Lege Artis Medicinae

[Living with Parkinson’s disease]

NÉMETH Éva

DECEMBER 10, 2009

Lege Artis Medicinae - 2009;19(12)

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Lege Artis Medicinae

[Christmas vaccine]

FRENKL Róbert

Lege Artis Medicinae

[Systemic adjuvant pharmacotherapy of colorectal cancer]

BODOKY György

[Colorectal cancer is one of the most frequent cancer in the postindustrial world; its most common form is adenocarcinoma. In Hungary, colorectal cancer has the second highest mortality among tumours. If diagnosed early, it might be successfully treated by surgery, however, chemotherapy is necessary to prevent tumor relapse and development of metastases and achieve adequate palliation. In the past few years, adjuvant treatment of colorectal cancer has improved substantially. Many new drugs have been developed, which are also being used in combination with previously known agents. This article will discuss the novelties in the field of adjuvant chemotherapy for colorectal cancer and the main guidelines of adjuvant treatment.]

Lege Artis Medicinae

[Insulin analogues and pregnancy]

TAMÁS GYULA, KERÉNYI ZSUZSA

[Near-normoglycaemic metabolic control in pregnant women with diabetes - started before conception in pregestational diabetes - decreases the frequency of maternal and foetal complications. Such control can be achieved by using optimalised systems of insulin therapy. A number of (ultra)rapid and long-acting insulin analogues became available during the last decade, which - on the basis of theoretical considerations - might be used to maintain normoglycaemia. Summarising the data available today, the use of rapid insulin analogues (lispro, aspart) seem to be effective and safe during pregnancy. Some questions arise, however, about their modes of application. The use of long-acting insulin analogues in pregnancy is currently not indicated. Further trials are needed to prove their efficacy and safety in diabetic pregnancy.]

Lege Artis Medicinae

[Resistant hypertension - differential diagnosis and therapy]

TISLÉR András

[Hypertension is considered resistant to therapy if the target blood pressure is not achieved despite treatment with three different types of antihypertensive drugs, including a diuretic. Causes of therapy resistance may be grouped into three broad categories: Pseudoresistance can be the result of inadequate blood pressure measurement technique, the “white-coat” effect or the patients’ noncompliance with pharmacological and nonpharmacological medical advices. Evaluation of the measurement technique - including the size of the cuff used - and blood pressure monitoring at home can help identify the causes of pseudoresistance. Secondary resistance comprises drug interactions and concomitant medical conditions that elevate blood pressure or antagonize antihypertensive therapy. In addition, secondary resistance can result from disorders associated with secondary hypertension, among which appropriate screening for hyperaldosteronism as well as for renoparenchymal and renovascular hypertension need special emphasis. Suboptimal therapy is frequently related to subclinical volume overload and the use of inappropriate type or dosing of diuretics. Furthermore, when choosing the optimal drug combination, care should be taken to inhibit the various systems that regulate blood pressure as much as possible. In addition to combining the most frequently used antihypertensive drugs, the use of aldosterone antagonists, vasodilators, nitrates or drugs affecting the central nervous system might help to optimise treatment.]

Lege Artis Medicinae

[The relevancy of measuring the level of D-dimer test in clinical practice]

PINCZÉS István, SPEER Gábor

[Plasma levels of D-dimer may rise in a number of pathological conditions, which might be relevant for diagnosis as well as for prognosis. Its concentration increases with age, perhaps because of the wide-spread co-morbidity. In this article we demonstrate the diagnostic role of Ddimer in the well-known thromboembolic diseases. Beyond that, we highlight the importance of measuring D-dimer levels in other, lesser-known conditions, about which important findings have been published, such as cardiovascular, inflammatory or malignant diseases. It seems that in these disorders - provided that appropriate clinical conditions are available -, measuring D-dimer levels might have a role not only in diagnosis but in the prognosis as well. Furthermore, our aim was to discourage inappropriate clinical practice. Ignoring to measure the D-dimer levels (for fear of it being high) might lead to diagnostic errors. On the other hand, routinely performing the D-dimer test without clinical consideration (in the hope of it being negative) might cause diagnostic confusion in case of unexpected positivity and - mostly because of false interpretation - lead to further, unnecessary examinations.]

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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

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

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

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 Neuroscience

[Health status and costs of ambulatory patients with multiple sclerosis in Hungary]

PÉNTEK Márta, GULÁCSI László, RÓZSA Csilla, SIMÓ Magdolna, ILJICSOV Anna, KOMOLY Sámuel, BRODSZKY Valentin

[Background and purpose - Data on disease burden of multiple sclerosis from Eastern-Central Europe are very limited. Our aim was to explore the quality of life, resource utilisation and costs of ambulating patients with multiple sclerosis in Hungary. Methods - Cross-sectional questionnaire survey was performed in two outpatient neurology centres in 2009. Clinical history, health care utilisation in the past 12 months were surveyed, the Expanded Disability Status Scale and the EQ-5D questionnaires were applied. Cost calculation was conducted from the societal perspective. Results - Sixty-eight patients (female 70.6%) aged 38.0 (SD 9.1) with disease duration of 7.8 (SD 6.7) years were involved. Fifty-five (80.9%) had relapsing-remitting form and 52 (76.5%) were taking immunomodulatory drug. The average scores were: Expanded Disability Status Scale 1.9 (SD 1.7), EQ-5D 0.67 (SD 0.28). Mean total cost amounted to 10 902 Euros/patient/year (direct medical 67%, direct nonmedical 13%, indirect costs 20%). Drugs, disability pension and informal care were the highest cost items. Costs of mild (Expanded Disability Status Scale 0-3.5) and moderate (Expanded Disability Status Scale 4.0-6.5) disease were 9 218 and 17 634 Euros/patient/year respectively (p<0.01), that is lower than results from Western European countries. Conclusion - Our study provides current inputs for policy making and contributes to understanding variation of costof- illness of multiple sclerosis in Europe.]