Quantitative measurements of regional lung ventilation using helium-3 MRI in a methacholine-induced bronchoconstriction model.

PURPOSE: To demonstrate ventilation changes in an animal model of methacholine-induced bronchoconstriction using hyperpolarized (HP) helium-3 (He-3) MRI. MATERIALS AND METHODS: Bronchoconstriction was induced in 11 healthy rats using an intravenous injection of methacholine. The He-3 was laser-polarized using a custom-built system. MRI studies were performed on a 2-Tesla bore magnet. Coronal dynamic ventilation images were obtained using a single inhalation of the laser-polarized He-3 gas before and after methacholine injection. Ventilation image series were processed on a pixel-by-pixel basis to generate three regional ventilation parameters: gas flow rate, filling time, and maximum gas volume. Student's paired t-test was used for analysis. RESULTS: Ventilation image series with a temporal resolution of 5 msec were obtained before and after methacholine challenge. Quantitative regional gas dynamic information demonstrated statistically significant differences between the baseline and constricted states. Following methacholine injection, the mean flow values were significantly lower for the right lung (RL) (P = 0.006) and left lung (LL) (P = 0.024), while the mean filling time was found to be greater (RL: P = 0.08, LL: P = 0.021). Gas volume values at maximum inspiration were found to be significantly lower after methacholine (RL: P = 0.002; LL: P = 0.036). CONCLUSION: He-3 MRI demonstrated and quantified regional ventilation changes in bronchoconstriction conditions in rats.

Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI).

BACKGROUND/AIMS: To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients, non-responders to interferon/ribavirin and study the dynamic of response. METHODS: In a double blind, multicenter, randomized trial, 200 non-responder patients received pegylated interferon 1.5 microg/kg per week and ribavirin 800-1200 mg/day, plus either amantadine 200 mg/day or placebo for 48 weeks. Endpoints were virological responses, ALT normalization, and histological benefit overtime. RESULTS: Twenty percent of all patients achieved a sustained virological response (SVR). This rate was 8% higher in the triple therapy group (24%) compared with the double therapy group (16%) (P = 0.22). A better virological response rate at week 24 was observed in the triple regimen group (43 vs 29%; P = 0.06), which was lost at week 48 suggesting viral escape. The biochemical response rate was also significantly higher with triple therapy at week 12 (63 vs 49%; P = 0.05) and week 24 (64 vs 49%; P = 0.03). Fibrosis stabilized or improved in 77% of all patients. CONCLUSIONS: Re-treatment of interferon/ribavirin non-responder patients should be encouraged since a substantial proportion benefits from re-treatment with pegylated interferon/ribavirin +/- amantadine. In triple therapy involving amantadine, a time wise response and an increased SVR rate in subgroups less prone to viral breakthrough suggest clues for existing controversies.

Prevention of implantable defibrillator shocks by cognitive behavioral therapy: a pilot trial.

BACKGROUND: Although psychological stress is known to favor ventricular arrhythmic events, there is no evidence that stress management intervention decreases ventricular electrical instability in implantable cardioverter-defibrillator (ICD) patients. The aim of the study was to determine whether cognitive behavioral therapy (CBT) results in a decrease of arrhythmic events requiring ICD intervention through an improvement in sympathovagal balance. METHODS: Of 253 consecutive ICD patients (age 59 +/- 10 years, 64 men), 70 were randomly assigned to CBT (n = 35) or conventional medical care (n = 35). Measures of heart rate variability, psychological well-being, and quality of life were assessed at baseline, 3 months, and 1 year. The primary outcome was appropriate ICD shock. RESULTS: Although, it was not statistically different, the number of patients requiring shocks was less in the CBT group than in the conventional treatment group. At 3 months, among patients without antiarrhythmic drugs, none of the subjects in the CBT group had experienced arrhythmic events requiring ICD intervention, as compared with 4 in the control group (P < .05). At 12 months, there was no difference in the number of arrhythmic events requiring therapy between the CBT group versus the control group. Among heart rate variability indexes, daytime pNN 50 and nocturnal SDNN improved significantly in the CBT group, as compared with the control group. CONCLUSIONS: By decreasing anxiety and possibly improving sympathovagal balance, cognitive behavior therapy may decrease the propensity for ventricular arrhythmias in ICD patients. However, these effects appear to be limited over time.

Evolution of lesion volume in acute stroke treated by intravenous t-PA.

