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Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes.Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations.In the normal brain - grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas.These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.A glioma kialakulásában szerepet játszik a Wnt-útvonal aberráns aktiválása az őssejtek dif­fe­ren­ciá­lódásának és fenntartásának szabályozása által. Kutatá­sunk célja volt meghatározni, hogy egyes Wnt-markerek milyen mértékben expresszálódnak a különböző grádiusú, szövettani eredetű és mutációs profilú gliomákban.Kilenc grádius II., 10 grádius III. és 72 grá­dius IV., műtéti úton eltávolított, formalinfixált paraffinba ágyazott gliomát vizsgáltunk. Az IDH1 132 kodon mutációs állapotát immunhisztokémia és piroszekvenálás módszereivel határoztuk meg minden tumorban. A II. és III. grádiusú astroglialis és oligodendroglialis tumorokat tovább vizsgáltuk p53- és ATRX-expresszióra immunhisztokémiával, és 1p19q kodelécióra fluoreszcens in situ hibridizációval. A nem kanonikus Wnt5a és Fzd2, vala­mint a kanonikus Wnt3a és β-katenin Wnt-útvonalmarkerek expressziós szintjét immunhisztokémiai úton határoztuk meg, és az expressziós értékeket összehasonlítottuk a tumorok grádiusa, hisztológiai eredete (asztrocitoid vs. oligodendroglioid) és az IDH1 R132H / C mutációk jelenléte vagy hiánya szerinti alcsoportokban.A normál agyi szövet vs. II–IV. grádiusú gliomák összehasonlítása során egy grádius szerinti fokozatos növekedést figyeltünk meg a Wnt5a, Wnt3a, Fzd2 és a β-katenin expressziójában. A II. és III. grádiusú gliomák astroglialis és oligodendroglialis szövettani ere­detű összehasonlítása során csak a Wnt5a-expresszió volt szignifikánsan magasabb az asztroglia-alcsoportban. Az IDH1 R132H / C mutáns és vad típusú gliomák összehasonlítása során a Wnt3 emelkedését találtuk a vad típusú grade II–IV. gliomák csoportjában.Ezek az adatok kibővítik a korábbi megfigyelések eredményeit, és összefüggést mutatnak a Wnt-útvonal aktivitása, valamint a gliomagrádius között. A Wnt-markerek expressziós szabályozásának további vizsgálata gliomákban már folyamatban van szövettani eredet vagy IDH-génmutációs státusz szerint, nagy felbontású molekuláris vizsgálatok alkalmazásával.

Background and aims - Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports - Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion - Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Congenital glioblastoma (cGBM) is a brain tumor very rarely observed in newborns and young infants, and differs in several respects from glioblastoma (GBM) of childhood and adulthood. Our aim was the presentation of a cGBM case with 14 days of postnatal survival at the Pediatric Oncology Center of the Markusovszky University Teaching Hospital in 2004. We investigated formalin-fixed, paraffin-embedded autoptic tumor samples of the newborn by immunohistochemical and molecular genetic (FISH and pyrosequencing) methods. We found polysomy of chromosome 2 and 5' deletion of the ALK gene in the glioma cells by ALK FISH. This result indicates the importance of molecular analyses in the diagnostic evaluation of cGBM, and raises the possibility of a personalized, targeted therapy (crizotinib, alectinib).

