Subarachnoid hemorrhage (SAH) is a disease with high risk of mortality and morbidity. Elderly patients have an even higher risk of poor outcome. The incidence of SAH increases with age and the elderly constitute a substantial and increasing proportion of the population. Thus, the management of elderly SAH patients is an imminent clinical challenge. Time trends in clinical management and outcome were investigated in 281 SAH patients aged ≥65 years admitted over an 18-year period. The volume of elderly patients, especially patients ≥70 years and patients in worse clinical condition increased over time. The proportion of patients with favorable outcome increased over time, without an increase in severely disabled patients. Technical results and clinical outcome of endovascular aneurysm treatment (EVT) was investigated in 62 elderly SAH patients. EVT can be performed in elderly SAH patients with high technical success, acceptable aneurysm occlusion degree, acceptable procedural complication rate, and fair outcome results. EVT was compared to neurosurgical clipping (NST) in 278 elderly SAH patients in the International Subarachnoid Aneurysm Trial. In good grade elderly SAH patients, EVT should probably be the favored treatment for internal carotid and posterior communicating artery aneurysms, while elderly patients with middle cerebral artery aneurysms appear to benefit from NST. Occurrence of secondary insults and their impact on clinical deterioration were studied in 99 patients with severe SAH. High intracranial pressure increased and high cerebral perfusion pressure decreased the risk of clinical deterioration. Elderly patients had less intracranial hypertension insults and more hypertensive, hypotensive and hypoxemic insults. Good outcome was achieved in 24% of elderly patients with severe SAH, and the proportion of severe disability was similar to that of younger patients. Patient age was not a significant predictor for vasospasm in 413 SAH patients when admission and treatment variables were adjusted for with multiple logistic regression.

Objective: This study aims to derive a clinically-applicable decision rule to predict the risk of symptomatic vasospasm, a neurological deficit primarily due to abnormal narrowing of cerebral arteries supplying an attributable territory, in aneurysmal subarachnoid hemorrhage (SAH). Methods: SAH patients presenting from 2002 to 2011 were analyzed using logistic regression and recursive partitioning to identify clinical, radiological, and laboratory features that predict the occurrence of symptomatic vasospasm. Results: The incidence of symptomatic vasospasm was 21.0%. On multivariate logistic regression analysis, significant predictors of symptomatic vasospasm included age 40-59 years, high Modified Fisher Grade (Grades 3 and 4), and anterior circulation aneurysms. Conclusion: Development of symptomatic vasospasm can be reliably predicted using a clinical decision rule created by logistic regression. It exhibits increased accuracy over the Modified Fisher Grade alone and may serve as a useful clinical tool to individualize vasospasm risk once prospectively validated in other neurosurgical centres.

Migraines are recurrent debilitating headaches that predominately afflict young women. The pathophysiology of migraines is still not well understood but is related to neurovascular dysfunction. Meningeal blood vessel dilation, extravasation of pro-inflammatory cytokines and activation of trigeminal afferent neurons promote migraine generation. Serotonin (5-HT) is an endogenous vasoactive peptide with diverse physiology. In meningeal blood vessels, serotonin causes vasoconstriction, however in coronary arteries, serotonin causes both vasodilation and vasoconstriction. In diseased coronary arteries, with impaired endothelial function, vasoconstriction predominates. Selective meningeal blood vessel serotonin agonists, termed ‘triptans’, have become the therapy of choice for migraine headaches. However, due to their constrictive effects on the coronary vasculature, triptans are not recommend in patients with known coronary artery disease, patients with greater than one coronary artery risk factor or patients with atherosclerotic cardiovascular disease risk (ASCVD) greater than ten percent. Triptan associated chest pain is a well-known phenomenon. Age, hypertension, dyspepsia, and Raynauds phenomenon are associated with triptan associated chest pain. Hypertension is the strongest risk factor for triptan associated chest pain in males. Although triptan associated chest pain is assumed to be cardiovascular due to its constrictive effect on the coronary vasculature, only a few cases of myocardial infarction, with documented ST elevation and/or troponin elevation, have been reported. Herein we report the case of a male patient with inferolateral ST elevation myocardial infarction, within minutes of receiving subcutaneous sumatriptan for migraine headache. The patient had a normal echocardiogram and electrocardiogram prior to sumatriptan use, and a normal cardiac catheterization afterwards.

