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patients with cognitive impairment or dementia,15 andin 18 trials in cognitively normal elderly people.16 Bothmeta-analyses concluded that physical activity had aprotective effect on cognitive function. A review of theNational Institutes of Health’s Computer Retrieval ofInformation on Scientific Projects database of currentlyfunded studies suggests that further information will beforthcoming over the next few years.

The evidence for a protective effect of moderateexercise on cognitive decline in elderly people isgrowing. Continued moderate exercise in elderlyindividuals has many other health benefits and is part ofa healthy lifestyle. Further research is needed to examinemechanisms that underlie the apparently amelioratingeffect of exercise on ageing-related brain disease, therelative value of different forms of exercise, and theassociations of duration and intensity of exercise withhealthy brain ageing.

Helen Petrovitch, Lon WhiteThe Honolulu-Asia Aging Study, Pacific Health Research Institute,and Kuakini Medical Center, Honolulu, HA, USA Hpetrovitch@phrihawaii.org

We have no conflicts of interest.

1 Rovio S, Kareholt I, Eeva-Liisa H, et al. Leisure-time physical activity atmidlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol2005; 4: 705–11.

2 Abbott RD, White LR, Ross GW, Masaki KH, Curb JD, Petrovitch H. Walkingand dementia in physically capable elderly men. JAMA 2004; 292: 1447–53.

3 Podewils LJ, Guallar E, Kuller LH, et al. Physical activity, APOE genotype,and dementia risk: findings from the Cardiovascular Health CognitionStudy. Am J Epidemiol 2005; 161: 639–51.

4 Yamada M, Kasagi F, Sasaki H, Masunari N, Mimori Y, Suzuki G.Association between dementia and midlife risk factors: the RadiationEffects Research Foundation Adult Health Study. J Am Geriatr Soc 2003;51: 410–4.

5 Qiu C, Karp A, von Strauss E, Winblad B, Fratiglioni L, Bellander T. Lifetimeprincipal occupation and risk of Alzheimer's disease in the Kungsholmenproject. Am J Ind Med 2003; 43: 204–11.

6 Bonaiuto S, Rocca WA, Lippi A, et al. Education and occupation as riskfactors for dementia: a population-based case-control study.Neuroepidemiology 1995; 14: 101–09.

7 Andel R, Crowe M, Pedersen NL, et al. Complexity of work and risk ofAlzheimer's disease: a population-based study of Swedish twins.J Gerontol B Psychol Sci Soc Sci 2005; 60: 251–58.

8 Scarmeas N, Zarahn E, Anderson KE, et al. Association of life activities withcerebral blood flow in Alzheimer disease: implications for the cognitivereserve hypothesis. Arch Neurol 2003; 60: 359–65.

9 Colcombe SJ, Kramer AF, Erickson KI, et al. Cardiovascular fitness, corticalplasticity, and aging. Proc Natl Acad Sci USA 2004; 101: 3316–21.

10 Hatta A, Nishihira Y, Kim SR, K et al. Effects of habitual moderate exerciseon response processing and cognitive processing in older adults.Jpn J Physiol 2005; 55: 29–36.

11 McCurry SM, Gibbons LE, Logsdon RG, Vitiello MV, Teri L. Nighttimeinsomnia treatment and education for Alzheimer's disease: a randomized,controlled trial. J Am Geriatr Soc 2005; 53: 793–802.

12 Mancuso M, Filosto M, Bosetti F, et al. Decreased platelet cytochrome coxidase activity is accompanied by increased blood lactate concentrationduring exercise in patients with Alzheimer disease. Exp Neurol 2003;182: 421–26.

13 Landi F, Russo A, Bernabei R. Physical activity and behavior in the elderly:a pilot study. Arch Gerontol Geriatr Suppl 2004; 9: 235–41.

14 Van de Winckel A, Feys H, De Weerdt W, Dom R. Cognitive andbehavioural effects of music-based exercises in patients with dementia.Clin Rehabil 2004; 18: 253–60.

15 Heyn P, Abreu BC, Ottenbacher KJ. The effects of exercise training onelderly persons with cognitive impairment and dementia: a meta-analysis.Arch Phys Med Rehabil 2004; 85: 1694–704.

16 Colcombe S, Kramer AF. Fitness effects on the cognitive function of olderadults: a meta-analytic study. Psychol Sci 2003; 14: 125–30.

