Pulse pressure variability is associated with unfavorable outcomes in acute ischaemic stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. METHODS: Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models. RESULTS: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90-day mortality (P < 0.001). Every 5-mmHg increase in the 24-h PP variability was independently associated with a 36% decrease in the likelihood of 90-day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52-0.80) and a 60% increase in the odds of 90-day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23-2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. CONCLUSIONS: Increased PP variability appears to be independently associated with adverse short-term and long-term functional outcomes of AIS patients treated with IVT.

Plasminogen activation in focal cerebral ischemia and reperfusion.

In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2%+/-8.5% and 19.4%+/-30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8%+/-42.2%, P < 0.05) but not in the cortex (43.0%+/-34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury (r = 0.873, P < 0.001). No such correlation was found in the cortex (r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.

Plasminogen activation in experimental permanent focal cerebral ischemia.

BACKGROUND: Previous experimental work using in situ zymography has shown very early increased plasminogen activation in ischemic regions after 3 h of ischemia with and without reperfusion. The objective of the present study was to evaluate the time course and extent of plasminogen activation in long-term permanent focal cerebral ischemia. MATERIAL AND METHODS: The middle cerebral artery in male Fisher rats was irreversibly occluded by electrocoagulation. Duration of ischemia was 48, 72, and 168 h. Occlusion was controlled in vivo by MRI at day 2. Plasminogen activation was detected by in situ zymography of 10 microm cryosections with an overlay containing plasminogen and the plasmin substrate caseine. Areas of plasminogen activation were compared to structural lesions (immunohistochemical loss of microtubule-associated protein 2; MAP 2). RESULTS: Compared to controls, increased plasminogen activation was observed in the basal ganglia and the cortex of the ischemic hemisphere after 48, 72, and 168 h (affected area of basal ganglia: 44.5+/-21.9, 70.1+/-2.3 and 66.6+/-2.8%, respectively; affected area of cortex: 63.4+/-9.8, 67.7+/-0.7 and 64.0+/-3.7%, respectively). The duration of ischemia had no significant influence on the extent of plasminogen activation. Areas of increased plasminogen activation significantly overlapped with and exceeded areas of MAP 2 loss (P<0.005). DISCUSSION: Permanent focal cerebral ischemia leads to increased plasminogen activation in ischemic regions. This plasminogen activation remains elevated at persistent levels over days. It may contribute to extracellular matrix (ECM) disruption, secondary hemorrhage, and brain edema in subacute stages of ischemic stroke.

The Mt. Diwata study on the Philippines 2000-treatment of mercury intoxicated inhabitants of a gold mining area with DMPS (2,3-dimercapto-1-propane-sulfonic acid, Dimaval).

Ninty-five inhabitants of the gold mining area of Mt. Diwata (on Mindanao, Philippines), who were diagnosed to be mercury (Hg) intoxicated, were orally treated with 2 x 200 mg of the chelating agent DMPS (Dimaval, Co. Heyl, Germany) for 14 days in the course of a UNIDO project focusing on mercury pollution abatement. Blood and urine samples before and after treatment, urine after the first application of DMPS and a hair sample were collected and analyzed for Hg. Before and after treatment extensive anamnestic data were collected, medical and neurological investigations and some neuro-psychological tests were performed. In spite of the short time of treatment most of the patients reported a marked improvement of the complaints which were stated by them before the therapy and which are characteristic for a chronic Hg intoxication, for example tremor, loss of memory, sleeplessness, metallic taste, etc. But even in some of the objective neurological parameters like hypo-mimia, Romberg test and tests for tremor/ataxia a statistical significant improvement could be found. Significant improvements could also be found in two neuro-psychological tests (pencil tapping and Frostig). In some cases an extreme high urinary Hg excretion was found under the chelating therapy with DMPS, and by this a distinct reduction of the Hg body burden. Nevertheless, in most cases Hg in blood and urine was not markedly decreased by the treatment. This shows that the duration of the treatment (14 days) was not sufficient for a permanent decrease in Hg. As DMPS excretes Hg mainly through the kidney, it can be concluded that in most cases even after 14 days of treatment there was an ongoing redistribution of Hg from other tissues to the kidney. In conclusion, this study proves that a chelating therapy with DMPS is highly effective even in the case of a mixed chronic and acute intoxication with an unknown combination of Hg vapor, inorganic Hg and organic Hg=methylmercury (MeHg), as characteristic for gold mining areas in the third world. Adverse side effects were rarely reported. Only in one case the medication had to be terminated after the first application due to an allergic skin reaction.