Ferenc Garzuly passed away after a long and productive life at the age of 84. He worked for almost 60 years at the Markusovszky University Teaching Hospital, where primarily led the laboratory of neuropathology and the department of neurology, but transferred to the department of pathology after his retirement. By authoring several books on rare diseases, he greatly enriched the case-based tea-ching approach in medicine. He described the Hun-garian type of transthyretin mutation causing the familial me-nin-go-cerebrovascular amyloidosis phenotype. The presentation of a special phenotype of Fabry disease associated with megadolichobasilar anomaly and a novel mutation in the alpha-galactosidase-A gene is also associated with his name.Garzuly Ferenc címzetes egyetemi tanár hosszú, aktív élet után hunyt el 84 évesen. Közel 60 éven át dolgozott a szombathelyi Markusovszky Egyetemi Oktatókórházban, ahol nevéhez fűződik a neuropatológiai laboratórium öt évtizedes tevékenysége. A neurológiai osztályt 20 éven át vezette, majd nyugdíjazása után a patológiai osztályon dolgozott haláláig. Több, ritka betegségeket tárgyaló könyv szerzője, a Magyar Klinikai Neurogenetikai Tár­saság alapító tagja. A nemzetközi szakmai irodalomban nevét a Fabry-betegség egy speciális mutációval társuló és megadochobasilaris elváltozással járó fenotípusának leírásával tette ismertté, és leírta a familiáris meningo­cerebrovascularis amyloidosis transthyretin mutációval járó magyar típusát.

Secretory meningioma is a rare form of meningiomas which differentiates from the meningothelial subtype. It is characterized by significant peritumor edema and distinct immunohistochemical and molecular genetic profiles. We present a middle aged female patient with secretory meningioma infiltrating the orbital bone from the primary cranial base location and causing exophthalmos, features rarely described with this tumor. Surgical resection was challenging because of the associated brain swelling and rich vascularization of the tumor. Imaging and immunohistochemical studies revealed characteristic hallmarks of secretory meningioma. While histologically it was a benign tumor, due to the orbital bone and soft tissue infiltration, postoperative management of neurological sequelae was challenging. This case highlights distinctive clinical, imaging and histological features along with individual characteristics of a rare form of meningiomas.

Abstract: Introduction and aim: A combination of Niemann-Pick- and Hallervorden-Spatz diseases led to the death of a 17-year-old boy in 1994. Genetic counseling necessitated further investigations in 2017. Meanwhile, the nomenclature of Hallervorden-Spatz disease has been abandoned. The author analyze the reasons for this change. Method: Professional activities of Hallervorden and Spatz during and after the Nazi euthanasia program are presented. Also, the scientific efforts that led to the discovery of the genetic background of the disease and ultimately to its new name are highlighted. Results: In nazi Germany, a large number of mentally disabled were killed. The majority of pediatric-brains were transferred to the “Kaiser Wilhelm Institut für Hirnforschung”, led by Hugo Spatz, and was included in the “Hallervorden collection”. Investigations exploring the connections between eponyms and nazi-activites started in the mid-1980s. This process was accelerated by the discovery of genetic alterations underlying disease entities, including neurodegeneration with brain iron accumulation (NBIA). NBIA has several subtypes, with the first being the disease described by Hallervorden and Spatz, and recently renamed to pantothenate kinase-associated neurodegeneration (PKAN). The case examined by the authors belongs to the third subtype, to the mitochondrial protein-associated neurodegeneration (MPAN). Conclusion: The works of the two noted neuropathologists strongly conflict with current ethical principles of human research studies. The buried “Hallervorden collection” in the Munich Waldfriedhof cemetery, and the memorial column erected there will remain a sad reminder of a time when a political system profoundly distorted the judgement of even academic physicians. Orv Hetil. 2017; 158(43): 1723–1727.

Comprehensive molecular characterization of and novel therapeutic approaches to glioblastoma have been explored as a result of advancements in biotechnologies. In this study, we aimed to bring basic research discoveries closer to clinical practice and ultimately incorporate molecular classification into the routine histopathological evaluation of grade IV gliomas. Integrated results of genome-wide sequencing, transcriptomic and epigenomic analyses by The Cancer Genome Atlas Network defined the classic, proneural, neural and mesenchymal subtypes of this tumor. In a retrospective cohort, we analyzed selected subgroup-defining molecular markers in formalin-fixed paraffin-embedded surgical specimens by immunohistochemistry. Quantitative and qualitative scores of marker expression were tested in hierarchical cluster analyses to evaluate segregations of the molecular subgroups, which then were correlated with clinical parameters including patients' age, gender and overall survival. Our study has confirmed the separation of molecular glioblastoma subgroups with clear trends regarding clinical correlations. Future analyses in a larger, prospective cohort using similar methods are expected to facilitate the development of a molecular diagnostic panel that may complement routine histological work up and support prognostication as well as treatment decisions in glioblastoma.