PURPOSE: To determine the evolution of the ischemic lesion volumes in a population treated with tissue plasminogen activator (t-PA), MRIs were performed before treatment and 24 hours later; final infarct size was evaluated 60 days later. MATERIALS AND METHODS: A total of 42 patients with hemispheric stroke were recruited for a thrombolytic study. Intravenous t-PA was given after MRI within the first seven hours after stroke onset. Volumes were evaluated on day 0 and day 1 with diffusion-weighted imaging (DWI), on day 60 with T2-weighted imaging (T2WI), and recanalization was assessed based on day 1 MR angiography (MRA). RESULTS: Lesion volume increased between day 0 and day 1, and decreased between day 1 and day 60. It was lower in the group of patients with recanalization on day 1 MRA. CONCLUSION: Volume analysis emphasizes the effectiveness of recanalization as a predictive factor for better outcome, based on final infarct size. The decrease in lesion volumes between day 1 and day 60 suggests that other factors leads to overestimation of day 1 abnormal diffusion volume. This could explain the delayed partial reversibility of the DWI abnormality.

Late auditory and event-related potentials can be useful to predict good functional outcome after coma.

OBJECTIVE: To investigate whether late auditory and event-related potentials, and in particular N100 and mismatch negativity, together with clinical parameters, can help to predict good functional outcome in comatose patients. DESIGN: Prospective cohort study. SETTING: Hospital. PARTICIPANTS: Consecutively sampled comatose patients (N=346) whose etiologies of coma were stroke (125 patients), brain injury (96 patients), anoxia (64 patients), complication of neurosurgery (54 patients), and encephalitis (7 patients). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Glasgow Outcome Scale score at 1 year postonset. Patients in a minimally conscious state and those who awoke and died during the follow-up period were classified separately. RESULTS: Univariate analysis showed that all variables studied, except brainstem auditory evoked potentials, correlated significantly with functional outcome. Mismatch negativity showed the highest positive predictive value for good outcome. A validated model was obtained with multivariate logistic analysis, including pupillary light reflex, N100, mismatch negativity, etiology, and age. CONCLUSIONS: Late auditory and event-related potentials, and particularly N100 and mismatch negativity, provide strong prognostic factors for good functional outcome. Furthermore, these components may enhance the accuracy of prognosis when associated with other clinical parameters available at the early stage of coma.

Quantitative study of nerves of the human left atrium.

OBJECTIVES: To quantify and study the distribution of innervation of the left atrium and the pulmonary veins in humans. BACKGROUND: Damage to cardiac nerves has been hypothesized as the explanation for successful radiofrequency ablation of atrial fibrillation. METHODS: From January 2003 to September 2003, histologic and quantitative studies of innervation of the left atrium and the pulmonary veins was performed in 43 consecutive necropsied adult hearts (30 men and 3 women; mean age 45.5 +/- 12.4 years). The left atrium was sectioned in 1-cm slices from left to right, with the plane of section perpendicular to the long axis of the heart. Sections of the pulmonary veins at their ostia and sections 1 cm away of this structure also were obtained. Nerve fiber density was counted manually for each case and expressed as the mean number per slice. RESULTS: Numerous epicardial nerve fibers and ganglia having distinct patterns of distribution in the left atrium were found. Nerve density was significantly higher at the ostia of the four pulmonary veins than in their distal part (7.1 +/- 2.1 vs 5.2 +/- 1.3 for left upper pulmonary vein; 6.3 +/- 1.5 vs 5.2 +/- 1.7 for right upper pulmonary vein; 7.4 +/- 2 vs 5.9 +/- 2 for left lower pulmonary vein; 6.7 +/- 1.8 vs 3.9 +/- 1.3 for right lower pulmonary vein). The left superior vein was significantly more innervated than the right inferior vein (12.3 +/- 3 vs 10.6 +/- 1.4). Gradients of innervation were found from right to left (9.8 +/- 4.6 vs 18.5 +/- 6.6, P < .05) and from the front to the rear of the atrium (17.2 +/- 6.4 vs 20.7 +/- 6.5, P < .05). The same heterogeneous distribution was observed at the myocardial level but with thinner nerve fibers, making quantification difficult. Only very thin nerve fibers were present in the endocardium. CONCLUSIONS: The human left atrium exhibits several gradients of innervation at discrete sites. These findings may have clinical implications for radiofrequency ablation of atrial fibrillation.