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment.

Smelter workers who were exposed to air-borne arsenic for a mean of 23 years, and age-matched referents, were examined with clinical, physiological, and neurophysiological methods. Exposure to arsenic in workroom air was estimated to have been around the Swedish occupational limits, which were 500 yg/m before 1975 and 50 yg/ra thereafter. An increased preval ence of Raynaud's phenomenon and a reduced finger systolic blood pressure (FSP) during local and general cooling were found in the smelter workers. Slight, but significant sub-clinical neuropathy, in the form of slightly reduced nerve conduction velocity (NCV) in two or more peripheral nerves, was more common among the arsenic workers than among the referents. There were positive correlations between cumulative exposure to arsenic, reduced NCV in three peripheral motor nerves, and decrease in FSP during cooling. Arsenic levels in urine were 1 ymole/1 (75 yg/1) in the arsenic workers and 0.1 ymole/1 in the referents. In 21 arsenic workers with no or very low exposure to vibra ting hand tools, the FSP during cooling had increased significantly after 3 years wit h the lower arsenic exposure. There was no change in FSP during the summer vacation, whereas urinary levels of arsenic decreased to normal values. Thus there seems to be a slow improvement of finger blood circ ulation which is independent of short-term fluctuations in the exposure to arsenic. No seasonal variation was found in FSP during cooling with the standardized method used. When the NCV-measurements were repeated five years later the difference between arsenic workers and referents had increased, despite the fact that 14 of the 47 arsenic workers had had no exposure to arsenic during the last 1-5 years. These observations indicate, that in subjects with long term exposure to arsenic, sub-clinical neuropathy is not reversible. Ten milligrams of Ketanserin, a serotonin receptor antagonist, was given intravenously to five arsenic workers with cold-induced vasospasm. Skin temperature and FSP during cooling increased significantly with Ketanserin as compared wit h saline solution. After oral treatment, 2 x 40 mg /day for four weeks, no significant increase of FSP during cooling or rise in skin temperature was found in six arsenic workers and eleven patients with Raynaud's phenomenon. The decrease of vasospastic tendency after intravenous injection of Ketanserin indicated that similar mechanisms might operate in arsenic-induced and other types of Raynaud's phenomenon. A general co nclusion from the five studies in this dissertation is that long-term occupational exposure to arsenic has had adverse effects on the peripheral circulation and nerve conduction. The tendency to vasospasm, but not the sub-clinical neuropathy, seemed to be reversible with decreasing exposure. / <p>S. 1-54: sammanfattning, s. 55-112: 5 uppsatser</p> / digitalisering@umu

Background: Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) has been extensively investigated, but the impact of collateralization remains unclear. We investigated the predictive value of collateral activation for delayed cerebral ischemia (DCI)-related infarctions and functional outcome. Methods: Data from 43 patients with CVS (January 2014 to August 2021) were evaluated for the angiographic presence of leptomeningeal and ophthalmic collaterals (anterior falcine artery (AFA), supratrochlear artery (STA), dorsal nasal artery (DNA)) on internal carotid artery angiograms. Vasospasm-related infarction and the modified Rankin Scale (mRS) score after six months were chosen as the endpoints. Results: 77% of the patients suffered from DCI-related infarctions. In 233 angiograms (at hospitalization, before spasmolysis, after six months), positive vessel signs were observed in 31 patients for STA, 35 for DNA, and 31 for AFA. The STA sign had the highest positive (84.6%) and negative (85.7%) predictive value for unfavorable outcome (mRS 4–6) in patients aged 50 years. DNA and AFA signs were not meaningful predictors for either endpoint. Leptomeningeal collaterals showed a positive Pearson’s correlation with the STA sign in 87.5% (p = 0.038) without providing any prediction for either endpoint. Conclusions: The STA sign is associated with clinical outcome in patients with CVS after SAH aged 50 years, and was correlated with the occurrence of leptomeningeal collaterals.

