C Counsell

University of Aberdeen, Aberdeen, Scotland, United Kingdom

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Publications (107)844.28 Total impact

  • JAMA The Journal of the American Medical Association 09/2014; 312(10):1058-1059. · 29.98 Impact Factor
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    ABSTRACT: There have been few comparative studies of microsurgical excision vs conservative management of cerebral cavernous malformations (CCM) and none of them has reliably demonstrated a statistically and clinically significant difference.METHODS: We conducted a prospective, population-based study to identify and independently validate definite CCM diagnoses first made in 1999-2003 in Scottish adult residents. We used multiple sources of prospective follow-up to assess adults' dependence and to identify and independently validate outcome events. We used univariate and multivariable survival analyses to test the influence of CCM excision on outcome, adjusted for prognostic factors and baseline imbalances.RESULTS: Of 134 adults, 25 underwent CCM excision; these adults were younger (34 vs 43 years at diagnosis, p = 0.004) and more likely to present with symptomatic intracranial hemorrhage or focal neurologic deficit than adults managed conservatively (48% vs 26%; odds ratio 2.7, 95% confidence interval [CI] 1.1-6.5). During 5 years of follow-up, CCM excision was associated with a deterioration to an Oxford Handicap Scale score 2-6 sustained over at least 2 successive years (adjusted hazard ratio [HR] 2.2, 95% CI 1.1-4.3) and the occurrence of symptomatic intracranial hemorrhage or new focal neurologic deficit (adjusted HR 3.6, 95% CI 1.3-10.0).CONCLUSIONS: CCM excision was associated with worse outcomes over 5 years compared to conservative management. Long-term follow-up will determine whether this difference is sustained over patients' lifetimes. Meanwhile, a randomized controlled trial appears justified.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CCM excision worsens short-term disability scores and increases the risk of symptomatic intracranial hemorrhage and new focal neurologic deficits.
    Neurology 07/2014; · 8.30 Impact Factor
  • Angus D. Macleod, Kate S. M. Taylor, Carl E. Counsell
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    ABSTRACT: This study was undertaken to perform a systematic review and meta-analysis of studies of mortality in Parkinson's disease (PD) and to investigate which factors were associated with mortality. We conducted comprehensive searches of studies reporting a ratio of mortality in PD versus controls, descriptive survival measures, or factors predicting survival; assessed study quality; and extracted relevant data. Descriptive analysis, meta-analysis, and meta-regression were performed as appropriate. Eighty-eight studies were included in the review with variable study methods and quality. Almost all studies reported increased mortality in PD (vs. controls), with mortality ratios ranging from 0.9 to 3.8, with major between-study heterogeneity. Inception cohorts were more consistent with a pooled mortality ratio of approximately 1.5. Inception cohorts, measurements at longer follow-up duration, and older study recruitment year were associated with lower mortality ratios, but these findings were not robust in sensitivity analyses. Within studies, mortality ratios increased over time. No robust evidence was found that mortality has decreased after the introduction of levodopa (L-dopa). On average, PD survival reduced by approximately 5% every year of follow-up, although there was significant heterogeneity. In post-mortem studies, mean duration until death ranged from 6.9 to 14.3 years. Increasing age and presence of dementia were most commonly associated with increased mortality. Parkinson's disease is associated with increased mortality, but major heterogeneity is seen in estimates of mortality, which is probably explained by variable methodology and patient selection. Individual-patient-data meta-analysis of high-quality inception studies with long-term follow-up would be the optimal way to investigate the factors influencing mortality. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 05/2014; · 5.63 Impact Factor
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    ABSTRACT: Infection with Epstein-Barr virus (EBV) is almost ubiquitous in humans and generally occurs at two ages: infantile, which is usually asymptomatic and associated with poorer socioeconomic conditions, and adolescent, which causes infectious mononucleosis (IM) in ~25% cases. The determinants of whether the infection causes IM remain uncertain. We aimed to evaluate seasonality and temporal trends in IM. Data from all Monospot tests, used as a marker for IM, were collected from the Grampian population over 16 years. Positive Monospot test results peaked at 17 years in females and 19 in males. Females had 16% more diagnoses, although 55% more tests. IM was ~38% more common in winter than summer. The annual rate of positive tests decreased progressively over the study period, from 174 /100 000 (95% CI 171-178) in 1997 to 67/100 000 (95% CI 65-69) in 2012. IM appears to be decreasing in incidence, which may be caused by changing environmental influences on immune systems. One such factor may be exposure to sunlight.Words 168.Funding The Medical Research Council and NHS Grampian-MS endowments.