Ethical issues of informed consent in acute stroke. Analysis of the modalities of consent in 56 patients enrolled in urgent therapeutic trials.

BACKGROUND: Many patients may be mentally incompetent or physically unable to give informed consent at the acute stage of stroke. Accordingly, we aimed to investigate the modalities of informed consent in urgent therapeutic stroke trials, the awareness of patients and relatives regarding stroke clinical trials and the impact of decision making on patients and relatives. METHODS: We present a study of 56 acute ischemic stroke patients who were randomized in 4 trials (2 trials testing neuroprotective agents, 1 testing thrombolysis and 1 testing antithrombotic agents). A standardized questionnaire was used to assess the modalities of informed consent in this setting. RESULTS: The mean age was 67.1 (SD 12.6) years. The mean baseline Scandinavian Stroke Scale (SSS) score was 23.8 (SD 10.5). Only 13 patients (23% of cases) gave consent while relatives gave consent for 43 patients (77%). The main reason for not getting consent from the patient was aphasia in 29 patients (67.4%). Multiple logistic regression analysis showed that the two independent factors influencing the ability to give consent are age and baseline neurological deficit as assessed by the SSS score. Concerning the psychological impact of consent, none of the 10 patients who answered our questionnaire declared feeling uncomfortable when giving consent, while 7 out of the 13 relatives who could be reached declared they felt uncomfortable, mainly because of the psychological stress induced by urgent decision making. CONCLUSIONS: Our study emphasizes the specific ethical difficulties of informed consent in the setting of acute stroke research. Only a minority of patients are able to give consent at the acute stage. Increasing age and neurological deficit are independent predictors of inability to give consent. Thus, the responsibility for consent usually relies on relatives with potential inaccuracy of decision concerning the patient's wish or even conflict of interest. Further evaluation of the psychological impact of decision on relatives is needed in this setting of acute stroke.

Influence of pretreatment MRI parameters on clinical outcome, recanalization and infarct size in 49 stroke patients treated by intravenous tissue plasminogen activator.

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome (p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion (p=0.009), and in patients with larger pretreatment PWI (p=0.001) and DWI (p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion (p=0.02) and a delayed time to peak (TTP) on pretreatment PWI (p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume (p=0.025). Recanalization was associated with a lower final infarct size (p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.

Predictive value of sensory and cognitive evoked potentials for awakening from coma.

OBJECTIVES: To determine the prognostic role of late auditory (N100) and cognitive evoked potentials (MMN) for awakening in a cohort of comatose patients categorized by etiology. METHODS: The authors prospectively studied a series of 346 comatose patients. Coma was caused by stroke (n = 125), trauma (n = 96), anoxia (n = 64), complications of neurosurgery (n = 54), and encephalitis (n = 7). Patients were followed for 12 months and classified as awake or unawake. Univariate and multivariate analyses were performed using regression logistic and Cox models. RESULTS: Pupillary light reflex, N100, middle-latency auditory evoked potentials, age, and etiology were the most discriminating factors for awakening. Statistical analysis showed that pupillary reflex was the strongest prognostic variable for awakening (estimated probability 79.7%). The estimated probability of awakening rose to 87% when N100 was present and to 89.9% when middle-latency evoked potentials (MLAEPs) were present. It was 13.7% when pupillary reflex was absent in anoxic patients. When MMN was present, 88.6% of patients awakened. No patient in whom MMN was present became permanently vegetative. CONCLUSION: Pupillary reflex is the strongest prognostic variable, followed by N100 and MLAEPs allowing a reliable model for awakening. The presence of MMN is a predictor of awakening and precludes comatose patients from moving to a permanent vegetative state. Evaluation of primary sensory cortex and higher-order processes by middle-latency-, late, and cognitive evoked potentials should be performed in the prognosis for awakening in comatose patients.

Magnetic resonance imaging: significance of early ischemic changes on computed tomography.