Background: Cerebral vasospasm (CVS) continues to account for high morbidity and mortality in patients surviving the initial aneurysmal subarachnoid hemorrhage (SAH). Nimodipine is the only drug known to reduce delayed cerebral ischemia (DCI), but it is believed not to affect large vessel CVS. Milrinone has emerged as a promising option. Our retrospective study focused on the effectiveness of the intra-arterial application of both drugs in monotherapy and combined therapy. Methods: We searched for patients with aneurysmal SAH, angiographically confirmed CVS, and at least one intra-arterial pharmacological angioplasty. Ten defined vessel sections on angiograms were assessed before and after vasodilator infusion. The improvement in vessel diameters was compared to the frequency of DCI-related cerebral infarction before hospital discharge and functional outcome reported as the modified Rankin Scale (mRS) score after 6 months. Results: Between 2014 and 2021, 132 intra-arterial interventions (144 vascular territories, 12 bilaterally) in 30 patients were analyzed for this study. The vasodilating effect of nimodipine was superior to milrinone in all intradural segments. There was no significant intergroup difference concerning outcome in mRS (p = 0.217). Only nimodipine or the combined approach could prevent DCI-related infarction (both 57.1%), not milrinone alone (87.5%). Both drugs induced a doubled vasopressor demand due to blood pressure decrease, but milrinone alone induced tachycardia. Conclusions: The monotherapy with intra-arterial nimodipine was superior to milrinone. Nimodipine and milrinone may be used complementary in an escalation scheme with the administration of nimodipine first, complemented by milrinone in cases of severe CVS. Milrinone monotherapy is not recommended.

No description available.

Ziel: Methergin und Ergonovin werden in der Literatur als gleichwertige Substanzen zum Nachweis koronarer Hyperreagibilität (VSAP) während der Koronarangiographie betrachtet. Ziel dieser Studie ist 1) die Sensitivität der 2 Substanzen zu vergleichen und 2) ihren vasokonstriktorischen Effekt auf menschliche Koronararterien quantitativ zu analysieren. Methoden: 1) Für die Ermittlung der Sensitivität wurden 340 Patienten ohne Koronararterienstenosen >50% mittels Provokations-Test untersucht. Davon 182 mit Ergonovin und 158 mit Methergin. Es erfolgten Subgruppenanalysen nach Geschlecht, Alter, Koronarrisikofaktoren und klinischer Symptomatik. 2) Die quantitative spastische Wirksamkeit der 2 Testsubstanzen wurde verglichen anhand der Analyse der Reaktion der Segmente mit diffusem Spasmus, der Segmente mit lokalem Spasmus und der benachbarten normalen Segmente aus Koronarangiographien von Patienten mit nachgewiesener VSAP. Das Testkollektiv besteht aus 17 Patienten. Bei 10 wurde der Spasmus mit Ergonovin ausgelöst, bei 7 mit Methergin. Die Kontrollgruppe bestand aus 18 Patienten (10 untersucht mit Ergonovin, 8 mit Methergin). Es erfolgten Subgruppenanalysen nach Geschlecht und Gefäßgröße. Resultate: 1) Die Sensitivität des Ergonovin-Tests (18%) ist signifikant (p / Objects: Methergine and Ergonovine are described in literature as similar for recognizing coronary hyperreagibility (VSAP) during coronary angiography. The purpose of this study is 1) to compare the sensitivity of both the substances and 2) to analyze the quantitative effect of arterial vasocontraction in human coronary arteries. Methods: 1) 340 patients without coronary stenosis where examined by provocation-tests to ascertain the sensitivity. 182 of them were treated with Ergonovine and 158 with Methergine followed by analysis of subgroupspecifications like gender, age, coronary risk factors and clinical symptoms. 2) The quantitative spasmodic effects of both testsubstabces were compared by means of analyses of the reaction of the segments with diffuse spasm also of the segments with local spasm and the near by localised normal segments from coronary angiographys from patients with variant angina (VSAP). 17 patients were in the testcollective. In 10 the spasm was triggered by Ergonovine, in 7 with Methergine. 18 patients were in the controlgroup (10 examined on Ergonovine, 8 on Methergine). The analysis of subgroups were carried out regarding gender and vasculardiameter. Results: 1) The sensitivity of the Ergonovine-tests (18%) is significantly (p

