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Clinical Neuroscience

JANUARY 30, 2020

[Current questions of multiple sclerosis: the secunder progressive form of the disease]

VÉCSEI László

[Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.]

Clinical Oncology

DECEMBER 10, 2018

[Treatment of head and neck cancer]

KATONA Csilla, LANDHERR László

[Head and neck cancers cause worldwide a signifi cant problem in health care systems. Despite great advances in therapeutic modalities its prognosis has not changed in the past few decades. It is mainly caused by classical risk factors, like alcohol consumption and smoking, but in a signifi cant number of oropharyngeal cancers HPV infection plays a major role, which is associated with a new patient group characterized by a much better prognosis and therapeutic response. In the diagnostic phase staging examinations (CT scan, MRI, FDG-PET) are also involved which are necessary to multidisciplinary decision making. It can be largely infl uenced by the patient’s preference. The therapy is based on multimodality approach; surgery, radiotherapy, chemoirradiation, chemotherapy and the combination of these are used in early or locally advanced tumours. Targeted agents like EGFR inhibitors are partly used in the recurrent/metastatic setting or in combination with radiotherapy. Immun checkpoint inhibitors are new therapeutic options for pretreated, recurrent/metastatic patients and their role is under investigation in earlier therapeutic lines. Several clinical trials aim treatment desintensifi cation strategies in HPV positive tumours. Molecular genetic tests try to defi ne subgroups of patients to plan individualized treatment. Regarding the signifi cant functional and aesthetic damage of both disease and treatment, supportive care and rehabilitation are of great importance.]

Clinical Neuroscience

MAY 30, 2019

[F-DOPA PET/MR based target definiton in the 3D based radiotherapy treatment of glioblastoma multiforme patients. First Hungarian experiences ]

SIPOS Dávid, TÓTH Zoltán, LUKÁCS Gábor, BAJZIK Gábor, HADJIEV Janaki, CSELIK Zsolt, REPA Imre, KOVÁCS Árpád

[Introduction - Radiotherapy plays important role in the complex oncological treatment of glioblastoma multiforme (GBM). The modern 3D radiotherapy treatments are based on cross-sectional CT and MR information, however more attention is being paid to functional hybrid imaging describing the biological and functional morphology of tumor lesions. 18F-DOPA is an amino acid tracer with high specificity and sensitivity, which may play an important role in the precise definition of target volume in the irradiation process of GBM patients. Our study presents the first experiences with 18F-DOPA based PET/CT/MR 3D irradiation planning process. Methods - In Hungary the 18F-DOPA radiotracer has been available for clinical use since September 2017. Between September 2017 and January 2018, at the Somogy County Kaposi Mór Teaching Hospital Dr. József Baka Diagnostic, Radiation Oncology, Research and Teaching Center 3 histologically verified glioblastoma multiforme patients received 18F-DOPA based 3D irradiation treatment. In the contouring process the native planning CT scanes were fused with the PET/MR series (T1 contrast enhanced, T2 and 18F-DOPA sequences). We defined 18F-DOPA uptake volume (BTV-F-DOPA), the T1 contrast enhanced MRI volume (GTV-T1CE), and the volume of the area covered by oedema on the T2 weighted MRI scan (CTV-oedema) in all patients. We also registered the BTV-F-DOPA volumes not covered by the conventional MR based target volumes. Results - Examining the 3 cases, the average volume of 18F-DOPA tumor was 22.7 cm3 (range 15.3-30.9; SD = 7.82). The average GTV T1 CE was found to be 8.7 cm3 (range 3.8-13.2; SD = 4.70). The mean CTV oedema volume was 40.3 cm3 (range 27.7-57.7; SD = 15.36). A non-overlapping target volume difference (BTV-F-DOPA not covered by CTV oedema area) was 4.5 cm3 (range 1-10.3; SD = 5.05) for PTV definition. Conclusion - Based on our results the tumor area defined by the amino acid tracer is not fully identical with the MRI defined T2 oedema CTV. 18F-DOPA defined BTV can modify the definiton of the PTV, and the radiotherapy treatment. ]

