Haemostatic drug therapies for acute primary intracerebral haemorrhage.

BACKGROUND: Because primary intracerebral haemorrhage (PICH) volume influences its outcome and a third of PICHs enlarge by a third within 24 hours of onset, early haemostatic drug therapy might improve outcome. OBJECTIVES: To examine the clinical effectiveness and safety of haemostatic drug therapies for acute PICH in a randomised controlled trial (RCT) design. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched May 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to August 2005) and EMBASE (1980 to August 2005). In an effort to identify further published, ongoing and unpublished studies we scanned bibliographies of relevant articles, searched international registers of clinical trials and research, and contacted authors and pharmaceutical companies. SELECTION CRITERIA: We sought RCTs of any haemostatic drug therapy for acute PICH, compared against placebo or open control, with relevant clinical outcome measures. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, reviewed the relevant studies, and extracted data from them. MAIN RESULTS: We found four phase II RCTs, involving adults aged 18 years or over, within four hours of PICH: 116 received placebo and 373 participants received haemostatic drugs (two received epsilon-aminocaproic acid (EACA) and 371 received recombinant activated factor VII (rFVIIa)). Haemostatic drugs appeared to reduce the risk of death or dependence on the modified Rankin Scale (grades 4 to 6) within 90 days of PICH (risk reduction 0.79 (95% confidence intervals (CI) 0.67 to 0.93)), but not when assessed by the extended Glasgow Outcome Scale (risk reduction 0.90 (95%CI 0.81 to 1.01)). There was a statistically significant excess of arterial thromboembolism at 160 mcg/kg rFVIIa. AUTHORS' CONCLUSIONS: Current evidence for the use of haemostatic drugs in the treatment of acute PICH cannot provide clear guidelines for clinical practice. Adults with acute PICH may benefit from haemostatic therapy with rFVIIa, but the evidence on major clinical outcomes is neither robust nor precise. Large phase III RCTs of rFVIIa - and other less costly drugs - are necessary.

Interventions for treating brain arteriovenous malformations in adults.

BACKGROUND: Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiotherapy/'radiosurgery' (using gamma knife, linear accelerator or proton beam), endovascular embolisation (using glues, particles, fibres, coils, or balloons), and staged combinations of these interventions. OBJECTIVES: To assess the clinical effects of interventions to treat brain AVMs in adults (with the aim of either partial obliteration or total eradication), using data published in randomised controlled trials. SEARCH STRATEGY: We searched: (1) the Cochrane Stroke Group Register (last searched December 2004); (2) medical literature databases (MEDLINE 1966 to 31 December 2004 and EMBASE 1980 to 31 December 2004); (3) on-line and paper journal surveillance; (4) the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005); (5) international registers of clinical trials; (6) bibliographies of relevant articles identified by (1) to (5); and (7) we sought unpublished data from manufacturers of interventional treatments for brain AVMs. SELECTION CRITERIA: We sought randomised trials of any or all of the interventions for brain AVMs, compared against each other or against usual medical therapy, with relevant clinical outcome measures. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria and reviewed the relevant studies. MAIN RESULTS: We did not find any randomised trials meeting our selection criteria. We found two randomised trials which tested the equivalence of two embolic agents for the pre-operative embolisation of brain AVMs (one published, one unpublished), but none of the primary or secondary outcome measures in these trials met our desired criteria; although important clinical outcomes were reported, meaningful comparison of the two treatment arms was impossible. We also excluded a third RCT which studied three different blood pressure lowering treatments to induce deliberate hypotension during surgical resection of brain AVMs, because the intervention was not the focus of this review. AUTHORS' CONCLUSIONS: There is no evidence from randomised trials with clear clinical outcomes, comparing different interventional treatments for brain AVMs against each other or against usual medical therapy, to guide the interventional treatment of brain AVMs in adults. One such trial (ARUBA), comparing interventional versus conservative management for unruptured brain AVMs, is being planned.

Combined forceps and catheter extraction of an oesophageal foreign body.

The extraction of impacted foreign bodies from the oesophagus is frequently performed using forceps under endoscopic guidance. We report the case of a 23-year-old prisoner who ingested a lump of cannabis resin which could not be removed from the upper oesophagus with forceps alone. We recommend the use of a Fogarty balloon catheter in conjunction with toothed forceps in such cases.

CSF opening pressure: reference interval and the effect of body mass index.

