Search

Bevezetés: A dystrophia myotonica a leggyakoribb felnőttkori, autoszomális domináns módon öröklődő izombetegségek csoportjába tartozik. Mindkét klinikai altípusának jellemzője a ’splicing’ mechanizmus zavara okán kialakult, kiterjedt mRNS- és következményes fehérje-funkciózavar. Mindez multiszisztémás betegség megjelenését idézi elő, az izomérintettségen túl szürke hályog, szívritmuszavar, csökkent légzési kapacitás, szénhidrát- és zsíranyagcsere-zavar, endokrinológiai eltérések és kognitív deficit kialakulásával. Több tanulmány említi a dystrophia myotonica 1-es típusában megfigyelhető nagyobb stroke-kockázatot. Célkitűzés: Vizsgálatunkban a Klinikánk gondozásában álló, a dystrophia myotonica 1-es típusában szenvedő 31 beteg részletes vizsgálatát végeztük el az ischaemiás stroke kockázati tényezőinek feltérképezése céljából. Módszer: A betegek kórtörténetének részletes áttekintését a Klinikánk laboratóriumában végzett vizsgálatok, valamint arteria (a.) carotis ultrahangvizsgálat követte. Eredmények: Betegeinknél atherogen dyslipidaemia, normális a. carotis intima és media vastagság volt azonosítható, ugyanakkor nagy arányban igazolódott supraventricularis szívritmuszavar. Megbeszélés: A nemzetközi irodalmi adatokkal egybehangzóan ezen vizsgálat is támogathatja azt a feltevést, mely szerint a dystrophia myotonica 1-es típusában észlelhető nagyobb ischaemiás stroke rizikó hátterében a leginkább releváns kockázati tényező a supraventricularis ritmuszavar (pitvarfibrilláció és ’flutter’) lehet. Következtetés: A dystrophia myotonica 1-es típusában szenvedő betegpopuláció hosszmetszeti követése során kiemelt figyelmet kell fordítanunk a kardiológiai gondozásra is. Orv Hetil. 2022; 163(49): 1962–1966.

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.

BACKGROUND: Telemedicine (TM) contributes to bridge the gap between healthcare facilities and patients' homes with neuromuscular disease (NMD) because of mobility issues. However, its deployment is limited due to difficulties evaluating subtle neurological signs such as mild weakness or sensory deficits. The COVID-19 pandemic has disrupted healthcare delivery worldwide, necessitating rapid measures implementation by health care providers (HCPs) to protect patients from acquiring SARS-CoV-2 while maintaining the best care and treatment.OBJECTIVES: Given the challenges faced by remote healthcare assistance of NMD patients, we aim to evaluate the use of TM in NMD during the COVID-19 pandemic.METHODS: Based on the Model for Assessment-of-Telemedicine-Applications (MAST), we conducted a survey amongst clinicians of the ERN EURO NMD (European-Reference-Network-for-Rare-Neuromuscular-Diseases).RESULTS: Based on 42 responses over 76 expected ones, our results show that the COVID-19 pandemic significantly increased the number of HCPs using TM (from 60% to 100%). The TM types most used during the COVID-19 period are teleconsultation and consultation by phone, particularly in the context of symptoms worsening in NMD patients with COVID-19 infection. Most European HCPs were satisfied when using TM but as a complementary option to physical consultations. Many responses addressed the issue of technical aspects needing improvement, particularly for elderly patients who need caregivers' assistance for accessing the TM platform.CONCLUSIONS: TM has been essential during COVID-19, but its use still presents some limitations for NMD patients with cognitive deficits or for first-time diagnosis. Thus, TM should be used as complement to, rather than substitute, for face-to-face consultations.

Összefoglaló. A dystrophia myotonica (DM) multiszisztémás, autoszomális domináns módon öröklődő, többségében felnőttkori izombetegség, melynek incidenciája 1 : 8000. A betegség kapcsán fellépő izomszöveti degeneráció a harántcsíkolt izomszövet átépülése mellett a szívizomszövetet is érinti, ami fontos oki szerepet játszik az érintett betegek csökkent várható élettartamában. A DM-ben szenvedők halálozásának közel egyharmadáért a cardiovascularis okok tehetők felelőssé. Esetriportunkban egy 52 éves, korábban kritikus bradycardia és I. fokú atrioventricularis blokk miatt pacemakerimplantáción átesett, DM-mel diagnosztizált nőbeteg kardiológiai utánkövetését mutatjuk be. A hirtelen szívhalál rizikóstratifikációja céljából elvégzett invazív elektrofiziológiai vizsgálat során kamrafibrilláció lépett fel, így a korábban implantált pacemakerelektródák mellé sokkelektróda került beültetésre, a pacemakerkészüléket implantálható kardioverter-defibrillátorra (ICD) cseréltük. Az 1 éves ICD-kontrollvizsgálat során azt találtuk, hogy a beültetés óta 22, tartós kamrai tachycardiával járó epizód lépett fel, melyek közül a készülék valamennyit sikeresen terminálta. Az eset bemutatásával szeretnénk rámutatni arra, hogy a magas cardiovascularis rizikócsoportba tartozó DM-betegek azonosítása kiemelkedő fontosságú lehet a hirtelen szívhalál megelőzése érdekében. Orv Hetil. 2021; 162(46): 1856–1858. Summary. Myotonic dystrophy (DM) is one of the most frequent adulthood diseases of the skeletal muscles, which develops multisystemic features and shows autosomal dominant trait. In DM, tissue degeneration affects not only the skeletal, but the cardiac muscle, too. In one third of the patients, the cause of death is of cardiac origin. We report on our patient’s case, who was diagnosed with DM at the age of 52, in whom episodes of critical bradycardia with first-degree atrioventricular block was detected, resulting in a pacemaker implantation. Invasive cardiac electrophysiological study was performed, during which ventricular fibrillation was registered. A shock electrode was added to the previously implanted pacemaker, enabling defibrillation in case of detection of a sustained ventricular arrhythmia. During the 1-year follow-up, 22 episodes of sustained ventricular tachycardia were identified, with the device successfully terminating the malignant arrhythmias. Our case shows that electrophysiological study and the succeeding implantation of an implantable cardiac defibrillator is highly important in identifying and terminating ventricular arrhythmias in high-risk DM patients. Orv Hetil. 2021; 162(46): 1856–1858.

