepet játszanak mind a krónikus gyulladásban, mind az oxidatív stresszben. Az L-arginin, az ADMA és az SDMA szérum­koncentrációját HPLC-vel mértük az intravénás immunglobulin- (IVIG-) kezelés előtt és után 10 MMN-es és 10 egészséges kontrollbetegben. Minden betegnél végez­tünk elektrofiziológiai mérést és vizsgáltuk az antiganglio­zid antitestek jelenlétét a szérumban.Az MMN-es betegeknél szignifikánsan magasabb az ADMA (p = 0,0048; 0,98 és 0,63) és az SDMA szérumszintje (p = 0,001; 0,88 és 0,51), mint az egészséges kontrolloknál, míg az L-arginin szintjében változást nem találtunk. Az életkorra mint kovariánsra kontrollálva (többszörös lineáris regresszióval) az ADMA- (B = –0,474; p = 0,041) és az SDMA- (B = –0,896; p0,0005) szérumszintek az MMN szignifikáns prediktorainak bizonyultak. Az IVIG-terápia szignifikánsan csökkentette az ADMA szérumkoncentrációját (p = 0,025; 0,98 és 0,84) és tendenciát mutatott az SDMA szintjének csökkentésére (p = 0,1; 0,88 és 0,74). Nem találtunk összefüggést a dimetil-aminok szintje és az antigangliozid antitestek jelenléte között. A motoros idegek kondukciós blokkhoz köthető motoros funkciózavara javult közvetlenül az IVIG-kezelést követően.A dimetil-aminok szintje emelkedett az MMN-betegek szérumában, és csökken IVIG-kezelés hatására. Ezek az eredmények támogatják az oxidatív stressz jelenlétét.

Összefoglaló. Bevezetés: A myasthenia gravis javallatával végzett csecsemőmirigy-eltávolítás sebésztechnikai szempontból lényegesen megváltozott az elmúlt közel 30 évben. A standard műtétnek számító transsternalis és transcervicalis thymectomia mellett elterjedt a videoasszisztált thoracoscopos sebészeti (VATS), később pedig a robot sebészeti megoldás is. Két intézetünkben 2011–2012-ben vezettük be a VATS thymectomiát. Módszer: A többféle technikai megoldás közül a mediastinumot a jobb mellüreg felől megközelítő utat választottuk. Eleinte 3, később 2 pontos perimammaris portot készítettünk a thymus elérésére a beteg háton fekvő helyzetében. Minden esetben ultrahangos vágóeszközt alkalmaztunk. Kiterjesztett thymectomiára törekedve a perithymikus zsírszövetet is eltávolítottuk, szélesen megnyitva a bal oldali mellüreget is. A betegek kiválasztásában az átlagos testsúlyú vagy soványabb betegeket részesítettük előnyben. Eredmények: 8 év és 4 hónap alatt 92 beteget műtöttünk a fenti módszerrel thymoma nélküli myasthenia gravis alapbetegséggel. 20 férfi és 72 nő. Átlagéletkor 33,1 év (19–75 év). A műtéti idő 35–160 percig terjedt, átlagosan 82,3 perc volt. A tömegesebb mediastinalis zsírszövet néhány betegnél nehezítette a tájékozódást és a maradéktalan eltávolítást. Műtét alatt 4 esetben érsérülés és 3 ellenoldali tüdősérülés következett be. Két konverziót végeztünk (1-1 sternotomia és thoracotomia). Idegsérülés nem történt. Tíz beteg igényelt néhány órás művi lélegeztetést a műtét után, a többi beteget a műtőasztalon extubáltuk. Reintubáció, tracheostomia, légzési elégtelenség, műtéti halálozás nem volt. Az intenzív ápolási idő átlaga: 1,1 (0–11) nap. A teljes kórházi ápolási idő átlaga: 4,8 (3–15) nap. A drenázsidő 1–4 nap, átlagosan 1,16 nap. Két beteg (2,41%) halt meg a műtétet követően 1 és 5 éven belül. További 81 beteg 12–108 (átlag: 48) hónapos követése során a myastheniás állapotban 21 (25,3%) betegnél komplett, 4 (4,82%) betegnél gyógyszeres remisszió, 20 (24,1%) betegnél minimális manifesztáció, 28 (33,73%) betegnél egyéb javulás volt megállapítható. 4 (4,82%) beteg állapota változatlan maradt, 4 (4,82%) betegé pedig romlott. Következtetés: A VATS thymectomia teljesen új utat jelent a transsternalis módszerben járatos sebészek számára. A tömegesebb mediastinalis zsírszövet nagyon megnehezíti a műtétet. A perioperatív szak nagyon kedvező a betegek számára, és a késői eredmények is elfogadhatóak. Kérdéses, hogy a thymus minden esetben maradéktalanul eltávolítható-e ezzel a módszerrel. Summary. Introduction: Surgical technique of thymectomy performed for treatment of myasthenia gravis has considerably changed in the last almost 30 years. In addition to standard interventions – transsternal and transcervical thymectomy –, video-assisted thoracoscopic interventions (VATS), later on robotic surgery came into general use. In our two institutions, we apply VATS thymectomy since 2011. Methods: There are several different surgical techniques for this purpose; we approached the mediastinum through the right thoracic cavity. We prepared initially 3, later on 2 perimammal ports for the access of the thymus; the patients were in supine position during surgery. We used an ultrasonic cutting device in all cases. In order to perform extended thymectomy, we removed the fatty tissue around the thymus and opened widely the left thoracic cavity, too. During patient enrollment, we preferred patients with normal or lower body weight. Results: During 8 years and 4 months, we operated on 92 patients using this method for myasthenia gravis without thymoma; there were 20 male and 72 female patients at the age of 33 years on average (19–75 years). Duration of surgery was 35–160 minutes, 82.3 minutes on average. The bulky fatty tissue around the thymus made the orientation and the complete removal more difficult in a few patients. We experienced vascular injury in 4 cases and injury of the contralateral lung in 3 cases. Conversion was necessary in 2 cases (1 sternotomy and 1 thoracotomy), there were no nerve injuries. Assisted ventilation was necessary in case of ten patients in the postoperative period for a few hours; all other patients were extubated on the operating table. There was no need for repeated intubation and tracheostomy; there was no respiratory insufficiency and perioperative mortality. Duration of ICU care was 1.1 days on the average (0–11 days), that of the total hospital care 4.8 days on average (3–15 days). Duration of thoracic drainage was 1.16 days on average (1–4 days). Two patients (2.41%) died within one and five years after surgery. During 12–108 months (48 months on average) follow-up of 81 patients, 21 patients (25.3%) suffering from myasthenia total recovery was observed, pharmacologic remission was achieved in 4 patients (5.3%), minimal manifestation remained in 23 patients (24.1%), while in 28 patients (33.73%) other improvement was observed. The status of 4 patients (4.82%) remained unchanged and that of 4 patients (5.3%) worsened. Conclusion: VATS thymectomy represents a completely new surgical method for surgeons having experience in transsternal surgical technique. Bulky mediastinal fatty tissue makes surgery very difficult. The perioperative period is advantageous for the patients and also the long term follow-up results are acceptable. It is questionable that the thymus can be completely removed with this method in all cases.

