Lege Artis Medicinae

[In the focus: periferal vascular diseases - Readers’ questions answered by dr. Éva Meskó]

MESKÓ Éva

JULY 20, 2006

Lege Artis Medicinae - 2006;16(07)

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Lege Artis Medicinae

[THE POTENTIAL ROLE OF THE SEMICARBAZIDESENSITIVE AMINE OXIDASE ACTIVITY IN THE DEVELOPMENT OF DIABETIC RETINOPATHY]

DURA Eszter

[Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, such as methylamine, into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. We have demonstrated that the activity of serum SSAO is significantly higher in type 2 diabetic patients with high-risk proliferative diabetic retinopathy compared to those without retinopathy. Our clinical results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The enzymatic conversion of the endogenous monoamines (e.g. methylamine, aminoacetone) into toxic aldehydes and hydrogenperoxide may be one of the possible mechanisms of the development of microangiopathy. Also, the vascular adhesion protein-1 (VAP-1) function of the molecule can cause leukostasis and leukocyte activation through increased leukocyte adhesion, resulting in worsening of the capillary circulation and hypoxia. Further prospective, larger studies are needed to elucidate the role of the possible association between serum SSAO activity and highrisk proliferative retinopathy in patients with type 2 diabetes. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.]

Lege Artis Medicinae

[Sustained oral anticoagulant therapy]

LENGYEL Mária

Lege Artis Medicinae

[DIARRHOEA AND PSEUDOMEMBRANOUS COLITIS ASSOCIATED WITH ANTIBIOTIC TREATMENT]

LAKATOS László, LAKATOS Péter László

[Antibiotic treatment is complicated by diarrhea in 5 to 25% of the cases. Its prevalence depends on the antibiotic used, the patient’s age, the concomittant diseases and the immune response. The severity of the diarrhoea is variable ranging from a mild self-limiting disease lasting for 1 or 2 days to a severe condition with high mortality. The diarrhea may result from a direct effect on the gut, but more commonly it is the consequence of changes in resident gut flora. Clostridium difficile is responsible for 10 to 20% of all antibiotic-associated diarrhea cases. The clinical presentation varies from asymptomatic carriage to fulminant pseudomembranous colitis. This latter typically develops as a nosocomial infection, mainly in patients treated with cephalosporins, amoxicillin-clavulanic acid combination or clindamycin. Risk factors are advanced age, severe underlying disease, treatment in an intensive care unit, long hospitalization and invasive medical procedures. The clinical picture is characterized by frequent, watery (occasionally bloody) diarrhea, abdominal pain, tenesmus, fever, weakness. Fulminant colitis develops in 3-5% of cases. The diagnosis is based on testing for C. difficile toxins, but in selected cases rapid diagnosis can be made by flexible sigmoidoscopy. The treatment consists of the withdrawal of the implicated antibiotic along with administration of oral metronidazole or vancomycin which target C. difficile itself. Most patients respond to this treatment; however, the mortality of fulminant cases or those with severe underlying disease is high. Fifteen to 20% of the patients relapse and management of the recurrent cases is difficult. Combination treatment, probiotics and/or passive immunization may be used. Preventive measures include judicious use of antibiotics and aggressive control of the spread of C. difficile infection.]

Lege Artis Medicinae

[Night Swim The Collages of Zsolt Sándor]

Lege Artis Medicinae

[WEGENER’S GRANULOMATOSIS PRESENTING AS MASTOIDITIS: A DIAGNOSTIC CHALLENGE]

NAGY Pál, Z.SZABÓ László, DOMJÁN Gyula, GADÓ Klára, BALOGH Károly

[INTRODUCTION - Wegener's granulomatosis has an uncertain pathomechanism, but is probably autoimmune in origin. In typical cases the mucosa of the nose, paranasal sinuses and of the lower respiratory tract, as well as the lungs and the kidneys are affected. Patients present with sinusitis, recurrent pneumonia or renal disease associated with microhaematuria, pyuria or azotaemia. Fever, polyarthralgia or polyarthritis may also occur. The underlying pathologic changes are necrotizing vasculitis, granulomas and parenchymal necrosis. The diagnosis is based on a combination of the clinical picture, microscopic findings and immunofluorescent demonstration of cANCA. CASE REPORT - A 27-year-old woman presented with symptoms of unilateral mastoiditis. In the following 7 months she underwent 7 operations in 4 hospitals for a locally progressive, destructive process of uncertain etiology showing a septic course. The clinical picture was not specific, the cANCA test was not definitive, and the histologic findings were initially interpreted as nonspecific inflammation. Repeated biopsies, multiple reviews of the microscopic specimens, consultations, differential diagnostic considerations, and, finally, the success of the treatment with corticosteroids and cyclophosphamide led to the diagnosis of Wegener’s granulomatosis. Currently the patient has been in remission for 32 months. CONCLUSION - The definitive diagnosis of Wegener’s granulomatosis, particularly of its localized or limited form, may be problematic despite well-defined diagnostic criteria. Setting up the correct diagnosis may take months or years. In case of unusual respiratory or otological symptoms, and in view of ineffective medical or surgical treatment, Wegener’s granulomatosis has to be considered. An atypical clinical picture, inconclusive histologic, radiologic and laboratory findings warrant the need for close collaboration of various specialists. This is particularly important since state-of-the-art therapy of Wegener’s granulomatosis promises a favourable prognosis.]

