Clinical Neuroscience

[Vasoreactivity impairment in brainstem and hemispherial small vessel disease, a comparative study]

PÁNCZÉL Gyula, BÖNÖCZK Péter, NAGY Zoltán

APRIL 20, 2002

Clinical Neuroscience - 2002;55(03-04)

[Aims - Cerebrovascular small vessel disease may lead to an impairment of vasoreactivity (VR). Vasoregulatory impairment in internal carotid artery distribution area has been established. In this study the authors sought the answer to the question if VR of vertebrobasilar (VB) territory was impaired in brainstem small vessel diseases and if vasoregulatory impairment differed between the two distribution territories. Methods - VR of carotid and VB territory was compared applying different functional tests (ventilation, tilting, acetazolamide) in 25 patients with brainstem lacunar infarcts, 20 patients with periventricular leukoaraiosis and in 35 control subjects. Cerebral blood flow velocity (CBFV) of basilar artery (BA) and middle cerebral artery (MCA) was monitored with transcranial Doppler (TCD), systemic blood pressure and CO2 partial pressure of expired air were also registered. Results - In the BA territory the VR was significantly smaller in the patient than in the control group (3.1± 4.6 cm/sec/kPa vs. 8.2 ± 6.2 cm/sec/ kPa, p=0.01) during hypercapnia. In a subgroup of patients with mean baseline CBFV<25 cm/sec, the VR was significantly smaller and PI nonsignificantly higher than in patients with baseline CBFV >25cm/s (VRCO2 1.5±2.0 cm/sec/kPa vs. 6.5±6.5 cm/sec/kPa, p=0.007; PI 1.11±0.30 vs. 1.0±0.26, p=0.4) indicating higher vascular resistance in the former group. Results of tilting tests showed similar but nonsignificant changes while acetazolamide tests revealed no differences between the two groups. In the MCA territory the VR was significantly lower in patients than in the controls during hypercapnia (4.7±3.7 cm/sec/kPa vs. 18.4±6.8 cm/sec/kPa, p< 0.001) and showed a nonsignificant tendency to be lower in patients than in controls during hypocapnia (14.6±13.8 cm/sec/kPa vs. 24.7±21.2 cm/sec/kPa, p=0.1). Although CBFV measurements during acetazolamide test tended to support these findings, they showed no significant differences between patients and controls. During head-up tilt the CBFV did not differ significantly between the two groups. The VRCO2 is significantly higher in the MCA than in the BA territory (18.4 CI95 2.98 vs. 10.1 CI95 3.01; p<0.001). The impairment of VRCO2 was more severe in the MCA territory (VR decreased to 26% of baseline in the MCA and to 34% in the BA territory). Conclusion - The capacity of carotid territory VR exceeds that of VB territory. The impairment of VR is present in both the carotid and VB territories and is more severe in the former region. The most feasible test to reveal this impairment is the hypercapnic test. There is a strong correlation between the extent of vasoregulatory impairment and baseline CBFV in brainstem small vessel diseases.]

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Clinical Neuroscience

[Marker molecules of endothelial cell dysfunction in acute ischemic stroke]

SZEGEDI Norbert, MAY Zsolt, ÓVÁRY Csaba, SKOPÁL Judit, NAGY Zoltán

[Introduction - In spite of all similarities, ischemic stroke cases representing 80% of the acute cerebrovascular accidents, different steps of platelet activation, coagulation and fibrinolytic cascade are involved in the patomechanism of the different stroke subtypes. The differentiation of the atherothrombotic, cardioembolic and lacunar forms of acute ischemic stroke is based on the comprehensive evaluation of clinical signs, neuroimaging technics, and diagnostic ultrasound, but also a significant effort was made to characterize the specifities of the underlying processes of the coagulation system by signal molecules, in order to clarify their possible role and to support the diagnostic and therapeutic decisions. Patients and methods - The von Willebrand factor was studied as the marker of endothelial injury in 34 acute ischemic stroke patients within 24 hours after the onset of their stroke, and repeatedly 2, 4, and 12 weeks thereafter. To determine the probable source of the von Willebrand factor, usually released not only by endothelial cells, but also by platelets, the authors simultaneously measured the levels of an additional endothelial marker, thrombomodulin, and a platelet activation marker, β-thromboglobulin. Results - The mean of von Willabrend factor levels measured in stroke patients on the first day was 123%, whereas the mean of the control group 72% (p<0.05). There was no significant difference according to stroke subtype. Von Willebrand values determined two weeks later showed a further 60% increase in stroke patients, and after a gradual fall their level remained above the concentration of the control group. The β-thromboglobulin level measured in stroke group was significantly higher, than in control individuals (171 IU/ml vs. 32 IU/ml, p<0.001). This was characteristic for atherothrombotic and cardioembolic stroke, but not for lacunar infarctions. If measured repeatedly, β-thromboglobulin levels decreased rapidly in the first two weeks, than somewhat slower. Soluble thrombomodulin was slightly elevated in stroke patients (4.24 ng/ml) compared to healthy subjects (3.81 ng/ml), without statistical significance, and without major differences between subgroups. Conclusions - While early determination of β-thromboglobulin can contribute to the differential diagnoses of the subtypes of ischemic stroke, the long-lasting elevation of von Willebrand factor may reflect endothelial dysfunction caused by several factors in the microvasculature of the penumbra.]

