Reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is an underdiagnosed condition which usually presents as severe headache with or without neurological deficit. We report the case of a 55-year-old woman who presented with headache and multifocal intracerebral haemorrhage. We review the literature regarding the presentation, pathophysiology and management of RCVS and discuss how to differentiate it from cerebral vasculitis.

Influences on parental evaluation of the content of early intervention following early identification of deafness: a study about parents' preferences and satisfaction.

BACKGROUND: Following early identification of deafness attention has now turned to early intervention of deaf children and their families. Improved outcomes associated with early identification and quality early intervention have been long predicated. However, the effectiveness of early intervention is mediated by parents' values, beliefs and preferences. How these mediate the nature of intervention is key to understand how early intervention impacts on outcomes. METHODS: Eighty-two parents of early identified deaf children participated in a longitudinal study (UK). Data from parents were collected through postal questionnaires. Parents provided repeated data on My Views on Services questionnaire (at 6-month interval). They also filled in once the Trait Emotional Intelligence questionnaire and a socio-demographic questionnaire. Statistical analyses were carried out to investigate parents' preferences and satisfaction with content of early intervention. RESULTS: Families had contact with a median of five professionals and 45 h of early intervention (on a 6-month basis). Parents view all content of early intervention as important. Content that supported parents to support their child was a priority for them. Length of involvement in early intervention and mothers' personal disposition did not have an effect on ratings of importance. However, mothers' educational background did influence ratings on the Supporting Parents subscale (F= 3.41; d.f. = 3 and 66; P= 0.023). Parents' satisfaction scores with content of early intervention were neutral (mean: 0.2; SD 0.8). Parents were more satisfied with contents that supported them to support their deaf child, than with those aimed to support themselves. Parents' satisfaction with content that supported themselves did increase with length of involvement in early intervention (t=-3.435; P= 0.004). Significant correlations (r= 0.221; r= 0.230; r= 0.252) between mothers' well-being and satisfaction scores were identified. CONCLUSION: These findings underscore the importance of understanding how parents' beliefs, values and perceived need impact on their experience of early intervention.

The role of endothelial dysfunction in the pathogenesis of neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric manifestations of systemic lupus erythematosus are common and disabling yet their pathogenesis is poorly understood. We investigated the role of cerebrovascular endothelial dysfunction in systemic lupus erythematosus and its neuropsychiatric manifestations. Subjects with systemic lupus erythematosus were recruited prospectively along with matched healthy control subjects. The presence of neuropsychiatric systemic lupus erythematosus syndromes was ascertained according to standard definitions. Cerebrovascular reactivity, an indicator of endothelial function, was measured using transcranial Doppler ultrasound. Sixty-one subjects (58 female, 3 male) with systemic lupus erythematosus and 70 control subjects were assessed. Sixty patients (98%) reported at least one neuropsychiatric manifestation, the most prevalent being headache and cognitive dysfunction. There was no significant difference in cerebrovascular reactivity between cases and controls (3.06 vs 3.06, p=0.99). Subjects with systemic lupus erythematosus and a history of stroke and/or transient ischaemic attack had significantly higher cerebrovascular reactivity than those without (3.99 vs 2.79, p = 0.007). No association was found between the presence of other neuropsychiatric syndromes or systemic lupus erythematosus-related variables and altered cerebrovascular reactivity. In conclusion, cerebrovascular endothelial dysfunction is not present in the majority of subjects with systemic lupus erythematosus. However, the role of endothelial dysfunction in the pathogenesis of stroke and transient ischaemic attack in systemic lupus erythematosus merits further investigation. Lupus (2010) 19, 797-802.

The ACR classification criteria for headache disorders in SLE fail to classify certain prevalent headache types.