A cocaína crack é a forma popular da cocaína nos dias de hoje, em decorrência do baixo custo relativo da droga e da rapidez dos seus efeitos no sistema nervoso central. São conhecidas alterações provocadas pela cocaína no coração de humanos e animais, sendo frequentes graves transtornos no sistema cardiovascular, muitas vezes fatais. Mas diante do crescente e preocupante aumento do uso dessa forma fumada da cocaína, particularmente pelos jovens, tornam-se necessários estudos experimentais utilizando-se a droga in natura, que não se encontra habitualmente disponibilizada para experimentos, diante das dificuldades legais. Este estudo objetivou a avaliação dos efeitos da inalação crônica da cocaína crack no coração de camundongos, tendo sido utilizados 24 animais BALB/c machos, jovens e adultos, 6 animais de cada grupo (n=6), que foram expostos à fumaça originada da queima de 5 g de cocaína, por 5 minutos, 5 dias da semana, durante 39 dias, em um período de dois meses; utilizouse uma câmara de inalação para a manutenção dos animais durante as sessões e os animais do grupo controle, em igual nº (n=6), foram mantidos no biotério em condições favoráveis. A droga teve como origem a apreensão policial (195,2 g) e o seu uso, na pesquisa previamente autorizada pela justiça. A análise farmacológica da droga constatou a presença de 57,66% de cocaína nas pedras de crack, satisfazendo as necessidades para a experiência. A quantificação de cocaína de 212,5 ng/ml no sangue dos animais também foi considerada representativa para os nossos objetivos de pesquisar alterações morfológicas no coração dos camundongos. Os resultados foram analisados pela One-Way-Anova e Modelo Linear Generalizado, e as diferenças consideradas significativas quando p< 0,05. Os estudos mostraram diminuição significativa da media (±DP) de peso dos corações nos animais expostos à droga, adultos e jovens, quando comparados com os grupos controles correspondentes. No grupo jovem, o aumento do número de núcleos, por área ventricular, pode ser relacionada com atrofia miocárdica dos ventrículos, direito e esquerdo (p< 0,001), demonstrada pela morfometria das fibras musculares estriadas cardíacas, utilizando-se o sistema de retículo de pontos. Nos adultos expostos, apesar da diminuição de peso do coração, a morfometria não constatou atrofia de miocárdio de nenhum dos lados (p> 0,05). Nos exames microscópicos das paredes ventriculares, com a coloração da hematoxilina-eosina, foi detectado, discreto número de fibras musculares cardíacas, com perda das estriações e hialinizações do citoplasma, favorecendo apoptose. A morfometria dos vasos coronarianos intramurais, com medições das luzes, camadas médias e adventícias demonstrou diminuição significativa da proporção (razão) luz/parede nos animais expostos, independente da idade, quando comparado com os grupos controle (p=0,001). Esses dados caracterizam a vasoconstrição por provável ação simpaticomimética da droga, justificando uma isquemia relativa no coração e conseqüente aumento da apoptose, bem documentada pela imunoistoquímica através da coloração do TUNEL. Esta imunocoloração marcou extensamente os núcleos de células apoptóticas, nos ventrículos direito e esquerdo dos animais expostos, quando comparado aos animais não expostos (p<0,001). A microscopia óptica com H&E e Picro-sirius sugeriu fibrose peri-adventicial nos animais expostos adultos A quantificação do colágeno, após a polarização, mostrou aumento não significativo, nos ramos coronarianos dos animais expostos adultos e interstício do ventrículo direito dos dois grupos expostos (p>0,05). As pesquisas realizadas com um modelo experimental inédito confirmam alterações anatomopatológicas já descritas na literatura, como a vasoconstrição com isquemia aguda e aumento da apoptose e mostram alterações ainda não referidas, em efeitos crônicos da cocaína, como a diminuição de peso do coração e atrofia do miocárdio. Os estudos, embora tenham limitações por não ter sido isolada outra substância eventualmente presente na amostra teste, constataram achados morfológicos importantes para a saúde pública, que devem ser pesquisados nas autópsias. Novos estudos são recomendados, utilizando-se outros tempos e ambientes de exposição, com e sem a associação de drogas, assim como porcentagens diferentes de cocaína no crack e isolando-se as substâncias presentes na droga in natura. / Crack cocaine is the currently popular form of cocaine, due to its low cost and rapid effects on the central nervous