cover image European Journal of Neurology

European Journal of Neurology

2015 - Volume 22
Issue 6 | June 2015
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Original Article

Background and purpose

Dementia is a neurodegenerative disorder that presents a progressive decline in cognitive function and loss of short‐term memory with age. Several studies have shown that statin, an oral lipid‐lowering drug, may reduce the risk of developing dementia. The objective of this study is to explore the association between statin and the development of dementia.

Methods

The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. The sample consisted of 123 300 patients ≥ 20 years of age, including 61 650 dementia patients with statin use and 61 650 patients without statin use who were eligible for inclusion in this study. Univariate and multivariate Cox proportional hazard regression analyses were performed to measure the effects of statin use on the risk of dementia.

Results

The beneficial effect of statin on dementia was significant after adjusting for sociodemographic factors and comorbidities (adjusted hazard ratio of 0.92, 95% confidence interval 0.86–0.98). The sex‐ and age‐specific analysis of adjusted hazard ratios showed a higher beneficial effect from statin treatment in women than in men, and the effect became more significant with age.

Conclusion

Statin therapy may help prevent the development of dementia, and both hydrophilic and lipophilic statins produce similar effects. However, the preventive characters and associated mechanisms must be further explored and identified.

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Authors:
C.‐S. Chuang, C.‐L. Lin, M.‐C. Lin, F.‐C. Sung and C.‐H. Kao
Article first published online:
18 Mar 2014 | DOI: 10.1111/ene.12402

Short Communication

Background and purpose

A population‐based case−control study in the city of Catania, Sicily, was carried out to determine restless legs syndrome (RLS) prevalence and its association with multiple sclerosis (MS).

Methods

Patients were randomly selected from a cohort of MS patients resident in the study area and a group of age and sex matched controls was enrolled from the general population. RLS was diagnosed according to the International Restless Legs Syndrome Study Group criteria.

Results

In total, 152 MS patients and 431 controls were included in the study. A significantly higher prevalence of RLS amongst MS patients (14.5%) compared with controls (6.0%) was detected, corresponding to an almost threefold increased risk (odds ratio 2.7, 95% confidence interval 1.4–5.0) of developing RLS. Spinal cord lesions in MS patients were associated with a higher risk of RLS (odds ratio 3.7, 95% confidence interval 1.1–13.5).

Conclusion

RLS was strongly associated with MS, with a significantly higher risk in patients presenting spinal cord lesions.

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Authors:
E. Bruno, A. Nicoletti, S. Messina, S. Lo Fermo, L. Raciti, G. Quattrocchi, V. Dibilio, V. Paradisi, D. Maimone, F. Patti and M. Zappia
Article first published online:
12 Mar 2014 | DOI: 10.1111/ene.12409

Editorial

Abstract

Click to view the accompanying paper in this issue.

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Authors:
C. J. Lavie, J. J. DiNicolantonio, J. H. O'Keefe and R. V. Milani
Article first published online:
08 Apr 2014 | DOI: 10.1111/ene.12430

Original Article

Background and purpose

Bilateral globus pallidus deep brain stimulation (GPi‐DBS) represents an effective and relatively safe therapy for different forms of refractory dystonia. The aim of this study was to assess, retrospectively, the effect of two different stimulation settings during GPi‐DBS in 22 patients affected by primary generalized or multi‐segmental dystonia.

Methods

Thirteen patients were stimulated using a voltage‐controlled setting whilst in the other nine patients a current‐controlled setting was used. Clinical features were evaluated for each patient at baseline, 6 months and 12 months after surgery by means of the Burke−Fahn−Marsden Dystonia Rating Scale.

Results

Globus pallidus deep brain stimulation was effective in all patients. However, comparing constant‐current and constant‐voltage stimulation, a better outcome was found in the current‐controlled group during the last 6 months of follow‐up.

Conclusions

Current‐controlled stimulation is effective during GPi‐DBS for primary dystonia and it could be a better choice than voltage‐controlled stimulation over long‐term follow‐up.

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Authors:
C. Lettieri, S. Rinaldo, G. Devigili, F. Pisa, M. Mucchiut, E. Belgrado, M. Mondani, S. D'Auria, T. Ius, M. Skrap and R. Eleopra
Article first published online:
10 Jul 2014 | DOI: 10.1111/ene.12515

Editorial

Abstract

Click to view the accompanying paper in this issue.

