cover image European Journal of Neurology

European Journal of Neurology

2016 - Volume 23
Issue 11 | November 2016
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CME Article

Background and purpose

Endovascular therapy (ET) is superior to intravenous thrombolysis (IVT) in selected patients with anterior circulation large vessel occlusions. However, it is unclear if this positive effect also applies to patients with extensive early ischaemic changes. The aim of this study was to analyze the impact of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on the CT angiography source images (SI) on outcome after ET or IVT.

Methods

Using our prospectively obtained stroke database and the admission SI‐ASPECTS divided into three groups (0–5, 6–7 and 8–10), primarily the rates of good outcome [modified Rankin Scale (mRS) ≤2 at discharge] after either ET ( = 255) or IVT ( = 479) were compared.

Results

A favorable SI‐ASPECTS (8–10) was present in 501 patients, 132 patients had a moderately favorable SI‐ASPECTS (6–7) and 101 patients had an unfavorable SI‐ASPECTS (0–5). Irrespective of the treatment modality, no patient with an unfavorable SI‐ASPECTS had a good outcome and 38% died during hospital stay. Whilst significantly more patients with a favorable SI‐ASPECTS had a good outcome after ET than after IVT (51% vs. 35%, < 0.01), there was only a non‐significant trend towards a good outcome after ET than after IVT in patients with a moderately favorable ASPECTS (25% vs. 14%, = 0.1).

Conclusion

Patients with extensive early ischaemic changes on CT scans (SI‐ ASPECTS ≤5) might not profit from ET. The impact of ET on outcome in patients with moderately favorable SI‐ASPECTS should be addressed in further trials.

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Authors:
K. Wasser, P. Papanagiotou, F. Brunner, H. Hildebrandt, M. Winterhalter, C. Roth and A. Kastrup
Article first published online:
14 Jul 2016 | DOI: 10.1111/ene.13068

Short Communication

Background and purpose

The awareness of and demand for neurological expertise in global health (GH) have emerged over recent years and have become more relevant due to the increasing numbers of refugees from developing countries arriving in Europe. This study aimed to assess the provision of GH education and opportunities for international exchange during neurology post‐graduate training with a focus on Europe.

Methods

We developed a questionnaire covering different aspects of and interest in GH education on behalf of the European Association of Young Neurologists and Trainees. Residents in neurology and junior neurologists (RJN) were approached to complete this survey.

Results

Completed questionnaires were returned by 131 RJNs, of whom 65.7% were women and 84.0% were between 26 and 35 years old. In total, almost one‐third (29.0%) of RJNs reported that their residency programs offered training in GH. Limited education was reported for women's or children's health and neurological disorders of immigrants and refugees, as only 22.1%, 25.2% and 22.1% of RJNs reported that such training was offered, respectively. The curriculum rarely included coverage of the global impact of neurological disorders. Definite plans to volunteer in a developing country were reported by 7.6%. The majority of the participants acknowledged the importance of GH training and international exchange during post‐graduate education.

Conclusion

This survey corroborates the interest in and appreciation of GH education by European RJNs. However, there are shortcomings in training and opportunities for international exchange. Academic neurology and international bodies, including the European Academy of Neurology, are requested to address this.

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Authors:
A. Sauerbier, A. Macerollo, O. Györfi, P. Balicza, M. Moarcas, V. Papp, P. Zis, L. Klingelhoefer, T. Saifee, W. Struhal and J. Sellner
Article first published online:
01 Aug 2016 | DOI: 10.1111/ene.13072

Editorial

Abstract

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Authors:
W. Grisold
Article first published online:
01 Aug 2016 | DOI: 10.1111/ene.13075

Original Article

Background and purpose

The aim was to determine the electrophysiological profile of our cohort of low density lipoprotein receptor related protein 4 (LRP4) positive myasthenia gravis (MG) patients.

Methods

A repetitive nerve stimulation (RNS) test and jitter analysis using a concentric needle electrode were performed in 17 LRP4 positive MG patients. The results were compared to 31 muscle‐specific tyrosine kinase (MuSK) positive and 28 acetylcholine receptor (AChR) positive MG patients.

Results

The RNS test was negative in almost all patients belonging to the LRP4/seronegative and LRP4/MuSK groups. It was positive most frequently in the AChR MG patients, especially those without anti‐LRP4 antibodies. The presence of anti‐LRP4 antibodies was connected to lower decrement values, whilst the independent presence of anti‐AChR or anti‐MuSK antibodies was connected to higher decrement values. Lowest jitter was recorded in patients with LRP4/seronegative MG. The highest percentage of pathological jitter analysis test results was present in MuSK and AChR MG patients. The isolate presence of anti‐LRP4 antibodies did not influence the mean consecutive difference values, whilst mean consecutive difference values were higher in the presence of anti‐AChR or anti‐MuSK antibodies.