system. Alterations caused by cocaine on the hearts of humans and animals are well known and severe disorders in the cardiovascular system, which are sometimes fatal, are frequent. Considering the growing concern regarding the increase in the use of this smoked form of cocaine, especially by young individuals, it becomes necessary to carry out experimental studies using the drug in its natural form, which is not usually available for experiments due to legal difficulties. The present study aimed at assessing the effects of the chronic inhalation of crack cocaine on the hearts of mice. A total of 24 BALB/c male animals were used in the experiment, both young and old, with 6 animals in each group (n=6), which were exposed to crack cocaine smoke that resulted from the burning of 5 g of cocaine, for 5 minutes, 5 days a week, for 39 days, except on weekends and holidays, during a two-month period. An inhalation chamber was used to keep the animals during the sessions, whereas the same number of animals from the control group (n=6) were kept at the animal facility of the institution under favorable conditions. The drug had been originally apprehended by the police in the course of criminal investigations and its use in research was previously authorized by the Department of Justice. The pharmacological analysis of the drug verified the presence of 57.66% of cocaine in the crack rocks, which satisfied the criterion used for the experience. The quantification of cocaine at 212.5 ng/mL in the blood of the animals was also considered representative for our objectives of assessing morphological alterations in the hearts of mice. The results were analyzed by One-Way-ANOVA and Generalized Linear Model, and the differences were considered significant when p<0.05. The studies showed a significant difference in the mean (±SD) weight of the hearts of the animals exposed to the crack cocaine smoke, both young and adult ones, when compared to the corresponding control groups. In the young group, the increased number of nuclei per ventricular area might be related to the myocardial atrophy of the right and left ventricles (p<0.001), demonstrated by the morphometry of the striated heart muscle fibers, using the system of point reticulum. In the exposed adult animals, in spite of the decreased heart weight, the morphometry did not show myocardial atrophy in neither side (p>0.05). The microscopic assessment of the ventricular walls, carried out with hematoxylin and eosin (H&E) staining, showed a small number of heart muscle fibers with loss of striations and hyalinization of the cytoplasm, which favored apoptosis. The morphometry of the intramural coronary vessels, with lumen, medial and adventitial layer measurement, showed a significant decrease in the lumen/wall ratio in exposed animals, regardless of age, when compared to the control group (p=0.001). These data characterize vasoconstriction, due to the probable sympatheticomimetic action of the drug, which justifies a relative ischemia of the heart and a consequent increase in apoptosis, well documented by immunohistochemistry through TUNEL staining. This immunostaining extensively identified the nuclei of apoptotic cells in the right and left ventricles of the exposed animals, when compared to the non-exposed animals (p< 0.001). Optical microcopy with H&E and Picrosirius suggested periadventitial fibrosis in the adult exposed animals. Collagen quantification after polarization showed a non-significant increase in the coronary branches of the adult exposed animals and in the right ventricular interstitium in the two exposed groups (p>0.05). The present study, carried out using a novel experimental model, confirmed the presence of anatomopathological alterations that had been previously described in the literature, such as vasoconstriction with acute ischemia and increased apoptosis and showed alterations that had not been previously reported as being chronic effects of cocaine, such as decreased heart weight and myocardial atrophy. Although there were limitations, considering that other substances eventually present in the test sample were not identified, the present study demonstrated important morphological findings for public health, which must be studied in autopsies. Further studies are recommended, using other exposure durations and environments, with and without the association of drugs, as well as different percentages of cocaine in crack rocks and isolating the substances present in the drug in its natural form.