Lege Artis Medicinae

JANUARY 20, 2019

[Animal-assisted therapies for the treatment of elderly dementia ]

SOMOGYI Szilvia

[The therapeutic value of the relationship between humans and animals should be considered in the cases of patients suffering from dementia with the onset in old age. This paper provides an overview of the animal assisted interventions in dementia. Reviews emphasize the positive effects of pet-keeping on mental and physical quality of life. However, it can also have adverse effects unless the pet is selected with caution. Regular animal assisted therapies within institutional framework provide a valuable potential programme for the patients in care. Articles published so far depict the physiological, social and psychological output variables of animal assisted therapies. The enhancement of social behavior is considered to be a specific factor of animal assisted therapies. Among the physiological symptoms the enhanced physical activity, the decrease of stress response and sympathic activation have been highlighted. Among the psychological functions reduction of state anxiety, mood lift and the reduction of negative emotions such as isolation and abandonment should be underlined. Acknowledging the available results, it seems that cognitive efficacy is less impacted directly by animal assisted therapies. However, promising results have been acquired in the alleviation of the behavioural and psychological symptoms related to dementia ]

Clinical Oncology

FEBRUARY 10, 2017

[The role of PET in clinical oncology]

LENGYEL Zsolt

[Positron emission tomography (PET) has earned an important role in clinical imaging, where it is used almost exclusively as hybrid modality such as PET/CT and PET/MR. The driving force behind the development of the method and the increasing clinical penetration of PET in the past two decades was clearly its use in Oncology. The most used tracer in PET is the 18 F-labeled fl uoro-deoxy-glucose (FDG). With the help of this molecule malignant tumors and their metastases, in which anaerobic glycolysis is typically increased, can be identifi ed with high sensitivity in the total body volume. However, FDG is not a tumor specifi c tracer, thus both false positivity and false negativity may occure which reduces the diagnostic accuracy. Indications of FDG PET studies in Oncology continuously evolved, owing to scientifi c publications, large scale national programs and even health-economic considerations. This publication describes the well-established indications of FDG PET/CT(MR) tests in cancer diagnostics and furthermore discusses more recent new PET tracers already being applied as well as those expected to be used in the future.]

Lege Artis Medicinae

JULY 20, 2017

[Fulvestrant: long-term survival and quality of life in a patient with hormone receptor-positive advanced breast cancer]

PINTÉR Tamás

[INTRODUCTION - There are lot of evidence showing the efficacy of fulvestrant therapy in HER-2 negative, HR-positive advanced metastatic breast cancer. CASE REPORT - A 75-year-old female had a mastectomy, followed by series of adjuvant and radiotherapy about 30 years ago. Later cutan metastases were removed several times. The endocrine therapy had to be stopped because of intolerance. An ER, PR positive, HER-2 negative cutan metastasis was resected 7 years ago for the last time. During regular checkup, 5 years ago pulmonary nodule and bone metastases were found, - PET-CT disclosed multiple metastatic lymph nodes as well. We started fulvestrant and bisphosphonate therapy. Thereafter, as imaging revealed, the malignant disease has stabilized, the patient has a good performance status, her musculo-skeletal pain has a presumably degenerative origin. DISCUSSION - Reported case corroborates the potential efficacy of fulvestrant and ibandronate in hormone sensitive breast cancer with good prognostic markers, even in the case of metastases in soft tissue and bone. This case supports the data, that in patients with not progressive bone metastases the frequency of administration of parenteral bisphosphonates may be reduced to every 3 months. Advanced metastatic breast cancer may be converted to a chronic disease in properly selected cases, and it could mean long-term survival with a good quality of life.]