We prospectively recorded CSF opening pressure in 242 adults who had a lumbar puncture with concomitant measurement of weight and height. The 95% reference interval for lumbar CSF opening pressure was 10 to 25 cm CSF. Body mass index had a small but clinically insignificant influence on CSF opening pressure.

Stroke.

Clearly, progress is being made in the investigation and evaluation of therapies for stroke, and the last two decades have seen stroke medicine come of age. The challenge now is to maintain this momentum with government support, transfer research findings into routine clinical practice and increase public awareness. This conference should have inspired its audience to do so, with clear evidence and good humour.

Ethical review of a multicentre study in Scotland: a weighty problem.

OBJECTIVE: To assess the current working practices of local research ethics committees (LRECs) in their review of a multicentre study approved by the new multicentre research ethics committee in Scotland. DESIGN: Observational data collected from correspondence with LRECs. SUBJECTS: All LRECs within the geographical area of the study in Scotland. INTERVENTIONS: None. OUTCOME MEASURES: Delay from application to calling an LREC meeting, to an initial LREC decision, to final LREC approval, and the number of A4 pages required. RESULTS: The median delay to review of an application at an LREC meeting was 28 days (range 14-97), the median delay from application to the time of LREC final approval was 39 days (range 21-109) and a total of 5,789 A4 pages (26.9 kg) were required to complete the application process. CONCLUSIONS: Despite recent standardisation of ethical review of multicentre research, elimination of unnecessary delay, cost and variation in LREC operating procedures is still necessary.

A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults.

By systematically reviewing the literature, we have found that there is very little information about the frequency and clinical course of arteriovenous malformations (AVMs) of the brain in adults because the methods of most studies have been flawed, and AVMs tend to be treated once they are discovered. The incidence of AVMs is approximately 1 per 100 000 per year in unselected populations, and the point prevalence in adults is approximately 18 per 100 000. AVMs account for between 1 and 2% of all strokes, 3% of strokes in young adults, 9% of subarachnoid haemorrhages and, of all primary intracerebral haemorrhages, they are responsible for 4% overall, but for as much as one-third in young adults. AVMs are far less common causes of first presentations with unprovoked seizures (1%), and of people presenting with headaches in the absence of neurological signs (0.3%). At the time of detection, at least 15% of people affected by AVMs are asymptomatic, about one-fifth present with seizures and for approximately two-thirds of them the dominant mode of presentation is with intracranial haemorrhage. The limited high quality data available on prognosis suggest that long-term crude annual case fatality is 1-1.5%, the crude annual risk of first occurrence of haemorrhage from an unruptured AVM is approximately 2%, but the risk of recurrent haemorrhage may be as high as 18% in the first year, with uncertainty about the risk thereafter. For untreated AVMs, the annual risk of developing de novo seizures is 1%. There is a pressing need for large, prospective studies of the frequency and clinical course of AVMs in well-defined, stable populations, taking account of their prognostic heterogeneity.

Internet resources for neurologists.

This fourth and final review in the JNNP internet series summarises the essential internet resources for adult and paediatric clinical neurology, neuroradiology, and neurophysiology. This article is freely available on the JNNP website (www.jnnp.com), where-within seconds-the complete list of recommended websites can be easily downloaded and incorporated into your web browser as a Bookmark/Favorite file. The further progress of clinical neurology on the world wide web will be monitored in JNNP Neuronline fillers and JNNP Neurology in Practice supplements.

The internet.

The growing use of email and the world wide web (WWW), by the public, academics, and clinicians-as well as the increasing availability of high quality information on the WWW-make a working knowledge of the internet important. Although this article aims to enhance readers' existing use of the internet and medical resources on the WWW, it is also intelligible to someone unfamiliar with the internet. A web browser is one of the central pieces of software in modern computing: it is a window on the WWW, file transfer protocol sites, networked newsgroups, and your own computer's files. Effective use of the internet for professional purposes requires an understanding of the best strategies to search the WWW and the mechanisms for ensuring secure data transfer, as well as a compendium of online resources including journals, textbooks, medical portals, and sites providing high quality patient information. This article summarises these resources, available to incorporate into your web browser as downloadable "Favorites" or "Bookmarks" from www.jnnp.com, where there are also freely accessible hypertext links to the recommended sites.

Integrated care pathways in multiple sclerosis rehabilitation: completing the audit cycle.