Myotonic dystrophy is one of the most common autosomal dominant inherited muscular diseases. In both subtypes, not only the musculoskeletal system but other organs are also affected as a result of mis-splicing of several messenger RNAs leading to the production of dysfunctional proteins. Cataract, reduced pulmonary capacity, rhythm disorders, glucose intolerance, dyslipidaemia, endocrinopathies and cognitive impairment are also obtained in patients with myotonic dystrophy.We aimed to assess the risk factors of ischaemic stroke in our patients.After a detailed review of the patients' medical history, laboratory and clinical tests and a carotid ultrasound examination were performed.We found atherogenic dyslipidaemia, high risk of cardiogenicembolism, and normal carotid artery intimal media thickness.Our result can suggest the role of atrial fibrillation and other supraventricular rhythm disorders as important risk factors for ischemic stroke in patients with myotonic dystrophy.During the longitudinal follow-up of the patient population suffering from dystrophia myotonica type 1, special attention must also be paid to cardiology care. Orv Hetil. 2022; 163(49): 1962-1966.Bevezetés: A dystrophia myotonica a leggyakoribb felnőttkori, autoszomális domináns módon öröklődő izombetegségek csoportjába tartozik. Mindkét klinikai altípusának jellemzője a ’splicing’ mechanizmus zavara okán kialakult, kiterjedt mRNS- és következményes fehérje-funkciózavar. Mindez multiszisztémás betegség megjelenését idézi elő, az izomérintettségen túl szürke hályog, szívritmuszavar, csökkent légzési kapacitás, szénhidrát- és zsíranyagcsere-zavar, endokrinológiai eltérések és kognitív deficit kialakulásával. Több tanulmány említi a dystrophia myotonica 1-es típusában megfigyelhető nagyobb stroke-kockázatot. Célkitűzés: Vizsgálatunkban a Klinikánk gondozásában álló, a dystrophia myotonica 1-es típusában szenvedő 31 beteg részletes vizsgálatát végeztük el az ischaemiás stroke kockázati tényezőinek feltérképezése céljából. Módszer: A betegek kórtörténetének részletes áttekintését a Klinikánk laboratóriumában végzett vizsgálatok, valamint arteria (a.) carotis ultrahangvizsgálat követte. Eredmények: Betegeinknél atherogen dyslipidaemia, normális a. carotis intima és media vastagság volt azonosítható, ugyanakkor nagy arányban igazolódott supraventricularis szívritmuszavar. Megbeszélés: A nemzetközi irodalmi adatokkal egybehangzóan ezen vizsgálat is támogathatja azt a feltevést, mely szerint a dystrophia myotonica 1-es típusában észlelhető nagyobb ischaemiás stroke rizikó hátterében a leginkább releváns kockázati tényező a supraventricularis ritmuszavar (pitvarfibrilláció és ’flutter’) lehet. Következtetés: A dystrophia myotonica 1-es típusában szenvedő betegpopuláció hosszmetszeti követése során kiemelt figyelmet kell fordítanunk a kardiológiai gondozásra is. Orv Hetil. 2022; 163(49): 1962–1966.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with a widespread occurrence and diverse effects. PACAP has well-documented neuro- and cytoprotective effects, proven in numerous studies. Among others, PACAP is protective in models of diabetes-associated diseases, such as diabetic nephropathy and retinopathy. As the neuropeptide has strong neurotrophic and neuroprotective actions, we aimed at investigating the effects of PACAP in a rat model of streptozotocin-induced diabetic neuropathy, another common complication of diabetes. Rats were treated with PACAP1-38 every second day for 8 weeks starting simultaneously with the streptozotocin injection. Nerve fiber morphology was examined with electron microscopy, chronic neuronal activation in pain processing centers was studied with FosB immunohistochemistry, and functionality was assessed by determining the mechanical nociceptive threshold. PACAP treatment did not alter body weight or blood glucose levels during the 8-week observation period. However, PACAP attenuated the mechanical hyperalgesia, compared to vehicle-treated diabetic animals, and it markedly reduced the morphological signs characteristic for neuropathy: axon–myelin separation, mitochondrial fission, unmyelinated fiber atrophy, and basement membrane thickening of endoneurial vessels. Furthermore, PACAP attenuated the increase in FosB immunoreactivity in the dorsal spinal horn and periaqueductal grey matter. Our results show that PACAP is a promising therapeutic agent in diabetes-associated complications, including diabetic neuropathy.

