-
[show abstract]
[hide abstract]
ABSTRACT: Neuromyeltis optica (NMO) is a neuroinflammatory disorder considered rare in Caucasian populations. However, accurate population-based epidemiological data for NMO and NMO spectrum disorder (NMO-SD) from Western populations employing validated diagnostic criteria remain limited. We sought therefore to estimate the prevalence and clinical features of NMO in a north European Caucasian population in South East Wales.
Patients were identified by a comprehensive, multistage ascertainment strategy employing a regional neuroinflammatory disease register, hospital diagnostic databases personal physician referrals and regional requests for anti-aquaporin-4 antibodies (anti-AQP4).
Fourteen Caucasian patients (11 patients with NMO and three with NMO-SD) were identified in a population of 712,572 (19.6/million; 95% CIs: 12.2-29.7). There was an excess of females (female:male 12:2), 11/14 were anti-AQP4 positive and 5/14 had disease onset under the age of 20 years.
This study suggests that NMO and related spectrum disorders are at least as frequent in Northern European populations as in non-Caucasian populations and that the demographic profile of prevalent patients differs from clinic-based cohorts.
European Journal of Neurology 10/2011; 19(4):655-9. · 3.69 Impact Factor
-
M Cossburn,
A A Pace,
J Jones,
R Ali,
G Ingram,
K Baker,
C Hirst,
J Zajicek,
N Scolding,
M Boggild, T Pickersgill,
Y Ben-Shlomo,
A Coles,
N P Robertson
[show abstract]
[hide abstract]
ABSTRACT: To define the rate, timing, and clinical risk factors for the development of autoimmune disease (AID) after alemtuzumab treatment for multiple sclerosis (MS).
We analyzed prospective clinical and serologic data from 248 patients with MS treated with alemtuzumab, with median follow-up of 34.3 months (range 6.7-107.3).
Novel AID developed in 22.2%. Thyroid AID was most frequent (15.7%). A range of hematologic, renal, and dermatologic AID were also observed as was asymptomatic development of novel autoantibodies. AID was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. No new cases of AID were identified 60 months or more after initial treatment and risk of AID was independent of total alemtuzumab dose or interval of dosage. While established risk factors for AID including sex and age had no impact on AID frequency, both family history (odds ratio = 7.31, 95% confidence interval 3.02-17.68) of AID and a personal smoking history (odds ratio = 3.05, 95% confidence interval 1.50-6.19) were predictive of AID expression.
Cumulative risk for AID in MS following alemtuzumab is 22.2%, most frequent between 12 and 18 months following first dose and evident for up to 5 years. Individual risk is modified by smoking and family history, which should be incorporated within the counseling process prior to treatment.
This study provides Class IV evidence that the risk of AID after alemtuzumab treatment for MS is time-limited and modified by external factors.
Neurology 08/2011; 77(6):573-9. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Neuromyelitis Optica (NMO) is a rare neuroinflammatory disorder with limited epidemiological data. Antibodies against aquaporin-4 (Aq4ab) are reported to be highly specific for NMO and NMO spectrum disorders (NMO-SD). In this study we determine the prevalence of these disorders and spectrum of clinical phenotype in a population-based sample and analyse clinical features that predict Aq4ab positivity. Cases were identified from the SE Wales neuroinflammatory database and regional requests for Aquaporin-4 testing. 10 patients (M2:8, age range 7-70) with NMO were identified of which 7 had positive Aq4ab, as well as two female patients with Aq4ab positive NMO-SD; a combined prevalence of 16/million (95% CI 10 to 25). Median disease duration was 4 years (range 1-34) and median relapse frequency 0.63/year (0.14-1.60). Median MS severity score (MSSS) was 8.10 (4.35-9.59) One third of cases had severe visual impairment. MSSS did not differ between those treated with immunosuppressants (5/12) and those not. Both NMO-SD cases had isolated longitudinally extensive transverse myelitis (LETM). Aq-4ab were positive in 9/79 (11.4%) sample requests. Test requests were most commonly associated with poorly recovered optic neuritis (56.6%). Logistic regression identified the presence of LETM on MR as the most predictive feature for NMO (Likelihood ratio=5.43). In this study we have established disease prevalence for NMO in a UK population-based sample and identified LETM as the main indication for Aq4ab testing.
Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e26-7. · 4.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aetiology of events initiating relapse in MS is unclear but it has been postulated that environmental factors linked to climatic change may act as triggers. We analyse month of relapse from data collected prospectively from a large population-based cohort of patients over a 5-year-period (2005-9) and examine associations with climatic variables. A total of 1473 relapses from 617 patients were modelled using Poisson regression. In order to minimise recall bias subgroup analyses were also performed on relapses from patients attending a self-referral relapse clinic (n=722), and surveyed by validated questionnaire (n=221). Compared to April (baseline) a trough in relapses was observed in September (relapse ratio 0.76, 95% CI 0.58 to 0.99, p=0.04) and January (relapse ratio 0.75, 95% CI 0.56 to 0.98, p=0.03). In addition there was a nonsignificant peak in relapses in June (relapse ratio 1.23, 95% CI 0.98 to 1.56, p=0.08). The pattern of relapses could be modelled by a sinusoidal curve p=0.0003. Furthermore the number of monthly sunshine hours predicted relapse frequency (relapse ratio 1.06, 95% CI 1.00 to 1.12, p=0.04 per standard deviation unit). The summer relapse frequency peak was replicated in clinic subgroup data but not in the questionnaire subgroup. This is the largest seasonal analysis of relapses and supports findings from prior small European studies of summer peaks and autumnal troughs. The causes for this seasonal variation remain unclear though sun exposure may be relevant.
Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e26. · 4.87 Impact Factor
-
M D Cossburn,
A A Pace,
J Jones,
R Ali,
G Ingram,
K Baker,
C Hirst,
J Zajicek,
N Scolding,
M Boggild, T Pickersgill,
A Coles,
Y Ben-Shlomo,
N P Robertson
[show abstract]
[hide abstract]
ABSTRACT: Alemtuzumab is a anti-CD52 humanised monoclonal antibody shown to be an effective treatment for relapsing multiple sclerosis (MS) in phase II studies but exhibits a unique adverse event profile. In limited follow-up studies development of autoimmune disease has been observed 20-30% of patients. Currently, the exact range and temporal evolution of autoimmune disease following treatment remains unclear but will have important implications for screening and safety monitoring. In this study we analyse prospective clinical and serological data from 225 patients treated with Alemtuzumab for a mean of 40.5 months (range 0.2-93.8). Novel autoimmune disease developed in 22.7%. Thyroid autoimmune disease was most common (17.8%) but a range of other autoimmune diseases including immune thrombocytopenic purpura, anti-GBM disease, neutropoenia, skin disorders and asymptomatic development of novel auto-antibodies was also observed. Risk of autoimmune disease was constant up to 55 months, following which there was a rapid decline, and independent of the number of treatments received or interval of dosage. Whilst established risk factors for autoimmune disease such as sex and age had no impact on autoimmune disease frequency, smoking was identified as a major risk factor with a relative risk of 4.95 for ever smokers. Risk of autoimmune disease in MS following alemtuzumab appears to be time limited and screening will need to continue for at least 5 years posttreatment. Individual risk for autoimmune disease is modified by external factors which should be incorporated within the counselling process prior to treatment.
Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e26. · 4.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epidemiological studies of multiple sclerosis suggest a trend of increasing disease prevalence in susceptible populations. The reasons for this are unclear and may be the results of methodological differences between studies, incomplete ascertainment or advances in technologies that allow the increased identification of early or mild disease. In addition, direct comparison of cross sectional prevalence estimates performed in different epochs in ethnically and geographically distinct populations may be inappropriate.
Using detailed phenotypic information and standardised methodology, a geographically defined Welsh population was resurveyed after a significant interval, establishing contemporary prevalence rates and examining demographic and clinical data to determine causes of changing disease frequency.
Disease prevalence increased 45% from 101 to 146 per 100,000 population over 20 years. The greatest increase was observed in women between the ages of 45 and 54 years. No significant increase in disease frequency was observed in the male population overall, or within specific age groups. There was no demographic evidence for a pattern of earlier age at onset or diagnosis to explain increased disease frequency or decrease in mean age of the prevalent population. In addition, we failed to identify a pattern of recognition of patients with less severe disability. Although there was a modest 13% increase of 2.2 years in mean disease duration, and eight new previously prevalent patients were identified, the main cause of rising disease frequency was related to a 2.8-fold increase in disease incidence for women over 23 years from 2.65 to 7.30/100,000/year increasing the sex ratio of incident patients from 1.8 to 4.3 (women:men).
Recent change in disease incidence and prevalence in this population is likely to be the result of environmental factors that have been operative in the past few decades in women alone and infers avoidable risk factors. Modelling of current overall incidence suggests a further increase in prevalence to 260 per 100 000 population within the next 20-40 years. Further studies are needed in order to identify recent changes in sex specific environment and lifestyle that confer susceptibility.
Journal of neurology, neurosurgery, and psychiatry 11/2008; 80(4):386-91. · 4.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In patients with multiple sclerosis (MS), the natural history of the disease is of considerable importance to predict and understand long-term outcome and inform choices made by patients and clinicians. This information should ideally be derived from data that reflects the entire disease course.
In this study, morbidity data from a prevalent cohort established in 1985 have been re-examined after an interval of 20 years to assess factors that may be important in determining outcome.
Of 379 patients who fulfilled criteria for definite or probable MS in the original population-based cohort, 221 (58.3%) had died, 149 (39.3%) were alive and 9 (2.4%) were untraceable. Mean Expanded Disability Status Scale (EDSS) score in 1985 was 5.15 (SD 2.7, range 0-9.5) and 8.01 (SD 2.6, range 0-10) in those alive in 2005. Mean worsening of EDSS scores in surviving patients was +3.02 EDSS points, but 14.0% had worsened by <1 EDSS point over 20 years. 61.4% of patients with EDSS 3.5-5.5 and 82.2% of those with an EDSS of <or=3 in 1985 had an EDSS of >or=6 after 20 years. Lower baseline EDSS scores (p<0.0001), higher pyramidal functional system score (p = 0.02) and a greater number of functional systems involved (p = 0.001) were significantly more likely to be associated with greater worsening of disability. Of those with benign disease in 1985, only 19% remained benign after 20 years of follow-up; however, 12.6% of patients had minimal disability after at least 20 years after their disease onset and 14% of patients failed to worsen by >or=1 EDSS point.
This study emphasises the importance of long-term epidemiological studies and the development of clinically relevant measures that effectively predict outcome and can guide decisions on therapeutic management.
Journal of neurology, neurosurgery, and psychiatry 03/2008; 79(10):1137-43. · 4.87 Impact Factor