A combination of Niemann-Pick- and Hallervorden-Spatz diseases led to the death of a 17-year-old boy in 1994. Genetic counseling necessitated further investigations in 2017. Meanwhile, the nomenclature of Hallervorden-Spatz disease has been abandoned. The author analyze the reasons for this change.Professional activities of Hallervorden and Spatz during and after the Nazi euthanasia program are presented. Also, the scientific efforts that led to the discovery of the genetic background of the disease and ultimately to its new name are highlighted.In nazi Germany, a large number of mentally disabled were killed. The majority of pediatric-brains were transferred to the "Kaiser Wilhelm Institut für Hirnforschung", led by Hugo Spatz, and was included in the "Hallervorden collection". Investigations exploring the connections between eponyms and nazi-activites started in the mid-1980s. This process was accelerated by the discovery of genetic alterations underlying disease entities, including neurodegeneration with brain iron accumulation (NBIA). NBIA has several subtypes, with the first being the disease described by Hallervorden and Spatz, and recently renamed to pantothenate kinase-associated neurodegeneration (PKAN). The case examined by the authors belongs to the third subtype, to the mitochondrial protein-associated neurodegeneration (MPAN).The works of the two noted neuropathologists strongly conflict with current ethical principles of human research studies. The buried "Hallervorden collection" in the Munich Waldfriedhof cemetery, and the memorial column erected there will remain a sad reminder of a time when a political system profoundly distorted the judgement of even academic physicians. Orv Hetil. 2017; 158(43): 1723-1727.

The product of the neurofibromin gene (NF1) belongs to the family of tumor suppressor proteins. Neurofibromin plays important roles in the negative regulation of signaling pathways where the Ras oncogen is involved. The protein and gene names were derived from the disease, neurofibromatosis type 1 that is caused by germline mutations in NF1 and inherited by an autosomal dominant manner. Besides germline mutations, acquired, somatic mutations are also observed in NF1 in several malignant and benign tumors. NF1 mutations have been identified in a great number of solid tumors, leukemias and malignant skin lesions (e.g. melanoma). Such mutations define certain subsets of gliomas. More specifically, a molecular subset of glioblastomas, termed the mesenchymal subtype, is most frequently associated with somatic NF1 deletions and mutations. The aim of this survey is to provide an overview of the most frequent alterations in the NF1 gene with their effects on the function of the protein and the biology of the cell, as well as of the resultant diseases. Simultaneously, we give some insight into ongoing research studies investigating abnormalities of NF1.A neurofibromin (NF1) gén terméke a tumorszuppresszor proteinek családjába tartozik. Fontos funkciót tölt be olyan jelátviteli útvonalak negatív szabályozásában, melyekben a Ras onkogén szerepet játszik. Nevét a neurofibromatózis betegségrõl kapta, amelynek kialakulásában a csíravonalban található és autoszomális domináns módon öröklõdõ mutációi fontos szerepet játszanak. Az NF1 génnek csíravonal-mutációin kívül szerzett, szomatikus mutációi is ismertek, melyek számos további malignus és benignus tumoros elváltozásban megtalálhatóak. Nagyszámú szolid tumorból, leukémiás sejtekbõl és malignus bõrelváltozásból (többek között melanómákból) is kimutatták az NF1 mutációit. A gliómák bizonyos csoportjaiban meghatározó szerepet játszik ez a gén. Ilyen például a glioblasztóma egyik molekuláris alcsoportja, a mezenhimális alcsoport, melyben az NF1 szomatikus deléciója és mutációja a leggyakrabban fordul elõ. Összefoglalónk célja, hogy áttekintést adjunk az NF1 gén leggyakoribb elváltozásairól, azoknak a neurofibromin proteinre gyakorolt hatásáról és sejtbiológiai következményeirõl, valamint a kapcsolódó betegségekrõl. Egyben rövid betekintést is nyújtunk az NF1 gén abnormalitásaival foglalkozó kutatások állásáról.