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Authors:
I. Beaulieu‐Boire and A. Fasano
Article first published online:
12 Aug 2014 | DOI: 10.1111/ene.12537

Review Article

Abstract

High socioeconomic status (SES) is generally associated with better health outcomes, but some research has linked it with an increased risk of multiple sclerosis (MS). The evidence for this association is inconsistent and has not previously been systematically reviewed. A systematic review of cohort and case–control studies in any language was conducted looking at the association between MS and SES. MEDLINE and EMBASE were searched for articles in all languages published up until 23 August 2013. Twenty‐one studies from 13 countries were included in the review. Heterogeneity of study settings precluded carrying out a meta‐analysis, and a qualitative synthesis was performed instead. Five studies, all from more unequal countries, reported an association between high SES and MS. Thirteen studies reported no evidence of an association, and three studies reported an association with low SES. These 16 studies largely came from more egalitarian countries. The evidence for an association between high SES and increased MS risk is inconsistent but with some indication of a stronger effect in countries and time periods with higher inequality. Firm conclusions are hampered by the failure of most studies to control for other important risk factors for MS.

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Authors:
R. Goulden, T. Ibrahim and C. Wolfson
Article first published online:
05 Nov 2014 | DOI: 10.1111/ene.12586

Short Communication

Background and purpose

The fluctuation of circadian blood pressure (BP) is of great diversity in patients with essential hypertension and may provide significant prognostic value for stroke. However, it remains uncertain whether reverse‐dipper pattern of BP influences the incidence of lacunar infarction in hypertensive patients.

Methods

In the current study, 362 hypertensive patients (195 males, 167 females) were enrolled. BP patterns were evaluated with 24‐h ambulatory BP monitoring (ABPM). Multinomial logistic regression was applied to analyse the possible relationships between lacunar infarction and various clinical risk factors such as ABPM.

Results

A total of 93 patients (25.7%) had reverse‐dipper BP pattern. Non‐dipper pattern of BP was observed in 179 hypertensive patients (49.4%) and dipper pattern in 90 patients (24.9%). The percentage of lacunar infarction was the highest in the patients with reverse‐dipper pattern compared with pure hypertension or atherothrombotic cerebral infarction (<0.05). After multinomial logistic regression analysis, reverse‐dipper pattern of BP (odds ratio 2.492; 95% confidence interval 1.133–5.479; <0.05) and age (odds ratio 1.084; 95% confidence interval 1.047–1.123; <0.01) were found to be directly associated with lacunar infarction.

Conclusions

Reverse‐dipper BP pattern may serve as an independent risk factor for lacunar infarction and more personalized BP management should be offered to the patients who have elevated nocturnal BP.

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Authors:
B. Yan, L. Peng, Q. Dong, F. Zheng, P. Yang, L. Sun, S. Gong, L. Zeng and G. Wang
Article first published online:
23 Jan 2015 | DOI: 10.1111/ene.12659

Letter to the Editor

Pendular nystagmus, palatal tremor and progressive ataxia in GM2‐gangliosidosis

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Authors:
E. Pretegiani, F. Rosini, P. Federighi, A. Cerase, M. T. Dotti and A. Rufa
Article first published online:
27 Apr 2015 | DOI: 10.1111/ene.12661

Letter to the Editor

Re: The association between chronic obstructive pulmonary disease and dementia: a population‐based retrospective cohort study

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Authors:
K.‐M. Liao
Article first published online:
27 Apr 2015 | DOI: 10.1111/ene.12676

Letter to the Editor

Reply: The association between chronic obstructive pulmonary disease and dementia: a population‐based retrospective cohort study

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Authors:
W.‐C. Liao, C.‐L. Lin, S.‐N. Chang, C.‐Y. Tu and C.‐H. Kao
Article first published online:
27 Apr 2015 | DOI: 10.1111/ene.12677

Original Article

Background and purpose

Essential tremor (ET) is amongst the most commonly encountered neurological disorders. Its hallmark feature is kinetic tremor. However, other tremors may also occur in ET patients, creating considerable diagnostic confusion amongst treating physicians. Hence, characterizing the prevalence and clinical accompaniments of these other tremors is of value. Surprisingly, there are few data on the prevalence of rest tremor in ET patients, and even fewer data on the clinical correlates of such tremor.