Conclusions

Low density lipoprotein receptor related protein 4 positive patients make a distinct MG subgroup with rarely detected pathological electrophysiological test results. The lack of influence of anti‐LRP4 antibodies on the different electrophysiological parameters brings into question the pathogenic role of anti‐LRP4 antibodies in MG.

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Authors:
A. V. Nikolic, S. D. Bojic, V. M. Rakocevic Stojanovic, I. Z. Basta and D. V. Lavrnic
Article first published online:
14 Jul 2016 | DOI: 10.1111/ene.13081

Review Article

Abstract

Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies , using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α‐synuclein (α‐SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α‐SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α‐SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.

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Authors:
P. Stirpe, M. Hoffman, D. Badiali and C. Colosimo
Article first published online:
22 Jul 2016 | DOI: 10.1111/ene.13082

Original Article

Background and purpose

The aim of our study was to examine the effect sizes of different cognitive function determinants in middle and early old age.

Methods

Cognitive functions were assessed in 11 711 volunteers (45 to 75 years old), included in the French CONSTANCES cohort between January 2012 and May 2014, using the free and cued selective reminding test (FCSRT), verbal fluency tasks digit–symbol substitution test (DSST) and trail making test (TMT) parts A and B. The effect sizes of socio‐demographic (age, sex, education), lifestyle (alcohol, tobacco, physical activity), cardiovascular (diabetes, blood pressure) and psychological (depressive symptomatology) variables were computed as omega‐squared coefficients (; part of the variation of a neuropsychological score that is independently explained by a given variable).

Results

These sets of variables explained from = 10% (semantic fluency) to = 26% (DSST) of the total variance. In all tests, socio‐demographic variables accounted for the greatest part of the explained variance. Age explained from = 0.5% (semantic fluency) to = 7.5% (DSST) of the total score variance, gender from = 5.2% (FCSRT) to a negligible part (semantic fluency or TMT) and education from = 7.2% (DSST) to = 1.4% (TMT‐A). Behavioral, cardiovascular and psychological variables only slightly influenced the cognitive test results (all < 0.8%, most < 0.1%).

Conclusion

Socio‐demographic variables (age, gender and education) are the main variables associated with cognitive performance variations between 45 and 75 years of age in the general population.

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Authors:
T. Mura, H. Amieva, M. Goldberg, J.‐F. Dartigues, J. Ankri, M. Zins and C. Berr
Article first published online:
20 Jul 2016 | DOI: 10.1111/ene.13087

Original Article

Background and purpose

Clinical management after transient ischaemic attack (TIA) is focused on stroke prevention; however, a number of small studies suggest that patients may experience ongoing residual impairments.

Methods

This was a retrospective matched‐cohort study using anonymized electronic primary care records from The Health Improvement Network database, which covers approximately 6% of the UK population. Adults (≥ 18 years old) who experienced a first TIA between 2009 and 2013 were matched in a ratio of 1:5 to controls by age, sex and general practice. The time to first consultation for fatigue, psychological impairment or cognitive impairment was estimated by Kaplan–Meier survivor functions and adjusted hazard ratios.

Results

A total of 9419 TIA patients and 46 511 controls were included. The Kaplan–Meier curves showed that TIA patients were more likely than controls to consult for all three impairments ( < 0.0001). Within 7.1 months (95% confidence interval (CI), 6.2–8.2), 25% of TIA patients consulted for psychological impairment compared with 23.5 months (95% CI, 22.5–24.6) for controls. Hazard ratios for TIA patients were 1.43 (95% CI, 1.33–1.54) for consulting for fatigue, 1.26 (95% CI, 1.20–1.31) for psychological impairment and 1.45 (95% CI, 1.28–1.65) for cognitive impairment.

Conclusions

Transient ischaemic attack is associated with significantly increased subsequent consultation for fatigue, psychological impairment and cognitive impairment. These findings suggest that impairments exist after initial symptoms of TIA have resolved, which should be considered by clinicians when treating TIA patients.

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Authors:
G. M. Turner, M. Calvert, M. G. Feltham, R. Ryan and T. Marshall
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13088

Original Article

Background and purpose

The incidence and case‐fatality rate (CFR) of primary intracerebral hemorrhage (PICH) over two decades were assessed in a prospective population‐based study.

Methods

Cases of incident first‐ever PICH were recorded over a 2‐year period (2011–2012) from multiple sources in the district of L'Aquila, central Italy. Included patients were followed up to 1 year after the event to ascertain CFRs. Current data were compared with those previously collected from 1994 through 1998.