Numerous professional groups and sections for the medical specialities have been organized since 1953 in the West-Transdanubian region of Hungary, but such association of neurologists had not occured. ESTABLISHING THE WEST-PANNONIC NEUROLOGICAL FORUM: The lack of regional collaboration among neurologists was related to several factors, among which the most important factor was the lack of a regional medical university, which could coordinate the professional activities. This severe gap necessitated in 1998 the organization of a professional group, that has become a driver for case-consulting conferences and different postgraduate trainings for the physicians specialized in neurology, neurosurgery and neurorehabilitation in counties of Győr-Moson-Sopron, Vas, Veszpr6m and Zala. THE FUNCTIONING OF THE FORUM: Meetings are organized twice a year for physicians and paramedical staff (nurses, hospital attendants, physiotherapists) on Thursdays afternoons in different towns of the region, in two sections. The lectures are followed by a buffet, after which everyone can get home before too late. Ocasionally guest-lecturers are invited to present scientific topics from Hungarian universities or abroad. However, the main form of the presentations is defined as case discussion.The numbers of platform and other presentations in the physicians's section have exceeded half a thousand, while in the paramedical section reached the three- hundreds. At the 38. meeting of the Forum in January of this year, the number of participants was more than two-hundreds, reflecting that both physicians and their coworkers are greatly interested in this form of interactions.

The peptide hormones ACTH, MSHs, β-lipotropin (β-LPH), and β-endorphin are all derived from the precursor molecule proopiomelanocortin (POMC). Using confocal laser microscopy and immunoelectron microscopy in human pituitary gland, we demonstrate a peroxisomal localization of β-endorphin and β-LPH in cells expressing the peroxisomal ATP-binding cassette-transporter adrenoleukodystrophy protein (ALDP). The peroxisomal localization of β-LPH and β-endorphin was not restricted to the pituitary gland but was additionally found in other human tissues that express high levels of ALDP, such as dorsal root ganglia, adrenal cortex, distal tubules of kidney, and skin. In contrast to the peptide hormones β-LPH and β-endorphin, which are derived from the C terminus of POMC, the N-terminal peptides ACTH, α-MSH, and γ-MSH were never detected in peroxisomes. This novel peroxisomal localization of β-endorphin and β-LPH in ALDP-positive cells was confirmed by costaining with ALDP and the peroxisomal marker catalase. Moreover, peroxisomal sorting of β-LPH could be modeled in HeLa cells by ectopic expression of a POMC variant, modified to allow cleavage and release of β-LPH within the secretory pathway. Although β-LPH and β-endorphin were only associated with peroxisomes in cells that normally express ALDP, the transporter activity of ALDP is not necessary for the peroxisomal localization, as demonstrated in tissues of X-linked adrenoleukodystrophy patients lacking functional ALDP. It remains to be elucidated whether and how the peroxisomal localization of POMC-derived hormones has a role in the endocrine dysfunction of peroxisomal disease.