Methods

Eight hundred and thirty‐one patients in four distinct settings (population, genetics study, study of environmental epidemiology, brain bank) underwent a detailed videotaped neurological examination that was reviewed by a senior movement disorders neurologist. Rest tremor was evaluated in several positions (seated, standing, lying down).

Results

The prevalence of rest tremor whilst seated or standing was lowest in the population‐based setting (1.9%), highest in the brain bank study (46.4%) and intermediate in the remaining two settings (9.6% and 14.7%, respectively). Rest tremor was restricted to the arms and was not observed in the legs. Rest tremor was associated with older age, longer disease duration (in some studies), greater tremor severity and, to some extent, the presence of cranial tremors.

Conclusions

Rest tremor can be a common clinical feature of ET. Its prevalence is highly dependent on the setting in which patients are evaluated, ranging from as low as 1% to nearly 50%. Rest tremor seems to emerge as a clinical feature with advancing disease. The anatomical substrates for this type of tremor remain unknown at present.

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Authors:
E. D. Louis, N. Hernandez and M. Michalec
Article first published online:
19 Mar 2015 | DOI: 10.1111/ene.12683

Original Article

Background and purpose

This was a retrospective study to assess the diagnostic value of the non‐ischaemic forearm exercise test in detecting McArdle's disease.

Methods

The study is a retrospective diagnostic study over 15 years (1999–2013) on a referred sample of patients suffering from exercise intolerance and various muscle complaints, generally with elevated creatine kinase (CK). In all, 1226 patients underwent the non‐ischaemic forearm exercise test. Blood lactate, ammonia and CK levels were analyzed. DNA analyses and/or muscle biopsies were assessed to confirm the diagnosis of McArdle's disease. The results of 60 volunteers were used to compare with the results of study subjects.

Results

In this cohort, 40 patients were finally diagnosed with McArdle's disease. Absolute values of lactate and ammonia rise were used to discriminate all McArdle patients from healthy patients. A sensitivity and specificity of respectively 100% and 99.7% were calculated. The 24‐h CK level showed no significant difference from the CK level at the day of the test and confirms the safety of the test.

Conclusions

This study has formally assessed the diagnostic value of the non‐ischaemic forearm exercise test in the detection of McArdle's disease. Very high sensitivity and specificity were observed. Furthermore, the test is easy to set up and to perform, it is non‐traumatic and cost effective. It may circumvent a muscle biopsy in McArdle patients presenting the most common mutations. Hence, it is a perfect and safe screening instrument to detect patients with McArdle's disease. Glycogen storage disease type III patients, however, may show similar patterns to McArdle patients.

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Authors:
J.‐Y. Hogrel, F. van den Bogaart, I. Ledoux, G. Ollivier, F. Petit, N. Koujah, A. Béhin, T. Stojkovic, B. Eymard, N. Voermans and P. Laforêt
Article first published online:
05 Mar 2015 | DOI: 10.1111/ene.12685

Original Article

Background and purpose

Cerebral infarction is a frequent and serious complication of aneurysmal subarachnoid hemorrhage (SAH). This study aimed to identify independent predictors of the timing of cerebral infarction and clarify its impact on disease course and patients’ outcome.

Methods

All consecutive patients with SAH admitted to our institution from January 2005 to December 2012 were analyzed. Serial computed tomography (CT) scans were evaluated for cerebral infarctions. Demographic, clinical, laboratory and radiological data of patients during hospitalization as well as clinical follow‐ups 6 months after SAH were recorded.

Results

Of the 632 analyzed patients, 320 (51%) developed cerebral infarction on CT scans. 136 patients (21.5%) with early cerebral infarction (occurring within 3 days after SAH) had a significantly higher risk of unfavorable outcome than patients with late infarction [odds ratio (OR) 2.94;  = 0.008], a higher in‐hospital mortality (OR 3.14;  = 0.0002) and poorer clinical outcome after 6 months (OR 0.54;  < 0.0001). The rates of decompressive craniectomy (OR 1.96,  = 0.0265), tracheostomy (OR 1.87,  = 0.0446), the duration of intensive care unit stay and mechanical ventilation were significantly higher in patients with early infarction. In multivariate analysis, Hunt and Hess grades 4 and 5 (OR 2.06,  = 0.008), Fisher grades 3 and 4 (OR 3.99,  = 0.014), sustained elevations of intracranial pressure >20 mmHg (OR 5.95,  < 0.0001) and early vasospasm on diagnostic angiograms (OR 3.01,  = 0.008) were predictors of early cerebral infarction.