Acute ischaemic stroke is a treatable condition. Whengiven promptly to a highly selected group of patients,alteplase improves outcome and reduces disability.1,2

Despite qualified regulatory approval throughoutEurope, the effect of acute therapy has been limited,largely because of the 3 h time window in whichtreatment must be given. The problem is compoundedby difficulties in early diagnosis of stroke; misdiagnosisrates of up to 19% and 33% for suspected strokepatients have been reported by stroke specialists3 andemergency room physicians,4 respectively. As many astwo-thirds of otherwise eligible patients may miss outon treatment because of delay in presentation and earlymisdiagnosis.5 Low uptake of acute treatment isparticularly apparent in the UK, which currently holds15th place in the European league table of

thrombolysis use. Widespread implementation oftreatment for acute stroke is arguably the mostimportant challenge facing stroke clinicians today.There is an urgent need for new strategies to improvediagnostic accuracy and reduce delays in referral tospecialist services.

In this issue of The Lancet Neurology, Nor andcolleagues6 report the development and validation of astroke recognition tool, the ROSIER (recognition ofstroke in the emergency room) scale. The scale has beendesigned to provide physicians in the emergency roomwith a framework within which to assess patients withsuspected stroke, therefore facilitating earlyidentification and appropriate referral. For such a systemto work, both high sensitivity and high specificity arerequired to minimise the number of eligible patients

Development and validation of a stroke recognition tool

Reflection and Reaction

“missed” while protecting hard-pressed stroke unitsfrom a deluge of inappropriate referrals.

This is not a new idea; several stroke assessment toolshave already been developed and validated, primarily foruse by paramedics.7–10 Diagnostic accuracy of these scalesis typically around 80%, but their sensitivity andspecificity profiles differ. ROSIER extends the use of thestroke assessment scales in the emergency room.Experience with paramedic scales suggests that the highlevel of training11 and clinical skills possessed byemergency-room physicians—applied in an environmentmore conducive to thorough assessment—would allowthe use of more complex assessments and thereby yieldbetter diagnostic accuracy.10

By use of regression modelling, Nor and colleaguesdeveloped a scoring system including items thought toreduce the likelihood of stroke (each given a score of–1), and items consistent with stroke (each given a scoreof �1). A total score of �0 is taken as being consistentwith stroke, whereas scores of �0 signify a lowprobability of stroke. The main differences betweenROSIER and the paramedic stroke scales are a specificquestion regarding syncope (which should increasespecificity) and an examination to identify visual-fielddefects (which should increase sensitivity).

Early use of ROSIER has very promising results.Sensitivity was 93% during the prospective validationphase, comparing very favourably with the paramedicstroke-recognition scales. Specificity was broadly similarto previous measures, although fewer patients withdisorders mimicking stroke were referred during the

validation phase of the study, suggesting that specificitymay improve as experience grows.

Most patients who receive thrombolytic therapypresent with total or partial anterior circulation stroke,which are readily identified by use of the ROSIER scale.However, a false negative rate of 7% would be alarming ifthese patients were all suitable for thrombolytic therapy.Six of seven of the missed stroke patients had mildsymptoms with an NIHSS score of �3, and the authorswould not have considered them for treatment. Thisdoes, however, highlight a potential weakness of theROSIER scale. Patients with stroke treated with alteplasein the UK tend to be more severely affected than thosetreated elsewhere in Europe, and by missing mild strokesthe ROSIER scale may not help to redress this imbalance.Posterior circulation stroke was most likely to be missedby ROSIER, a potential problem as this subgroup ofpatients is subject to early complications, best managedby specialists after prompt referral. These issues shouldbe highlighted during training of emergency-room staff.Nor and colleagues state that the inclusion of eye-movement assessment into the ROSIER scale would haveled to the detection of two other strokes and increasedsensitivity to 95%, and this merits further consideration.

The ROSIER scale is an important step forward. Earlyexperience with thrombolysis has emphasised thechallenge facing stroke clinicians in the rapididentification and investigation of their patients, andNor and colleagues deserve praise for developing a well-designed, robust instrument to help with this task.ROSIER represents a further step along the road tooptimum acute stroke care—with only 1–2% of patientsin our leading centres receiving thrombolytic treatment,there is still a long way to go.

Jesse Dawson, Matthew WaltersAcute Stroke Unit, Western Infirmary, Glasgow, UKgcl203@clinmed.gla.ac.uk

We have no conflicts of interest.

1 The National Institute of Neurological Disorders and Stroke rt-PA StrokeStudy Group. Tissue plasminogen activator for acute ischemic stroke.N Engl J Med 1995; 333: 1581–87.

2 Hacke W, Donnan G, Fieschi C, et al. Association of outcome with earlystroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PAstroke trials. Lancet 2004; 363: 768–44.

3 Libman RB, Wirkowski E, Alvir J, Rao TH. Conditions that mimic stroke inthe emergency department: implications for acute stroke trials.Arch Neurol 1995; 52: 1119–22.

4 Ulaki SD, Topinka MA, Frasser WR. The accuracy of the emergencyphysician at diagnosing CVA/transient ischaemic attack in the acute caresetting. Acad Emerg Med 2000; 7: 1165.