The rehabilitation of progressive neurological disorders, such as Multiple Sclerosis (MS) requires comprehensive, expert management which is demanding of both time and resources. Mechanisms to monitor and audit both process and outcome are therefore essential. Integrated care pathways (ICPs) which detail the expected interventions during a given episode of clinical care, provide such a mechanism. In this study three cohorts of patients (totalling 125 episodes) with clinically definite progressive MS underwent a rehabilitation programme audited through ICPs. The cohorts were similar in relation to disability and age. Variations (departures from the expected pathway) were documented for both the rehabilitation process and goal achievement. Duration of stay reduced from 28 days for the first cohort to 18 days for the third and there was greater multidisciplinary input and carer involvement over time. Goal achievement increased from 79% for the first cohort to 87% for the third and there was an increased emphasis on cognitive function and fatigue management in relation to goals set. ICPs provide an excellent mechanism for closing the audit loop and have the potential to play an important role in improving service provision in MS.

Transverse myelopathy and radiculomyelopathy associated with pulmonary atypical Mycobacterium infections.

Myelopathy is a well recognised but rare association with Mycobacterium tuberculosis infection, but has not been described with atypical mycobacteria. We report two cases of disabling myelopathy in association with pulmonary infection by Mycobacterium kansasii and Mycobacterium malmoense; the myelopathy is presumed to be a para-infectious phenomenon.

Prevalence of adults with brain arteriovenous malformations: a community based study in Scotland using capture-recapture analysis.

OBJECTIVE: To conduct a population based study of brain arteriovenous malformation (AVM) prevalence. METHODS: Multiple, overlapping sources of case ascertainment were used to establish the point prevalence of brain AVMs in the adult population of the Lothian health board of Scotland. Patients were sought retrospectively from all local general (family) practitioners, neurologists, neurosurgeons, stroke physicians, the specialist AVM clinic at the regional neuroscience centre, and routine coding of hospital discharge data. Case notes, brain imaging, and pathology reports were reviewed to validate each patient's diagnosis and to ensure that each was alive, over the age of 16 years, and resident in the geographical area of the study on the prevalence date of 30 June 1998. RESULTS: Of 148 potentially eligible people, 93 adults met the inclusion criteria. There were 40 women and 53 men. Men were significantly younger than women on the prevalence date (median age 39 years v 51 years, p = 0.003). Of those included, 25 (27%) had radiological evidence of prior therapeutic obliteration of their brain AVM and 9 (10%) had coexisting aneurysms. The minimum crude brain AVM prevalence was 15 per 100 000 adults and capture-recapture analysis gave an ascertainment adjusted prevalence of 18 (95% confidence interval 16 to 24) per 100 000 adults. CONCLUSIONS: The minimum estimate of brain AVM prevalence helps to assess its burden and comparative epidemiology and stresses the importance of brain AVMs as a cause of long term disability in adults.

Spontaneous intracranial hypotension causing confusion and coma: a headache for the neurologist and the neurosurgeon.

Spontaneous intracranial hypotension presenting with confusion and coma has rarely been reported. A case is presented and the clinical features of spontaneous intracranial hypotension are discussed.

Systemic lupus erythematosus, thrombocytopenia, microangiopathic haemolytic anaemia and anti-CD36 antibodies.

Thrombocytopenia in patients with acute systemic lupus erythematosus (SLE) frequently presents the clinician with considerable diagnostic and therapeutic difficulties. In this Grand Round, we present a 48-yr-old woman with a 7 yr history of lupus, who presented with acute proliferative glomerulonephritis and nephrotic syndrome, pneumonia, profound hypocomplementaemia and a severe microangiopathic haemolytic anaemia with associated thrombocytopenia. Her thrombocytopenia proved initially refractory to conventional immunosuppressive therapy, and corticosteroids, and resolved only with plasma exchange and repeated fresh frozen plasma infusions. Serological testing revealed high-titre antinuclear antibodies (ANA) and markedly raised antibodies to double-stranded (ds) DNA, but no significant elevation in anticardiolipin antibodies. Platelet-associated IgG and IgM and antibodies to the CD36 glycoprotein antigen, expressed on platelets and endothelium, were detected in the serum. We address some of the difficult diagnostic and management issues raised by this complex patient and the possible immunopathological links between antibodies to CD36, immune-mediated red cell destruction, thrombocytopenia and thrombotic microangiopathic haemolytic anaemia.