[Leber's hereditary optic nerve neuropathy]. / Leberova hereditárna neuropatia zrakového nervu.

The authors present a case report of 26 years old man with bilateral optic nerve neuropathy. Detection of heteroplasmic mutation of mitochondrial DNA at G3460A site confirmed the suspicion on Lebers hereditary optic nerve neuropathy (LHON). Genetic and environmental factors of the disease and various accompanying neurologic and other symptoms, which can together with the optic nerve defect participate in the development of of the LOHN clinical pattern are discussed. (Ref. 12.)

Acute-onset migrainous aura mimicking acute stroke: MR perfusion imaging features.

BACKGROUND AND PURPOSE: In a very limited number of cases, acute migrainous aura may mimic acute brain infarction. The aim of this study was to recognize patterns of MR perfusion abnormalities in this presentation. MATERIALS AND METHODS: One thousand eight hundred fifty MR imaging studies performed for the suspicion of acute brain infarction were analyzed retrospectively to detect patients with acute migrainous aura not from stroke. All patients were examined clinically by 2 neurologists and underwent a standard stroke MR imaging protocol, including PWI. Two radiologists reviewed the perfusion maps visually and quantitatively for the presence, distribution, and grade of perfusion abnormalities. RESULTS: Among 1850 MR imaging studies, 20 (1.08%) patients were found to have acute migrainous aura. Hypoperfusion was found in 14/20 patients (70%) with delayed rMTT and TTP, decreased rCBF, and minimal decrease in rCBV. In contrast to the typical pattern in stroke, perfusion abnormalities were not limited to a single vascular territory but extended to >1. Bilateral hypoperfusion was seen in 3/14 cases. In 11/14 cases, hypoperfusion with a posterior predominance was found. TTP and rMTT were the best maps to depict perfusion changes at visual assessment, but also rCBF maps demonstrated significant hypoperfusion in quantitative analysis. In all patients, clinical and imaging follow-up findings were negative for stroke. CONCLUSIONS: Acute migrainous aura is rare but important in the differential diagnosis among patients with the suspicion of acute brain infarction. Atypical stroke perfusion abnormalities can be seen in these patients.

Microvascular damage following experimental sinus-vein thrombosis in rats.

We evaluated effects of thrombosis of the superior sagittal sinus, its bridging and cortical veins (SVT) on the cerebral microvasculature in rats. Cryosections of brains ( n=7) were examined for venous infarction and microvascular basal lamina damage 3 h after SVT by immunohistochemical staining of microtubule-associated protein 2 and collagen type IV. Microvessels in the infarctions showed a decrease in the number (23.5+/-6.1%, P<0.002) and the total area (24.9+/-6.5%, P<0.011) of collagen type IV-positive vessels in contrast to control areas (21.7+/-12.4%, P<0.007; and 26.3+/-15.1%, P<0.026 in contrast to control areas of unoperated animals). This study showed a significant alteration of the cerebral microvasculature in SVT, which might contribute to edema and hemorrhagic transformation.

Unique case of eleven Bell's palsy episodes.

Bell's palsy (BP) is a peripheral facial nerve paralysis of unknown etiology. It is not a life-threatening condition; however, incomplete recovery may leave an individual stigmatized functionally, occupationally as well as socially. Recurrent paralyses are seldom, noted in 7-8% of all BP cases. More than two BP relapses are even less frequent. Adour et al. (1977) reported only two patients with four BP episodes from 1700 patients. Only one patient with more than four BP recurrences in the group containing 2414 BP cases were reported by Yanagihara et al. (1984). The highest reported number of BP recurrences in the accessible literature has been nine. We are presenting an unusual patient who suffered a total of eleven relapses of an idiopathic facial nerve palsy. Description of the case along with review of the relevant literature are discussed.