Headache is a common symptom described by patients with systemic lupus erythematosus (SLE). It is uncertain whether both the prevalence and phenotype of headache disorders seen in patients with SLE are similar to those in the general population. The current American College of Rheumatology (ACR) classification of headache disorders includes only five categories, included 'Intractable headache, non-specific', which is not further defined. The International Headache Society (IHS) has produced a classification which aims to include all recognized headache disorders. We compared the performance of the IHS and ACR criteria in 61 subjects with SLE. Whereas reference to the IHS criteria enabled classification of all headache disorders seen in the cohort, use of the ACR criteria resulted in failure to classify 22% of headache disorders. We suggest that the ACR criteria require revision. Until this is done, IHS criteria should be used in all future studies of headache in SLE.

United Kingdom school-entry hearing screening: current practice.

OBJECTIVE: To determine if the school-entry hearing screening (SEHS) programme continues to make a useful contribution to the identification of childhood hearing impairment in the light of the recent implementation of universal newborn hearing screening, and thereby to inform future policy development. DESIGN: Postal questionnaire survey to determine current implementation and effectiveness of SEHS SETTING: 244 school health services managed within primary care and acute trusts throughout the UK. PARTICIPANTS: 229 SEHS service leads approached; 195 responded. MAIN OUTCOME MEASURE: Details of implementation; positive predictive value of the screening test and its referral criteria. RESULTS: Implementation of the SEHS is variable, and there is no national approach to data collection, audit and quality assurance. Less than 10% of services had available robust data. The yield from screening ranges from 0.05% to 0.59% for permanent sensorineural hearing impairment and from 0.07% to 0.44% for permanent conductive hearing impairment. The positive predictive values from screen referral vary from 0.62% to 12.16% for permanent sensorineural hearing impairment and 1.24% to 17.56% for permanent conductive hearing impairment. CONCLUSION: This comprehensive survey provides a previously unavailable national examination of the SEHS. The few available data on yield indicate that the SEHS may have a small but important role to play in identification of childhood hearing impairment, but the overwhelming conclusion is the urgent need for national guidelines on implementation of this screening programme to determine its value since the implementation nationally of universal newborn hearing screening.

Current practice, accuracy, effectiveness and cost-effectiveness of the school entry hearing screen.

OBJECTIVES: To describe and analyse in detail current practice of school entry hearing screening (SES) in the UK. DATA SOURCES: Main electronic databases were searched up to May 2005. REVIEW METHODS: A national postal questionnaire survey was addressed to all leads for SES in the UK, considering current practice in terms of implementation, protocols, target population and performance data. Primary data from cohort studies in one area of London were examined. A systematic review of alternative SES tests, test performance and impact on outcomes was carried out. Finally, a review of published studies on costs, plus economic modelling of current and alternative programmes was prepared. RESULTS: The survey suggested that SES is used in most of England, Wales and Scotland; just over 10% of respondents have abandoned the screen; others are awaiting national guidance. Coverage of SES is variable, but is often over 90% for children in state schools. Referral rates are variable, with a median of about 8%. The test used for the screen is the pure tone sweep test but with wide variation in implementation, with differing frequencies, pass criteria and retest protocols; written examples of protocols were often poor and ambiguous. There is no national approach to data collection, audit and quality assurance, and there are variable approaches at local level. The screen is performed in less than ideal test conditions and resources are often limited, which has an impact on the quality of the screen. The primary cohort studies show that the prevalence of permanent childhood hearing loss continues to increase through infancy. Of the 3.47 in 1000 children with a permanent hearing loss at school screen age, 1.89 in 1000 required identification after the newborn screen. Newborn hearing screening is likely to reduce significantly the yield of SES for permanent bilateral and unilateral hearing impairments; yield had fallen from about 1.11 in 1000 before newborn screening to about 0.34 in 1000 for cohorts that had had newborn screening, of which only 0.07 in 1000 were unilateral impairments. Just under 20% of permanent moderate or greater bilateral, mild bilateral and unilateral impairments, known to services as 6-year-olds or older, remained to be identified around the time of school entry. No good-quality published comparative trials of alternative screens or tests for SES were identified and studies concerned with the relative accuracy of alternative tests are difficult to compare and often flawed by differing referral criteria and case definitions; with full pure tone audiometry as the reference test, the pure tone sweep test appears to have high sensitivity and high specificity for minimal, mild and greater hearing impairments, better than alternative tests for which evidence was identified. There is insufficient evidence regarding possible harm of the screen. There were no published studies identified that examined the possible effects of SES on longer term outcomes. No good-quality published economic evaluations of SES were identified and a universal SES based on pure tone sweep tests was associated with higher costs and slightly higher quality-adjusted life-years (QALYs) compared with no screen and other screen alternatives; the incremental cost-effectiveness ratio for such a screen is around 2500 pounds per QALY gained; the range of expected costs, QALYs and net benefits was broad, indicating a considerable degree of uncertainty. Targeted screening could be more cost-effective than universal school entry screening; however, the lack of primary data and the wide limits for variables in the modelling mean that any conclusions must be considered indicative and exploratory only. A national screening programme for permanent hearing impairment at school entry meets all but three of the criteria for a screening programme, but at least six criteria are not met for screening for temporary hearing impairment. CONCLUSIONS: The lack of good-quality evidence in this area remains a serious problem. Services should improve quality and audit screen performance for identification of previously unknown permanent hearing impairment, pending evidence-based policy decisions based on the research recommendations. Further research is needed into a number of important areas including the evaluation of an agreed national protocol for services delivering SES to make future studies and audits of screen performance more directly comparable.