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More than 160 years after the first systematic descriptionof multiple sclerosis (MS), our therapeutic tools forstopping disease progression are still limited, and there isnot even a cure, let alone a way of repairing damage to thenervous system. A major reason for limited treatmentoptions for MS is disease heterogeneity. MS can presentwith relapses and remissions or steady progression ofneurological disability, meaning the disease course isunpredictable in each patient. The pathological hallmarkin patients with acute and relapsing disease is theformation of focal inflammatory demyelinating lesions inwhite matter.1 Studies at the cellular and molecular levelsled to the classification of actively demyelinating MSplaques into distinct pathological patterns I-IV of MS.2

More than 80% of analysed lesions are pattern I withcellular cytotoxicity or pattern II with antibody andcomplement mediated demyelination. As yet there is nounequivocal surrogate marker that is indicative of orassociated with these lesion patterns.

Plasmapheresis made its way into neuroimmunologyin the 1980s, via myasthenia gravis to autoimmuneneuropathies, and finally into long-term MS treatment,mostly in combination with cytotoxic immuno-suppressive therapy.1 Although, plasmapheresis did notseem promising in modifying long-term relapsing orprogressive MS, Weinshenker and colleagues3 re-introduced plasmapheresis. In Weinshenker andcolleagues’ elegant, placebo-controlled, cross-overstudy, they offered plasmapheresis to those patientswith severe attacks of MS or inflammatory demyelinatingdisease who did not respond to (repeated) steroid pulsetherapy, thus indirectly selecting for patients in whomdisease pathology presumably was non-cellularinflammation—likely the same as pattern II, in whichdemyelination is caused by the deposition of antibodiesand activated complement.2 Weinshenker and colleagues

observed substantial amelioration with 45% of patientsreceiving seven treatment sessions of plasmapheresis.Importantly, plasmapheresis had to be given within6 weeks after onset of symptoms. On the basis of thiscontrolled study, the usefulness of plasmapheresis hasalso been extended to severe optic neuritis in patientswith MS or clinically isolated syndromes.4 In ourexperience, four or five plasmapheresis sessions, each at40 mL/kg bodyweight, were sufficient to yield similarresults. Limitations of this series4 arise from the open-study design, as a result of regulatory stipulations in theGerman medical system.

Keegan and colleagues5 studied histopathologicalpatterns in patients with fulminant attacks of MS andtreatment response to plasmapheresis. This consortiumof scientists, guided by the Mayo clinic, retrospectivelyanalysed 23 people who had had brain biopsy because offulminant inflammatory attacks in the presence oftumefactive lesions on MRI and for whom sufficient tissuewas available for molecular typing. Primary treatmentresponse was assessed independently from and withoutknowledge of the immunopathological classification.Four of the patients had to be excluded because otherdiagnoses were finally made or concomitant medicationwas taken. Finally, of the 19 remaining patients, threepatients had pattern I, ten patients had pattern II, and sixpatients had pattern III (distal oligodendrogliopathy). Theresults were clear and unequivocal; all patients of patternII responded to plasmapheresis with a median interval of3 days, whereas none of the other individuals improvedaccording to an established grading scale.3 During follow-up, two patients died and showed the same lesion patternon autopsy as in the biopsy.

This study is the first time that treatment success hasbeen associated with histopathological changes in MS.Although the treatment groups are small, the “black-

5 Azzimondi G, Bassein L, Fiorani L, et al. Variables associated with hospitalarrival time after stroke: effect of delay on the clinical efficiency of earlytreatment. Stroke 1997; 28: 537–42.

6 Nor AM, Davis J, Sen B, et al. The Recognition of Stroke in the EmergencyRoom (ROSIER) scale: development and validation of a stroke recognitioninstrument. Lancet Neurol 2005; 4: 727–34.

7 Kothari R, Pancioli A, Lui T, Brott T, Broderick J. Cincinnati PrehospitalStroke Scale: reproducibility and validity. Ann Emerg Med 1999;33: 373–78.

8 Harbison J, Massey A, Barnett L, Hodge D, Ford GA. Rapid ambulance

protocol for acute stroke. Lancet 1999; 353: 1935.9 Kidwell CS, Starkman S, Eckstein M, Weems K, Saver JL. Identifying stroke

in the field: prospective validation of the Los Angeles prehospital strokescreen (LAPSS). Stroke 2000; 31: 71–76.

10 Bray JE, Martin J, Cooper G, Barger B, Bernard S, Bladin C. Paramedicidentification of stroke: community validation of the MelbourneAmbulance Stroke Screen. Cerebrovasc Dis 2005; 20: 28–33.

11 Wojner-Alexandrov AW, Alexandrov AV, Rodriguez D, Persse D, Grotta JC.Houston paramedic and emergency stroke treatment and outcomes study(HoPSTO). Stroke 2005; 36: 1512–18.

Towards individualised multiple-sclerosis therapy