Results

In all, 115 patients (52 men; 45.2%) with a first‐ever PICH were included. Mean age ± SD was 77.4 ± 11.8 years. The hemorrhage was lobar in 43 (37.4%) patients, deep in 56 (48.7%), in the posterior fossa in 11 (9.6%) and intraventricular or multiple localized in five (4.3%). Crude annual incidence rate was 19.3 per 100 000 and 14.8 per 100 000 when standardized to the 2011 European population, indicating a 48% reduction comparing data of 2011–2012 to those of 1994–1998 (incidence rate ratio 0.52; 95% confidence interval 0.43–0.64; < 0.001). In 2011–2012, the 7‐day CFR was 27.8%, the 30‐day CFR was 42.6% and the 1‐year CFR was 52.2%; the 1‐year standardized mortality ratio was 0.81 (95% confidence interval 0.63–1.04) compared with 1994–1998.

Conclusions

The annual incidence rate of PICH was lower than that found two decades before and close to the rates recently found in other western countries. Data also indicated a non‐significant trend towards a decrease in mortality, which nonetheless remained high, pointing to the need for more appropriate treatments in order to reduce PICH severity and mortality.

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Authors:
S. Sacco, R. Ornello, D. Degan, C. Tiseo, F. Pistoia and A. Carolei
Article first published online:
25 Jul 2016 | DOI: 10.1111/ene.13099

Original Article

Background and purpose

ASTRAL, SEDAN and DRAGON scores are three well‐validated scores for stroke outcome prediction. Whether these scores predict stroke outcome more accurately compared with physicians interested in stroke was investigated.

Methods

Physicians interested in stroke were invited to an online anonymous survey to provide outcome estimates in randomly allocated structured scenarios of recent real‐life stroke patients. Their estimates were compared to scores' predictions in the same scenarios. An estimate was considered accurate if it was within 95% confidence intervals of actual outcome.

Results

In all, 244 participants from 32 different countries responded assessing 720 real scenarios and 2636 outcomes. The majority of physicians' estimates were inaccurate (1422/2636, 53.9%). 400 (56.8%) of physicians' estimates about the percentage probability of 3‐month modified Rankin score (mRS) > 2 were accurate compared with 609 (86.5%) of ASTRAL score estimates ( < 0.0001). 394 (61.2%) of physicians' estimates about the percentage probability of post‐thrombolysis symptomatic intracranial haemorrhage were accurate compared with 583 (90.5%) of SEDAN score estimates ( < 0.0001). 160 (24.8%) of physicians' estimates about post‐thrombolysis 3‐month percentage probability of mRS 0–2 were accurate compared with 240 (37.3%) DRAGON score estimates ( < 0.0001). 260 (40.4%) of physicians' estimates about the percentage probability of post‐thrombolysis mRS 5–6 were accurate compared with 518 (80.4%) DRAGON score estimates ( < 0.0001).

Conclusions

ASTRAL, DRAGON and SEDAN scores predict outcome of acute ischaemic stroke patients with higher accuracy compared to physicians interested in stroke.

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Authors:
G. Ntaios, F. Gioulekas, V. Papavasileiou, D. Strbian and P. Michel
Article first published online:
25 Jul 2016 | DOI: 10.1111/ene.13100

Original Article

Background and purpose

We investigated the effect of stress hyperglycemia on the functional outcomes of non‐diabetic hemorrhagic stroke. In addition, we investigated the usefulness of intensive rehabilitation for improving functional outcomes in patients with stress hyperglycemia.

Methods

Non‐diabetic hemorrhagic stroke patients were recruited and divided into two groups: intracerebral hemorrhage (ICH) ( = 165) and subarachnoid hemorrhage (SAH) ( = 156). Each group was divided into non‐diabetics with or without stress hyperglycemia. Functional assessments were performed at 7 days and 3, 6 and 12 months after stroke onset. The non‐diabetic with stress hyperglycemia groups were again divided into two groups who either received or did not receive intensive rehabilitation treatment. Serial functional outcome was compared between groups.

Results

For the ICH group, patients with stress hyperglycemia had worse modified Rankin Scale, National Institutes of Health Stroke Scale, Functional Ambulatory Category and Korean Mini‐Mental State Examination scores than patients without stress hyperglycemia. For the SAH group, patients with stress hyperglycemia had worse scores on all functional assessments than patients without stress hyperglycemia at all time‐points. After intensive rehabilitation treatment of patients with stress hyperglycemia, the ICH group had better scores on Functional Ambulatory Category and the SAH group had better scores on all functional assessments than patients without intensive rehabilitation treatment.

