Early molecular oxidative stress biomarkers of ischemic penumbra in acute stroke.

OBJECTIVES: To assess whether plasma biomarkers of oxidative stress predict diffusion-perfusion mismatch in patients with acute ischemic stroke (AIS). METHODS: We measured plasma levels of oxidative stress biomarkers such as F2-isoprostanes (F2-isoPs), total and perchloric acid Oxygen Radical Absorbance Capacity (ORACTOT and ORACPCA), urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguoanosine, and inflammatory and tissue-damage biomarkers (high-sensitivity C-reactive protein, matrix metalloproteinase-2 and -9) in a prospective study of patients with AIS presenting within 9 hours of symptom onset. Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI sequences were analyzed with a semiautomated volumetric method. Mismatch was defined as baseline mean transit time volume minus DWI volume. A percent mismatch cutoff of >20% was considered clinically significant. A stricter definition of mismatch was also used. Mismatch salvage was the region free of overlap by final infarction. RESULTS: Mismatch >20% was present in 153 of 216 (70.8%) patients (mean [±SD] age 69.2 ± 14.3 years, 41.2% women). Patients with mismatch >20% were more likely to have higher baseline plasma levels of ORACPCA (p = 0.020) and F2-isoPs (p = 0.145). Multivariate binary logistic regression demonstrated that lnF2-isoP (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.19-4.98, p = 0.014) and lnORACPCA (OR 4.18, 95% CI 1.41-12.41, p = 0.010) were independent predictors of >20% PWI-DWI mismatch and the stricter mismatch definition, respectively. lnORACTOT significantly predicted mismatch salvage volume (>20% mismatch p = 0.010, stricter mismatch definition p = 0.003). CONCLUSIONS: Elevated hyperacute plasma levels of F2-isoP and ORAC are associated with radiographic evidence of mismatch and mismatch salvage in patients with AIS. If validated, these findings may add to our understanding of the role of oxidative stress in cerebral tissue fate during acute ischemia.

Oral Hygiene in Patients with Parkinson's Disease.

Parkinson's disease is a chronic progressive neurodegenerative disorder with a multifactorial etiology. The symptoms are characterized by motor disorders - tremor, rigidity, bradykinesia and postural instability, which hinder oral hygiene. Oral and dental health in Parkinson's disease has been under-documented and findings are conflicting. Moreover, a number of dentists have limited experience regarding the management of these patients. This article reviews literature published within the last fifteen years, to better understand the impact of this disease in oral health. A literature search (MEDLINE and PUBMED), using keywords Parkinson Disease and Oral Hygiene, yielded 27 articles, from which 20 were selected. All of the articles were published in English in the last 15 years.

Safety of full-dose intravenous recombinant tissue plasminogen activator followed by multimodal endovascular therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: The optimal management of stroke patients who fail treatment with intravenous recombinant tissue plasminogen activator (rt-PA) remains unknown. A study was undertaken to establish whether treatment with a standard intravenous t-PA dose (0.9 mg/kg) followed by multimodal endovascular therapy would have a similar safety profile to reduced dose (0.6 mg/kg) bridging therapy. METHODS: A retrospective analysis was performed of a prospectively collected database. All patients treated with full-dose t-PA and endovascular therapy were included. The primary safety endpoints included ECASS-III symptomatic intracranial hemorrhage (sICH) and ECASS parenchymal hematomas (PH). Secondary safety endpoints included severe systemic bleeding and 90-day mortality. Clinical efficacy endpoints included rates of recanalization (TICI 2-3), ambulation at hospital discharge and 90-day independent outcomes (mRS 0-2). RESULTS: 106 consecutive patients (mean age 69 ± 17 years; mean baseline NIH Stroke Scale 17.8 ± 4.8; 55% women; occlusion sites: MCA-M1 60.4%; MCA-M2 6.6%; ICA-T 19.8%; tandem cervical ICA+MCA-M1 7.5%; basilar artery 5.7%) were identified over a 10-year period. The sICH rate was 8.5% and the PH-1, PH-2 and subarachnoid hemorrhage rates were 2.8%, 8.5% and 2.8%, respectively. There were two (1.9%) severe groin hematomas. The recanalization rate was 66%. At hospital discharge, 41.4% of the patients were ambulatory. The rate of independent functional outcomes at 90 days was 24%; however, this sample is biased since nearly all deaths were captured but detailed 90-day functional outcomes were missing in 27 patients. The 90-day death rate was 32.4%. CONCLUSION: Combined treatment with full-dose intravenous rt-PA followed by multimodal endovascular therapy seems to be associated with similar rates of sICH to that of bridging therapy with reduced rt-PA dosage.