Conclusion

Early cerebral infarction after SAH is associated with severe clinical course and unfavorable outcome and can be reliably predicted by poor initial clinical condition, thick subarachnoid clot, early angiographic vasospasm and sustained elevations of intracranial pressure.

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Authors:
R. Jabbarli, M. Reinhard, W.‐D. Niesen, R. Roelz, M. Shah, K. Kaier, B. Hippchen, C. Taschner and V. Van Velthoven
Article first published online:
24 Feb 2015 | DOI: 10.1111/ene.12686

Original Article

Background and purpose

To investigate the association of anemia on admission with ischaemic stroke (IS), stroke severity and early functional outcome in patients with cervical artery dissection (CeAD) or with IS of other causes (non‐CeAD‐IS patients).

Methods

The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) study without pre‐existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb < 12 g/dl in women and Hb < 13 g/dl in men) or moderate to severe (Hb < 10 g/dl in women and Hb < 11 g/dl in men). Stroke severity on admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). Outcome after 3 months was assessed with the modified Rankin Scale (mRS‐3mo). Unfavorable outcome was defined as mRS‐3mo ≥ 3.

Results

Amongst 1206 study patients (691 CeAD and 515 non‐CeAD), 87 (7.2%) had anemia, which was moderate to severe in 18 (1.5%) patients. Anemia was associated with female sex in both study samples, but no further associations with risk factors or comorbidities were observed. In CeAD patients, anemia was associated with occurrence of stroke ( = 0.042). In both study samples, anemic patients had more severe strokes (CeAD, = 0.023; non‐CeAD, = 0.005). Functional outcome was not associated with anemia in general, but moderate to severe anemia was significantly associated with unfavorable outcome ( = 0.004).

Conclusion

Anemia on admission was associated with stroke in CeAD patients and with more severe strokes in both study samples. Moderate to severe anemia may predict unfavorable outcome.

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Authors:
L. Kellert, M. Kloss, A. Pezzini, T. M. Metso, A. J. Metso, S. Debette, D. Leys, V. Caso, V. Thijs, A. Bersano, E. Touzé, T. Tatlisumak, H. Gensicke, P. A. Lyrer, J. Bösel, S. T. Engelter and C. Grond‐Ginsbach
Article first published online:
24 Feb 2015 | DOI: 10.1111/ene.12687

Original Article

Background and purpose

Oxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative defences. Indeed, there is growing evidence of HO−bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression.

Methods

A cross‐sectional case−control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug‐naïve PD subjects and controls. Afterwards, PD subjects were included in a 2‐year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels.

Results

Seventy‐five PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PD patients compared with controls ( < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III ( = 0.283) at baseline evaluation. At 2‐year follow‐up, indirect relationships between bilirubin levels and UPDRS part III ( = 0.028) and between bilirubin levels and levodopa‐equivalent daily dosage ( = 0.012) were found.

Conclusions

Parkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD.

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Authors:
M. Moccia, M. Picillo, R. Erro, K. Longo, M. Amboni, G. Santangelo, R. Palladino, R. Allocca, O. Caporale, M. Triassi, M. T. Pellecchia, P. Barone and C. Vitale
Article first published online:
05 Mar 2015 | DOI: 10.1111/ene.12688

Original Article

Background and purpose

No subgroups of patients with higher treatment effects have been clearly detected in multiple sclerosis (MS). The aim of the present work was to evaluate whether there are subgroups of relapsing−remitting MS (RRMS) patients who are more responsive to treatments.

Methods

All published randomized clinical trials in RRMS reporting a subgroup analysis of treatment effect were collected. Two main outcomes, the annualized relapse rate (ARR) and the disability progression, were studied. The treatment effect in each subgroup was reported as a relative effect (RE), defined as the treatment effect in the subgroup relative to the overall effect. A meta‐analysis was run to compare the RE between subgroups.

Results

Six trials (6693 RRMS patients) were included. Treatment effects on ARR were significantly higher in younger than in older subjects (RE = 0.83 vs. RE = 1.30,  < 0.001), in patients with than those without gadolinium activity (RE = 0.86 vs. RE = 1.15,  = 0.005) and in patients with lower than in those with higher Expanded Disability Status Scale (RE = 0.96 vs. RE = 1.23,  = 0.02), and on disability progression in younger than in older subjects (RE = 0.82 vs. RE = 1.28,  = 0.017).