Absztrakt: A status epilepticus a második leggyakoribb, sürgősségi kezelést igénylő neurológiai állapot. Halálozása 15–25%. A „time is brain” elve a status epilepticus kezelésére is igaz: minél korábban kezdjük a megfelelő kezelést, annál nagyobb valószínűséggel tudjuk megállítani a progressziót. Magas szintű evidenciákon alapuló kezelési protokollal a status epilepticus progressziója az esetek 75–90%-ában megelőzhető, az indukált kóma és a halálos kimenetel elkerülhető. A status epilepticus kezelése akkor a legsikeresebb, ha már a korai szakban megkezdjük a parenteralis benzodiazepinterápiát: im. midazolám (0,2 mg/tskg, max. 10 mg). Szabad véna esetén lehet vénásan is adni a benzodiazepint (10 mg diazepám iv). Ha az első benzodiazepinbolusra nem reagál a status epilepticus, állandósult (benzodiazepinrefrakter) status epilepticusról beszélünk. Ilyenkor a benzodiazepin ismétlésével párhuzamosan nem benzodiazepin típusú, gyorsan ható vénás antiepileptikumot is adni kell: iv. valproát (40 mg/kg, max. 3000 mg, 10 perc alatt) vagy levetiracetám (60 mg/kg, max. 4500 mg, 10 perc alatt) javasolt. Az 1 órán túl is tartó, sem benzodiazepinre, sem antiepileptikumra nem reagáló, refrakter status epilepticust neurointenzív osztályon, teljes narcosissal (indukált kómával) kell kezelni. Az indukált kómát gyors hatású anesztetikummal lehet elérni, elsősorban propofol–midazolám kombinációval. Orv Hetil. 2020; 161(42): 1779–1786.

Small fiber neuropathy develops due to the selective damage of the thin fibers of peripheral nerves. Many common diseases can cause this condition, including diabetes, infections, autoimmune and endocrine disorders, but it can occur due to genetic alterations, as well. Eighty-five skin biopsy-proven small-fiber neuropathy cases were analyzed. Forty-one (48%) cases were idiopathic; among secondary types, hypothyreosis (9.4%), diabetes mellitus (7%), cryoglobulinemia (7%), monoclonal gammopathy with unproved significance (4.7%), Sjögren’s disease (3%), and paraneoplastic neuropathy (3%) were the most common causes. Two-thirds (68%) of the patients were female, and the secondary type started 8 years later than the idiopathic one. In a vast majority of the cases (85%), the distribution followed a length-dependent pattern. Intraepidermal fiber density was comparable in idiopathic and secondary forms. Of note, we found significantly more severe pathology in men and in diabetes. Weak correlation was found between patient-reported measures and pathology, as well as with neuropathic pain-related scores. Our study confirmed the significance of small fiber damage-caused neuropathic symptoms in many clinical conditions, the gender differences in clinical settings, and pathological alterations, as well as the presence of severe small fiber pathology in diabetes mellitus, one of the most common causes of peripheral neuropathy.

Absztrakt: Bevezetés: Alfred Blalock 80 éve közölt első műtéte óta a thymectomia a myasthenia gravis kezelésének fontos részévé vált. A külföldön már elfogadott többféle műtéti eljárás ellenére itthon 2006-ig a szegycsonti feltárás szinte kizárólagos módszer volt a csecsemőmirigy eltávolításában. Közleményünkben ennek a módszernek a közvetlen sebészi következményeit, szövődményeit elemezzük. Módszerek: A Budai MÁV Kórház Sebészeti Osztályán 34 év alatt 1002 transsternalis thymectomia történt myasthenia gravis (MG) diagnózisú betegeken. A műtéteket neurológiai javallatra végeztük el, alapos kivizsgálás és ideggyógyászati-belgyógyászati előkészítés után. A thymomával társult betegségben a thymus és a tumor eltávolítása kettős indikációjú volt. A 34 év alatt egyaránt jelentősen módosult a neurológiai javallat és az előkészítés, a perioperatív kezelés és a műtéti technika is. Az eredményeket a legjellemzőbb műtéti technika (egyszerű és kiterjesztett thymectomia) alapján két korszakra tagolva, a thymomás és a reoperáción átesett betegek adatait pedig elkülönítve jelenítjük meg, elsősorban a légzéssel összefüggő szövődményekre koncentrálva. Eredmények: A betegek életkora 8 és 73 év között volt, átlagosan 32 év. Nő/férfi arány: 3,5:1. Az MG thymomával társult a betegek 12,7%-ában. Tizenegy betegnél rethymectomia, további két betegnél pedig szívműtét után resternotomia történt. Az első, 19 éves periódus először operált, csak myastheniás 525 betegéből 21,3%-ban következett be légzési elégtelenség a műtét után, sürgős reintubáció 12,8%-ban, tracheostomia 11,2%-ban történt. A második, 15 éves periódus 338 betegénél 12,7%-ban volt posztoperatív légzési elégtelenség, 7,1%-ban sürgős reintubációval, mindössze 1,2%‑ban légcsőmetszéssel kiegészítve. A 126 thymomás betegnél 19,1%-ban következett be légzési elégtelenség, 12,8%-os reintubációval és 20,6%-os tracheostomia aránnyal. A 13 reoperált betegnél 46,1%-ban lépett fel légzési elégtelenség, 15,4%-os reintubációval és 46,1%-os tracheostomia aránnyal. Súlyos sebészi szövődmény a teljes anyagban is kevés volt: 2 szegycsonti vérzés reoperációt igényelve, 1 további reoperáció drénbeszakadás miatt, 4 mediastinitis az első periódusban, két szívsérülés és egy szegycsont szétválás a második időszakban. A teljes műtéti halálozás 1,4% volt: első periódus (1,3%), második periódus (0,3%), thymomás csoport (4%) és a reoperációk után (7,7%). Következtetések: Történeti áttekintésben jelentősen csökkent a transsternalis thymectomia súlyos légzési és légúti szövődményeinek, valamint halálozásának aránya, de a műtétet követő légzési elégtelenség és a szegycsontátvágás sebészi kockázata továbbra is reális veszélynek tekinthető.