    BMC Infectious Diseases 03/2014; 14(1):151. · 3.03 Impact Factor
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    ABSTRACT: Introduction There have been few incidence studies of vascular parkinsonism (VP), progressive supranuclear palsy (PSP), and parkinsonian-type multiple system atrophy (MSA-P). We measured the age-, gender- and socioeconomic-specific incidence rates for these conditions in north-east Scotland. Methods Incident non drug-induced parkinsonian patients were identified prospectively over three years by several overlapping methods from a baseline primary care population of 311,357. Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using the diagnosis by established research criteria at latest follow-up were calculated for each condition by age, gender, and socioeconomic status. Results Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence was 3.2 per 100,000 (95% confidence interval (CI) 2.2-4.3) for VP, 1.7 per 100,000 (95% CI 1.0-2.4) for PSP, and 1.4 per 100,000 (95% CI 0.8-2.1) for MSA-P. VP and MSA-P were more common in men (age-adjusted male to female ratios 2.58 (95% CI 1.65-3.83) and 8.65 (95% CI 4.73-14.5) respectively). Incidence did not vary with socioeconomic status. Discussion This is the first community-based, prospective study to report the incidence of vascular parkinsonism and the third to report the incidence of PSP and MSA-P. Further follow-up and comparison with similar studies in different populations will yield valuable prognostic and aetiological information on these conditions.
    Parkinsonism & Related Disorders 01/2014; · 3.27 Impact Factor
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    ABSTRACT: To determine which clinical measures of disease progression in Parkinson's disease (PD) can feasibly be measured across the disease spectrum and which are most sensitive to change. Understanding the feasibility of measuring clinical outcomes and their sensitivity to change is crucial when choosing outcome measures for trials of putative neuroprotective drugs in PD. People with clinically defined PD were identified from an on-going long-term follow-up study of incident parkinsonian patients. Annual follow-up included a motor UPDRS, MMSE, Schwab and England, and a timed-walk. In cases of advanced consent a full UPDRS, timed hand-taps, MMP, PDQ-39, EuroQol-5Dindex, EQ-VAS and the Barthel index were also completed. Using data from consenting patients who completed each annual follow-up, percentage completion of collection for each measure over five years was examined. In a subset that completed three years of follow-up, linear mixed modelling was used to determine if clinical measures changed significantly over time. Sensitivity to change was assessed by grouping the measures (motor impairment, disability, quality of life, and cognition) and comparing the percentage change in each from baseline. Annual percentage completion of all measures (n=203 at baseline) was high (>80%) over five years. Change over time was examined in 176 patients who had completed three-years of follow-up. All measures, except the stigma (P=0.102) and social (P=0.177) subsections of the PDQ-39, demonstrated significant progression over three-years. The PDQ-39 summary index and its subsections were most sensitive to change (motor impairment, PDQ-39 mobility; disability, PDQ-39 ADL; quality of life, PDQ-39 summary index; cognition, PDQ-39 cognition). Collection of all examined clinical measures was feasible. The PDQ-39 summary index and subsections were most sensitive to change.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. · 4.87 Impact Factor
  • David McGhee, Carl Counsell
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    ABSTRACT: Undertake a systematic review to assess what potential surrogate markers for disease progression in Alzheimer's disease exist, whether any meet the criteria for use in clinical trials, and if not which looks most promising. Literature searches were conducted in MEDLINE (1950 to 2011) and Embase (1980 to 2011). Five separate search strategies were run in each database. The first four were based on free-text words identified through background reading of relevant review articles. These searches included potential(1) blood,(2) urine or cerebrospinal fluid (CSF),(3) imaging and(4) neurophysiological biomarkers. A fifth search using generic terms for biomarkers based on index headings was also run in both databases. The electronic searches were limited to human studies. Reference lists of included articles and relevant review articles were checked to identify any studies which the electronic search strategy may have missed. We included studies of participants with a diagnosis of probable Alzheimer's disease made by applying formal criteria. Studies which included participants with prodromal Alzheimer's disease or Mild Cognitive Impairment (MCI) were only included if conversion from MCI to Alzheimer's disease was confirmed in all participants by clinical