Diseases with peripheral motor symptoms are a rare, but important subgroup of the all peripheral neuropathies, radiculopathies and neuronopathies. In these mostly progressive neuropathies, the clinical features include pure motor symptoms with weakness and wasting of the striated muscles. The differentiation of these diseases is frequently a challenge for qualified clinical neurologists. A careful history taking, the disease time course, the findings of routine clinical physical examination and the electrophysiological studies are all necessary in the diagnostic procedure. The aim of this publication is to overview the clinical characteristics of the pure motor peripheral neuropathies, to consider the diagnostic steps and the differential diagnosis, and finally to summarize the treatment options.

Abstract: Myotonic dystrophy is one of the most common, autosomal dominantly inherited adult-onset muscle disorders. Two types of the disease are known: type 1 is characterized by distal weakness and myotonia, but type 2 is associated with proximal weakness and milder clinical course. It is also called as Steinert Disease, which affects the heart conduction system, the internal secretional glands, the ocular lens as well as carbohydrate-, fat metabolism and gonadal functions. These systemic symptoms have high impact on the quality of life and might impact on patients’ survival. Here we would like to emphasize these clinical conditions and the diagnostic possibilities. We hope our recommendations can help neurologists and general practitioners to achieve an optimal and individual care for patients suffering from this muscle disease. Orv Hetil. 2019; 160(37): 1447–1454.

Összefoglaló. A dystrophia myotonica (DM) multiszisztémás, autoszomális domináns módon öröklődő, többségében felnőttkori izombetegség, melynek incidenciája 1 : 8000. A betegség kapcsán fellépő izomszöveti degeneráció a harántcsíkolt izomszövet átépülése mellett a szívizomszövetet is érinti, ami fontos oki szerepet játszik az érintett betegek csökkent várható élettartamában. A DM-ben szenvedők halálozásának közel egyharmadáért a cardiovascularis okok tehetők felelőssé. Esetriportunkban egy 52 éves, korábban kritikus bradycardia és I. fokú atrioventricularis blokk miatt pacemakerimplantáción átesett, DM-mel diagnosztizált nőbeteg kardiológiai utánkövetését mutatjuk be. A hirtelen szívhalál rizikóstratifikációja céljából elvégzett invazív elektrofiziológiai vizsgálat során kamrafibrilláció lépett fel, így a korábban implantált pacemakerelektródák mellé sokkelektróda került beültetésre, a pacemakerkészüléket implantálható kardioverter-defibrillátorra (ICD) cseréltük. Az 1 éves ICD-kontrollvizsgálat során azt találtuk, hogy a beültetés óta 22, tartós kamrai tachycardiával járó epizód lépett fel, melyek közül a készülék valamennyit sikeresen terminálta. Az eset bemutatásával szeretnénk rámutatni arra, hogy a magas cardiovascularis rizikócsoportba tartozó DM-betegek azonosítása kiemelkedő fontosságú lehet a hirtelen szívhalál megelőzése érdekében. Orv Hetil. 2021; 162(46): 1856-1858. Summary. Myotonic dystrophy (DM) is one of the most frequent adulthood diseases of the skeletal muscles, which develops multisystemic features and shows autosomal dominant trait. In DM, tissue degeneration affects not only the skeletal, but the cardiac muscle, too. In one third of the patients, the cause of death is of cardiac origin. We report on our patient's case, who was diagnosed with DM at the age of 52, in whom episodes of critical bradycardia with first-degree atrioventricular block was detected, resulting in a pacemaker implantation. Invasive cardiac electrophysiological study was performed, during which ventricular fibrillation was registered. A shock electrode was added to the previously implanted pacemaker, enabling defibrillation in case of detection of a sustained ventricular arrhythmia. During the 1-year follow-up, 22 episodes of sustained ventricular tachycardia were identified, with the device successfully terminating the malignant arrhythmias. Our case shows that electrophysiological study and the succeeding implantation of an implantable cardiac defibrillator is highly important in identifying and terminating ventricular arrhythmias in high-risk DM patients. Orv Hetil. 2021; 162(46): 1856-1858.

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.

Myotonic dystrophy is one of the most common, autosomal dominantly inherited adult-onset muscle disorders. Two types of the disease are known: type 1 is characterized by distal weakness and myotonia, but type 2 is associated with proximal weakness and milder clinical course. It is also called as Steinert Disease, which affects the heart conduction system, the internal secretional glands, the ocular lens as well as carbohydrate-, fat metabolism and gonadal functions. These systemic symptoms have high impact on the quality of life and might impact on patients' survival. Here we would like to emphasize these clinical conditions and the diagnostic possibilities. We hope our recommendations can help neurologists and general practitioners to achieve an optimal and individual care for patients suffering from this muscle disease. Orv Hetil. 2019; 160(37): 1447-1454.Absztrakt: A dystrophia myotonica az egyik leggyakoribb felnőttkori, autoszomális domináns módon öröklődő izombetegség. Két típusa ismert, az 1-es típusban distalis izomtünetek és myotonia alakul ki, a 2-es típust enyhébb izomtünetek és proximalis dominancia jellemzi. A szerzői néven Steinert-betegségként ismert kórkép a vázizomrendszeren túl elsősorban a szív ingerületképző és -vezető rendszerét, a belső elválasztású mirigyek működését, a szénhidrát- és zsíranyagcserét, a szemlencsét, valamint az ivarmirigyek funkcióját érinti. Az izmok károsodásának tünettana mellett megjelenő egyéb szervi kórállapotok a betegek életminőségét és túlélését jelentősen befolyásolják. Ezért tartjuk szükségesnek, hogy e szempontok figyelembevételével végezzük izombetegeink neurológiai gondozását. Közleményünkben igyekszünk kiemelni e multiszisztémás jellegű betegség klinikai megjelenésének főbb pontjait, valamint a diagnosztikai lehetőségek eszköztárát. Következtetéseink támpontot adhatnak a fenti kórképpel diagnosztizált betegek gondozását végző orvosok számára, az egyénre szabott követés megvalósításához. Orv Hetil. 2019; 160(37): 1447–1454.

