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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.

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.

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 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.

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.

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.