Variable phenotype including Leigh syndrome with a 9185T>C mutation in the MTATP6 gene.

We describe 15 members of a Caucasian family with an apparently homoplasmic T-->C mutation at nucleotide position 9185 (9185T>C) in the mtDNA encoded MTATP6 (ATPase 6) gene. The clinical phenotype is extremely variable and includes late-onset Leigh syndrome (LS), isolated demyelinating peripheral neuropathy and neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP). Following recent reports of this same mutation in a single case and in a family with late-onset LS and NARP-like features, our paper emphasises the role of MTATP6 in LS and expands the associated clinical phenotype further.

Accurate, practical and cost-effective assessment of carotid stenosis in the UK.

OBJECTIVES: To determine whether less invasive imaging tests [ultrasound (US), magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and contrast-enhanced MRA (CEMRA)], alone or combined, could replace intra-arterial angiography (IAA), what effect this would have on strokes and deaths, endarterectomies performed and costs, and whether less invasive tests were cost-effective. DATA SOURCES: Electronic databases covering the years 1980-2003 inclusive, updated to April 2004. Key journals from 1990 to the end of 2002. REVIEW METHODS: The authors constituted a panel of experts in stroke, imaging, vascular surgery, statistics and health economic modelling. The accuracy of less invasive carotid imaging was systematically reviewed using Standards for Reporting of Diagnostic Accuracy (STARD) methodology, supplemented by individual patient data from UK primary research and audit studies. A systematic review of the costs of less invasive tests, outpatient clinics, endarterectomy and stroke was performed, along with a microcosting exercise. A model of the process of care following a transient ischaemic attack (TIA)/minor stroke was developed, populated with data from stroke epidemiology studies in the UK, effects of medical and surgical interventions, outcomes, quality of life and costs. A survey of UK stroke prevention clinics provided typical timings. Twenty-two different carotid imaging strategies were evaluated for short- and long-term outcomes, quality-adjusted life-years (QALYs) and net benefit. RESULTS: In 41 included studies (2404 patients, median age 60-65 years), most data were available on 70-99% stenosis. CEMRA was the most accurate [sensitivity 0.94, 95% confidence interval (CI) 0.88 to 0.97; specificity 0.93, 95% CI 0.89 to 0.96], compared with US, MRA and CTA, which were all similar (e.g. for US: sensitivity 0.89, 95% CI 0.85 to 0.92; specificity 0.84, 95% CI 0.77 to 0.89). Data for 50-69% stenoses and on combinations of tests were too sparse to be reliable. There was heterogeneity between studies for all imaging modalities except for CTA. The individual patient data (2416 patients) showed that the literature overestimated test accuracy in routine practice and that, in general, tests perform with higher sensitivity and specificity in asymptomatic than in symptomatic arteries. In the cost-effectiveness model, on current UK timings, strategies allowed more patients to reach endarterectomy very quickly, and where those with 50-69% stenosis would be offered surgery in addition to those with 70-99%, prevented most strokes and produced greatest net benefit. This included most strategies with US as first or repeat test, and not those with IAA. However, the model was sensitive to less invasive test accuracy, cost and timing of endarterectomy. In patients investigated late after TIA, test accuracy is crucial and CEMRA should be used before surgery. CONCLUSIONS: In the UK, less invasive tests can be used in place of IAA if radiologists trained in carotid imaging are available. Imaging should be carefully audited. Stroke prevention clinics should reduce waiting times at all stages to improve speed of access to endarterectomy. In patients presenting late after TIA, test accuracy is very important and US results should be confirmed by CEMRA, as patients with 50-69% stenosis are less likely to benefit. More data are required to define the accuracy of the less invasive tests, with improvements made in the data collection methods used and how data are presented. Consideration should also be given to the use of new technologies and randomised trials.