Conclusions

This study formally shows that in RRMS higher treatment effects are associated with characteristics of earlier (lower age and Expanded Disability Status Scale) and more active (higher gadolinium activity) disease.

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Authors:
A. Signori, I. Schiavetti, F. Gallo and M. P. Sormani
Article first published online:
19 Mar 2015 | DOI: 10.1111/ene.12690

Original Article

Background and purpose

The susceptibility vessel sign (SVS) on T2*‐weighted magnetic resonance imaging has been reported in several studies as a negative predictor of early recanalization after intravenous thrombolysis. The meaning of SVS regarding the results of mechanical thrombectomy with stent retrievers was investigated.

Methods

Susceptibility vessel sign presence and length were studied in 153 acute ischaemic stroke patients (82 men; mean ± SD age 59 ± 17 years, baseline National Institutes of Health Stroke Scale score 17.2 ± 6.5) from three stroke centres, treated with either mechanical thrombectomy alone ( = 84) or bridging therapy ( = 69). Variables were compared between recanalizers, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b, and non‐recanalizers (TICI<2b).

Results

The SVS was present in 113 (73.8%) patients. There was no association between the presence of SVS and recanalization, obtained in 86 (56.2%) patients, in the whole population [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.53–2.92, =0.84) and in treatment subgroups (bridging: OR = 0.91, 95% CI 0.29–2.87, =1.0; thrombectomy alone: OR = 1.85, 95% CI 0.48–7.16, =0.54). However, in SVS+ patients, recanalization decreased with SVS length (OR 0.94 for each additional mm, 95% CI 0.89–0.99; =0.02).

Conclusions

The success of recanalization in acute stroke patients treated with stent retrievers was related to thrombus length but not to the presence of SVS.

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Authors:
S. Soize, A. L. Batista, C. Rodriguez Regent, D. Trystram, M. Tisserand, G. Turc, I. Serre, W. Ben Hassen, M. Zuber, D. Calvet, J.‐L. Mas, J.‐F. Meder, J. Raymond, L. Pierot, C. Oppenheim and O. Naggara
Article first published online:
19 Mar 2015 | DOI: 10.1111/ene.12693

Original Article

Background and purpose

The Rio score (RS) and the modified Rio score (MRS) are two scoring systems that can identify the early predictive factors of disability progression in relapsing−remitting multiple sclerosis (RRMS) patients treated with interferon‐β (IFN‐β). The objective of the study was to validate the usefulness of the RS and MRS in a large cohort of multiple sclerosis patients treated with IFN‐β in daily clinical practice.

Methods

The analysis included a cohort of RRMS patients treated with different formulations of IFN‐β for at least 1 year. The RS and MRS were used to classify the patients after 1 year of treatment. Multivariate analysis was performed to identify predictive variables of suboptimal response at 5 years, defined as Expanded Disability Status Scale confirmed progression or switching to a second‐line therapy.

Results

Sixty‐nine of 416 included patients were considered as suboptimal responders at 5‐year evaluation. The possible score range was 0–3. A higher risk of suboptimal response was found for RS and MRS in the presence of ≥2 scores (hazard ratio 3.0, = 0.002, and hazard ratio 5.0,  < 0.0001, respectively).

Conclusions

Our study confirmed, in a daily clinical setting, that MRS had a better specificity and accuracy than RS in identifying the patients who will have a poor response to long‐term IFN‐β treatment.

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Authors:
M. Romeo, V. Martinelli, M. Rodegher, E. Perego, S. Maida, M. P. Sormani, G. Comi, Lucia Moiola, Bruno Colombo, Filippo Martinelli‐Boneschi, Donatella De Feo, Federica Esposito, Giuseppe Liberatore, Merlini Arianna, Maria Josè Messina, Giulia Pavan, Marta Radaelli, Maria Assunta Rocca and Francesca Sangalli
Article first published online:
06 Apr 2015 | DOI: 10.1111/ene.12695

Original Article

Background and purpose

Early prediction of long‐term disease evolution is a major challenge in the management of multiple sclerosis (MS). Our aim was to predict the natural course of MS using the Bayesian Risk Estimate for MS at Onset (BREMSO), which gives an individual risk score calculated from demographic and clinical variables collected at disease onset.