Glioblastoma (GBM) is a highly heterogeneous and aggressive brain tumor. Comprehensive genomic and transcriptomic analyses revealed that GBM segregates into three subgroups with characteristic signaling pathways. The Wnt pathway recently received increasing attention with the recognition of its importance in tumor development and recurrence through the promotion of glioma stem cells. As an extension of our previous translational studies, here we tested the possible interactions between key subgroup markers (IDH-1 R132H, EGFRvIII and both cytoplasmic and nuclear loss [c-/n-] of NF-1 expression) and the canonical (Wnt3a and beta-catenin) and non-canonical (Wnt5a and Fzd2) Wnt pathway markers by immunohistochemistry. These analyses revealed increased expression levels of both Wnt pathway markers with significant quantitative differences within, but not among subgroups. Wnt5a and Fzd2 levels were higher than the canonical marker levels in all subgroups. The strongest evidence for correlation between expression levels of the EGFRvIII subgroup marker and the Fzd2 Wnt marker was found, but weaker correlations also could be noted for IDH-1 R132H and NF-1 and some Wnt markers. The correlations detected between markers of the canonical and non-canonical pathways raised the possibility of cross-talk between the two pathways. Analyses of tumors with various NF-1 expression patterns (c+/n-; c-/n+ combined with c+/n+, and c-/n-) revealed that aberrant nuclear accumulation of NF-1 is accompanied by nuclear accumulation of beta-catenin, suggesting that they may act synergistically to define the tumor's biology. Altogether, our study presents expression characteristics of Wnt ligands and receptors, and suggests complex molecular interactions in subgroups of GBM.

Abstract: Orofacial pain is the common name of a variety of disorders from inflammatory diseases to neuropathic pain syndromes. This condition is quite common, it may involve 7% of the whole population. Patients (and doctors) are not aware of the origin of their complaints, therefore initial management falls among the variety of healthcare professionals. The aim of our review was to summarize the current evidence of chronic orofacial pain including diagnosis, management and pitfalls. Orv Hetil. 2019; 160(27): 1047–1056.

Background Population-based clinical studies in neuromyelitis optica spectrum disorder (NMOSD) and epidemiological and clinical comparisons of White ethnicities are missing. In a large population-based international cohort, we extensively characterized aquaporin-4 antibody seropositive (AQP4-Ab+) NMOSD, and also compared the clinical, radiological and epidemiological features between two European populations residing in different areas. Methods Between self-reported Danish and Hungarian ethnicities, we compared the population-based clinical features, disability outcomes, and death of 134 AQP4-Ab+ NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis (IPND) criteria. For precise comparison of epidemiology, we conducted a population-based head-to-head comparative study of the age-standardized prevalence (January 1, 2014) and incidence (2007–2013) of AQP4-Ab+ NMO/NMOSD among adults (≥16 years) in Denmark (4.6 million) and Hungary (6.4 million) by applying 2015 IPND (NMOSD) criteria and 2006 Wingerchuk (NMO). Results Danes were more likely to present with transverse myelitis and were more affected by spinal cord damage on long-term disability. Hungarians presented most often with optic neuritis, although visual outcome was similar in the groups. No differences were observed in sex, disease course, relapse rate, autoimmune comorbidity, mortality, brain MRI, and treatment strategies. The age-standardized prevalence estimates of AQP4-Ab+ NMOSD (2015 IPND criteria) in Denmark vs. Hungary were 0.66 vs. 1.43 (/100,000) while incidence rates were 0.04 vs. 0.11 (/100,000 person-years); similar differences were found based on the 2006 NMO criteria. Conclusions This head-to-head comparative study indicates different disease characteristics and epidemiology among White populations in Europe, and substantiates the need for population-based genetic and environmental studies in NMOSD.

The absence of nigral hyperintensity is a promising MR marker for Parkinson’s disease (PD), but its small size imposes limitations on its routine use. Our aim was to compare Multi Echo Data Image Combination (MEDIC), segmented echo-planar imaging (EPISEG) and fluid-attenuated inversion recovery (FLAIR) sequences, as well as both magnitude (MAG) and susceptibility-weighted imaging (SWI) reconstructions of single-echo gradient echo for nigral hyperintensity imaging. Twenty-five healthy and twenty PD subjects were included. Sensitivity to motion artefacts, confidence of the radiologist in interpretation, rate of nondiagnostic scans and diagnostic accuracy were assessed. EPISEG was less motion-sensitive than MEDIC, MAG, and SWI, while FLAIR was less motion-sensitive than MAG and SWI. The reviewers were more confident when using EPISEG compared to any other techniques and MEDIC was superior to FLAIR. The proportions of nondiagnostic scans were lower for EPISEG than for other sequences. The best diagnostic performance was achieved for EPISEG (sensitivity = 65%, specificity = 96%). Using EPISEG, the absence of nigral hyperintensity in PD was associated with higher Hoehn-Yahr stage and MDS-UPDRS II + III. Nigral hyperintensity may be intact at the very early stages of PD. The promising properties of EPISEG may help the transfer of nigral hyperintensity imaging into daily clinical practice.

Abstract: Introduction: Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation. Aim: We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs. Method: We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status. Results: 76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p

This month (December, 2018), an extensive two-part book on thermoregulation [1,2] was released by Elsevier within the series “Handbook of Clinical Neurology” – one of the time-honored publications ...

We have recently reported that the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. The aim of the present study was to gather additional data on the role of TRPA1 by investigating the time course of behavioural alterations and morphological changes in cuprizone-treated TRPA1 receptor gene-deficient mice. Demyelination was induced by feeding male wild-type (WT) and TRPA1 gene-deleted (TRPA1 KO) mice with 0.2% cuprizone for 6 weeks. Behavioural tests were performed once per week to follow cuprizone-induced functional changes. Mechanonociceptive thresholds were investigated by a dynamic plantar aesthesiometer and von Frey filaments. Motor performance was assessed by accelerating RotaRod and horizontal grid tests. For the study of spontaneous activity, the open field test was used. The time course of corpus callosum demyelination was also followed weekly by magnetic resonance imaging (MRI). Histological analysis of myelin loss was performed with Luxol Fast Blue (LFB) staining at week 3 and electron microscopy (EM) at week 6. Astrocyte and microglia accumulation at week 3 was assessed by immunohistochemistry (IHC). Cuprizone treatment induced no changes in mechanonociception or motor performance. In the open arena, cuprizone-treated mice spent more time with locomotion, their mean velocity was significantly higher and the distance they travelled was longer than untreated mice. No statistical difference was detected between WT and TRPA1 KO mice in these parameters. On the other hand, significantly increased rearing behaviour was induced in WT mice compared to TRPA1 KO animals. Morphological changes detected with MRI, LFB, IHC and EM analysis revealed reduced damage of the myelin and attenuated accumulation of astrocytes and microglia in cuprizone-treated TRPA1 KO animals, at each examined time point. Our recent data further suggest that inhibition of TRPA1 receptors could be a promising therapeutic approach to limit central nervous system damage in demyelinating diseases.

Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of multiple sclerosis, characterized by demyelination of the corpus callosum (CC) and other brain regions. The exact mechanisms of CZ action are still arguable, but it seems that the only affected cells are the mature oligodendrocytes, possibly via metabolic disturbances caused by copper deficiency. During the pathogenesis of multiple sclerosis, high amount of deposited iron can be found throughout the demyelinated areas of the brain in the form of extracellular iron deposits and intracellularly accumulated iron in microglia. In the present study, we used the accepted experimental model of 0.2% CZ-containing diet with standard iron concentration to induce demyelination in the brain of C57BL/6 mice. Our aim was to examine the changes of iron homeostasis in the CC and as a part of the systemic iron regulation, in the liver. Our data showed that CZ treatment changed the iron metabolism of both tissues; however, it had more impact on the liver. Besides the alterations in the expressions of iron storage and import proteins, we detected reduced serum iron concentration and iron stores in the liver, together with elevated hepcidin levels and feasible disturbances in the Fe-S cluster biosynthesis. Our results revealed that the CZ-containing diet influences the systemic iron metabolism in mice, particularly the iron homeostasis of the liver. This inadequate systemic iron regulation may affect the iron homeostasis of the brain, eventually indicating a relationship among CZ treatment, iron metabolism, and neurodegeneration.

Primary cilia are small, special cellular organelles that provide important sensory and signaling functions during the development of mammalian organs and coordination of postnatal cellular processes. Dysfunction of primary cilia are thought to be the main cause of ciliopathies, a group of genetic disorders characterized by overlapping developmental defects and prominent neurodevelopmental features. Although, disrupted cilia-linked signaling pathways have been implicated in the regulation of numerous neuronal functions, the precise role of primary cilia in the brain are still unknown. Importantly, studies of recent years have highlighted that different functions of primary cilia are reflected by their diverse morphology and unique signaling components localized in the ciliary membrane. In the present study, we conducted a comparative analysis of the expression pattern, distribution and length of adenylyl cyclase 3, somatostatin receptor 3, and ADP-ribosylation factor-like protein 13B expressing primary cilia in the mouse brain. We show that cilia of neurons and astrocytes display a well characterized distribution and ciliary marker arrangements. Moreover, quantitative comparison of their length, density and occurrence rate revealed that primary cilia exhibit region-specific alternations. In summary, our study provides a comprehensive overview of the cellular organization and morphological traits of primary cilia in regions of the physiological adult mouse brain.

Background and purpose Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement. Methods In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds. Results The target coordinates showed no significant differences (Mann-Whitney test, p > 0.05), however we found significant difference in fiducial coordinates (p < 0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm). Conclusion Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.

Abstract: We report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine- and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood. With the presentation of this case we would like to point out that in the differential diagnosis of recurrent rhabdomyolysis inherited metabolic disorders should be considered regardless of the patient’s age. Orv Hetil. 2017; 158(46): 1873–1882.

Introduction: To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of disability, from the societal perspective, in HUF 2015. Results: A total of 521 patients (mean age 47 years) participated; 85% were below retirement age, and of these, 47% were employed. Employment was related to disability and MS affected productivity at work for 82% of those working. Overall, 94% and 66% of patients experienced fatigue and cognitive difficulties as a problem, respectively. The mean utility and annual costs were 0.691 and 3,432,000HUF at Expanded Disability Status Scale (EDSS) 0–3, 0.491 and 5,262,000HUF at EDSS 4–6.5 and 0.076 and 6,235,000HUF at EDSS 7–9, respectively. The average cost of a relapse was estimated at 240,500HUF. Conclusion: This study illustrates the burden of MS on Hungarian patients and provides current data that are important for the development of health policies.

Introduction - Complex regional pain syndrome is a di-stressing neuropathic pain condition without known etiology and evidence based treatment. Case presentation - Here a posttraumatic severe case of complex regional pain syndrome is presented, successfully treated by amitriptyline monotherapy. Amitriptyline is one of the most effective evidence based treatments of peri-pheral diabetic neuropathic pain and other neuropathic pain syndromes. Discussion - Amitriptyline seems to be effective to decrease pain, autonomic and motor symptoms in chronic regional pain syndrome. Conclusion - Controlled trials may be warranted to test the effectiveness of amitriptyline in complex regional pain syndrome.

Background and purpose: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. Methods: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. Results: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52–2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08–1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56–2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98–1.46) per 1 000 000 person-years. Conclusions: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

Transient receptor potential ankyrin 1 (TRPA1) receptors are non-selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons, however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice. In the present study we aimed at investigating mGFAP-Cre conditional TRPA1 knockout mice in the cuprizone model. These animals were generated by crossbreeding GFAP-Cre+/&minus, and floxed TRPA1 (TRPA1Fl/Fl) mice. Cuprizone was administered for 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, demyelination and glial activation was also investigated by histological methods. The results of the MRI showed that demyelination was milder at weeks 3 and 4 in both homozygous (GFAP-Cre+/&minus, TRPA1Fl/Fl) and heterozygous (GFAP-Cre+/&minus, TRPA1Fl/&minus, ) conditional knockout animals compared to Cre&minus, /&minus, control mice. However, by week 6 of the treatment the difference was not detectable by either MRI or histological methods. In conclusion, TRPA1 receptors on astrocytes may transiently contribute to the demyelination induced by cuprizone, however, expression and function of TRPA1 receptors by other cells in the brain (oligodendrocytes, microglia, neurons) warrant further investigation.