A hétköznapi klinikai gyakorlatban a központi idegrendszer gombás fertőzései gyakoribbá váltak. Ennek leginkább ismert okai a kortikoszteroidok, immunszuppresszív gyógyszerek, citosztatikumok, antibiotikumok egyre szélesebb körű alkalmazása, az AIDS elterjedése, az életben tartható koraszülöttek mind nagyobb száma. A szerzők a diagnosztikus problémák illusztrálására eseteket mutatnak be.Esetismertetés:1. Multifokális haemorrhagiás agyi infarktus generalizált aspergillosis következtében, köpenysejtes malignus lymphomában. 2. Éretlen koraszülöttben kialakult cerebralis microabscessusok szisztémás candidiasis talaján. 3. A comb térfoglaló daganatát utánzó, az agyban radiológiailag metasztázisnak tűnő tályogot, a tüdőben gyulladást okozó lethalis actinomycosis. 4. Idegsebészeti szövetmintából diagnosztizált nocardiosis. A visszatérő, migráló pneumonia, majd agyi tályogok miatt hosszasan kezelt beteg a megfelelő terápiára gyógyult.Megbeszélés:Fel kell készülnünk a veszélyeztetett betegek gombás infekciójának kialakulására – elsősorban aspergillosisra és candidiasisra –, ezek jelentős része a központi idegrendszerre is ráterjed. Az actinomycosis és a nocardiosis kezelésre jobban reagál, felismerésük, kezelésük életmentő.Következtetések:Terápiás kilátásaink javulnak, ha a nagy rizikójú betegek jelentős mortalitást okozó mycosisainak lehetőségével számolva, azokat időben – még az idegrendszeri részvétel előtt – kórismézzük és kezeljük.

Fabry disease is a rare, progressive lysosomal storage disorder caused by mutation in the GAL gene and an impaired function of the alpha-galactosidase A enzyme. The enzymatic defect results in the progressive accumulation of glycosphingolipids in endothelial cells, smooth muscle cells, leucocytes and fibroblasts leading to organ damage in the skin, eye, nervous system, kidney and heart. Major clinical manifestations include acroparesthesis, angiokeratoma, corneal opacities, vascular diseases of the heart, kidney, and the central nervous system. Enzyme replacement therapy has recently become available for the treatment of Fabry patients. In this review the authors describe clinical features of Fabry disease in 31 Hungarian patients. At the time of this analysis the database consisted of 31 cases (15 males, 16 females) of whom 5 have died (4 males, 1 female). The most common disease-specific manifestation was angiokeratoma in males, and eye symptoms in females. 25% of female subjects were symptom free. Genotyping was performed in all cases and disease-causing mutations were found in all families. Three new mutations were identified. Twelve patients (8 males and 4 females) are currently receiving enzyme replacement therapy.

Identification of etiological connections among virtually distinct diseases in a patient may be sometimes challenging. We report a unique case with two B cell malignancies and an inflammatory leukoencephalopathy. Three days prior to admission, the elderly male patient developed fatigue, headaches, recurrent vomiting, memory disturbances, depression and somnolence. Clinical, laboratory and imaging evaluations as well as post mortem histological studies were performed. Simultaneous presence of primary central nervous system B cell lymphoma, temporal lobe inflammatory leukoencephalopathy and multiple (smoldering) myeloma, was revealed by the detailed work up in the treatment-naïve patient. Based on recent data from genomic studies, we propose that a sequential evolution of molecular pathology lead to the co-occurrence of multiple myeloma and primary central nervous system B cell lymphoma in this patient, and interpret the development of the temporal lobe leukoencephalopathy as a likely paraneoplastic complication of smoldering myeloma.

In Central European tick-borne encephalitis (TBE) mechanisms of tissue destruction are poorly understood. To evaluate the contribution of immunological mechanisms to tissue injury, the authors immunohistochemically analyzed paraffin-embedded autoptic brain tissue of 26 human TBE cases. In the parenchymal compartment, there was a predominance of macrophages/microglia and cytotoxic T cells. In addition, it was found that granzyme B-expressing lymphocytes were in close contact with TBE-expressing neurons up-regulating caspase-3. These findings indicate that cellular and humoral pathways of the immune system, especially granzyme B-releasing cytotoxic T cells and macrophages/microglia, mainly contribute to tissue destruction in TBE.