Methods

An observational study was carried out collecting data from MS patients included in MSBase, an international registry. Disease impact was studied using the Multiple Sclerosis Severity Score (MSSS) and time to secondary progression (SP). To evaluate the natural history of the disease, patients were analysed only if they did not receive immune therapies or only up to the time of starting these therapies.

Results

Data from 14 211 patients were analysed. The median BREMSO score was significantly higher in the subgroups of patients whose disease had a major clinical impact (MSSS≥ third quartile vs. ≤ first quartile,  < 0.00001) and who reached SP ( < 0.00001). The BREMSO showed good specificity (79%) as a tool for predicting the clinical impact of MS.

Conclusions

BREMSO is a simple tool which can be used in the early stages of MS to predict its evolution, supporting therapeutic decisions in an observational setting.

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Authors:
R. Bergamaschi, C. Montomoli, G. Mallucci, A. Lugaresi, G. Izquierdo, F. Grand'Maison, P. Duquette, V. Shaygannejad, R. Alroughani, P. Grammond, C. Boz, G. Iuliano, C. Zwanikken, T. Petersen, J. Lechner‐Scott, R. Hupperts, H. Butzkueven, E. Pucci, C. Oreja‐Guevara, E. Cristiano, M. P. Pia Amato, E. Havrdova, R. Fernandez‐Bolanos, T. Spelman and M. Trojano
Article first published online:
25 Mar 2015 | DOI: 10.1111/ene.12696

Original Article

Background and purpose

Beta‐interferons (IFNβ) are the most widely prescribed drugs for patients with multiple sclerosis (MS). However, whether or not treatment with IFNβ can delay secondary progressive MS (SPMS) onset remains unknown. Our aim was to examine the association between IFNβ exposure and SPMS onset in patients with relapsing−remitting MS (RRMS).

Methods

A retrospective cohort study using British Columbia (Canada) population‐based clinical and health administrative data (1985–2008) was conducted. RRMS patients treated with IFNβ ( = 794) were compared with untreated contemporary ( = 933) and historical ( = 837) controls. Cohort entry was the first clinic visit during which patients became eligible for IFNβ treatment (baseline). The outcome was time from baseline to SPMS onset. Cox regression models with IFNβ as a time‐dependent exposure were adjusted for sex, and baseline age, disease duration, disability, *socioeconomic status and *comorbidities (*available for the contemporary cohorts only). Additional analyses included propensity score adjustment.

Results

The median follow‐up for the IFNβ‐treated, untreated contemporary and historical controls were 5.7, 3.7 and 7.3 years, and the proportions of patients reaching SPMS were 9.2%, 11.8% and 32.9%, respectively. After adjustment for confounders, IFNβ exposure was not associated with the risk of reaching SPMS when either the contemporary or the historical untreated cohorts were considered (hazard ratio 1.07; 95% confidence interval 0.93–1.48, and hazard ratio 1.04; 95% confidence interval 0.74–1.46, respectively). Further adjustments and the propensity score yielded results consistent with the main analysis.

Conclusions

Amongst patients with RRMS, use of IFNβ was not associated with a delayed onset of SPMS.

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Authors:
T. Zhang, A. Shirani, Y. Zhao, M. E. Karim, P. Gustafson, J. Petkau, C. Evans, E. Kingwell, M. van der Kop, F. Zhu, J. Oger and H. Tremlett
Article first published online:
06 Apr 2015 | DOI: 10.1111/ene.12698

Original Article

Background and purpose

Several studies have assessed the risk of ischaemic heart diseases in migraineurs, drawing different conclusions. To define and update the issue, a systematic review and meta‐analysis of the available observational studies was performed.

Methods

PubMed and EMBASE were systematically searched up to April 2014 for observational studies dealing with the risk of any form of ischaemic heart disease in migraineurs. Studies assessing migraine as exposure and several types of ischaemic heart disease as outcomes were included in the analysis. A random effects model was used to pool the effect sizes.

Results

Out of 3348 records, 15 studies (one case−control, one cross‐sectional and 13 cohort studies) were identified and were included in the meta‐analysis. The pooled analysis indicated an increased risk of myocardial infarction (pooled adjusted effect estimate 1.33, 95% confidence interval 1.08–1.64;  = 0.007) and of angina (pooled adjusted effect estimate 1.29, 95% confidence interval 1.17–1.43;  < 0.0001) in migraineurs compared to non‐migraineurs.