UNLABELLED: The significance of early ischemic changes (EICs) on CT remains controversial. MRI may provide relevant information in patients with EICs. METHODS: EICs were assessed in patients with acute ischemic stroke. MRI was promptly performed at presentation after CT and repeated on day 1. The relationship between EICs and MRI parameters was assessed with one-way ANOVA for analysis of continuous variables and by the chi2 test for the analysis of variables with a binary outcome. RESULTS: Fourty-eight patients underwent CT and MR imaging before treatment with recombinant tissue plasminogen activator (age: 63 +/- 14 years). EICs were graded as absent in 28 patients, <33% in 15 patients, and >33% of the middle cerebral artery (MCA) territory in 5 patients. NIHSS score was higher in patients with EICs that covered more than one third of the MCA territory (19 +/- 3) compared to those without EICs (12 +/- 5; p = 0.04). Patients who had major EICs had a larger acute lesion volume in diffusion-weighted imaging (DWI; 140 +/- 78 cm3) compared to those without EICs (33 +/- 51 cm3, p < 0.0001). Regional cerebral blood flow, regional cerebral blood volume, time to peak and mean transit time values were not significantly different in the study groups. CONCLUSION: EICs reflect mainly a larger DWI lesion.

Glenohumeral arthrosis in anterior instability before and after surgical treatment: incidence and contributing factors.

BACKGROUND: Few large series of arthropathy related to anterior glenohumeral instability are available in the orthopaedic literature, preventing analysis of the incidence and the risk factors of preoperative and postoperative glenohumeral arthritis. HYPOTHESIS: Anterior stabilization surgery influences the risk factors of glenohumeral arthritis. STUDY DESIGN: Retrospective review. METHODS: There were 570 patients who underwent an instability procedure. Clinical and radiographic preoperative data were collected for these patients. Arthritis was evaluated preoperatively and postoperatively with the Samilson classification. The mean age at surgery was 31.9 years. Follow-up averaged 6.5 years. RESULTS: The preoperative incidence of arthritis was 9.2%. Arthritic risk factors were older age at the initial dislocation and at surgery, increased length of time from the initial dislocation until surgery, and the presence of osseous glenoid rim lesions. Postoperative arthritis in patients without any preoperative arthritis occurred in 19.7% and was correlated with older age at the initial dislocation and at surgery, increased number of dislocations, and longer follow-up. Decreased external rotation at latest follow-up correlated with arthritis, although whether this was the cause or the effect was unclear. CONCLUSIONS: Similar factors contribute to preoperative and postoperative arthritis in patients with anterior glenohumeral instability, suggesting that surgery does not influence the risk factors of arthritis. Although decreased external rotation with the arm at side statistically correlated with arthritis in this study, the authors were unable to establish this as an effectual relationship because nearly all patients with glenohumeral osteoarthritis, whether instability related or not, have decreased external rotation.

Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial.

PURPOSE: The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures. PATIENTS AND METHODS: Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray. RESULTS: Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P =.004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival. CONCLUSION: A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse.

The influence of pregnancy in multiple sclerosis has been a matter of controversy for a long time. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large prospective study which aimed to assess the possible influence of pregnancy and delivery on the clinical course of multiple sclerosis. We report here the 2-year post-partum follow-up and an analysis of clinical factors which might predict the likelihood of a relapse in the 3 months after delivery. The relapse rate in each trimester up to the end of the second year post-partum was compared with that in the pre-pregnancy year. Clinical predictors of the presence or absence of a post-partum relapse were analysed by logistic regression analysis. Using the best multivariate model, women were classified as having or not having a post-partum relapse predicted, and this was compared with the observed outcome. The results showed that, compared with the pre-pregnancy year, there was a reduction in the relapse rate during pregnancy, most marked in the third trimester, and a marked increase in the first 3 months after delivery. Thereafter, from the second trimester onwards and for the following 21 months, the annualized relapse rate fell slightly but did not differ significantly from the relapse rate recorded in the pre-pregnancy year. Despite the increased risk for the 3 months post-partum, 72% of the women did not experience any relapse during this period. Confirmed disability continued to progress steadily during the study period. Three indices, an increased relapse rate in the pre-pregnancy year, an increased relapse rate during pregnancy and a higher DSS (Kurtzke's Disability Status Scale) score at pregnancy onset, significantly correlated with the occurrence of a post-partum relapse. Neither epidural analgesia nor breast-feeding was predictive. When comparing the predicted and observed status, however, only 72% of the women were correctly classified by the multivariate model. In conclusion, the results for the second year post-partum confirm that the relapse rate remains similar to that of the pre-pregnancy year, after an increase in the first trimester following delivery. Women with greater disease activity in the year before pregnancy and during pregnancy have a higher risk of relapse in the post- partum 3 months. This is, however, not sufficient to identify in advance women with multiple sclerosis who are more likely to relapse, especially for planning therapeutic trials aiming to prevent post-partum relapses.