LGMD1D is an autosomal dominant limb girdle muscular dystrophy caused by variants in the DNAJB6 gene. This is typically an adult-onset disorder characterized by moderately progressive proximal muscle weakness without respiratory or bulbar involvement; however phenotypic variability is often observed with some individuals having earlier onset and more severe symptoms. Here, we present a family with a novel NM_005494.2:c.271T > G p.(Phe91Val) variant in DNAJB6 with a late-onset, mild and slowly progressive form of the disease, including one individual, who in her 7th decade of life has subclinical LGMD1D with only mild features on muscle biopsy and MRI. Unlike previously reported cases where missense variants affecting the Phe91 amino acid residue are associated with a more severe form of the disease, this family represents the mild end of the LGMD1D clinical spectrum. Therefore, this family adds further complexity to the genotype-phenotype correlation in DNAJB6-associated muscular dystrophies.

Background Idiopathic inflammatory myopathies (IIM) are characterised by muscle weakness due to muscle inflammation, various organ involvements and the presence of certain specific autoantibodies. Objectives To assess survival and characterise subsets based on muscle biopsy and myositis specific autoantibodies. Methods Eighty-two patients with muscle biopsy proven IIM were included in the study. Muscle biopsy was reevaluated and cathegorized by the same investigator (EP). All cases had myositis specific (MSA) and myositis associated (MAA) antibody tests. The MSAs and MAAs (Jo-1, PL-7, PL-12, Mi-2, SRP, Pm-Scl, Ku, ribosomal, AMA-M2) were tested with Western-blot. Dermatomyositis/DM/, polymyositis/PM/, juvenile PM/DM, inclusion body myositis/IBM/, overlap myositis/OM/ and immune mediated necrotizing myopathy/IMNM/were identified based on clinical data, immunserology and muscle biopsy. Patients were treated with glucocorticoids/cytostatics, interstitial lung disease was treated with pulse cyclophosphamide in 15/43 cases. Survival analysis was perfomed by Kaplan Meier test. Results Fifty-nine women and 23 men with a mean age of 49.3±14.6 years were included. Mean follow-up of the patients was 7.5±4.5 years. Interstitial lung disease (ILD) (51.2%), arthritis (51.2%), Raynaud’s phenomenon (42.7%), skin symptoms (45.1%), dysphagia (24.4%) and significant cardiac involvement (15.9%) were the most prevalent disease manifestations. 15 cases were associated with malignancies. The distribution of myositis subsets is as follows: 26.8% (n=22) PM, 30.5% (n=25) DM, 1.2% (n=1) juvenile PM/DM, 8.5% (n=7) IBM, 22% (n=18) OM, and 11% (n=9) IMNM. Malignancy was most frequently associated with IMNM (7 out of 9 patients). Altogether 18 patients died from which 15 deaths can be connected to myositis related events. Eight patients died of malignancies (4 in the IMNM, 2 in the PM and 2 in the DM group), 5 patients due to cardiac events (heart failure, arrythmia), 2 due to lung fibrosis and 3 by unknown causes. The worst prognosis with a 10 year survival of 31% was in the IMNM subgroup (p Patients with antisynthetase antibody-positivity had worse prognosis compared with patients with other antibodies or no identifiable antibodies (10 year survival of 55%, n=16) (p Conclusions The worst survivals were seen in the IMNM and PM groups, due to the high frequency of the underlying malignancies and cardiac manifestations. Although ILD was the most frequent involvement, it was not a major determinant of outcome. Disclosure of Interest None declared

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.

Background: Idiopathic inflammatory myopathies (IIM) are characterised by chronic muscle inflammation, various organ involvements and the presence of certain specific autoantibodies. Objectives: We assessed survival and characterized subsets based on muscle biopsy and myositis specific autoantibodies (MSAs). Methods: Eighty-two patients with muscle biopsy proven IIM were included in the study. All cases had MSA and myositis associated antibody (MAA) tests (Jo-1, PL-7, PL-12, Mi-2, SRP, Pm-Scl, Ku, ribosomal, AMA-M2) using Western-blot kits. Survival analysis was performed by Kaplan Meier test. Results: Fift y-nine women and 23 men with a mean age of 49.3 ± 14.6 years and with 7.5 ± 4.5 years of mean follow-up time were included. Interstitial lung disease (ILD) (51.2%), arthritis (51.2%), Raynaud’s phenomenon (42.7%), skin symptoms (45.1%), dysphagia (24.4%) and significant cardiac involvement (15.9%) were the most prevalent disease manifestations. 15 cases were associated with malignancies. Myositis subsets were as follow: 26.8% (n=22) polymyositis /PM/, 30.5% (n=25) dermatomyositis/DM/, 1.2% (n=1) juvenile PM/DM, 8.5% (n=7) inclusion body myositis /IBM/, 22% (n=18) overlap myositis /OM/, and 11% (n=9) immune mediated necrotizing myopathy /IMNM/. Malignancy was most frequently associated with IMNM (7 out of 9 patients). Altogether 18 patients died from which 15 deaths can be connected to myositis related events. Eight patients died of malignancies, 5 patients due to cardiac events (heart failure, arrythmia), 2 due to lung fibrosis and 3 by unknown causes. The worst prognosis with a 10-year survival of 31 % was in the IMNM subgroup (p

Limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous muscular diseases that predominantly affect the proximal muscles. Pathogenic variants in TNPO3 have been associated with a rare, autosomal dominant limb-girdle muscular dystrophy 1F (LGMD1F) in a large Italian-Spanish family and an isolated LGMD1F case. Here we present two individuals from a Hungarian family with an early-onset, slowly progressive muscular dystrophy. Both the female proband and her affected son had delayed early motor milestones including first walking at 14 months and 18 months, respectively. Both present with progressive weakness of facial, bulbar, axial, and distal muscles especially of the lower extremities. Electromyography indicated myogenic damage and muscle biopsy from the proband showed myopathic alterations with sarcoplasmic masses and signs of mitochondrial dysfunction. Exome sequencing of the female proband identified a novel c.2767delC p.(Arg923AspfsTer17) variant in TNPO3. Sanger sequencing confirmed the presence of the TNPO3 variant in the affected son; the unaffected son did not have the variant. The identification of the c.2767delC variant further supports the clinical significance of TNPO3 and expands the clinical spectrum of TNPO3-associated LGMD1F.

To perform a pilot study assessing possible efficacy, safety, and optimal dosage of pramipexole in essential tremor.Twenty-nine patients with essential tremor were enrolled into this 16-week-long study. After recording baseline condition, 2 different dosages of immediate-release formulation of pramipexole were evaluated (1.05 mg/d and 2.1 mg/d in 3 identical dosages). Subsequently, immediate- and extended-release formulations were compared. The Fahn-Tolosa-Marin Tremor Rating Scale, Activities of Daily Living, the EuroQol instrument for detecting health-related outcome, and Clinical Global Impression of Improvement Scale were obtained. After completing the study, a rater blinded to the treatment reassessed the tremor rating scales based on video recordings.Twenty-four patients (82.6%) completed the study. Causes for discontinuation were adverse effects of pramipexole: intolerable nausea (n = 3), daytime sleepiness (n = 1), and anxiety (n = 1). Twenty-one patients had a score of less than 3 on the Clinical Global Impression of Improvement Scale (treatment responders, 72.4%). All the major outcome values demonstrated significant improvement. The severity of tremor was reduced by 52.0% (43.7 vs 20.8 points, Fahn-Tolosa-Marin Tremor Rating Scale), and the EuroQol instrument for detecting health-related outcome score improved from 0.69 to 0.91 (P0.01). The dose of 2.1 mg was more effective than that of 1.05 mg; however, both the immediate- and extended-release formulations were equally efficacious. After completion of the study, 15 patients (51.7% of the enrolled patients) wanted to remain on pramipexole treatment.This pilot study suggests that pramipexole may be effective in the treatment of essential tremor. However, further controlled studies are required.

Based on several open-label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double-blind placebo-controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty-two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real-rTMS (90% of resting motor threshold, 5 Hz, 600 pulses-a-day for 10 days) over the left DLPFC, and another group receiving sham-rTMS. An investigator blinded to the treatment performed three video-taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long-term effect). Mini-Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn-Yahr, Epworth Sleepiness, Visual Analog and Montgomery-Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS-III by 7.5 points (31.9%, P = 0.06). In the sham-treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials.

Sleep problems are one of the most common non-motor symptoms of Parkinson’s disease (PD). The Parkinson’s disease Sleep Scale 2nd version (PDSS-2) was published in 2011 showing satisfactory clinimetric results. We performed an independent testing of the scale adding further information on its clinimetric properties. In this nationwide study 537 PD patients were enrolled. Besides PDSS-2, we assessed Patient’s Global Impression-Severity (PGI) scale on sleep disturbances, Non-motor Symptoms Scale and MDS-UPDRS. Following the Classical Theory of Tests we performed descriptive data analysis, factor analysis, reliability, validity and precision measurements. Subsequently, we evaluated cut-off value for detecting clinically meaningful sleep problems based on receiver operating characteristics analysis. Based on the PGI scale, 161 patients (30.0 %) did not reported any sleep problems. Factor analysis revealed almost the same factor structure described by the original PDSS-2 validation study. Cronbach’s alpha was 0.863 and all item had good item-total correlation. PDSS-2 demonstrated high convergent validity with Non-Motor Symptoms Scale and Clinical Global Impression-Severity and non-motor part of MDS-UPDRS, and divergent validity with age, gender, education level, disease-duration and Hoehn–Yahr Stages. Presence of sleep problems was identified by scores >10.5 points on PDSS-2 (sensitivity 85.3 %, specificity 60.8 %, diagnostic accuracy 78.1 %); whereas scores >19.5 points indicated marked sleep-related problems (specificity 68.5 %, sensitivity 78.0 %, diagnostic accuracy 74.3 %). Independent and cross-cultural validation of patient reported outcomes is essential to confirm or reject the findings obtained by the developers of the scale. Our results demonstrate that fundamental clinimetric properties of the PDSS-2 are satisfactory.