follow-up. We made no restriction on participant's age, disease duration, or drug treatment. We only included studies with a longitudinal design, in which the putative biomarker and clinical measure were both measured at least twice, as this is the only appropriate design to use when developing a biomarker for disease progression. We included studies of any test used to investigate disease progression in Alzheimer's disease, including (but not restricted to) imaging, blood, CSF and neurophysiological tests. We looked for associations of the change in the test result over time with the change in any clinical measure of disease progression-impairment, global cognitive function, disability, handicap, and quality of life. Associations to individual symptoms, parts of scoring systems, mood, disease duration, complications related to therapy and treatment status were excluded. Only papers available in full and in English were included. We assessed study quality using criteria we developed after a recent similar systematic review in Parkinson's disease. Fifty-nine studies were finally included. The most commonly examined biomarker was brain MRI, which was examined in 17 (29%) of the included studies. The median follow-up time in the included longitudinal studies was only 1.0 years (IQR 0.8-1.7). Included studies were generally of poor quality with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and inappropriate statistical analyses. We found insufficient evidence to recommend the use of any biomarker for disease progression in Alzheimer's disease clinical trials at present. This finding may reflect the poor quality of most previous studies in this area. We, therefore, present a provisional roadmap for conducting future studies to develop biomarkers for disease progression in Alzheimer's disease.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. · 4.87 Impact Factor
  • Nicholas W Scott, Angus D Macleod, Carl E Counsell
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    ABSTRACT: Levodopa is the mainstay of treatment for Parkinson's disease (PD) but is associated with potentially-disabling drug-induced motor fluctuations and dyskinesias. Previous studies have suggested that both of these complications develop in about 40% patients treated with levodopa for 4-6 years 1. However, most of these studies were not in truly-representative PD cohorts and there is little evidence as to which factors influence the onset of these complications. We used data from an established, community-based, incident cohort of individuals with Parkinson's disease with ongoing, long-term follow-up. For this analysis we only included patients who have been treated with dopaminergic drugs. We gathered demographic and clinical data at baseline and each year (including asking patients about development of complications, taking detailed drug histories and determining UPDRS motor and complications of treatment scores). From drug histories we calculated the cumulative levodopa-equivalent dose (LED) at 3 years from diagnosis (mg levodopa-equivalent dose×number of days of treatment×10(-5); one unit is equivalent to nearly 100 mg levodopa a day for 3 years). We performed survival analysis with Kaplan-Meier curves and Cox proportional hazards modelling to assess which factors independently influence the development of motor complications. 195 incident PD patients (59.5% male, mean age at diagnosis 72.1 years) were included in the analysis. 135 patients (69%) started treatment with levodopa, 44 (23%) with a dopamine agonist (24 of whom subsequently received levodopa) and 16 (8%) with a monoamine oxidase B inhibitor (9 of whom subsequently received a dopamine agonist and 12 levodopa). Mean daily LED was 234mg (SD 125). 32 patients (16.4%) had developed motor fluctuations and 43 (22.1%) had developed dyskinesias (see Figure 1A and 1B) after a mean follow-up duration from diagnosis of 52 months (and mean treatment duration of 43 months). Only 11 patients (5.6%) developed dyskinesias which were problematic to the extent that treatment changes were warranted. Kaplan-Meier analysis showed that about 30% had motor fluctuations and about 40% had dyskinesias by 5 years of treatment with dopaminergic therapy. Factors independently associated with the development of motor fluctuations were age at diagnosis in years (Hazard ratio [HR] 0.96 [95% confidence interval 0.93-0.99], p=0.007) and cumulative LED (HR 1.53 [1.23-1.91], p<0.001). The development of dyskinesias was independently associated with female sex (HR 2.02 [1.09-3.75], p=0.02), motor UPDRS score at diagnosis (HR 1.03 [1.00-1.06], p=0.04) and cumulative levodopa-equivalent dose (HR 1.37 [1.10-1.07], p=0.004). Figure 1Kaplan-Meier estimates of the probability that PD patients on a dopaminergic therapy will be free from motor fluctuations (A) and dyskinesias (B). In a truly-representative PD cohort, after 5 years of treatment, about 30% develop motor fluctuations and about 40% develop dyskinesias, most of which were mild. Younger age and higher exposure to dopaminergic therapy are associated with motor fluctuations and female sex, higher parkinsonian impairment at diagnosis and higher cumulative LED are associated with dyskinesia onset.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. · 4.87 Impact Factor