Nearly 6000 autoptic studies were carried out during the last 50 years at the Laboratory of Neuropathology, Markusovszky University Teaching Hospital, Hungary.The aim of the authors was to present those previously frequent and often fatal conditions that can be prevented or treated today.Retrospective analyses of the neuropathological documentations.Measles-related subacute sclerosing panencephalitis caused death in 13 cases, the last occurred in 1991. The mandatory vaccination against the causative virus has eliminated this severe neurological complication. Fourteen lives were lost due to herpes simplex encephalitis, including the last case seen in 1999. Feasibility of early diagnosis and the availability of acyclovir therapy resulted in better outcome without fatality. Tuberculous meningitis still occurred in most recent years, although only sporadically. Recognition of this condition is not straightforward due to its rarity, and considerations for this disease are often omitted from the routine differential diagnosis. The generally low mortality rates in tick borne encephalitis further dropped after the introduction of vaccination. Altogether only 8 such cases were documented. The last fatal cases of neurolues were seen in the 1990s. However, syphilis itself has not disappeared, and the number of cases with newly acquired infection continues to rise. The introduction of intrathecal methotrexate and radiotherapy made possible the prevention or effective treatment of meningeal leukosis. A careful coordination of these treatment modalities, however, is important as nervous system complications may develop in the form of disseminated necrotizing leukoencephalopathy that is also reflected in the records.The 50-year neuropathology documentation reflects changes in the occurrence of diseases, and it calls attention to those disorders which can be prevented or treated today, but may represent diagnostic challenges.Bevezetés: A Markusovszky Egyetemi Oktatókórház Neuropatológiai Laboratóriumában az elmúlt 50 évben közel 6000 esetben történt autopsziás vizsgálat. Célkitűzés: A szerzők célja azon korábban gyakori, magas mortalitású betegségek bemutatása, amelyek ma már megelőzhetőek vagy kezelhetőek. Módszer: A neuropatológiai dokumentáció retrospektív áttekintése. Eredmények: A morbilli vírusa okozta szubakut szklerotizáló panencephalitis miatt 13 beteg halt meg, az utolsó haláleset 1991-ben volt. A kötelező védőoltás bevezetése vetett véget a halálos megbetegedésnek. Herpes simplex encephalitis miatt 14-en vesztették életüket, az utolsó 1999-ben. A korai diagnosztizálás feltételeinek javulása és az aciclovirkezelés tette lehetővé a halálesetek elkerülését. Meningitis basilaris tuberculosa szórványosan, de az utóbbi években is előfordult. Felismerése nem könnyű, ritkasága miatt kikerült a rutindiagnosztika gondolatmenetből. Kullancsencephalitisben a védőoltások elérhetővé válása folyamatosan tovább csökkentette a különben is ritka, összesen 8 esetben dokumentált halálos esetek számát. Fatális kimenetelű neuroluessel az 1990-es években találkoztak utoljára, de a syphilis nem tűnt el, sőt a friss fertőzések száma emelkedik. A meningiosis leukaemica kivédését az intrathecalis methotrexat adása és radioterápia tette lehetővé, amelyek alkalmazása azonban óvatosságot igényel, a szerzők esetei között is jegyzett disszeminált nekrotizáló leukoencephalopathia kialakulásának lehetősége miatt. Következtetések: A Neuropatológiai Laboratórium 50 éves dokumentációja tükrözi a betegségek előfordulásának változásait, és felhívja a figyelmet azokra a kórképekre, amelyek ma már megelőzhetők vagy kezelhetők, de diagnosztikus kihívást is jelenthetnek. Orv. Hetil., 2014, 155(43), 1722–1728.

Aim: To report a child with an extensive tumor invading multiple anatomical structures within the left side of her neck. Material and methods: Presentation of a case including patient’s history, physical exam, molecular data, MRI imaging, histopathology and molecular genetics. Results: The life-threatening compression as well as the dislocation of the trachea required meticulous surgical removal of the tumor. Histology revealed a plexiform neurofibroma related to a frame shift mutation in the NF1 gene. Conclusion: Surgical removal of this extensive tumor saved the patient’s life. The long term success of management will be related to the effectiveness of the maintenance therapy that currently includes interferon-α2a. This report highlights unique aspects of a rare but life threatening condition in a young girl.