A recent study has proved that unilateral deep brain stimulation (DBS) of the subthalamic nucleus has bilateral effects. However, it is still unclear whether unilateral ventral intermediate thalamic nucleus (Vim) DBS exerts exclusively contralateral or bilateral effects on tremor. Previous studies demonstrated a clinically irrelevant improvement on the nontarget side after thalamic stimulator implantation, which was considered to be solely the result of mechanical effects. We report here the case of a 55-year-old woman in whom unilateral thalamic DBS can stop the disabling postural-kinetic tremor in both hands. Simultaneous surface electromyography (sEMG), accelerometry, and video recordings were obtained to evaluate the underlying mechanism. After the right Vim DBS was turned off, moderate rest tremor appeared in both hands accompanied by bilateral bursts on sEMG. Because right hand tremor cannot simply reflect the mechanical overflow of the left side, the bilateral improvement caused by right Vim DBS is probably due to an active tremor reduction in this particular case.

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.

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.

Dynamin2 (DNM2) gene mutations may result in Charcot-Marie-Tooth disease and centronuclear myopathy. Here, we present a patient suffering from cardiomyopathy and centronuclear myopathy with repetitive discharges and mild axonal neuropathy due to DNM2 mutation. Detailed cardiological and neurological examinations, electrophysiological tests, muscle biopsy, and molecular genetic analysis were performed. The patient developed left bundle branch block at age 40 and was fitted with a pacemaker at the age of 43. The patient has severe heart failure, ptosis, strabism, facial and proximal muscle weakness. Electrophysiological investigations found myopathy, complex repetitive discharges, and axonal neuropathy. Skeletal muscle biopsy detected centronuclear myopathy and cytochrome C oxidase (COX) negative fibers. Genetic analysis detected a pathogenic c.1105C>T (p.R369W) DNM2 gene mutation and heteroplasmic multiple mitochondrial DNA (mtDNA) deletion. Our data broadens the phenotypic spectrum of DNM2 mutations. The presence of the multiple mtDNA deletions may provide new aspects to understanding the pathogenesis of multisystemic symptoms in patients with DNM2 mutations.

The mitochondrial DNA A3243G transition is a fairly common mutation which often associates with a MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) phenotype, however, a broad variety in the associated clinical picture has also been described. The patient reported here developed a generalized seizure at age 12, which was followed by bilateral hearing loss and occasional fatigue. The maternal inheritance pattern of hearing loss pointed to a possible mitochondrial origin, which was confirmed by molecular analysis of the mitochondrial DNA, revealing a heteroplasmic A3243G transition. Interestingly, muscle biopsy showed ragged-red fibers in the proband, which is unusual in the deafness-associated forms of this mitochondrial disorder. In addition to hearing impairment in four generations of the family, fatal cerebral embolization in the mother and fatal heart attack in the maternal grandmother (both at age 33) also occurred. On the contrary, diabetes, which usually accompanies the hearing loss variant, was specifically absent in all generations. The unusual manifestations associated with this mutation somewhat differentiate this family from the already known variants.

Objective: The effect of chemical sympathectomy on experimental autoimmune encephalomyelitis (EAE) was studied in interferon-γ (IFN-γ) knockout C57BL/6 mice. Methods: Mice were immunized with myelin oligodendrocyte glycoprotein (MOG)35–55 peptide. Sympathectomy was achieved by subcutaneous administration of 6-hydroxydopamine. Results: We showed previously that wild-type mice developed a mild form of EAE with complete recovery. Sympathectomy caused more serious disease and mice did not recover completely, indicating that the sympathetic nervous system (SNS) downmodulates the process of EAE. The clinical signs of disease were more serious in untreated IFN-γ–/– mice than in wild-type animals. Unexpectedly, sympathectomy resulted in suppression of active EAE in IFN-γ–/– mice, implying that control of actively induced EAE by the SNS depends on INF-γ and the integrity of the cytokine network. We also induced EAE by passive transfer of MOG35–55-reactive lymph node cells, and this disease was aggravated by sympathectomy in both wild-type and knockout animals. Conclusions: Our study supports the idea that the integrity of the whole cytokine network is necessary to maintain normal nervous-immune system interactions.

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.

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.

Experimental autoimmune encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune disease that can be protected against by stimulating regulatory cells. Here we examined whether EAE can be purposefully modulated by stimulating Vα14 NK T cells with the CD1d-restricted ligand α-galactosylceramide (α-GC). EAE induced in wild-type C57BL/6 (B6) mice was not appreciably altered by injection of α-GC. However, EAE induced in IL-4 knockout mice and IFN-γ knockout mice was enhanced or suppressed by α-GC, respectively. This indicates that the IL-4 and IFN-γ triggered by α-GC may play an inhibitory or enhancing role in the regulation of EAE. We next studied whether NK T cells of wild-type mice may switch their Th0-like phenotype toward Th1 or Th2. Notably, in the presence of blocking B7.2 (CD86) mAb, α-GC stimulation could bias the cytokine profile of NK T cells toward Th2, whereas presentation of α-GC by CD40-activated APC induced a Th1 shift of NK T cells. Furthermore, transfer of the α-GC-pulsed APC preparations suppressed or enhanced EAE according to their ability to polarize NK T cells toward Th2 or Th1 in vitro. These results have important implications for understanding the role of NK T cells in autoimmunity and for designing a therapeutic strategy targeting NK T cells.