Conclusions

Based on our data indicating an association of migraine with myocardial infarction and angina and on previous data showing an association of migraine, and particularly migraine with aura, with an increased risk for stroke, migraine can be appropriately considered an overall risk factor for cardiovascular diseases.

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Authors:
S. Sacco, R. Ornello, P. Ripa, C. Tiseo, D. Degan, F. Pistoia and A. Carolei
Article first published online:
25 Mar 2015 | DOI: 10.1111/ene.12701

Original Article

Background and purpose

Occlusive cerebrovascular moyamoya disease (MMD) is rare and has been characterized mainly in Asian countries, so far. In recent years, MMD has been increasingly reported worldwide, raising the question whether its clinical presentation would vary amongst different ethnic backgrounds. Here, a homogeneous series of 153 patients with MMD are reported and the specific clinical features of this rare disease amongst European Caucasians are highlighted.

Methods

A total of 153 European Caucasians with MMD who were treated in our institution between 1997 and 2014 were retrospectively identified. Demographic data, clinical symptoms, angiographic characteristics and functional hemodynamic studies were analyzed.

Results

Moyamoya disease presented with a female predominance of 2,9:1.,78% presented with a typical MMD, 17% with a unilateral MMD and 5% with an atypical MMD. 16% of our patients belonged to the pediatric population. Overall, 81% and 8.5% of our cohort presented initially with ischaemic and hemorrhagic manifestation, respectively. The rate of hemorrhagic manifestation of MMD amongst the pediatric group was slightly higher (12%). Angiographic analysis revealed steno‐occlusive involvement of the posterior circulation in 34% with a higher involvement in pediatric patients (64%) compared to adults (28%).

Conclusions

The characterization of our homogeneous European Caucasian cohort reveals several significant differences compared to Asian cohorts. In contrast, MMD presents similarly amongst European and North American cohorts, suggesting that non‐Asian MMD is characterized by distinct clinical features.

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Authors:
G. Acker, S. Goerdes, U. C. Schneider, P. Schmiedek, M. Czabanka and P. Vajkoczy
Article first published online:
06 Apr 2015 | DOI: 10.1111/ene.12702

EFNS‐ENS/EAN Guideline/CME Article

Background and purpose

Previous studies have indicated clinical benefits of a combination of cholinesterase inhibitors (ChEI) and memantine over ChEI monotherapy in Alzheimer's disease (AD). Our objective was the development of guidelines on the question of whether combined ChEI/memantine treatment rather than ChEI alone should be used in patients with moderate to severe AD to improve global clinical impression (GCI), cognition, behaviour and activities of daily living (ADL).

Methods

A systematic review and meta‐analysis of randomized controlled trials based on a literature search in ALOIS, the register of the Cochrane Dementia and Cognitive Improvement Group, was carried out with subsequent guideline development according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results

Pooled data from four trials including 1549 AD patients in the moderate to severe disease stage demonstrated significant beneficial effects of combination therapy compared to ChEI monotherapy for GCI [standardized mean difference (SMD) −0.20; 95% confidence interval (CI) −0.31; −0.09], cognitive functioning (SMD −0.27, 95% CI −0.37; −0.17) and behaviour (SMD −0.19; 95% CI −0.31; −0.07). The quality of evidence was high for behaviour, moderate for cognitive function and GCI and low for ADL. Agreement of panellists was reached after the second round of the consensus finding procedure. The desirable effects of combined ChEI and memantine treatment were considered to outweigh undesirable effects. The evidence was weak for cognition, GCI and ADL so that the general recommendation for using combination therapy was weak.

Conclusions

We suggest the use of a combination of ChEI plus memantine rather than ChEI alone in patients with moderate to severe AD. The strength of this recommendation is weak.

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Authors:
R. Schmidt, E. Hofer, F. H. Bouwman, K. Buerger, C. Cordonnier, T. Fladby, D. Galimberti, J. Georges, M. T. Heneka, J. Hort, J. Laczó, J. L Molinuevo, J. T. O'Brien, D. Religa, P. Scheltens, J. M. Schott and S. Sorbi
Article first published online:
25 Mar 2015 | DOI: 10.1111/ene.12707

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Article first published online:
27 Apr 2015 | DOI: 10.1111/ene.12752