Commentary: Perception of remorse by mock jurors in a capital murder trial.

The study by Corwin et al. adds to the emerging but limited data on the impact of defendant remorse on sentencing decisions. The authors studied verbal and nonverbal expressions of defendant remorse and whether they were perceived as remorseful by mock jurors. They found that incongruent verbal and nonverbal behavior, as well as mock jurors' willingness to approach emotional situations, resulted in more lenient sentences for defendants. An overarching and as yet unanswered validity concern regarding this line of research in general is whether the use of undergraduate mock jurors reliably models real jurors in actual courtroom settings.

Skull base tumor in a patient with phacomatosis pigmentovascularis.

A 58-year-old man with clinical diagnosis of phacomatosis pigmentovascularis (PPV) experienced tinnitus and progressive hearing loss due to a jugular foramen tumor.Attached to the tumor capsule, were several pigmented spots. Pathological examination revealed a tumor composed by two different tissues, namely a Schwannoma grade I associated with a leptomeningeal blue nevus. The neuropathological aspects of this unusual association are discussed. The association of PPV with a pigmented skull base tumor has not been described to date and illustrates the importance of systemic examination in PPV.

Predicting clinical outcome in comatose cardiac arrest patients using early noncontrast computed tomography.

BACKGROUND AND PURPOSE: Early assessment of the likelihood of neurological recovery in comatose cardiac arrest survivors remains challenging. We hypothesize that quantitative noncontrast computed tomography (NCCT) combined with neurological assessments, are predictive of outcome. METHODS: We analyzed data sets acquired from comatose cardiac arrest patients who underwent CT within 72 hours of arrest. Images were semiautomatically segmented into anatomic regions. Median Hounsfield units (HU) were measured regionally and in the whole brain (WB). Outcome was based on the 6-month modified Rankin Scale (mRS) score. Logistic regression was used to combine Glasgow Coma Scale (GCS) score measured on Day 3 post arrest (GCS_Day3) with imaging to predict poor outcome (mRS>4). RESULTS: WB HU (P=0.02) and the ratio of HU in the putamen to the posterior limb of the internal capsule (PLIC) (P=0.004) from 175 datasets from 151 patients were univariate predictors of poor outcome. Thirty-three patients underwent hypothermia treatment. Multivariate analysis showed that combining median HU in the putamen (P=0.0006) and PLIC (P=0.007) was predictive of poor outcome. Combining WB HU and GCS_Day3 resulted in 72% [61% to 80%] sensitivity and 100% [73% to 100%] specificity for predicting poor outcome in 86 patients with measurable GCS_Day3. This was an improvement over prognostic performance based on GCS_Day3≤8 (98% sensitive but 71% specific). DISCUSSION: Combining density changes on CT with GCS_Day3 may be useful for predicting poor outcome in comatose cardiac arrest patients who are neither rapidly improving nor deteriorating. Improved prognostication with CT compared with neurological assessments can be achieved in patients treated with hypothermia.

Pharmacokinetics of extended-release dipyridamole following administration through a gastrostomy tube: an open-label, case-control, two-centre study.

BACKGROUND: Many stroke survivors have severe dysphagia and are unable to take antithrombotic medications orally. OBJECTIVE: To evaluate whether dipyridamole concentrations achieved in the plasma of patients taking an extended-release formulation of the medication through a gastrostomy tube (G-tube) are therapeutic and similar to those achieved in the plasma of patients who receive the drug orally. METHODS: This was an open-label, case-control, two-centre study conducted in two academic centres in a metropolitan area. Patients included were those admitted following an acute cerebral infarction, with an indication for antiplatelet therapy for secondary prevention. Twelve patients with severe dysphagia requiring G-tube placement were cases, and 12 patients who were able to swallow safely served as controls. The components of Aggrenox (extended-release dipyridamole/aspirin [acetylsalicylic acid]), suspended in water, were administered twice daily for 5 days through the G-tube. The 12 control patients without dysphagia took the medication orally. Dipyridamole plasma concentrations were compared between the groups at three different timepoints on the fifth day: 2, 6 and 12 hours after administration. The main outcome measure was dipyridamole plasma concentrations on day 5 at all three timepoints. RESULTS: No significant difference in dipyridamole plasma concentrations between the groups was found at 2 hours (p = 0.18), 6 hours (p = 0.92) or 12 hours (p = 0.69). CONCLUSION: Dipyridamole plasma concentrations obtained following administration of extended-release dipyridamole through a G-tube in dysphagic patients achieved similar therapeutic levels to those obtained in patients taking the medication orally.