Early fibrinogen degradation coagulopathy is predictive of parenchymal hematomas in cerebral rt-PA thrombolysis: a study of 157 cases.

BACKGROUND: Little is known about the coagulation factors as predictors of cerebral bleeding in rt-PA thrombolysis. The aim of this study was to determine what early coagulation parameters could predict early hemorrhagic lesions. METHODS: Consecutive patients were included in the Lyon rt-PA protocol. Early hematomas (within 24 hours), diagnosed on an anatomoradiological basis (symptomatic and not symptomatic) were considered for the study. Fibrinogen and fibrin(ogen) degradation products (FDP) were assessed at entry and at 2 and 24 hours after the beginning of thrombolysis. RESULTS: Of 157 patients, 11 had early parenchymal hematomas (7%), 31 had early hemorrhagic infarcts (19.7%), and 115 had no bleeding (73.2%). In logistic regression, FDP at 2 hours was the single predictor of parenchymal hematomas (OR: 2.5; CI: 1.09 to 5.8), whereas an increase of FDP >200 mg/L multiplied the odds of parenchymal hematoma by 4.95 (IC: 1.09 to 22.4). Early parenchymal hematomas were indicative of a poor prognosis at 3 months (P=0.001). CONCLUSIONS: Early parenchymal hematomas appear as both "malignant" and exclusively related to an explosive increase of FDP at 2 hours, ie, an early fibrinogen degradation coagulopathy (EFDC). All patients scheduled to rt-PA thrombolysis should have an assay of FDP 2 hours after the beginning of thrombolysis: patients with an established EFDC (FDP >200 mg/L) should be monitored specifically, with no antithrombotic drug during the first 72 hours. Patients with FDP >100 mg should share the same monitoring.

Abdominal CT angiography before surgery as a predictor of postoperative death in acute aortic dissection.

OBJECTIVE: The purpose of our study was to search for a relationship between postoperative death in acute aortic dissection and abdominal helical CT findings before surgery. MATERIALS AND METHODS: We retrospectively included 48 patients admitted to our institution for emergent surgery of acute aortic dissection diagnosed with helical CT angiography. We recorded postoperative deaths and analyzed abdominal helical CT vessels and parenchymal abnormalities, including the presence of dissected abdominal aortic branches, a compressed aortic lumen, and low enhancement of the parenchyma in abdominal organs. RESULTS: Among the 48 patients, 11 died after surgery. Postoperative death occurred in one of five patients with low enhancement of the parenchyma in one abdominal organ and in seven of eight patients with low enhancement of the parenchyma in at least two abdominal organs. The postoperative death rates strongly correlated with the number of low-enhanced abdominal organs per patient (p < 0.00005) but did not correlate with the number of dissected abdominal aortic branches. CONCLUSION: The rate of abdominal organs with low enhancement of the parenchyma seen on CT before surgery is a strong factor in outcome in patients with acute aortic dissection. Additional analysis of low enhancement of the parenchyma in abdominal organs on CT might be a useful tool to detect, before surgery, patients at risk of postoperative death.

Thrombolysis for ischemic stroke in patients with old microbleeds on pretreatment MRI.

BACKGROUND: Old asymptomatic microbleeds (MBs) visualized on T2-weighted MRI are indicative of microangiopathy. They may be a marker of increased risk of intracerebral hemorrhage (ICH) following thrombolysis. However, data regarding this potential risk are limited. METHODS: A retrospective analysis of pretreatment T2-weighted MRI was performed in consecutive stroke patients who received intravenous tissue plasminogen activator (tPA). We aimed to assess the impact of MBs on the risk of cerebral bleeding. The frequency and location of MBs were assessed and compared with the location of ICH after thrombolysis. RESULTS: Forty-four patients were studied. MBs were present on pretreatment MRI in 8 cases (18.2%). At day 1, symptomatic ICH occurred in none of 8 patients with MBs versus 1 of 36 patients without (NS). At day 1, ICH occurred in 3 of 8 patients with MBs versus 10 of 36 patients without (NS). At day 7, symptomatic ICH occurred in 1 of 8 patients with MBs versus 2 of 36 patients without (NS). At day 7, ICH occurred in 5 of 8 patients with MBs versus 12 of 36 patients without (NS). No ICH occurred at the site of an MB. ICH occurred within the ischemic area in all patients who bled. CONCLUSIONS: Our study suggests that stroke patients with a small number of MBs on pretreatment MRI could be treated safely with thrombolysis. Larger prospective studies are needed to address the predictive value of detection of MBs with regard to the risk of tPA-induced ICH.