Conclusions

Stress hyperglycemia affects the long‐term prognosis of non‐diabetic hemorrhagic stroke patients. Among stress hyperglycemia patients, intensive rehabilitation can enhance functional improvement after stroke.

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Authors:
J. A. Yoon, D. Y. Kim, M. K. Sohn, J. Lee, S.‐G. Lee, Y.‐S. Lee, E. Y. Han, M. C. Joo, G.‐J. Oh, J. Han, S. W. Lee, M. Park, W. H. Chang, Y.‐I. Shin and Y.‐H. Kim
Article first published online:
22 Jul 2016 | DOI: 10.1111/ene.13101

Original Article

Background and purpose

Repetitive transcranial magnetic stimulation (rTMS) changes the excitability of the motor cortex and thereby has the potential to enhance motor recovery after stroke. This randomized, sham‐controlled, double‐blind study was to compare the effects of high‐frequency versus low‐frequency rTMS on motor recovery during the early phase of stroke and to identify the neurophysiological correlates of motor improvements.

Methods

A total of 69 first‐ever ischemic stroke patients with motor deficits were randomly allocated to receive five daily sessions of 3‐Hz ipsilesional rTMS, 1‐Hz contralesional rTMS or sham rTMS in addition to standard physical therapy. Outcome measures included motor deficits, neurological scores and cortical excitability, which were assessed at baseline, after the intervention and at 3‐month follow‐up.

Results

The rTMS groups manifested greater motor improvements than the control group, which were sustained for at least 3 months after the end of the treatment sessions. 1‐Hz rTMS over the unaffected hemisphere produced more profound effects than 3‐Hz rTMS in facilitating upper limb motor performance. There was a significant correlation between motor function improvement and motor cortex excitability change in the affected hemisphere.

Conclusions

Repetitive transcranial magnetic stimulation is a beneficial neurorehabilitative strategy for enhancing motor recovery in the acute and subacute phase after stroke.

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Authors:
J. Du, L. Tian, W. Liu, J. Hu, G. Xu, M. Ma, X. Fan, R. Ye, Y. Jiang, Q. Yin, W. Zhu, Y. Xiong, F. Yang and X. Liu
Article first published online:
18 Jul 2016 | DOI: 10.1111/ene.13105

Original Article

Background and purpose

Very little is known about the progression of non‐motor symptoms (NMSs) in Parkinson's disease (PD) and there are no longitudinal studies exploring this topic from the earliest stage, when patients receive the diagnosis. We here report on the progression of NMSs over 4 years from diagnosis in a cohort of , previously untreated, patients with PD.

Methods

Consecutive (disease duration < 2 years), untreated patients with PD were enrolled in this observational study. Evaluations were then scheduled every 2 years and included assessment of motor and non‐motor features as well as of quality of life measures.

Results

Sixty‐one patients were prospectively followed‐up for 4 years from diagnosis. The majority of NMSs increased over time and significantly affected quality of life, whereas motor disability did not. There was no significant association between NMSs and dopaminergic therapy in terms of both drug class and total levodopa‐equivalent daily dosage. Excessive daytime sleepiness was the only NMS correlating with therapy with dopamine agonists. Female patients were more likely to have worse quality of life.

Conclusions

Non‐motor symptoms significantly increase over time, with a different progression rate for each one. NMSs significantly affect quality of life in PD and we here demonstrated that this was especially the case when patients were in their (motor) honeymoon period. Future trials should target non‐dopaminergic networks and consider NMSs in their outcomes.

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Authors:
R. Erro, M. Picillo, C. Vitale, M. Amboni, M. Moccia, G. Santangelo, M. T. Pellecchia and P. Barone
Article first published online:
20 Jul 2016 | DOI: 10.1111/ene.13106

Editorial

Abstract

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Authors:
C. Colosimo and R. Bhidayasiri
Article first published online:
09 Sep 2016 | DOI: 10.1111/ene.13123

Editorial

Outcome scores in status epilepticus – predicting the complex clinical situation

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Authors:
S. Jayalakshmi and S. Vooturi
Article first published online:
09 Sep 2016 | DOI: 10.1111/ene.13124

Letter to the Editor

Abstract

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Authors:
T. Kawada
Article first published online:
18 Oct 2016 | DOI: 10.1111/ene.13126

Editorial

Abstract

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Authors:
D. P. Richman
Article first published online:
18 Oct 2016 | DOI: 10.1111/ene.13169

Calendar

Calendar

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Authors:
Article first published online:
18 Oct 2016 | DOI: 10.1111/ene.13188