  • Angus D Macleod, Carl E Counsell
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    ABSTRACT: Previous studies have demonstrated negative associations between cigarette smoking, alcohol consumption and caffeine intake and Parkinson's disease (PD), but most data come from unrepresentative cohorts (1). One previous study suggested different associations with these exposures in different PD phenotypes (2). There are no data describing change in these exposures after diagnosis: a differential change between cases and controls would introduce bias to prevalence-based case-control studies. We recruited a community-based, inception cohort of PD and matched controls and gathered data about previous duration and intensity of cigarette smoking and alcohol and caffeine intake with face-to-face questionnaires. We calculated odds ratios and adjusted odds ratios using logistic regression analysis to examine the associations between these exposures and PD and the tremor-dominant and postural instability and gait difficulty (PIGD) subtypes. We also assessed the change in exposures after recruitment in patients and controls with a linear mixed model. 201 patients with PD and 249 controls were analysed. Moderate and high cumulative levels of smoking, OR 0.42 (0.24-0.74) and 0.48 (0.28-0.82) respectively; high alcohol intake, OR 0.27 (0.13-0.56); and moderate and high caffeine consumption, ORs 0.48 (0.28-0.82) and 0.39 (0.22-0.68) respectively; were statistically significant negative associations with PD. There were statistically significant inverse trends between rising levels of consumption for each exposure and PD (P<0.001 for smoking, P=0.003 for alcohol and P<0.001 for caffeine). A similar pattern of associations with these exposures was seen in the PIGD and tremor-dominant patients as in the whole PD group. Smoking and alcohol consumption declined after diagnosis, but not at different rates between patients and controls. Our study therefore provides further evidence for dose-dependent negative associations between these exposures and PD in a truly-representative inception cohort. We found no evidence of different associations with the tremor-dominant and PIGD PD subtypes. The lack of a differential reduction in exposure is important for interpretation of prevalent studies.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. · 4.87 Impact Factor
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    ABSTRACT: Simple, robust and clinically meaningful outcome measures are required for neuroprotective trials in Parkinson's disease (PD). We explored the feasibility of using a new composite binary outcome measure of 'dead or dependent' in PD clinical trials, using data from an on-going prospective follow-up study of an incident cohort of patients with PD. Two hundred incident patients underwent annual follow-up, including assessment of the Hoehn and Yahr stage (H&Y) and Schwab and England activities of daily living scale (S&E). Annual scores were converted into binary variables (H&Y<3 versus H&Y≥3, and S&E≥80% versus S&E<80%). A new outcome of 'dead or dependent' versus 'alive and independent' was also created, with dependence in activities of daily living defined as a S&E<80%. Using these data, sample sizes were calculated for hypothetical three-year randomised control trials (RCTs) of neuroprotective agents in which the trial outcome was either defined by a binary clinical variable, all-cause mortality, or PD-related mortality. The largest sample sizes were required to use PD-related mortality (n=1808 in each study arm), and all-cause mortality (n=713) as the trial outcome. The new outcome of 'death or dependency' required the smallest sample size of all the outcome measures (n=261), including the other binary measures (H&Y≥3, n=565; S&E<80%, n=407). 'Death or dependency' is a feasible and potentially important new composite outcome measure for PD trials, including neuroprotective trials, although more work needs to be done to confirm this.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. · 4.87 Impact Factor
