Cognition after malignant media infarction and decompressive hemicraniectomy - a retrospective observational study

Abstract Background Decompressive hemicraniectomy is a life-saving procedure for patients with malignant middle cerebral artery infarctions. However, the neuropsychological sequelae in such patients have up to now received little attention. In this study we not only describe neuropsychological deficits but also the quality of life and the extent of depression and other psychiatric symptoms in patients after complete media infarction of the non-speech dominant hemisphere. Methods 20 patients from two different university hospitals (mean ± standard deviation: 52 ± 14 years of age) who had undergone hemicraniectomy with duraplasty above the non-speech dominant hemisphere at least one year previously were examined using a thorough neurological and neuropsychological work-up. The quality of life and the extent of psychiatric problems were determined on the basis of self-estimation questionnaires. The patients were asked whether they would again opt for the surgical treatment when considering their own outcome. 20 healthy persons matched for age, gender and education served as a control group. Results All patients but one were neurologically handicapped, half of them severely. Age was significantly correlated with poorer values on the Rankin scale and Barthel index. All cognitive domain z values were significantly lower than in the control group. Upon re-examination, 18 of 20 patients were found to be cognitively impaired to a degree that fulfilled the formal DSM IV criteria for dementia. Conclusions Patients with non-speech dominant hemispheric infarctions and decompressive hemicraniectomy are at high risk of depression and severe cognitive impairment.</p

Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine

AIMS: Some children with malaria and convulsions also have concurrent bacterial meningitis. Chloramphenicol is used to treat the latter whereas phenytoin is used for convulsions. Since chloramphenicol inhibits the metabolism of phenytoin in vivo, we studied the effects of chloramphenicol on phenytoin pharmacokinetics in children with malaria. METHODS: Multiple intravenous (i.v.) doses of chloramphenicol succinate (CAP) (25 mg kg-1 6 hourly for 72 h) and a single intramuscular (i.m.) seizure prophylactic dose of fosphenytoin (18 mg kg-1 phenytoin sodium equivalents) were concomitantly administered to 15 African children with malaria. Control children (n = 13) with malaria received a similar dose of fosphenytoin and multiple i.v. doses (25 mg kg-1 8 hourly for 72 h) of cefotaxime (CEF). Blood pressure, heart rate, respiratory rate, oxygen saturation, level of consciousness and convulsion episodes were monitored. Cerebrospinal fluid (CSF) and plasma phenytoin concentrations were determined. RESULTS: The area under the plasma unbound phenytoin concentration-time curve (AUC(0, infinity ); means (CAP, CEF): 58.5, 47.6 micro g ml-1 h; 95% CI for difference between means: -35.0, 11.4), the peak unbound phenytoin concentrations (Cmax; medians: 1.12, 1.29 micro g ml-1; 95% CI: -0.5, 0.04), the times to Cmax (tmax; medians: 4.0, 4.0 h; 95% CI: -2.0, 3.7), the CSF:plasma phenytoin ratios (means: 0.21, 0.22; 95% CI: -0.8, 0.10), the fraction of phenytoin unbound (means: 0.06, 0.09; 95% CI: -0.01, 0.07) and the cardiovascular parameters were not significantly different between CAP and CEF groups. However, mean terminal elimination half-life (t1/2,z) was significantly longer (23.7, 15.5 h; 95% CI: 1.71, 14.98) in the CAP group compared with the CEF group. Seventy per cent of the children had no convulsions during the study period. CONCLUSIONS: Concomitant administration of chloramphenicol and a single i.m. dose of fosphenytoin alters the t1/2,z but not the other pharmacokinetic parameters or clinical effects of phenytoin in African children with severe malaria. Moreover, a single i.m. dose of fosphenytoin provides anticonvulsant prophylaxis in the majority of the children over 72 h. However, a larger study would be needed to investigate the effect of concomitant administration of multiple doses of the two drugs in this population of patients

Different binding pattern of antibodies to prion protein on lymphocytes from patients with sporadic Creutzfeldt–Jakob disease

In Creutzfeldt-Jakob disease (CJD), progressive neuronal cell death probably occurs as a result of a change in conformation of the physiological prion protein (PrPC). There is evidence of participation of the lymphatic system and in particular of lymphocytes in the intracorporeal transportation of the pathological prion protein (PrPSc) in new variant CJD and scrapie. Using fluorescence cytometry, we investigated a possible alteration of PrPC on lymphocytes of patients with sporadic CJD. We demonstrated a significantly lower binding pattern of antibodies (3F4) against physiological prion protein to lymphocytes of patients with sporadic CJD (n = 16) compared with control patients. In contrast this difference was not found on platelets (n = 23). For the first time we were able to present a measurable difference of antibody binding on lymphocytes of patients with CID. One interpretation of this finding is that lymphocytes patrolling the brain bind and transport PrPSc which has a lower binding affinity for the antibodies directed against physiological PrP. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved

Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke

Background and Purpose-Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke. Methods-This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40 000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for. Results-Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke. Conclusions-Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis. (Stroke. 2009;40:e647-e656.