Clinical Neuroscience

MAY 30, 2017

The role of the insula in the parieto-frontomedial epileptic network. Clues from successful surgical treatment

BALOGH Attila, AIMEN Anwar, KELEMEN Anna, ERÕSS Loránd, FABÓ Dániel

We present a case of MRI negative SMA seizure with the seizure onset zone in the secondary leg area on the superior bank of the Sylvian fissure, localized with multiscale electro-clinical and neuroradiological examinations. The 34-year-old female patient’s intractable epilepsy started at age 14. She had diffuse pain aura in her left leg followed by tonic posturing with fully preserved consciousness suggesting parieto-fronto-medial seizure propagation. Her daily nocturnal SMA seizures became drug-resistant. Multiple 3T MRI images and neuropsychological evaluations were normal. Interictal PET detected a right parietal and insular FDG hypometabolism. The seizure onset zone and the symptomatogenic zone were localized by invasive electrophysiology. The insular deep electrode showed the propagation of ictal activity with an onset in the secondary sensory leg area through the insula to the fronto-medial surface. Eighteen spontaneous seizures, electrical cortical stimulation and cortical mapping confirmed the designated area of the resection, which was later proved macroscopically abnormal during surgery. The histological and immunohistological workup confirmed focal cortical dysplasia (IIb type). Postoperative postprocessing morphometry of the preoperative MRI study confirmed the lesion in the right inferior parietal lobe. The patient remained seizure free after surgery for more than 4 years, and medication free for the last two years. Our results concluded that the insula has a „relay” or „node” function in the parieto-opercular-fronto-medial epileptic network. The insular functional connectivity predisposed frontal propagation of the epileptic activity in the connectome of her epilepsy. The three-way insular structural connectivity has determining function on the seizure propagation.

Clinical Oncology

SEPTEMBER 15, 2016

[Novelties in the management of Hodgkin lymphoma]

ILLÉS Árpád, MOLNÁR Zsuzsa, MILTÉNYI Zsófia

[Hodgkin lymphoma is a lymphoproliferativ disease, it is about 12-18% of all lymphomas. It has typical morphologic, clinical and therapeutic features, which can distinguish from other lymphoma types. Due to risk- and PET/CT adapted treatment Hodgkin lymphoma is a curable lymphoma with an 80-90% long-term survival, however, refracter- and relapsed patients’ therapy is a great challange. Cure rate can increase due to the development of the diagnostic and treatment modalities, but the use of standard recommendation is necessary. The aim of this review is to show new WHO 2016 lymphoma classifi cation, role of the new diagnostic options, especially 18FDG-PET/CT, Lugano classifi cation and fi rst-line and salvage therapeutic possibilities and to introduce the immunotherapy, like brentuximab vedotin and PD1 inhibitors. Certain points of hemopoietic stem cell transplantation will be also covered.]

Clinical Oncology

SEPTEMBER 05, 2015

[Up-to-date treatment of head and neck cancers]

PACZONA Róbert, CSENKI Melinda, HIDEGHÉTY Katalin

[The head and neck squamous cell cancer is often detected at an advanced stage, resulting in dismal prognosis despite the relevant developments of the oncotherapy in the last decades. The introduction of new techniques, new drugs and combinations though improves the survival for certain subgroups of patients, meanwhile the organ-function preservation and side effects reduction approaches lead to improved quality of life. The preventive-supportive care prior and during the therapy (dental care, nutrition, toxicity management) and the complex rehabilitation has paramount importance. MRI and 18FDG PET-CT and the advanced methods of molecular pathology became part of the diagnostic work up. The selection of the therapy based on the tumor characteristics, HPV detection, on the patient’s condition and wishes, as well as on multi-disciplinary team decision based on the available technical options. Early stage tumors can be successfully treated either by surgery alone or by radiation therapy. For locally advanced cases concomittant chemo-radiotherapy stays in the axis of the complex management using advanced radiation technique (IGRT-adaptive- IMRT) with cisplatin (or if contraindicated with cetuximab), which could be complemented by induction chemotherapy and/or surgery. Several new approaches are currently being tested in clinical studies after establishment of cisplatine-cetuximab treatment for recurrent/metastatic tumors. In the future, detection of molecular processes and driver mutations could result in development of more effective targeted anti-tumor agents, and individual molecular tumor profi le guided therapy, including the various forms and combinations with emerging immunotherapy.]

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.