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Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Creutzfeldt-Jakob Disease: A single center experience and systemic analysis of cases in Turkey

USLU Ilgen Ferda, ELIF Gökçal, GÜRSOY Esra Azize, KOLUKISA Mehmet, YILDIZ Babacan Gulsen

We aimed to analyze the clinical, laboratory and neuroimaging findings in patients with sporadic Creutzfeldt-Jakob disease (CJD) in a single center as well as to review other published cases in Turkey. Between January 1st, 2014 and June 31st, 2017, all CJD cases were evaluated based on clinical findings, differential diagnosis, the previous misdiagnosis, electroencephalography (EEG), cerebrospinal fluid and cranial magnetic resonance imaging (MRI) findings in our center. All published cases in Turkey between 2005-2018 were also reviewed. In a total of 13 patients, progressive cognitive decline was the most common presenting symptom. Two patients had a diagnosis of Heidenhain variant, 1 patient had a diagnosis of Oppenheimer-Brownell variant. Seven patients (53.3%) had been misdiagnosed with depression, vascular dementia, normal pressure hydrocephalus or encephalitis. Eleven patients (87%) had typical MRI findings but only 5 of these were present at baseline. Asymmetrical high signal abnormalities on MRI were observed in 4 patients. Five patients (45.4%) had periodic spike wave complexes on EEG, all appeared during the follow-up. There were 74 published cases in Turkey bet­ween 2005 and 2018, with various clinical presentations. CJD has a variety of clinical features in our patient series as well as in cases reported in Turkey. Although progressive cognitive decline is the most common presenting symptom, unusual manifestations in early stages of the disease might cause misdiagnosis. Variant forms should be kept in mind in patients with isolated visual or cerebellar symptoms. MRI and EEG should be repeated during follow-up period if the clinical suspicion still exists.

Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Hypertension and nephrology

[Association between cyclothymic affective temperament and hypertension]

NEMCSIK János, BATTA Dóra, KŐRÖSI Beáta, RIHMER Zoltán

[Affective temperaments (cyclothymic, hypertymic, depressive, anxious, irritable) are stable parts of personality and after adolescent only their minor changes are detectable. Their connections with psychopathology is well-described; depressive temperament plays role in major depression, cyclothymic temperament in bipolar II disorder, while hyperthymic temperament in bipolar I disorder. Moreover, scientific data of the last decade suggest, that affective temperaments are also associated with somatic diseases. Cyclothymic temperament is supposed to have the closest connection with hypertension. The prevalence of hypertension is higher parallel with the presence of dominant cyclothymic affective temperament and in this condition the frequency of cardiovascular complications in hypertensive patients was also described to be higher. In chronic hypertensive patients cyclothymic temperament score is positively associated with systolic blood pressure and in women with the earlier development of hypertension. The background of these associations is probably based on the more prevalent presence of common risk factors (smoking, obesity, alcoholism) with more pronounced cyclothymic temperament. The scientific importance of the research of the associations of personality traits including affective temperaments with somatic disorders can help in the identification of higher risk patient subgroups.]

Clinical Neuroscience

[Advanced Parkinson’s disease characteristics in clinical practice: Results from the OBSERVE-PD study and sub-analysis of the Hungarian data]

TAKÁTS Annamária, ASCHERMANN Zsuzsanna, VÉCSEI László, KLIVÉNYI Péter, DÉZSI Lívia, ZÁDORI Dénes, VALIKOVICS Attila, VARANNAI Lajos, ONUK Koray, KINCZEL Beatrix, KOVÁCS Norbert

[The majority of patients with advanced Parkinson’s disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson’s disease; the proportion of Parkinson’s patients with advanced Parkinson’s disease, the referral process, and the clinical features used to characterize advanced Parkinson’s disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson’s patients identified as advanced patients according to physician’s judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson’s disease status was assessed with Unified Parkinson’s Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson’s disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. Overall, 2627 patients with Parkinson’s disease from 126 sites were documented. In Hungary, 100 patients with Parkinson’s disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson’s disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson’s disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). Physicians in Hungarian movement disorder centers assessed that half of the Parkinson’s patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson’s disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.]