Background: Niemann-Pick’s type B (NP-B) disease is a rare, autosomal recessive visceral storage disorder related to a lysosomal accumulation of sphingomyelin, which is caused by mutations in the sphingomyelinase gene, SMPD1.Case report: We present a boy who had normal early development, but from one year of age, he showed progressive manifestations of hepatosplenomegaly, somatomotor retardation and cardiopulmonary dysfunction. The activity of the sphingomyelinase enzyme was very low in his fibroblasts. He died at 17 years of age from cardio-respiratory insufficiency. Gross pathology and histology of the internal organs were compatible with Niemann-Pick’s disease. His brain and spinal cord displayed no signs of storage disease, confirming the subtype of NP-B. Unexpectedly, however, significant accumulation of iron was seen in the substantia nigra, subthalamic nuclei, putamen, globus pallidus and some cortical regions accompanied by axonal spheroids. Brain iron accumulation is the hallmark of a disease group termed neurodegeneration with brain iron accumulation (NBIA). Sequencing of the known NBIA disease genes was unsuccessful in the proband’s DNA isolated from formalin-fixed, paraffin-embedded blocks, but both asymptomatic parents were heterozygous carriers of the same c19orf12 deletion.Conclusions: This case initially raised the question as to whether two rare autosomal recessive disorders, NP-B and a subtype of NBIA could have co-occurred in our patient, or the lipid dysmetabolism due to sphingomyelinase deficiency caused secondary brain iron accumulation. Genetic analyses in the parents suggested the former possibility by identifying a c19orf12 gene deletion known to underlie in homozygous state Mitochondrial Membrane Protein Associated Neurodegeneration.

Dystonia is a syndrome characterized by sustained muscle contraction. It is frequently causing twisting and repetitive movements, or leading to development abnormal postures. The management of the disease is usually consists of medication, surgical interventions, botulinum toxin injection, or other complementary methods. The authors have been using the botulinum toxin treatment since 1991.The goal of the study was to investigate the efficacy and safety of the botulinum toxin injection, in patients with focal dystonia and hemifacial spasm.A total of 94 patients diagnosed with cervical dystonia (n=33), blepharospasm (n=32), or hemifacial spasm (n=29) were treated. The mean age of the patients was 62.4 years, and the mean duration of the therapy was 6.8 years. The medication took place with local injection of botulinum toxin type A. The efficacy of the treatment was assessed with Patient Global Impression scale. The authors also evaluated the side effects and complications of the therapy, as well as the causes of the treatment discontinuation.The botulinum toxin treatment was effective in 92% of the patients. It is a great importance that the therapy resulted significantly improvement in 56% of the patients. There was no significant difference neither among the types of the dystonia (cervical dystonia 87%, blepharospasm 93%, and hemifacial spasm 96%), nor among the medications (Botox 92%, Dysport 92%) in point of efficacy. Temporary weakness occurred only at 6 patients. There was neither serious side effect, nor complication related to the treatment.The authors can conclude that the botulinum toxin injection is effective and safe therapy, in the patients with cervical dystonia, blepharospasm, and hemifacial spasm.

Hepatitis C virus (HCV) infection is common in the general population and may coincide with disease in the central and peripheral nervous system. Interferon-α (IFN-α) is used as treatment for HCV infection. The therapeutic benefit is assumed to result from activation of natural killer cells and CD8+ T cells. Despite its beneficial effects, it has been associated with a number of autoimmune disorders, such as chronic inflammatory demyelinating polyneuropathy and multiple sclerosis. Several clinical reports including magnetic resonance imaging exist, but neuropathological confirmation of MS associated with IFN-α therapy and HCV infection is lacking. We report a case of a female patient with chronic HCV infection who developed `acute MS'-like demyelinating disease after IFN-α administration, with extensive lesions throughout brain and thoracic spinal cord. The patient died after a disease duration of 6 months. Brain autopsy revealed Baló-like demyelinating plaques with positive HCV sequences within florid lesions. The development of fulminant demyelinating disease after administration of IFN-α suggests that autoimmune mechanisms such as T cell mediated tissue damage might be initiated or aggravated by IFN-α therapy. Additionally, the presence of HCV RNA within the demyelinated lesion indicates a possible role in triggering or propagating disease. Multiple Sclerosis 2007; 13: 1100—1106. http://msj.sagepub.com