The effect of chemical sympathectomy induced with 6-hydroxydopamine (OHDA) on experimental autoimmune encephalomyelitis (EAE) was studied in wild type and IL-4 −/− C57BL/6 (B6) mice. When actively sensitized with myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide, control B6 mice developed a mild form of EAE with full recovery. The sympathectomized mice developed paralysis with higher maximum disease score and did not recover completely, indicating that the sympathetic nervous system (SNS) down-modulates the process of EAE. Unexpectedly, however, sympathectomy resulted in suppression of EAE in IL-4 −/− mice, implying that control of actively induced EAE by the SNS depends on the genetic background of mice. We also induced EAE by passive transfer of MOG 35–55 -reactive lymph node cells, and this disease was augmented by sympathectomy in both wild type and knockout animals. Further experiments showed that changes in T cell populations and the activity of antigen presenting cells might be responsible for the altered immune response and clinical course after sympathetic ablation. Our studies indicate that the absence of a single cytokine can severely alter nervous–immune system interactions.

We describe a Hungarian Roma family, originally investigated for autosomal dominant distal muscular atrophy. The mother started toe walking at 3 years and lost ambulation at age 27. Her three daughters presented with early steppage gait and showed variable progression. Muscle biopsies were nonspecific showing myogenic lesions in the mother and lesions resembling neurogenic atrophy in the two siblings. To identify the causative abnormality whole exome sequencing was performed in two affected girls and their unaffected father, unexpectedly revealing the MYH7 mutation c.4849_4851delAAG (p.K1617del) in both girls, reported to be causative for Laing distal myopathy. Sanger sequencing confirmed the mutation in the affected mother and third affected daughter. In line with variable severity in Laing distal myopathy our patients presented a more severe phenotype. Our case is the first demonstration of Laing distal myopathy in the Roma and the successful use of whole exome sequencing in obtaining a definitive diagnosis in ambiguous cases.

We investigated the microglial reaction around cobalt-labeled degenerating neurons and nerve fibers in the frog central nervous system. The aim of these studies was to reveal the routes of migrating microglial cells during debris removal and the effect of seasonal changes on this process in a cold-blooded animal. Oculomotor and spinal motoneurons were filled with cobaltous-lysine complex through their axons. In the torus semicircularis and the isthmic nucleus, neurons were labeled with iontophoretically applied cobaltous-lysine complex through their injured dendrites and axons. The animals were left to survive for 1 to 50 days. During the summer, oculomotor neurons disintegrated by the seventh postoperative day. The debris from the neurons were phagocytosed by microglia-like cells identified by the presence of cobalt in their cytoplasm. Some of these cells were wedged between ependymoglial cells of the cerebral aqueduct, others appeared at the pial surface of the mesencephalon. The speed of this process was twice as fast during the summer as during the winter. Part of cobalt-labeled microglial cells in the torus semicircularis and the isthmic nucleus moved toward the ependyma of the optic ventricle and the cerebral aqueduct, respectively. Cobalt-loaded microglial cells did not move toward the surface in the spinal cord and the deep part of mesencephalic tegmentum, and left the brain probably via blood vessels. We conclude that microglial cells loaded with phagocytosed tissue debris may leave the brain tissue via three routes and their activity depends on the environmental temperature.

Mitochondrial diseases are a significant part of neuromuscular diseases. Majority of them is multisystemic disorder. The diagnosis can be established in more and more cases. Beyond the routine neurological examination imaging methods (MRI and MR-spectroscopy) and electrophysiology (EMG, ENG, EEG, evoked potential tests) might be helpful in setting the diagnosis. Raised blood lactate level supports the diagnosis. Muscle biopsy demonstrates mitochondrial abnormalities in the majority of cases. The positivity of genetic tests is low, because the amount of mitochondrial DNA alterations is different in tissues. Therefore other tissue than blood (mainly muscle) is necessary for genetic tests. The other reason is that the respiratory chain is under double -mitochondrial and nuclear - genetic control, and testing the nuclear genes are available only in selected laboratories. The treatment is limited, mainly symptomatic.

The morphology of projection neurons of the isthmic nucleus was studied in Rana esculenta, R. nigromaculata, Bufo marinus, B. bufo gargarizans, and Xenopus laevis from a comparative anatomical point of view. The main point of this work was to provide an anatomical basis for electrophysiological studies. Neurons projecting to the ipsilateral optic tectum were labeled by retrograde transport of horseradish peroxidase and cobaltous lysine complex injected into the optic tectum. Contralaterally projecting cells were filled by injecting the tracer substances into the crossed isthmotectal tract. Cells of the anterior nonrim cortex and the rostral part of the medulla project to the ipsilateral tectum. A band of cells in the middle of the medulla, a few cells in the caudal part of the medulla, and most of the neurons in the rim cortex project to the contralateral tectum. Five types of neurons were distinguished in the rim cortex of R. esculenta. Most of them have piriform perikarya and their dendrites arborize in the rim neuropil. In the medulla of the isthmic nucleus of R. esculenta, seven types of neurons were distinguished. Most of these neurons also exist in the other species. Medullary cells are piriform, fusiform, or multipolar, and are variable in size and in dendritic arborization. The isthmic neurons of the two Ranae and Bufo species are similar. The dominant cell types in Xenopus are multipolar with extensive dendritic arborization, which occupies more space in the nucleus than in the other species. Neurons with narrow dendritic trees may represent a system of fine resolution, and those neurons with extensive dendritic arborization may belong to a coarser system.