Absztrakt

Orofacial pain is the common name of a variety of disorders from inflammatory diseases to neuropathic pain syndromes. This condition is quite common, it may involve 7% of the whole population. Patients (and doctors) are not aware of the origin of their complaints, therefore initial management falls among the variety of healthcare professionals. The aim of our review was to summarize the current evidence of chronic orofacial pain including diagnosis, management and pitfalls. Orv Hetil. 2019; 160(27): 1047-1056.Absztrakt: Az orofacialis fájdalom egy gyűjtőszó, mely sokféle kórképet takarhat a gyulladásos kórképektől kezdve a neuropathiás fájdalomig. Maga a kórkép nem ritka, akár a populáció 7%-át érintheti. Sokszor maguk a betegek sem tudják, hogy panaszokkal fogászhoz vagy más szakemberhez forduljanak. A régió sok szakma határterületét képezi (fogászat, fülészet, szemészet, neurológia stb.), így nem meglepő, hogy egy-egy beteg akár 6–7 specialistánál megfordul. Összefoglaló közleményünk célja, hogy áttekintést adjunk a krónikus orofacialis fájdalommal járó kórképek diagnózisáról, az esetleges differenciáldiagnosztikai lehetőségekről és kezelési módokról. Orv Hetil. 2019; 160(27): 1047–1056.

One of the models to investigate the distinct mechanisms contributing to neurodegeneration in multiple sclerosis is based on cuprizone (CZ) intoxication. CZ is toxic to mature oligodendrocytes and produces demyelination within the central nervous system but does not cause direct neuronal damage. The CZ model is suitable for better understanding the molecular mechanism of de- and remyelination processes of oligodendrocytes. CZ is a copper chelating agent and it also affects the iron metabolism in brain and liver tissues. To determine the early effect of CZ treatment on iron homeostasis regulation, cytosolic and mitochondrial iron storage, as well as some lipid metabolism genes, we investigated the expression of respective iron homeostasis and lipid metabolism genes of the corpus callosum (CC) and the liver after short-term CZ administration. In the present study C57BL/6 male mice aged four weeks were fed with standard rodent food premixed with 0.2 w/w% CZ for two or eight days. The major findings of our experiments are that short-term CZ treatment causes significant changes in iron metabolism regulation as well as in the expression of myelin and lipid synthesis-related genes, even before apparent demyelination occurs. Both in the CC and the liver the iron uptake, utilization and storage are modified, though not always the same way or to the same extent in the two organs. Understanding the role of iron in short-term and long-term CZ intoxication could provide a partial explanation of the discrepant signs of acute and chronic MS. These could contribute to understanding the development of multiple sclerosis and might provide a possible drug target.

Background: The minimal clinically important difference is the smallest change of scores clinically meaningful to patients. Objectives: We aimed to calculate these threshold values in association with the International Parkinson and Movement Disorder Society UPDRS (MDS-UPDRS) Parts I and II and to evaluate the feasibility of the composite score of Part I and II (MDS-UPDRS I+II) as an outcome. Methods: Nine hundred eighty-five paired investigations of 365 patients were reviewed, implementing three different techniques simultaneously. Results: Based on the ordinal regression modeling, the MDS-UPDRS I+II score is an applicable outcome measure. Any improvement greater than 2.64 points or any worsening more than 2.45 points on MDS-UPDRS Part I represent a minimal, yet clinically meaningful change. In reference to Part II, the smallest changes considered clinically relevant were 3.05 and 2.51 points for improvement and deterioration, respectively. The thresholds for MDS-UPDRS I+II were 5.73 points for improvement and 4.70 points for worsening. Conclusions: Our minimal clinically important difference thresholds can be utilized in clinical practice in judging clinical relevance. © 2016 International Parkinson and Movement Disorder Society

The combination of obstructive sleep apnea syndrome and vascular malformation within the head and neck region is a rare condition, and interestingly, only a few cases have recently been published. Propagation of the vascular mass to the larynx and pharynx can cause breathing and swallowing difficulties. Due to these sypmtoms, examination and initiation of appropriate therapy for such patients are indeed challenging. We reviewed the literature available and present our case of a 64 year old woman emphasizing the complaints of sleep apnea syndrome and vascular malformation of the face and neck region. Polygraphic examination detected severe obstructive sleep apnea syndrome. The MR examination of the neck revealed extensive vascular mass narrowing the pharyngo-laryngeal region, thereby causing temporal bone destruction on the right side with intracranial propagation. ENT examination demonstrated significant narrowing of the pharyngeal lumen and the laryngeal aditus caused by multiple hemangiomas. CPAP titration showed the minimalization of the apnea-hypopnea index on the effective pressure level. Regular CPAP usage resulted in diminishing a majority of the patient's complaints. Our examination clearly demonstrates, obstructive sleep apnea syndrome coupled with significantly obstructing vascular malformation in the head and neck region can be effectively treated safely with a CPAP device, if surgical therapy is not possible. We summarized our findings and the data available in the literature to set up recommendations for the appropriate examination and therapy (including mask fit, etc.) of vascular malformations and hemangiomas causing pharyngo-laryngeal obstruction.

Multiple sclerosis is a chronic inflammatory, demyelinating degenerative disease of the central nervous system. Current treatments target pathological immune responses to counteract the inflammatory processes. However, these drugs do not restrain the long-term progression of clinical disability. For this reason, new therapeutic approaches and identification of novel target molecules are needed to prevent demyelination or promote repair mechanisms. Transient Receptor Potential Ankyrin 1 (TRPA1) is a nonselective cation channel with relatively high Ca2+ permeability. Its pathophysiological role in central nervous system disorders has not been elucidated yet. In the present study, we aimed to assess the distribution of TRPA1 in the mouse brain and reveal its regulatory role in the cuprizone-induced demyelination. This toxin-induced model, characterized by oligodendrocyte apoptosis and subsequent primary demyelination, allows us to investigate the nonimmune aspects of multiple sclerosis. We found that TRPA1 is expressed on astrocytes in the mouse central nervous system. Interestingly, TRPA1 deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. Our data suggest that TRPA1 regulates mitogen-activated protein kinase pathways, as well as transcription factor c-Jun and a proapoptotic Bcl-2 family member (Bak) expression resulting in enhanced oligodendrocyte apoptosis. In conclusion, we propose that TRPA1 receptors enhancing the intracellular Ca2+ concentration modulate astrocyte functions, and influence the pro or anti-apoptotic pathways in oligodendrocytes. Inhibition of TRPA1 receptors might successfully diminish the degenerative pathology in multiple sclerosis and could be a promising therapeutic target to limit central nervous system damage in demyelinating diseases. GLIA 2016;64:2166-2180.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a developmental brain disorder characterized by an enlarged brain size with bilateral perisylvian polymicrogyria and a variable degree of ventriculomegaly. MPPH syndrome is associated with oromotor dysfunction, epilepsy, intellectual disability and postaxial hexadactyly. The molecular diagnosis of this disorder is established by the identification of a pathogenic variant in either AKT3, CCND2 or PIK3R2. Previously reported AKT3 variants are associated with various brain abnormalities and may lead to megalencephaly. MPPH syndrome is usually due to germline pathogenic AKT3 variants. Somatic mosaic pathogenic variants associated with hemimegalencephaly, which is similar to MPPH, have also been observed. A Hungarian Roma family with two half-siblings, which present with intellectual disability, dysmorphic features, epilepsy, brain malformations, and megalencephaly was studied. Whole exome sequencing (WES) analysis was performed. WES analysis revealed a heterozygous c.1393C > T p.(Arg465Trp) pathogenic missense AKT3 variant in both affected half-siblings. The variant was verified via Sanger sequencing and was not present in the DNA sample from the healthy mother, which was derived from peripheral blood, suggesting maternal germline mosaicism. In conclusion, this is the first report in which maternal germline mosaicism of a rare pathogenic AKT3 variant leads to autosomal dominantly inherited MPPH syndrome.

Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation.We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs.We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status.76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p0.01, Fisher's exact test). While 67% of seizure-free patients were employed, only 19% of patients not free from disabling seizures were hired.Our results resemble the international tendencies and success rate, proving epilepsy surgery as an available, valid and effective treatment in well selected patients. Orv Hetil. 2019; 160(7): 270-278.Absztrakt: Bevezetés: Az epilepszia krónikus, súlyos neurológiai betegség, mely jelentősen befolyásolja az életminőséget. A megfelelő indikációval végzett epilepsziasebészeti beavatkozás rohammentességet eredményezhet, mely önmagában vagy rehabilitációt követően jelentősen javíthatja az életminőséget. Célkitűzés: Jelen tanulmányunk célkitűzése a Pécsi Epilepszia Centrumban 2005 és 2016 között epilepsziasebészeti beavatkozáson átesett betegek posztoperatív eredményeinek felmérése. Módszer: Az adatgyűjtés a betegek klinikai anyagának áttekintésén túlmenően kérdőívek alkalmazásával történt, a rohamállapot értékelésén kívül a foglalkoztatottsági státuszra mint az életminőség egyik fontos indikátorára is fókuszálva. Eredmények: Reszektív epilepsziasebészeti beavatkozás 72 esetben történt. A betegek 76%-a tartósan rohammentessé vált. A betegek 10%-ánál műtét után csak igen ritkán lépett fel roham, 7%-uknak jelentősen csökkent a rohamszáma, míg 7%-ban nem változott érdemben a rohamállapot. A rohammentes és a nem rohammentes betegek csoportjainak foglalkoztatottsági adatait vizsgálva azt találtuk, hogy a rohammentesség befolyásolja a páciensek elhelyezkedési lehetőségeit. A rohammentes betegek 67%-a állt foglalkoztatottság alatt, míg a nem rohammenteseknek mindössze a 19%-a (p0,01, Fisher-féle egzakt teszt). Következtetés: Eredményeink a nemzetközi adatoknak megfelelve alátámasztják az epilepszia reszektív sebészi kezelésének klinikai és szociális eredményességét. Orv Hetil. 2019; 160(7): 270–278.

Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement.In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds.The target coordinates showed no significant differences (Mann-Whitney test, p0.05), however we found significant difference in fiducial coordinates (p0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm).Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.A mély agyi stimuláció a gyógyszeres kezeléssel nem befolyásolható mozgászavarok műtéti kezelésének rutinszerűen alkalmazott módszere. A műtétet a klinikai gyakorlatban elsősorban Parkinson-kór, essentialis tremorok, és dystoniák kezelésére alkalmazzuk. A célterületek többsége MR morfológiai vizsgálatokkal jól láthatóvá tehető. A mágneses erőterek növelésével azonban a képi információ torzulása következik be, ami oda vezethet, hogy az MR-képen látott anatómiai struktúrák a valóságban nem ugyanott helyezkednek el. Arra keres­tük a választ, hogy az 1 T, és 3 T mágneses erőterekben kijelölt célkoordinátákban, valamint az MR lokalizációs keret referenciapontjainak koordinátáiban (rodmarking accuracy) kimutatható-e eltérés.Hat, Parkinson-kórban szenvedő beteg mély agyi stimulációs műtéti tervezése kapcsán a subthalamicus magokat jelöltük ki célpontként. A két különböző mágneses térben nyert koordinátaadatokat statisztikai módszerekkel hasonlítottuk össze.Az 1 T és a 3 T erőterekben végzett cél­koordináta összehasonlító eredményeink matematikailag ugyan mutattak eltérést, azonban ez nem volt szignifikáns (Mann-Whitney-próba, p0,05). Ugyanakkor az MR-lokalizáló keret referenciapont koordinátáinak (accuracy) összehasonlítása során szignifikáns (p0,01) különbséget találtunk. Ez az érték az erősebb mágneses térben nagyobb számadatot mutatott (3T accuracy átlag ± SD: 0,8 ± 0,3 mm), mint a gyengébb mágneses térben (1T accuracy átlag ± SD: 0,4 ± 0,2 mm).Előzetes eredményeink nem igazoltak matematikailag szignifikáns eltérést a célkoordinátákban az 1 T és 3 T erősségű mágneses terek összehasonlítása során.

PURPOSE: To comprehensively analyze ictal piloerection (IP) in a large number of subjects.METHODS: We performed a systematic review on case report studies of patients diagnosed with IP (1929-2017) with additional cases included from the Department of Neurology of University of Pécs, the National Institute of Clinical Neurosciences, and Odense University Hospital. Each included case was characterized regarding patient history, IP seizure characteristics, diagnostic work-up, and therapy. Comparative analyses were also carried out based on sex and pathology.RESULTS: Altogether, 109 cases were included. We observed a strong male predominance (p CONCLUSION: IP was particularly associated with autoimmune encephalitis and high-grade glioma, suggesting IP's particular clinical importance in directing diagnostic work-up.

We describe sequence analysis of the mitochondrial DNA of five Hungarian patients diagnosed with probable LHON, who do not carry any of the three primary point mutations. We report three novel mutations, one of which might have a pathogenic role.