An analysis of the costs of implementing the National Newborn Hearing Screening Programme in England.

OBJECTIVE: The primary aim of this analysis was to prospectively assess the full economic costs associated with implementing Newborn Hearing Screening Programme (NHSP) based on a two-stage screen, transient evoked otoacoustic emissions followed, if there is no clear response, by automated auditory brainstem response. Economic data were also collected from the Infant Distraction Test Screening (IDTS) service performed by health visitors at around eight months of age, which was being phased out. A comparison of costs and outcomes associated with NHSP and IDTS was conducted. DESIGN: 20 NHSP sites were invited to provide detailed cost data on NHSP implementation and 14 of these sites were selected to provide costs on the IDTS service that was being supplanted. RESULTS: There was marked variability in the costs. Given the higher yield of NHSP sites, the average cost per case detected across NHSP sites (31,410 pounds/case) was approximately half that of IDTS sites (69,919 pounds/case). Including family costs, the average total cost per case of NHSP (34,826 pounds/case) was almost a quarter of IDTS (117,942 pounds/case). CONCLUSIONS: Family costs and cost per case associated with NHSP are considerably less than that with IDTS. These findings support the policy of implementation of NHSP and the phasing out of the IDTS.

Intraspinal microstimulation preferentially recruits fatigue-resistant muscle fibres and generates gradual force in rat.

Intraspinal microstimulation (ISMS), a novel rehabilitative therapy consisting of stimulation through fine, hair-like microwires targeted at the ventral spinal cord, has been proposed for restoring standing and walking following spinal cord injury. This study compared muscle recruitment characteristics of ISMS with those produced by peripheral nerve cuff stimulation (NCS). Thirty-three minutes of either ISMS or NCS at 1, 20 or 50 s(-1) and 1.2 x threshold (T) amplitude depleted glycogen from muscle fibres of vastus lateralis and rectus femoris. ISMS and NCS were also carried out at 20 s(-1) and 3.0T. Muscle serial sections were stained for glycogen and for myosin heavy chain (MHC)-based fibre types using a panel of monoclonal antibodies. The results of this study show that ISMS recruited fatigue-resistant (FR) fibres at 2.9, 1.9, 1.7 and 2.5 times their relative MHC content at 1, 20 and 50 s(-1) 1.2T and 20 s(-1) 3.0T, respectively. In contrast, NCS recruited FR fibres at 1.2, 1.0, 2.1 and 0.0 times their MHC content at 1, 20 and 50 s(-1) 1.2T and 20 s(-1) 3.0T, respectively. The proportion of FR fibres recruited by ISMS and NCS was significantly different in the 20 s(-1) 3.0T condition (P < 0.0001). We also report that force recruitment curves were 4.9-fold less steep (P < 0.019) for ISMS than NCS. The findings of this study provide evidence for the efficacy of ISMS and further our understanding of muscle recruitment properties of this novel rehabilitative therapy.

Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study).

BACKGROUND: The incidence of stroke is predicted to rise because of the rapidly ageing population. However, over the past two decades, findings of randomised trials have identified several interventions that are effective in prevention of stroke. Reliable data on time-trends in stroke incidence, major risk factors, and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence. We aimed to obtain these data. METHODS: We ascertained changes in incidence of transient ischaemic attack and stroke, risk factors, and premorbid use of preventive treatments from 1981-84 (Oxford Community Stroke Project; OCSP) to 2002-04 (Oxford Vascular Study; OXVASC). FINDINGS: Of 476 patients with transient ischaemic attacks or strokes in OXVASC, 262 strokes and 93 transient ischaemic attacks were incident events. Despite more complete case-ascertainment than in OCSP, age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29% (relative incidence 0.71, 95% CI 0.61-0.83, p=0.0002). Incidence declined by more than 50% for primary intracerebral haemorrhage (0.47, 0.27-0.83, p=0.01) but was unchanged for subarachnoid haemorrhage (0.83, 0.44-1.57, p=0.57). Thus, although 28% more incident strokes (366 vs 286) were expected in OXVASC due to demographic change alone (33% increase in those aged 75 or older), the observed number fell (262 vs 286). Major reductions were recorded in mortality rates for incident stroke (0.63, 0.44-0.90, p=0.02) and in incidence of disabling or fatal stroke (0.60, 0.50-0.73, p<0.0001), but no change was seen in case-fatality due to incident stroke (17.2% vs 17.8%; age and sex adjusted relative risk 0.85, 95% CI 0.57-1.28, p=0.45). Comparison of premorbid risk factors revealed substantial reductions in the proportion of smokers, mean total cholesterol, and mean systolic and diastolic blood pressures and major increases in premorbid treatment with antiplatelet, lipid-lowering, and blood pressure lowering drugs (all p<0.0001). INTERPRETATION: The age-specific incidence of major stroke in Oxfordshire has fallen by 40% over the past 20 years in association with increased use of preventive treatments and major reductions in premorbid risk factors.

Effect of upper airway obstruction in acute stroke on functional outcome at 6 months.

BACKGROUND: The aim of this study was to determine whether upper airway obstruction occurring within the first 24 hours of stroke onset has an effect on outcome following stroke at 6 months. Traditional definitions used for obstructive sleep apnoea (OSA) are arbitrary and may not apply in the acute stroke setting, so a further aim of the study was to redefine respiratory events and to assess their impact on outcome. METHODS: 120 patients with acute stroke underwent a sleep study within 24 hours of onset to determine the severity of upper airway obstruction (respiratory disturbance index, RDI-total study). Stroke severity (Scandinavian Stroke Scale, SSS) and disability (Barthel score) were also recorded. Each patient was subsequently followed up at 6 months to determine morbidity and mortality. RESULTS: Death was independently associated with SSS (OR (95% CI) 0.92 (0.88 to 0.95), p<0.00001) and RDI-total study (OR (95% CI) 1.07 (1.03 to 1.12), p<0.01). The Barthel index was independently predicted by SSS (p = 0.0001; r = 0.259; 95% CI 0.191 to 0.327) and minimum oxygen saturation during the night (p = 0.037; r = 0.16; 95% CI 0.006 to 0.184). The mean length of the respiratory event most significantly associated with death at 6 months was 15 seconds (sensitivity 0.625, specificity 0.525) using ROC curve analysis. CONCLUSION: The severity of upper airway obstruction appears to be associated with a worse functional outcome following stroke, increasing the likelihood of death and dependency. Longer respiratory events appear to have a greater effect. These data suggest that long term outcome might be improved by reducing upper airway obstruction in acute stroke.