Feasibility and safety of combined percutaneous coronary intervention and therapeutic hypothermia following cardiac arrest.

REVIEW: Mild therapeautic hypothermia (MTH) has been associated with cardiac dysrhythmias, coagulopathy and infection. After restoration of spontaneous circulation (ROSC), many cardiac arrest patients undergo percutaneous coronary intervention (PCI). The safety and feasibility of combined MTH and PCI remains unclear. This is the first study to evaluate whether PCI increases cardiac risk or compromises functional outcomes in comatose cardiac arrest patients who undergo MTH. METHODS: Ninety patients within a 6-h window following cardiac arrest and ROSC were included. Twenty subjects (23%) who underwent PCI following MTH induction were compared to 70 control patients who underwent MTH without PCI. The primary endpoint was the rate of dysrhythmias; secondary endpoints were time-to-MTH induction, rates of adverse events (dysrhythmia, coagulopathy, hypotension and infection) and mortality. RESULTS: Patients who underwent PCI plus MTH suffered no statistical increase in adverse events (P=.054). No significant difference was found in the rates of dysrhythmias (P=.27), infection (P=.90), coagulopathy (P=.90) or hypotension (P=.08). The PCI plus MTH group achieved similar neurological outcomes (modified Rankin Scale (mRS)

Preemptive analgesic effect of lidocaine in a chronic neuropathic pain model / Efeito analgésico preemptivo da lidocaína em modelo de dor crônica neuropática

Preemptive analgesia inhibits the progression of pain caused by surgical lesions. To analyze the effect of lidocaine on postoperative pain relief, we performed compression of the right sciatic nerve in Wistar rats and observed the differences on behavior between the group that received lidocaine and the group that was not treated with the local anesthetics pre-operatively. Group 1 was not operated (control); group 2 underwent the sciatic nerve ligature without lidocaine; group 3, underwent surgery with previous local infiltration of lidocaine. Group 2 showed significantly longer scratching times with a peak on day 14 post-operative (p=0.0005) and reduction in the latency to both noxious (p=0.003) and non-noxious (p=0.004) thermal stimulus. Group 3 presented significantly shorter scratching times (p=0.004) and longer latency times when compared to Group 2. Preemptive use of lidocaine 2 percent can potentially reduce the postoperative neuropathic pain associated with sciatic nerve compression.

A analgesia preemptiva inibe a progressão da dor causada por lesão cirúrgica. Para analisar o efeito da lidocaína na diminuição da dor pós-operatória, submetemos ratos Wistar a compressão cirúrgica do nervo ciático e observamos diferenças em alguns padrões de comportamento entre o grupo tratado com lidocaína pré-operatória e o grupo não-tratado com o anestésico local. O grupo 1 não foi operado (controle); o grupo 2, submetido a ligadura do nervo ciático sem lidocaína, apresentou significativo aumento do tempo de coçar-se com um pico no 14º pós-operatório (p=0.0005) e redução na latência para os estímulos térmicos nocivo (p=0.003) e não-nocivo (p=0.004); o grupo 3, operado com a droga preemptiva, demonstrou significativo decréscimo no tempo de coçar-se (p=0.004) e maiores tempos de latência quando comparados aos do grupo 2. O uso preemptivo da lidocaína 2 por cento pode, potencialmente, reduzir a dor neuropática pós-operatória associada à compressão do nervo ciático.

Preemptive analgesic effect of lidocaine in a chronic neuropathic pain model.

Preemptive analgesia inhibits the progression of pain caused by surgical lesions. To analyze the effect of lidocaine on postoperative pain relief, we performed compression of the right sciatic nerve in Wistar rats and observed the differences on behavior between the group that received lidocaine and the group that was not treated with the local anesthetics pre-operatively. Group 1 was not operated (control); group 2 underwent the sciatic nerve ligature without lidocaine; group 3, underwent surgery with previous local infiltration of lidocaine. Group 2 showed significantly longer scratching times with a peak on day 14 post-operative (p=0.0005) and reduction in the latency to both noxious (p=0.003) and non-noxious (p=0.004) thermal stimulus. Group 3 presented significantly shorter scratching times (p=0.004) and longer latency times when compared to Group 2. Preemptive use of lidocaine 2% can potentially reduce the postoperative neuropathic pain associated with sciatic nerve compression.