The combination of obstructive sleep apnea syndrome and vascular malformation within the head and neck region is a rare condition, and interestingly, only a few cases have recently been published. Propagation of the vascular mass to the larynx and pharynx can cause breathing and swallowing difficulties. Due to these sypmtoms, examination and initiation of appropriate therapy for such patients are indeed challenging. We reviewed the literature available and present our case of a 64 year old woman emphasizing the complaints of sleep apnea syndrome and vascular malformation of the face and neck region. Polygraphic examination detected severe obstructive sleep apnea syndrome. The MR examination of the neck revealed extensive vascular mass narrowing the pharyngo-laryngeal region, thereby causing temporal bone destruction on the right side with intracranial propagation. ENT examination demonstrated significant narrowing of the pharyngeal lumen and the laryngeal aditus caused by multiple hemangiomas. CPAP titration showed the minimalization of the apnea-hypopnea index on the effective pressure level. Regular CPAP usage resulted in diminishing a majority of the patient's complaints. Our examination clearly demonstrates, obstructive sleep apnea syndrome coupled with significantly obstructing vascular malformation in the head and neck region can be effectively treated safely with a CPAP device, if surgical therapy is not possible. We summarized our findings and the data available in the literature to set up recommendations for the appropriate examination and therapy (including mask fit, etc.) of vascular malformations and hemangiomas causing pharyngo-laryngeal obstruction.Az obstruktív alvási apnoe betegség kialakulásában funkcionális és alkati okok mellett számos strukturális eltérés is szerepet játszik. Ilyenek például a nyakra és fejre lokalizálódó vascularis malformációk, melyek ritka kórállapotok, csak néhány esettanulmány található a szakirodalomban. A garat és gége irányába történő propagációjuk jelentős légzési nehezítettséget, esetenként alvásfüggő légzészavart eredményezhet. Tekintettel a szűkös ismeretanyagra, ilyen esetekben az alvásfüggő légzészavar kivizsgálása és megfelelő kezelése nagy kihívást jelent. Az irodalmi adatok áttekintése mellett bemutatjuk egy 64 éves nőbeteg esetét, akinél a kifejezett nappali aluszékonyság mögött obstruktív alvási apnoe betegség igazolódott. Kialakulásában a fej-nyak régió vascularis malformációja játszik kulcsszerepet. Fül-orr-gégészeti és kontrasztos koponya-MR az arcon látható elváltozás mellett a vascularis malformáció kiterjedt pharingealis és laringealis szűkületét okozó propagációját jelezte, jobb temporalisan intracranialis terjedéssel. A CPAP-légsínterápia alkalmazása során az alvásfüggő légzészavar normalizálódását és a beteg panaszainak csökkenését tapasztaltuk. Vizsgálataink azt bizonyították, hogy a fej-nyak régió vascularis malformációjával kombinálódott obstruktív alvási apnoe betegség biztonságosan kezelhető CPAP-légsínterá-piával, amennyiben sebészeti megoldás nem lehetséges. Az irodalmi adatok és saját esetünk kapcsán kivizsgálási és terápiás ajánlást fogalmazunk meg, mely tartalmazza a szükséges diagnosztikai eljárások mellett a hatékony CPAP és maszkhasználat lehetőségeit is.

Background. Female Parkinson’s disease (PD) patients seem to experience not only more severe motor complications and postural instability but also more pronounced depression, anxiety, pain, and sleep disturbances.Objective. The aim of the present study was to evaluate the role of sex as a possible independent predictor of HRQoL in PD.Methods. In this cross-sectional study, 621 consecutive patients treated at the University of Pécs were enrolled. Severity of PD symptoms was assessed by MDS-UPDRS, UDysRS, Non-Motor Symptoms Scale, PDSS-2, Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale, Lille Apathy Rating Scale, and Addenbrooke Cognitive Examination. HRQoL was assessed by PDQ-39 and EQ-5D. Multiple regression analysis was performed to estimate the PDQ-39 and EQ-5D index values based on various clinical factors.Results. Although females received significantly lower dosage of levodopa, they had significantly more disabling dyskinesia and worse postural instability. Anxiety, pain, sleep disturbances, and orthostatic symptoms were more frequent among females while sexual dysfunction, apathy, and daytime sleepiness were more severe among males. Women had worse HRQoL than men (EQ-5D index value:0.620±0.240versus0.663±0.229,p=0.025, and PDQ-39 SI:27.1±17.0versus23.5±15.9,p=0.010). Based on multiple regression analysis, sex was an independent predictor for HRQoL in PD.Conclusions. Based on our results, female sex is an independent predictor for having worse HRQoL in PD.

Background: A recent evidence-based guideline demonstrated that bilateral repetitive transcranial magnetic stimulation (rTMS) over the motor cortex (M1) can improve motor symptoms of Parkinson's disease (PD). We conducted a randomized, double-blind, placebo-controlled study to evaluate the impact of bilateral M1 rTMS on depression in PD. Methods: Forty-six patients with PD and mild-to-moderate depression were randomly assigned to active (n = 23) and sham (n = 23) rTMS. Two patients in the sham group did not complete the protocol because of reasons unrelated to the study. High-frequency rTMS was applied over the primary motor cortex bilaterally for 10 days. An investigator blinded to the treatment performed three video-taped examinations on each patient: before stimulation (baseline), and 1 day (short-term effect) and 30 days after the treatment session ended (long-term effect). The primary end point was the changes in depression, while secondary end points included health-related quality of life scales and Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: In the actively treated group, not only did the severity of depression improve (from 17 to 7 points, Montgomery-Åsberg Depression Rating Scale, median values, p < 0.001), but also the health-related quality of life (from 25.4 to 16.9 points, PDQ-39 summary index, median values, p < 0.001). Besides, we could also demonstrate an improvement in MDS-UPDRS Motor Examination (from 26 to 20 points, median values, p < 0.05). In the sham-treated group, none of the examined tests and scales improved significantly after treatment. Conclusions: Our results demonstrate the beneficial effects of high-frequency bilateral M1 rTMS on depression and health-related quality of life in PD. However, this effect of rTMS should also be confirmed in patients with severe depression by further clinical trials.

Neuroimaging findings suggest that excessive Internet use shows functional and structural brain changes similar to substance addiction. Even though it is still under debate whether there are gender differences in case of problematic use, previous studies by-passed this question by focusing on males only or by using gender matched approach without controlling for potential gender effects. We designed our study to find out whether there are structural correlates in the brain reward system of problematic Internet use in habitual Internet user females. T1-weighted Magnetic Resonance (MR) images were collected in 82 healthy habitual Internet user females. Structural brain measures were investigated using both automated MR volumetry and voxel based morphometry (VBM). Self-reported measures of problematic Internet use and hours spent online were also assessed. According to MR volumetry, problematic Internet use was associated with increased grey matter volume of bilateral putamen and right nucleus accumbens while decreased grey matter volume of orbitofrontal cortex (OFC). Similarly, VBM analysis revealed a significant negative association between the absolute amount of grey matter OFC and problematic Internet use. Our findings suggest structural brain alterations in the reward system usually related to addictions are present in problematic Internet use.