Endothelial nitric oxide gene haplotypes and risk of cerebral small-vessel disease.

BACKGROUND AND PURPOSE: Genetic influences are important in multifactorial cerebral small-vessel disease (SVD) and may act via endothelial dysfunction. Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) is a key mediator of endothelial function. We determined the role of 3 potentially functional eNOS polymorphisms (T-786C, intron 4ab, G894T) located toward the 5' flanking end of the gene as risk factors for SVD and different SVD subtypes: isolated lacunar infarction (n=137) and ischemic leukoaraiosis (n=160). METHODS: Three hundred patients with SVD and 600 community controls were studied. Genotypes were determined through polymerase chain reaction with or without restriction fragment digestion. Nitrate (NO(x)) levels were determined in a subgroup by use of a Griess method. Polymorphisms were tested individually and in combination with haplotype analysis. RESULTS: The intron 4a variant was protective against SVD. This effect was confined to isolated lacunar infarction (odds ratio, 0.55; 95% confidence interval, 0.35 to 0.86; P=0.01). Haplotypes encountered were significantly different in this subtype compared with controls (P=0.001), with the -786C promoter/intron 4a combination particularly underrepresented. NO(x) levels were associated with the T-786C locus (P=0.03) but only in the presence of the intron 4a allele (P=0.07 for interaction). CONCLUSIONS: The intron 4ab insertion/deletion genotype was associated with isolated lacunar infarction. Haplotype and functional studies suggested that the protective effect of the 4a variant could be mediated through changes in eNOS promoter activity and increased NO levels. The specific association with isolated symptomatic lacunar infarction and not ischemic leukoaraiosis may reflect different etiopathogeneses of the 2 subtypes. Lack of NO could predispose to localized microatheroma in proximal arterioles rather than diffuse arteriosclerosis affecting distal perforating vessels.

Minimal response levels for visual reinforcement audiometry in infants.

The aim of this study was to determine normative values for minimal response levels (MRLs) for normal-hearing young infants using insert earphone visual reinforcement audiometry (VRA). The subjects were 46 normally developing infants aged between 33 and 50 weeks who had hearing sensitivity assumed to be within normal limits and no evidence of middle ear dysfunction. VRA was carried out using insert earphones with warble tone stimuli, generated from an AC33 audiometer and calibrated to ISO 389-2 for insert earphones in adults. The frequencies assessed were 500 Hz, 1 kHz, 2 kHz and 4 kHz. In total, 102 MRLs were obtained, with an approximately equal number of MRLs per frequency. Mean MRLs for 500 Hz, 1 kHz, 2 kHz and 4kHz were 16 dB HL, 13 dB HL, 7 dB HL and 6 dB HL, respectively. Standard deviations were close to 6 dB for all frequencies. Mean MRLs at the lower frequencies were significantly greater than MRLs at the two higher frequencies. MRLs did not vary significantly with age. The results obtained from this study suggest significant infant adult differences when testing hearing using VRA with insert earphones, particularly at lower frequencies. Possible reasons for this and the clinical use of these normative values are discussed.

Very early risk of stroke after a first transient ischemic attack.

