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Clinical Neuroscience

JULY 30, 2020

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

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.

Clinical Oncology

MAY 10, 2018

[Tumor-associated neurological syndromes]

GORKA Eszter, FABÓ Dániel

[Tumor associate neurological symptoms are heterogeneous clinical entities with diverse etiologies, that may infl uence both the central, and peripheral neural system, as a primary or secondary tumor, may due to immune mediated processes. In our review, we summarize the neural syndromes frequently occurring in oncological practice. We focus on the most frequent neuronal tumors, the brain metastases, that are recently affected by the new targeted and immunotherapies showing increasing intracranial activities. We provide details on paraneoplastic neurological syndromes, because, in spite of their relatively rare occurrence, the modern diagnostic protocols may contribute to early diagnosis that are mandatory for detecting the underlying tumor. Finally we describe the neurological side effects of various oncotherapies, such as PD1 inhibitors, that are accompanied by 3% incidence of neurological complications, and chemotherapy related polyneuropathies. We provide support for anticonvulsive drug selection also, based on their drug-interaction profi le.]

Clinical Neuroscience

MAY 30, 2017

Case report of a woman with anti amphiphysin positive stiff person syndrome

MANHALTER Nóra, GYÖRFI Orsolya, BOROS Erzsébet, BOKOR Magdolna, FAZEKAS Ferenc, DÉNES Zoltán, FABÓ Dániel, KAMONDI Anita, ERÕSS Loránd

Stiff person syndrome is a rare neuroimmunological disease, characterized by severe, involuntary stiffness with superimposed painful muscle spasms, which are worsened by external stimuli. The classical form is associated with high levels of antibodies against glutamic acid decarboxylase. One of the variant forms is associated with antibodies against amphiphysin. This entity is a paraneoplastic syndrome, caused primarily by breast cancer, secondarily by lung cancer. Symptomatic therapy of anti amphiphysin positive stiff person syndrome includes treatment with benzodiazepines and baclofen (including intrathecal baclofen therapy). The effect of immunological therapies is controversial. Treatment of the underlying cancer may be very effective. In this report, we describe a 68 year old female presenting with an unusally rapidly developing anti amphiphysin positive stiff person syndrome, which was associated with breast cancer. Her painful spasms abolished after intrathecal baclofen treatment was initiated. Her condition improved spontaneously and significantly after cancer treatment, which enabled to start her complex rehabilitation and the simultaneous dose reduction of the intrathecal baclofen. The bedridden patient improved to using a rollator walker and the baclofen pump could be removed 18 monthes after breast surgery. This highlights the importance of cancer screening and treatment in anti amphiphysin positive stiff person syndrome cases.

Clinical Neuroscience

JULY 30, 2016

Four cases of GABAB receptor encephalitis

SZŐTS Mónika, MORTEN Blaabjerg, KONDZIELLA Daniel, DIÓSZEGHY Péter, BAJZIK Gábor, BERKI Tímea, KÁLMÁN Endre, NAGY Ferenc, ILLÉS Zsolt

GABAB receptor (gamma-aminobutyric acid type B receptors - GABABR) encephalitis is a rare manifestation of autoimmune encephalitides. We report four cases - including the first two Hungarian patients - with some peculiar features. One patient developed subacute disorientation and almost complete loss of short-term memory, but no epilepsy. Without immunotherapy, his memory spontaneously improved up to mild cognitive impairment in six weeks. GABABR antibodies persisted in his serum, and 18 months later, FDG-PET detected abnormal mediastinal lymph nodes and small cell lung cancer (SCLC). Another patient had persistently decreased sodium content in the peripheral blood. In those three patients who died, CSF was abnormal, but CSF was not pathological in the patient, who spontaneously improved. Brain MRI indicated signal intensity changes in the medial temporal areas in three cases. SCLC was found in three patients. Only the patient, who spontaneously improved, survived for more than 24 months. In summary, our cases show that (i) GABABR encephalitis may develop without epilepsy; (ii) the severe short-term memory loss can spontaneously improve; (iii) persistent hyponatremia can be present in the blood; (iv) the patient with benign course without epilepsy and CSF abnormality survived; (v) spontaneously remitting encephalitis can precede SCLC by 1.5 year, which emphasizes that repeated search for cancer is of paramount importance even in cases with spontaneous improvement.

Clinical Neuroscience

MARCH 30, 2014

[Association of temporal lobe inflammatory leukoencephalopathy with two B cell malignancies]

GARZULY Ferenc, HAHN Katalin, IVÁNYI János László, KERESKAI László, GÁBOR Valéria, KOVÁCS G. Gábor, BUDKA Herbert, KÁLMÁN Bernadette

[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 treatmentnaïve 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.]