Clinical Neuroscience

[The problems of the post-stroke care]

CSORNAI Márta

[All patients having had stroke or TIA require special post-hospital care, being mainly the task of general pracititioners. The number of patients surviving stroke in Hungary is approximately 30 000/year. An important focus of care is secondary prevention: antithrombotic treatment and risk factors reduction. In case of residual signs of stroke, rehabilitation must also be organized and supported by the general practitioner. Medical conditions of cerebrovascular patients requiring special care demand are reviewed by the author. In this respect, some post-stroke conditions like dementia and depression require extra attention.]

Clinical Neuroscience

[New methods in stroke intensive therapy: hemicraniectomy in patients with complete middle cerebral artery infarction and treatment of intracerebral and intraventricular hemorrhage with urokinase]

KAKUK Ilona, MAJOR Ottó, GUBUCZ István, NYÁRY István, NAGY Zoltán

[Life-threatening, complete middle cerebral artery infarction occurs in up to 10% of all stroke patients. The “malignant media occlusion” is an infarction occupying more than 50% of middle cerebral artery territory. The malignant, space-occupying supratentorial ischemic stroke is characterised by a mortality rate of up to 80%. Several reports indicate, that hemicraniectomy in this situation can be life-saving. Hemicraniectomy increases cerebral perfusion pressure and optimises retrograde perfusion via the leptomeningeal collateral vessels. A case of a patient is presented, having progressive neurological deterioration due to massive cerebral infarctions. The patient rehabilitation was successful. Decompressive surgery is life saving and can also give acceptable functional recovery. Hemorrhagic stroke is due to stroke in 15% of cases and in 10%, it is “spontaneous” intracerebral hematoma. The intracerebral and intraventricular hemorrhage represents one of the most devastating types of stroke associated with high morbidity and mortality. The 30-day mortality rate is 35% to 50% and most survivors are left with a neurological disability. The value of surgical therapy is debatable. The aspiration and urokinase therapy of the hematoma of intracerebral hemorrhage could improve final neurological outcome. Spontaneous, nontraumatic intraventricular hemorrhage frequently carries a grave prognosis. A large part of morbidity after intraventricular hemorrhage is related to intracranial hypertension from hydrocephalus. One patient presented had intracerebral hemorrhage and another had intraventricular hemorrhage treated with urokinase. Rapid and extensive reduction in the amount of intracerebral and intraventricular blood occurred. Urokinase lysis is safe and can be a potentially beneficial intervention in intracerebral and intraventricular hemorrhage. By performing decompressive craniectomy, the neurologists of stroke departments and intensive care units with the neurosurgeons will have to play major role in the management of stroke patients.]

Clinical Neuroscience

[CONGRESS CALENDAR]

Clinical Neuroscience

[Genetics and hemostasis in young stroke patients]

PONGRÁCZ Endre, TORDAI Attila, CSORNAI Márta, NAGY Zoltán

[Background and purpose - The classical risk factors did not explain all the possible ethiology of cerebral stroke. Genetic polymorphisms responsible for thrombophilia were implicated recently as risk factors of stroke. In this geneticoepidemiological study the author’s aim was to analyse the tendency of genetic polymorphisms to cluster in a cohort of young and elderly stroke patients and in healthy subjects in Hungary. Methods - 253 patients with stroke were compared with 173 healthy blood donors on the basis of genetic polymorphisms of platelet GP IIb/IIIa receptor (33 LeuPro), prothrombin gene G20210A, Factor V Leiden mutation, ACE I/D, methylenetetrahydrofolate reductase (MTHFR) and β fibrinogen gene G455A. These data were acquired using PCR. Questionnaires were used to investigate the family history and to determine the risk factor profile. The subtypes of stroke were analysed in a stroke cohort grouped according to different polymorphisms. Results - An increased frequency of GP IIIa heterozygousity was found as compared to a West-European stroke cohort (31% versus 19%). The prothrombin gene variant (2.9% European and 4.8% in Hungary) was also found to increase in frequency. In young stroke patients (age <50) compared with control subjects the odds ratios were higher: in prothrombin gene (OR: 4.9), in Leiden mutation (OR: 1.67), in fibrinogen gene (OR: 1.64) and in MTHFR(+/+) (OR: 1.58). Clustering of two polymorphisms could only be detected in young patients. These clustering polymorphisms were GP IIb/IIIa with prothrombin G20210A variant (OR: 6.74, 95% CI 1.1-18.2) and prothrombin gene variant with MTHFR (OR: 5.3, CI95 1.2-8.3). Conclusion - Selected and clustered genetic polymorphisms of haemostatic factors could be responsible for the high stroke morbidity in Central Europe. The presence and clustering tendency of these factors have been described in young stroke victims.]

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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.

Lege Artis Medicinae

[Comment to the article titled “Exploratory study of outcomes of blood sample mass examinations by rank correlations”]

Lege Artis Medicinae

[The author’s response to the comment on “Exploratory study of outcomes of blood sample mass examinations by rank correlations”]

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.

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