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    ABSTRACT: Introduction Cognitive decline is common in Parkinson's disease (PD) but may not be adequately identified by the mini-mental state examination (MMSE), which is better suited to Alzheimer's disease. The mini-mental Parkinson (MMP) examination is a cognitive screening tool designed in French specifically for PD. We aimed to establish the validity and reliability of the English language version of the MMP compared with the MMSE. Methods People with various stages of PD underwent testing with the MMP and MMSE, which was then compared with a reference standard battery of neuropsychological tests to identify those with significant cognitive impairment. Results Forty-nine patients were recruited. Both the MMP and MMSE were significantly correlated with scores on all the neuropsychological tests in the validation battery. The median MMP score was proportionally lower (80% of maximum) than the MMSE (90% of maximum) in PD patients with cognitive impairment and those with prior neuropsychiatric complications but there was no difference between the MMP and MMSE in areas under the curves (0.84) for detecting cognitive impairment. Test-retest reliability of the MMP was good (intra-class correlation coefficient 0.793). An MMP of 28 or lower out of 32 detected cognitive impairment with 87% sensitivity and 76% specificity. Discussion The English language version of the MMP has now been validated. It detects more cognitive deficits in PD patients than the MMSE and identifies significant cognitive impairment in those with PD at least as well as the MMSE.
    Current Aging Science 06/2013;
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    PLoS Medicine 06/2013; · 15.25 Impact Factor
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    ABSTRACT: BACKGROUND: Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist. METHODS: MEDLINE and EMBASE (1950--2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. RESULTS: 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality - cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. CONCLUSION: We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.
    BMC Neurology 04/2013; 13(1):35. · 2.56 Impact Factor
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    ABSTRACT: There have been few high quality incidence studies of Parkinson's disease (PD). We measured age-, gender- and socioeconomic-specific incidence rates for parkinsonism and PD in north-east Scotland, and compared our results with those of previous high quality studies. Incident patients were identified prospectively over three years by several overlapping methods from primary care practices (total population 311,357). Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Drug-induced parkinsonism was excluded. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using clinical diagnosis at latest follow-up were calculated for all parkinsonism and for PD by age, gender and socioeconomic status. Meta-analysis with similar studies was performed. Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence of parkinsonism was 28.7 per 100,000 (95% confidence interval (CI) 25.7-31.8) and PD 17.9 per 100,000 (95% CI 15.5-20.4). PD was more common in men (age-adjusted male to female ratio 1.87:1, 95% CI 1.55-2.23) but there was no difference by socioeconomic status. Meta-analysis of 12 studies showed an incidence of PD (adjusted to the 1990 Scottish population) of 14.6 per 100,000 (95% CI 12.2-17.3) with considerable heterogeneity (I2 95%), partially explained by population size and recruitment duration. The incidence of PD was similar to other high quality studies. The incidence of PD was not affected by socioeconomic status.
    Parkinsonism & Related Disorders 02/2013; · 3.27 Impact Factor
  • Clare Harris, Alice Kiger, Carl Counsell
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    ABSTRACT: AIM: To describe factors people consider important in deciding whether or not to donate their brain for research after death. BACKGROUND: Brain tissue retrieved at post-mortem is needed to further research into neurological conditions such as Parkinson's disease. Previous research has focussed mainly on attitudes to organ donation for transplantation. DESIGN: Data were gathered and analysed using a qualitative approach based on grounded theory. METHODS: Nineteen people who had made a decision about brain donation, five people with Parkinson's and 14 unaffected individuals, were identified through theoretical sampling. Interviews conducted between September 2007-January 2008 were analysed to identify themes representing the concerns of participants, when making a decision. FINDINGS: The three main themes identified were views and beliefs about post-mortem, the importance of family and the things people do not talk about. Although participants were more familiar with the concept of organ donation for transplantation, unanimous support was expressed for brain donation for research. However, beliefs about death and post-mortem, influence of family and the difficulty in talking and thinking about things to do with death all posed barriers to consent when actually asked to make a decision. For some, however, being asked had acted as a catalyst, transforming previously held positive attitudes into a decision to consent. CONCLUSION: Guidelines for asking developed from these findings highlight the importance of discussing the issue to raise awareness in potential donors, involving family members, and giving accurate and appropriate information to inform, reassure and to dispel misconceptions.