BACKGROUND The pathophysiology of cervical dystonia is poorly understood. Increased brain iron deposition has been described in different movement disorders. Our aim was to investigate brain iron content in patients with cervical dystonia, using R2* relaxation rate, a validated MRI marker of brain iron level. METHODS Twelve female patients with primary focal cervical dystonia (mean age: 45.4 ± 8.0 years) and 12 age-matched healthy female subjects (mean age: 45.0 ± 8.0 years) underwent 3T MRI to obtain regional R2* relaxation rates of the thalamus, caudate nucleus, putamen, and globus pallidus (GP). Regions of interest were delineated automatically on T1-weighted MRIs. RESULTS R2* values in the putamen were positively correlated with age. Patients with cervical dystonia showed elevated R2* values in the GP. CONCLUSIONS This pilot study provides the first quantitative support for increased brain iron deposition in cervical dystonia. Further studies are needed to explore the implications of this finding.

Introduction: Parkinson’s disease is a well known representant 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. Aim: The authors discuss characteristics and therapeutic interventions in Parkinson’s disease related sleep disturbances. Method: The authors reviewed and summarised literature data on sleep disorders in Parkinson’s disease published in the PubMed database up to January 2015. Results: 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 desease on sleep and concomitant sleep disorders constitute the background of the patient’s complains. Conclusions: 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. Orv. Hetil., 2015, 156(27), 1091–1099.

Bilateral paramedian thalamic stroke is characterized by hypersomnia, vertical gaze palsy, amnestic alteration, and apathic state. Combined lesion of the paramedian thalamus and mesencephalon bilaterally is extremely rare. Little is known about the breathing disturbances of the particular region due to the lesion. The following describes the specific case of a woman, age 62, with bilateral paramedian thalamic and mesencephalic stroke. Initially, the patient’s complaints exhibited altered vigilance and vertical gaze palsy. Notably, following the acute phase, fluctuating hypersomnia was detected. The MRI (brain) revealed an ischemic lesion in the medial part of the mesencephalon and paramedian thalamus, bilaterally. The aim of the present study is to elucidate the involvement and characteristics of sleep-related breathing abnormalities in the clinical manifestation of the combined paramedian thalamic and mesencephalic stroke. Polysomnographic recordings were accomplished seven times with 1-week interval between the consecutive recordings, toward investigating the early changes of sleep and sleep-related breathing abnormalities. Sleep structure examination featured a decrease in N3 and REM ratio and an increase in N1 and N2 ratio with minimal improvement during the recovery period. In contrast, significant changes were found in the breathing pattern: the initial central apnea dominance was followed by obstructive apneas with a gradual decrease of the total pathological respiratory events. In addition to the structural abnormality of the sleep regulating network, sleep-disordered breathing is another possible cause of hypersomnia in patients afflicted with the present localization of the lesion.

Background: Sleep problems are among the most common non-motor symptoms of Parkinson’s disease (PD). The PD Sleep Scale 2nd version (PDSS-2) improved the original PDSS by adding more items on different aspects of sleep problems, making it a more robust tool to evaluate the severity of sleep disturbances. However, previous studies on deep brain stimulation (DBS) have not used the PDSS-2. Objective: To determine if the PDSS-2 could detect improvement reliably in sleep problems after bilateral subthalamic nucleus DBS for PD. Methods: In this prospective study, 25 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. Severity of PD symptoms were assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS). Presence and severity of sleep disturbances were specifically measured by PDSS-2. Results: Total score of MDS-UPDRS improved from 81 (median, interquartile-range: 63–103) to 55 points (median, IQR: 46–75, p < 0.001). Health-related quality of life, measured by PDQ-39, also improved from 29 (IQR: 18–40) to 15 (IQR: 9–28) points (p = 0.002). Most domains of NMSS also improved. At baseline 13 patients reported sleep problems, but 1 year after DBS implantation only 3 did (p = 0.012). Although only 6 out of 15 items showed a significant decrease after DBS implantation, the total score of PDSS-2 decreased from 24 (IQR: 17–32) to 10 (IQR: 7–18) points (P < 0.001). Conclusions: Based on our results, PDSS-2 can detect improvements in sleep quality reliably after DBS implantation.

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). Orv. Hetil., 2015, 156(23), 915–926.

Background. Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by numerous motor and nonmotor symptoms. Neurocognitive disorders (NCD) are one of the most troublesome problems and their diagnosis is often challenging. Methods. We compared the sensitivity and specificity of several versions of Addenbrooke Cognitive Examination (ACE, ACE-III, and Mini-ACE) on 552 subjects with PD. Normal cognition, mild and major NCD were judged in accordance with the respective criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition. Subsequently, we applied the receiver operation characteristic (ROC) analysis in comparison of different education levels. Results. For subjects with education level 0–8 and 9–12 years, the ACE-III had the best discriminating capabilities for mild NCD (cut-off scores: 83.5 and 85.5 points, respectively), while Mini-ACE was the best for subjects having education > 12 years (cut-off score: 25.5 points). For detecting major NCD, ACE-III had the best diagnostic accuracy in all levels of education (cut-off scores: 70.5, 77.5, and 78.5 points for subjects having education level 0–8, 9–12, and >12 years, respectively). Conclusion. ACE-III and its nested version, the Mini-ACE, had the best screening abilities for detecting mild and major NCD in PD.

Wide variety of the movements (from the physiologic body position changes to different pathologic events) can be seen during the sleep period. The most important types of these movements are the sleep related events (from the parasomnias to the restless leg related movements), the movement disorders and the epilepsy related events. To differentiate between these events is required special skill, which is based on appropriate characterisation of the events (for example timing, repetition, pattern), the polysomnographic and video-EEG examination and validated questionnaires (FLEP scale). The appropriate differential diagnostics and therapy must be based on the knowledge of the relationship of the sleep architecture and movement events. This review would like to provide guideline for the understanding and recognizing the nature of the sleep related movements.

BACKGROUND The recently published "EarlyStim" study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. METHODS We reviewed the data of 39 young (< 60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pecs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job ("Job+" group, n = 15) and retired patients (without active job, "Job-" group, n = 24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. RESULTS As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p < 0.01, McNemar test). CONCLUSION Although our retrospective study has several limitations, our results fit well with the conclusions of "EarlyStim" study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.

BACKGROUND AND PURPOSE 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. METHODS 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 achieved > or =13 PD-Q score (unclear or possible neuropathic pain) were further assessed by the DN4 questionnaire. Patients with PD-Q score >18 or DN4 score 4 were considered to have PeNP and they completed the EQ-5D health questionnaire. RESULTS 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, p