European validation of a standardized clinical description of multiple sclerosis.

OBJECTIVES: The EDMUS system is a clinical database specifically tailored to the description of multiple sclerosis (MS). The EVALUED (Evaluation of the EDMUS system) study is an European project with two objectives: 1) to assess the inter-examiner reliability of the whole EDMUS system; 2) to validate the EDMUS-Grading Scale (EGS),which is a simplified version of the Kurtzke Disability Status Scale (DSS). METHODS: The protocol included 12 neurologists working in pairs within six European centres (Bari, Basel, Florence, London, Lyon, Würzburg). They assessed independently 30 MS patients in their centre, filling in the EDMUS forms. The reliability of the system was assessed on selected key items in the history of the MS onset, the clinical course and the disease course classification. The clinical examination of the patients permitted an assessment of the Kurtzke Expanded Disability Status Scale (EDSS) and the EGS. Level of agreement was measured in terms of kappa and weighted kappa indexes whenever appropriate. RESULTS: The study included 180 patients with definite or probable MS of whom 37% were males. Age was 35.8+/-9.6 years (mean +/- SD), disease duration 7.8+/-5.7 years, and mean EDSS score 4.1+/-2.2. The disease course was relapsing-remitting in 67%, secondary progressive in 22%, and progressive from disease onset in 11%. For key items of the history, the inter-examiner reliability level ranged from moderate to excellent. Concerning the disability scales, perfect agreement was reached in 59 % for EDSS and 78% for EGS. The close correlation and linear association (r=0.94, p<0.0001) between both scales demonstrated EGS's construct validity. CONCLUSION: The EDMUS system allows a consistent clinical description of MS using a common language. This standardized follow-up of MS patients is valuable especially in studies requiring a critical mass of informative patients.

Hypointense transcerebral veins at T2*-weighted MRI: a marker of hemorrhagic transformation risk in patients treated with intravenous tissue plasminogen activator.

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2*-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week (r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).

Evidence for deficiencies in perceptual and semantic olfactory processes in Parkinson's disease.

Olfactory deficits have been reported in Parkinson's disease (PD) and are thought to represent a sensitive marker of the disease. The aim of the present study was to examine the differential contribution in olfactory dysfunction of perceptual and semantic processes of odours in PD patients. Twenty-four PD patients (12 males and 12 females) and 24 control subjects (12 males and 12 females) were tested. The experiment included two sessions. Initially, 12 odorants were delivered, one per minute. For each odour, subjects were asked to rate intensity, pleasantness, familiarity and edibility using linear rating scales. The odorants were again presented and the subjects were asked to identify them. The four olfactory judgements and odour identification were severely disturbed in PD patients when compared to control subjects. These findings demonstrate major deficits for all cognitive tasks of olfactory judgement in PD, and suggest that PD is associated with disruption of olfactory areas situated in the temporal lobes and also in the prefrontal cortex.

QT dynamicity and sudden death after myocardial infarction: results of a long-term follow-up study.

INTRODUCTION: The aim of this study was to determine whether impaired adaptation of the QT interval to changes in heart rate predicts sudden death after an acute myocardial infarction. METHODS AND RESULTS: The Groupe d'Etude du Pronostic de l'Infarctus du Myocarde (GREPI) trial was a prospective multicenter study designed to evaluate the long-term outcome of myocardial infarction. QT dynamicity was evaluated in 265 patients by analyzing 24-hour Holter recordings obtained 9 to 14 days after myocardial infarction. The linear regression slope of QT intervals measured to the apex and to the end of the T wave (QTe) plotted against RR intervals was calculated using a dedicated Holter algorithm. The value of QT/RR in predicting sudden death and total mortality was compared with those of ejection fraction, heart rate variability, and late potentials. Mean follow-up was 81 +/- 27 months. There were 73 deaths, of which 23 were sudden. Of all the parameters, an increased diurnal QTe/RR slope (>0.18) was the strongest independent predictor of sudden death (relative risk 6.07, confidence interval 1.48-24.95, P = 0.01). CONCLUSION: Increased diurnal QTe dynamicity is independently predictive of sudden death among patients with myocardial infarction. This simple parameter may help to stratify risk and select patients who may benefit from antiarrhythmic prophylaxis.