A 15 years old male was operated because of incidentally found intercostal schwannoma. Two years later severe cerebellar ataxia and left sided anacusis developed. MRI revealed bilateral vestibularis tumors and multiple cervical intradural extramedullary myelin compressing lesions. After partial resection of the huge left sided cerebello-pontine tumor, histologically schwannoma, and the extirpation of the multiple cervical meningiomas the patient died three months later due to septic complications. The 24 years old mother had been operated on similar lesions 12 years earlier, after two weeks postoperative period she died. Her 14 years old twins are living, a boy also with bilateral acoustic tumours and a girl who is intact. Genetic investigation revealed CT nonsense mutation at position 193 in the exon 2 of the NF2 gene. This mutation cause premature truncation of the gene protein and is probably in connection with the clinically severe phenotype. Early diagnosis of this type of neurofibromatosis is mandatory concerning the therapy.

Central European tick-borne encephalitis (TBE) is caused by a flavivirus vectored by the Ixodes ricinus tick. In severe infections, TBE presents as (myelo)meningoencephalitis with considerable mortality. Characteristic neuropathologic changes feature a multinodular to patchy polioencephalomyelitis accentuated in spinal cord, brainstem, and cerebellum. Visualization of viral infection by immunohistochemistry has not yet been achieved. We analyzed immunohistochemically the distribution of viral antigens and its correlation with neuropathologic changes, serological data, and disease duration in 28 brains of cases with a clinical diagnosis of TBE and neuropathologically confirmed (meningo)encephalomyelitis. In 20 brains (including 10 seropositives), viral antigens were detectable. These cases were characterized by relatively short clinical duration ranging from 4 to 35 days. Immunoreactivity was most prominent in perikarya and processes of Purkinje cells and large neurons of dentate nucleus, inferior olives, and anterior horns. In addition, immunoreactivity was detected in neurons of other brainstem nuclei, isocortex, and basal ganglia. There was an inverse topographical association of severe inflammatory changes with presence of viral antigens. Some cytotoxic T cells were in direct contact with tick-borne encephalitis virus (TBEV)-infected neurons. We conclude that 1) TBE viral antigens are immunohistochemically detectable in brains of fatal cases with relatively short natural clinical course; 2) TBE virus neurotropism preferentially targets large neurons of anterior horns, medulla oblongata, pons, dentate nucleus, Purkinje cells, and striatum; 3) topographical correlation between inflammatory changes and distribution of viral antigens is poor; and 4) immunologic mechanisms may contribute to nerve cell destruction in human TBE.

Fabry's disease is an X-linked lysosomal storage disorder. alpha-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predominant affection of the vertebrobasilar circulation are one of the major sources of morbidity in Fabry's disease. We present a Hungarian family with Fabry's disease caused by a new mutation in the alpha-galactosidase A gene (GLA), and describe a variant expression of the disease. Megadolichobasilar anomaly was diagnosed in two male patients in the family who died of thrombosis. In another female patient who had suffered from disturbance of the vertebrobasilar circulation, a strongly dilated basilar artery without thrombosis was found at autopsy. Another three family members had basilar strokes and large and elongated basilar arteries on MRI. Genetic analysis disclosed a c.47T--C missense mutation resulting in L16P in the amino acid sequence of the alpha-galactosidase protein. This report suggests that megadolichobasilar anomaly is potentially life-threatening, and that L16P is a disease-causing mutation in patients with Fabry's disease. Early enzyme replacement therapy may prevent the development of these irreversible cerebrovascular complications.