Pompe's disease is an autosomal recessive disease caused by deficiency of acid-alpha-glucosidase.Authors analyzed the phenotype of 11 Hungarian patients with Pompe's disease and evaluated clinical parameters and response to enzyme replacement therapy during a long-term follow-up in 8 patients.One patient with atypical infantile form presented with cardiomyopathy and a very slow progression of motor deficits; after 2 years of enzyme replacement therapy no disability was present at the age 6 years. Another patient was asymptomatic at the age of 2.5 years. The adult onset form was characterized by slight to prominent limb-girdle myopathy with an age of onset between 20 and 50 years. In 3 of such cases respiratory insufficiency was also present.Hungarian patients with Pompe's disease presented with a wide phenotypic variability ranging from atypical early childhood form with slowly progressive course to late-onset limb-girdle myopathy with variable courses. Enzyme replacement therapy resulted in significant improvement in motor and respiratory functions in most of the patients.

Here, we present a male infant with clinical signs of typical Leigh syndrome. The first symptom, myoclonus was presented already on the 5th day of life; at 7 months of age limb convulsions and cerebral paresis with hypotonia were developed. At the age of 11 months, MRI verified increased signal intensity in the entire mesencephalon and medulla oblongata; while gray matter proton spectroscopy revealed presence of lactate increase in the brain. At age of 17 months, the child died in cardiorespiratory arrest. After autopsy, the diagnosis of Leigh syndrome was established; using DNA isolated from skeletal muscle and liver, heteroplasmic (>50%) mitochondrial 11777C>A was detected in the fourth subunit of NADH dehydrogenase enzyme (MTND4) encoding gene, which causes Arg → Ser replacement. The mutation was also detected in low copy number in blood of mother. Albeit this mutation type is well recognized as a typical mtDNA mutation, according the reports available on the PubMed, this mutation was described only in four patients with wide phenotypic variations; here, we reviewed the characteristic clinical features of them. Taken together, the earliest onset of symptoms, the nature of the first presentation signs, the most rapid progression, the character of minor additional symptoms, and the early fatal outcome differentiate the phenotypic variant of the proband presented here from cases reported so far by others.

Progressive multifocal leukoencephalopathy is a rare disease caused by the reactivation of an opportunistic agent, JC virus almost in every cases in immunodeficient conditions. The disease is characterized by multifocal demyelinating lesions of the central nervous system and causes death within a few months. The authors report two patients: a 67 year-old male treated because of chronic lymphoid leukemia, and a 19 year-old male having a hereditary immunodeficiency, X-linked hyper IgM syndrome. In both cases continuously progressive right, later both hemispheric signs were detected. Cerebrospinal fluid was not helpful. Brain MRI showed bilateral large, white matter lesion. The progression was not influenced by the treatment, finally both patient died ten and six weeks after the appearance of first complaints. The diagnosis was confirmed by brain biopsy and autopsy in both cases. Our cases demonstrate that progressive multifocal leukoencephalopathy can develop in various immunodeficiencies.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease resulting in loss of upper and lower motoneurons. Here we analyzed the clinical and epidemiological data of 202 ALS patients admitted to our department between 1950 and 2004. Risk and protective factors influencing onset and progression of the disease were examined. We also analyzed the relationship between first clinical symptoms/signs and prognosis of the disease. Our data suggest the importance of toxic factors in the initiation of the disease and the effect of clinical phenotype on the progression of ALS.

A 53-year-old woman underwent several ischemic stroke-like episodes and later developed incomplete, bilateral ophthalmoplegia, left vision deterioration, and bilateral tremor. The clinical course, laboratory data, and muscle histology led to a diagnosis of mitochondrial encephalomyopathy. No other etiology could be identified in the background of her disabling bilateral postural-kinetic tremor. As this tremor did not respond to pharmacological therapy, left thalamotomy and subsequently right thalamic deep brain stimulator (DBS) implantation were performed, which resulted in an excellent clinical outcome. The Fahn-Tolosa-Marin Tremor Rating Scale improved from 110 to 11 points. This case suggests that the rare tremor caused by mitochondrial encephalopathy may be treated long-term with either thalamotomy or thalamic DBS implantation.

Adult-onset acid maltase deficiency myopathy is a rare lysosomal storage disease with an autosomal recessive pattern of inheritance. The disease can be manifested with respiratory insufficiency and fatigue.A case of a 45-year-old male patient is presented, and difficulty in diagnosis is discussed.The patient had been repeatedly examined because of hypersomnia, dyspnea and fatigue for a full year before a neurological consultation was requested. Artificial ventilation resulted in a dramatic improvement of his symptoms. Neurological examination revealed myopathy. Electrophysiological myotonia and glycogen storage in muscle biopsy specimen suggested acid maltase deficiency. The diagnosis was established by genetic testing detecting the previously described homozygous c.-45TG mutation in the alpha-glucosidase gene.Rare hereditary neurological diseases can be also suspected as cause of chronic unexplained respiratory insufficiency resulted in hypersomnia and fatigue due to hypercapnia and myopathy. A proper diagnosis can contribute to early diagnosis and introduction of enzyme replacement therapy may reduce or stop clinical progression. Genetic diagnosis can also provide a possibility for prenatal testing.