    Journal of Advanced Nursing 07/2012; · 1.53 Impact Factor
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    ABSTRACT: To compare the risk of epileptic seizures in adults during conservative management or following invasive treatment for a brain arteriovenous malformation (AVM). We used annual general practitioner follow-up, patient questionnaires, and medical records surveillance to quantify the 5-year risk of seizures and the chances of achieving 2-year seizure freedom for adults undergoing AVM treatment compared to adults managed conservatively in a prospective, population-based observational study of adults in Scotland, newly diagnosed with an AVM in 1999-2003. We identified 229 adults with a new diagnosis of an AVM, of whom two-thirds received AVM treatment (154/229; 67%) during 1,862 person-years of follow-up (median completeness of follow-up 97%). There was no significant difference in the proportions with a first or recurrent seizure over 5 years following AVM treatment, compared to the first 5 years following clinical presentation in conservatively managed adults, in analyses stratified by mode of presentation (intracerebral hemorrhage, 35% vs 26%, p = 0.5; seizure, 67% vs 72%, p = 0.6; incidental, 21% vs 10%, p = 0.4). For patients with epilepsy, the chances of achieving 2-year seizure freedom during 5-year follow-up were similar following AVM treatment (n = 39; 52%, 95% confidence interval [CI] 36% to 68%) or conservative management (n = 21; 57%, 95% CI 35% to 79%; p = 0.7). In this observational study, there was no difference in the 5-year risk of seizures with AVM treatment or conservative management, irrespective of whether the AVM had presented with hemorrhage or epileptic seizures.
    Neurology 07/2012; 79(6):500-7. · 8.30 Impact Factor
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    ABSTRACT: A marked response to dopamine replacement therapy is important in supporting a diagnosis of idiopathic Parkinson's disease (PD). The aim of the study was to compare PD patients' subjective rating of improvement with measured improvement on a number of scales. People with clinically defined PD were identified from a prospective long term follow-up study of incident parkinsonian patients. Changes in the Unified Parkinson's Disease Rating Scale (UPDRS) (activities of daily living and motor subsections), timed tests and Parkinson's Disease Questionnaire, full version, between assessments immediately before starting adequate dopamine replacement and the two subsequent follow-up assessments (mean 6 and 12 months after baseline) were calculated. These were compared with the patients' own subjective ratings of improvement (nil, slight, moderate, good, excellent). 133 patients were included (mean age 71 years, 56% men). Thirty-eight patients were treated with a dopamine agonist and 95 with l-dopa (median l-dopa equivalent dose 300 mg). Most patients showed improvements in their measured scores but there was no statistically significant association between these scores and the patient subjective response, except for the motor UPDRS at the first follow-up. A third of those who showed no improvement in their motor UPDRS at the first follow-up rated their improvement as moderate or better, while 29% of those whose motor UPDRS improved by over 50% said they had no or slight improvement. PD patients' subjective ratings of their degree of improvement often do not accurately reflect the degree of objective change in parkinsonian impairment or disability. Clinicians should record a simple measure of motor impairment before and after treatment to assess treatment response more accurately.
