Lege Artis Medicinae

[A new medical field is born - The first world congress of immuno-genomics, Budapest]

PÓS Zoltán, WIENER Zoltán

DECEMBER 20, 2004

Lege Artis Medicinae - 2004;14(12)

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Lege Artis Medicinae

[SCIENTIFIC DIGEST]

Lege Artis Medicinae

[LETHAL SEPTIC INFECTION IN RHEUMATOID ARTHRITIS]

BÉLY Miklós, APÁTHY Ágnes

[INTRODUCTION - The lethal septic infection was studied in a randomized (non-selected) autopsy population of 234 in-patients with rheumatoid arthritis. The patients died at the National Institute of Rheumatology between 1970 and 1999. PATIENTS AND METHOD - The aims of this study were to determine the prevalence of lethal septic infection with or without purulent arthritis in rheumatoid arthritis; the relationship between purulent arthritis and lethal septic infection; the clinically missed diagnosis of lethal septic infection and purulent arthritis; the influence of the main complications and associated diseases on lethal septic infection with and without purulent arthritis; the pathogens in lethal septic infection; and the clinico-laboratory parameters associated with lethal septic infection in rheumatoid arthritis. RESULTS - Lethal septic infection was found in 31 (13.24%) of 234 rheumatoid arthritis patients. Purulent arthritis complicated lethal septic infection in 15 (6.4%) of 31 patients. There was a significant association between lethal septic infection and purulent arthritis. Sepsis was detected clinically in 17 of 31 lethal cases and purulent arthritis was detected 9 of 15 septic infection complicated with suppurative articular processes. The coexistent complications (systemic vasculitis, AA amyloidosis), and associated diseases (tuberculosis with or without miliary dissemination, malignant tumors, diabetes mellitus) did not influence the prevalence of septic infection. The most frequent pathogenic agents were: Staphylococcus aureus, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella species, Streptococcus species. The patients with septic infection had significantly lower levels of beta-globulin, and higher values of Waaler-Rose or latex fixation test in comparison to patients without septic infection or without complications. CONCLUSION - Lethal septic infection may exist in rheumatoid arthritis without the classical clinical symptoms of sepsis, and clinically latent suppurative processes may be found at autopsy. The missed clinical diagnosis of a fatal complication is explained by the weak immune response and atypical clinical symptoms of elderly patients mainly treated with steroids and immunosuppressive drugs.]

Lege Artis Medicinae

[Hungarian Cannot be Used Indeed? Anglicisms in the Hungarian Medical Language]

NÉMETH Éva

Lege Artis Medicinae

[THE PRACTICE AND PROBLEMS OF EVIDENCED BASED DRUG TREATMENT]

KERPEL-FRONIUS Sándor

[The organization, the budget and the practical delivery of modern healthcare are all based upon the sum of available evidences. However, in the individualized drug therapeutic decisions beside the external evidences the personal experience of the treating physician as well as the preferences and expectations of the patients must be represented with equal emphasis. Without the interaction of these three modern, patient oriented medicine is not conceivable. Evidenced based drug application is primarily based upon the results of prospective, randomized, controlled clinical trials. The individual experiences and the systematic observations represent the lowest level of the evidence hierarchy. The results of the clinical studies are expressed as the absolute difference of the results of the treated and control groups and as relative values relating the outcome of the experimental group to the control, respectively. In practice the easily interpretable term "number needed to treat" is widely used. It shows how many patients have to be treated relative to the control group in order to observe the expected therapeutic outcome in one case. The wealth of evidences cannot be efficiently used without systematization in the daily practice. Therefore, the data collected from the independent publications containing the primary evidences are subjected to a joint statistical evaluation. Thereafter, the results are combined in systematic reviews by independent experts following thorough weighting without prejudice. Then short summaries, more easily and rapidly digested by practicing physicians are made according to the same principle. They are restricted to the presentation of the problem, the tabulation of the summarized data and the conclusion. It is expected that in the future systems combining the electronically stored patient's data with external evidences making possible the patient oriented presentation of the sum and hierarchy of evidences will be extensively used.]

Lege Artis Medicinae

[SEPSIS AS A NEW DISEASE - PROBLEMS IN HUNGARY]

LUDWIG Endre

[In our current understanding sepsis is a systemic inflammatory response syndrome to infections mediated by cytokines, an uncontrolled progression which may result in multiorgan failure and in the final stage septic shock. There are no pathognomic clinical signs or laboratory parameters in the early stage of sepsis and the diagnosis can be easily missed if the possibility is overlooked. One of the crucial points of therapy is early diagnosis: the mortality rate of severe sepsis is about 20% and that of septic shock is about 40-50%. The cornerstones of the therapy are the eradication of the focus of sepsis (surgical intervention and antimicrobial treatment), standard intensive care and the intervention in the pathophysiological process of sepsis. For successful treatment a multidisciplinary approach is required: only the early diagnosis and the teamwork of different specialists can decrease the mortality rate that is higher in Hungary than the international average.]

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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

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

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.

Clinical Neuroscience

Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm

BÉRES-MOLNÁR Anna Katalin, FOLYOVICH András, SZLOBODA Péter, SZENDREY-KISS Zsolt, BERECZKI Dániel, BAKOS Mária, VÁRALLYAY György, SZABÓ Huba, NYÁRI István

The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo­gical examination excluded mycotic etiology of the aneu­rysm and “normal aneurysm wall” was described. The brain stem haemorrhage – Duret bleeding – was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

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.