Objective-The association between brain atrophy and permanent functional deficits in multiple sclerosis and the temporal relation between atrophy and the clinical disease course have seldom been investigated. This study aims to determine the amount of infratentorial and supratentorial atrophy in patients by comparison with healthy controls, to establish the relation between atrophy and disability, and to derive the rates of volume loss in individual patients from their estimated disease durations. Methods-Three dimensional acquired MRI was performed on 20 relapsingremitting and 20 secondary progressive multiple sclerosis patients and 10 control subjects. Volume data on infratentorial and supratentorial structures were obtained using the Cavalieri method of modern design stereology in combination with point counting. Corpus callosal sectional area and "T2 lesion load" were also determined. Particularly for infratentorial structures, estimated rates of atrophy were higher in relapsing-remitting than secondary progressive patients, suggesting that atrophy, perhaps mainly due to tract degeneration, begins early in multiple sclerosis and may relate predominantly to acute inflammatory events, with or without other gradual non-inflammatory processes later in the disease course. (J Neurol Neurosurg Psychiatry 1999;66:323-330) Results-Significantly

Objectives-Recent phase III clinical trials of immunomodulatory therapies in relapsing-remitting multiple sclerosis have shown significant benefits of active treatment on relapse related end points, but eVects on disability outcomes have been inconsistent. These apparent discrepancies could be due to diVerences in the clinical end points employed, the behaviour of placebo cohorts, or both. Methods-Disability data from the placebo cohorts of two large phase III studies, the United States glatiramer acetate trial (Copolymer 1 Multiple Sclerosis Study Group) and the multinational interferon -1a trial (PRISMS Study Group) were combined and masked (n=313). Two groups of disability outcome measures were assessed. Firstly, measures of disability change (2 year EDSS diVerence and area under the EDSS/time curve, AUC) were calculated. Secondly, conventional disease progression end points ("confirmed progression" and "worsening to EDSS 6.0") were evaluated by using Kaplan-Meier analysis and compared with a categorical classification based on EDSS trends. Results-The average increase in disability for the entire cohort as assessed by mean 2 year EDSS change (<0.5 EDSS point) or mean AUC (+0.57 EDSS-years) was small. For the "confirmed progression" end points, increasing the stringency of the definition lowered their incidence (from 32% with 1.0 point at 3 months, to 9% with 2.0 points at 6 months), but did not improve the positive predictive accuracy for "sustained progression" maintained to the end of the study. The error rate for this outcome was about 50%. Worsening to EDSS 6.0 was a more reliable end point, but had even lower sensitivity (incidence <10%). EDSS trend analysis showed markedly heterogeneous disease courses, which were then categorised into "stable" (26%), "relapsing-remitting" (59%), and "progressive" (15%) courses. Patients with the last course had deteriorated considerably by the end of 2 years (mean worsening of 2.0 EDSS points). Conclusion-In relapsing-remitting multiple sclerosis treatment trials, the conventional measure of mean EDSS change has low sensitivity, whereas the widely applied confirmed progression end points have high error rates regardless of their definition stringency. Alternative methods with better data utilisation include AUC summary measures and categorical disease trend analysis. The heterogeneity of disability outcomes in short trials, combined with unreliable clinical end points, diminishes the credibility of therapeutic claims aimed at reducing irreversible neurological deficits. The behaviour of patients treated with placebo should be carefully analysed before conclusions are drawn on the eYcacy of putative treatments. (J Neurol Neurosurg Psychiatry 2000;68:450-457)

Aim Image-guided sclerotherapy is becoming the preferred treatment for low-flow vascular malformations in head and neck region. The authors review the management protocol for this condition and evaluate its clinical outcomes. Methods Children with low-flow vascular malformations in head and neck region undergoing sclerotherapy from 2010 to 2013 were reviewed. All patients were assessed by pediatric surgeons and interventional radiologists in the multidisciplinary vascular anomalies clinic. Ultrasonography and intravenous contrast enhanced magnetic resonance imaging were performed preoperatively. Under general anesthesia with endotracheal intubation, sclerotherapy were performed with ultrasonographic and fluoroscopic guidance. Sodium tetradecryl sulfate (STS) foam or ethanolamine was used for venous malformation and doxycycline for lymphatic malformations as primary sclerosants, whereas 98% ethanol was reserved as an adjuvant sclerosant in selected cases of repeated procedures. Perioperative dexamethasone 0.2 mg/kg thrice daily was administered to decrease postsclerotherapy swelling and single dose intravenous mannitol 0.5 g/kg was given to minimize thromboembolic complications. Postoperatively, patients were admitted to intensive care unit for mechanical ventilation under deep sedation for airway protection. Results Overall 13 children (8 male and 5 female) with a mean age of 25 months (range, 2 mo-11 y) underwent a total of 25 sessions of image-guided staged sclerotherapy. There were five venous and eight lymphatic malformations. Location wise there were eight cervical, one lingual, one parotid, one lip, one facial, and one palatal lesions. Six patients had obstructive airway symptoms. Five patients required staged sclerotherapies from two to six sessions. There were no airway and thromboembolic complications. One patient had bleeding while another had recurrent swelling following sclerotherapy for lymphatic malformations and they were treated by aspiration. Significant size reductions of more than 50% volume were achieved in all patients. All patients with obstructive symptoms showed improvement. Conclusion Sclerotherapy is a safe and effective treatment for head and neck vascular malformations in children. Routine perioperative protocol is essential to reduce airway

Real-time engagement of brain-injured patients in the goal setting process during early inpatient rehabilitation is achievable, but requires a structured multidisciplinary assessment of need. We found it increases the number of domains in which goals are set and includes functional areas not rated by commonly used global measures of outcome during inpatient rehabilitation.