BACKGROUND AND PURPOSE: The commonly quoted early risks of stroke after a first transient ischemic attack (TIA)-1% to 2% at 7 days and 2% to 4% at 1 month-are likely to be underestimates because of the delay before inclusion into previous studies and the exclusion of patients who had a stroke during this time. Therefore, it is uncertain how urgently TIA patients should be assessed. We used data from the Oxford Community Stroke Project (OCSP) to estimate the very early stroke risk after a TIA and investigated the potential effects of the delays before specialist assessment. METHODS: All OCSP patients who had a first-ever definite TIA during the study period (n=209) were included. Three analyses were used to estimate the early stroke risk after a first TIA starting from 3 different dates: assessment by a neurologist, referral to the TIA service, and onset of first TIA. RESULTS: The stroke risk from assessment by a neurologist was 1.9% [95% confidence interval (CI), 0.1 to 3.8] at 7 days and 4.4% (95% CI, 1.6 to 7.2) at 30 days. The 7- and 30-day stroke risks from referral were 2.4% (95% CI, 0.3 to 4.5) and 4.9% (95% CI, 1.9 to 7.8), respectively, and from onset of first-ever TIA were 8.6% (95% CI, 4.8 to 12.4) and 12.0% (95% CI, 7.6 to 16.4), respectively. CONCLUSIONS: The early risk of stroke from date of first-ever TIA is likely to be higher than commonly quoted. Public education about the symptoms of TIA is needed so that medical attention is sought more urgently and stroke prevention strategies are implemented sooner.

Crystallization of the membrane-containing bacteriophage PRD1 in quartz capillaries by vapour diffusion.

Crystals of bacteriophage PRD1, a virus containing an internal lipid bilayer, have been grown in thin-walled quartz capillary tubes by vapour diffusion as a means of eliminating mechanical handling of the crystals during data collection. It has been found that the addition of polyethylene glycol 20 000 (PEG 20K) to the mother liquor that bathes the crystals allows far higher resolution diffraction intensities to be observed. Growing and treating the crystals in this way has produced a small number of crystals which are particularly amenable to X-ray diffraction analysis.

Effects of incremental levels of continuous positive airway pressure on cerebral blood flow velocity in healthy adult humans.

Sleep disordered breathing is common in patients with cerebrovascular disease, and could exacerbate the cerebral damage in acute stroke. Data about the effects of continuous positive airway pressure (CPAP) upon cerebral perfusion are conflicting. We investigated whether increasing levels of CPAP may affect cerebral haemodynamics, assessed by transcranial Doppler (TCD) in normal humans. A group of 25 healthy young volunteers were evaluated before (CPAP0-pre), during (CPAP5, CPAP10 and CPAP15, denoting CPAP at 5, 10 and 15 cmH(2)O respectively) and after (CPAP0-post) application of incremental levels of CPAP delivered through a mouthpiece. The mean cerebral blood flow velocity (CBFV) and the pulsatility index (PI; an indirect measure of cerebrovascular resistance) in the middle cerebral artery were measured with TCD. Respiratory rate, heart rate, end-tidal carbon dioxide pressure (PETCO(2)), transcutaneous haemoglobin oxygen saturation (SpO(2)), mean arterial blood pressure and anxiety score were also recorded. Compared with CPAP0-pre, CBFV was significantly decreased as higher levels of CPAP were applied (P <0.0001). CPAP15 increased PI (P <0.05), ETCO(2) was reduced by CPAP10 and CPAP15 (P <0.0001), and anxiety score and SpO(2) increased at all levels of CPAP (P <0.05). Heart rate, respiratory rate and mean arterial pressure did not change. The decrease in CBFV was correlated with the fall in P ETCO(2) (CPAP15) and the increase in PI (CPAP10, CPAP15) (P <0.05). In conclusion, even low levels of CPAP delivered through a mouthpiece in awake, young volunteers led to a decrease in CBFV, measured by TCD. This fall in CBFV was associated with hypocapnia and with an increase in both cerebrovascular resistance and anxiety due to breathing against positive pressure. As the negative consequences of a fall in CBFV may outweigh the therapeutic effects of CPAP in the post-stroke setting, further studies of the cerebrovascular effects of CPAP with different interfaces in elderly patients with and without stroke are needed before intervention trials can be performed safely.