    Journal of neurology, neurosurgery, and psychiatry 05/2012; 83(10):1001-5. · 4.87 Impact Factor
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    ABSTRACT: 30 years ago very high multiple sclerosis (MS) prevalence rates were recorded in northern Scotland. A prevalence study was repeated in Aberdeen, Orkney and Shetland to see if prevalence rates had changed, assess which factors affect prevalence and record disability status. Hospital, general practice and laboratory records were searched to identify prevalent MS patients (alive and registered with a participating general practice on 24 September 2009). Records were reviewed to confirm diagnoses applying Poser definite and probable and McDonald diagnostic criteria. Disability status (Expanded Disability Status Scale) was recorded from records and questionnaires. Rates were standardised to the Scottish population. 590 patients were found (Aberdeen 442, Orkney 82, Shetland 66). Mean age and disease duration were 53 and 19.4 years, respectively. The standardised prevalence rates for Poser probable/definite MS per 100, 000 were: combined area 248 (95% CI 229 to 269), Orkney 402 (95% CI 319 to 500), Shetland 295 (95% CI 229 to 375) and Aberdeen 229 (95% CI 208 to 250). McDonald diagnostic criteria gave a lower prevalence (202, 95% CI 198 to 206). Prevalence was highest in women (2.55:1, 95% CI 2.26 to 2.89) with about 1 in 170 women in Orkney affected. Prevalence was lowest in the most deprived socioeconomic group. 45% had significant disability (Expanded Disability Status Scale ≥6). The prevalence of MS has increased in the overall area, most markedly in Orkney, then Shetland, over the past 30 years. This increase could be due to a number of factors, but rising incidence as reflected by a rising sex ratio, influenced by gene-environment interaction, is the most likely. Orkney has the highest prevalence rate recorded worldwide.
    Journal of neurology, neurosurgery, and psychiatry 05/2012; 83(7):719-24. · 4.87 Impact Factor
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    ABSTRACT: models to predict functional status post-stroke have utility in balancing groups in randomised trials, for outcome comparison between stroke centres and may assist in outcome prediction. This study aimed to develop models of both excellent [modified Rankin score (mRS) 0-1] and devastating outcomes (mRS of 5-6). patients admitted with ischaemic or haemorrhagic stroke in 2001-02 to the Halifax Infirmary, Canada, were enrolled. Sixteen clinical variables from the first neurological assessment and six radiological variables from the acute CT scan were used to the model outcome at 6 months. five hundred and thirty-eight stroke patients were enrolled. Thirty per cent had an excellent outcome and 30% had a devastating outcome. Three models of the excellent outcome were developed [area under the receiver operator curve (AUC) 0.866-882] including the variables age, pre-stroke functional status, stroke severity, ability to lift both arms, walk independently, normal verbal Glasgow Coma Scale and leukoaraiosis. Predictive models of the devastating outcome (AUC of 0.859-0.874) included additional variables living alone pre-stroke and total anterior circulation stroke. The simplest models of both outcomes were externally validated (AUC of 0.856-0.885). this study demonstrates new externally validated predictive models of both excellent and devastating outcomes. Leukoaraiosis was the only independent radiological predictor of both outcomes. Living alone pre-stroke predicted devastating outcome post-stroke.
    Age and Ageing 03/2012; 41(4):560-4. · 3.82 Impact Factor
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    ABSTRACT: Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location. We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM. 139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0-5·7 vs 29·5%, 4·1-55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1-15·4 vs 42·4%, 26·8-58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1-33·4) in year 1 to 5·0% (0·0-14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17). The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.
    The Lancet Neurology 03/2012; 11(3):217-24. · 23.92 Impact Factor

Publication Stats

2k Citations
844.28 Total Impact Points

Institutions

  • 2001–2014
    • University of Aberdeen
      • Division of Applied Health Sciences
      Aberdeen, Scotland, United Kingdom
  • 1996–2009
    • The University of Edinburgh
      • Division of Clinical Neurosciences
      Edinburgh, SCT, United Kingdom
    • Hospital Universitario La Paz
      • Servicio de Neurología
      Madrid, Madrid, Spain
  • 2008
    • University Hospital Crosshouse
      Cill Mheàrnag, Scotland, United Kingdom
  • 1994–2002
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom
  • 1999
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      • Department of Neurology
      Newcastle-on-Tyne, England, United Kingdom