Clinical Neuroscience

OCTOBER 05, 2013

[Characterization of CD4+ and CD8+ Tregs in a Hodgkin’s lymphoma patient presenting with myasthenia-like symptoms]

KRAUSZ Ludovic Tibor, MAJOR Zoltán Zsigmond, MURESANU Dafin Fior, CHELARU Eugen, NOCENTINI Giuseppe, RICCARDI Carlo

[The co-occurrence of Hodgkin’s lymphoma (HL) and myasthenia gravis (MG) is a rare phenomenon that is sometimes considered a paraneoplastic manifestation. There are a few documented cases in which myasthenia symptoms manifested only after the surgical removal of the tumor. However, the biological basis of this association is unknown. One hypothesis is that it derives from the infiltration of the residual thymic tissue by the developing tumor. In our case, the myasthenic symptoms led to the HL diagnosis. Our objective was to investigate the T cell phenotype in a HL patient presenting myasthenia-like symptoms. In patients with autoimmune disease, Tregs are usually decreased, but in some diseases, they appear to be increased. It has been speculated that this phenomenon may occur due to a homeostatic attempt by the immune system to control the expansion of auto-reactive effector cells. In the described patient the proportion of lymphoma infiltrating Tregs was high (more than 10% of CD4+ and 1.34% of CD8+ cells), suggesting that Tregs are increased in patients suffering from HL and eventually of myasthenia gravis. Treg involvement in HL is controversial and is currently under investigation. In this context, our data may contribute to a better understanding of the underlying mechanism of the link between HL and autoimmune phenomena.]

Lege Artis Medicinae

SEPTEMBER 15, 2006

[RHEUMATIC DISEASES AND MALIGNANCIES - PARANEOPLASTIC SYNDROMES]

SZEKANECZ Éva, ANDRÁS Csilla, KISS Emese, TAMÁSI László, SZÁNTÓ János, SZEKANECZ Zoltán

[Numerous malignancies may be associated with musculoskeletal symptoms. In paraneoplastic syndromes, the rheumatic disease is related to the tumour development and the removal or treatment of the underlying malignancy results in the improvement of rheumatic symptoms. Sometimes it is the bad responsiveness of the rheumatic disease to conventional therapies that calls the attention to an underlying malignant condition. Therefore, in case of an unusual disease course a thorough search for malignancies is indicated. The authors give a thematic review on the most common paraneoplastic rheumatic syndromes and discuss the general diagnostic and therapeutic guidelines.]

Hungarian Immunology

MARCH 20, 2006

[Paraneoplastic diseases of the locomotor system]

ANDRÁS Csilla, SZÁNTÓ János, SZEKANECZ Zoltán, CSIKI Zoltán, ILLÉS Árpád, SZEKANECZ Éva, DANKÓ Katalin

[Paraneoplasias in rheumatology can be present in different forms of arthropathies, myopathies. In addition, we often see atypical forms of systemic autoimmune diseases. Vasculitis is mainly associated with lymphoproliferative diseases. The direct invasion of bones and joints is not present in paraneoplasia, as this entity is a collection of symptoms generated by the tumour itself by producing biologic mediators, hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplasia is of outmost importance because it attires attention to the presence of tumour in the organism and thus enables us for early treatment of the malignancy. Monitoring of the severity of paraneoplastic symptoms serves as a marker for determination of efficacy of the targeted oncological therapy. On the other side, because these severe symptoms affect the patient's quality of life and can lead even to death their in time recognition and treatment is extremely important.]

Clinical Neuroscience

SEPTEMBER 30, 2008

[Paraneoplastic chronic demyelinating neuropathy and lambert-eaton myasthenic syndrome associated with multiple anti-neural antibodies and small-cell lung cancer]

RÓZSA Csilla, VINCENT Angela, ARÁNYI Zsuzsanna, KOVÁCS G. Gábor, KOMOLY Sámuel, ILLÉS Zsolt

[Lambert-Eaton myasthenic syndrome (LEMS) developed in a patient with presumed chronic inflammatory demyelinating polyneuropathy (CIDP) and negative chest CT. Since antibodies against both Hu and voltage-gated calcium channel (VGCC) were detected, repeated chest CT was performed, which eventually showed a pulmonary mass lesion. Biopsy revealed small cell lung cancer (SCLC) indicating the importance of repeated chest CT in LEMS even when an existing autoimmune-like disease and negative CT may suggest an autoimmune origin. This is the first report of paraneoplastic CIDP and LEMS associated with anti-Hu, anti-VGCC and SCLC.]

Clinical Neuroscience

JULY 20, 2011

[Recent changes in the paradigm of limbic encephalitis]

ILLÉS Zsolt

[In the recent years, novel antibodies associated with limbic encephalitis have been described, which target such extracellular receptors or proteins that have been already indicated in the pathogenesis of hereditary or degenerative diseases. In a number of cases, where pathogenic role of antibodies generated against the voltage-gated potassium channel (VGKC) had been presumed, antibodies against a trans-synaptic scaffolding protein, LGI1 were indicated. Antibody response against NMDA-receptors has been suggested as a major cause of limbic encephalitis especially in young females, resulting in a typical clinical syndrome sometimes triggered by an ovarian teratoma. Antibodies against other receptors essential in synaptic transmission and plasticity (AMPA and GABAB receptors) have been also indicated, partially elicited by paraneoplastic processes. Such antibodies against surface proteins result in severe but potentially treatable diseases due to reversible internalization of the antigens crosslinked by the bivalent antibodies. In contrast, the rare classical onconeural antibodies reacting with intracellular targets (anti-Hu, anti-Ta/Ma2, anti- CV2/CRMP5) may elicit additional symptoms beside limbic encephalitis and the prognosis of such syndromes is poor.]