cover image European Journal of Neurology

European Journal of Neurology

2020 - Volume 27
Issue 5 | May 2020
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Original Article

Background and purpose

Visual snow syndrome is a recently described condition of unknown prevalence. We investigated the prevalence in a representative population sample from the UK and tested the hypothesis that visual snow syndrome is associated with young age, headache, tinnitus and mood impairment.

Methods

Using a crowdsourcing platform, we recruited a representative sample of 1015 adult laypeople from the UK, matched for age, gender and ethnicity according to national census data. Participants were unprimed, i.e. were inquired about the ‘frequency of certain medical conditions’ but not ‘visual snow syndrome’.

Results

A total of 38 of 1015 participants reported symptoms compatible with visual snow [3.7%; 95% confidence interval (CI), 2.7–5.2] and 22/1015 met criteria for visual snow syndrome (2.2%; 95% CI, 1.4–3.3). The female‐to–male ratio for visual snow syndrome was 1.6:1. Subjects with visual snow syndrome were older (50.6 ± 14 years) than the population mean (44.8 ± 15 years), although this was not statistically different ( = 0.06). Of 22 participants with visual snow syndrome, 16 had mood symptoms (72.7%;  = 0.01), 12 had headache (54.5%;  = 0.06), including five with visual migraine aura (22.7%;  = 0.15) and 13 had tinnitus (59.1%;  < 0.001). No participant had diabetes or a cleft lip (control questions). Following a multivariable regression analysis to adjust for age and gender, only the association between visual snow syndrome and tinnitus remained significant (odds ratio, 3.93; 95% CI, 1.63–9.9;  = 0.003).

Conclusions

The UK prevalence of visual snow syndrome is around 2%. We confirmed an association with tinnitus, but unprimed laypeople with visual snow syndrome are on average older than those seeking medical attention.

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Authors:
D. Kondziella, M. H. Olsen and J. P. Dreier
Article first published online:
23 Feb 2020 | DOI: 10.1111/ene.14150

EAN Guideline

Background and purpose

Patients with acquired brain injury and acute or prolonged disorders of consciousness (DoC) are challenging. Evidence to support diagnostic decisions on coma and other DoC is limited but accumulating. This guideline provides the state‐of‐the‐art evidence regarding the diagnosis of DoC, summarizing data from bedside examination techniques, functional neuroimaging and electroencephalography (EEG).

Methods

Sixteen members of the European Academy of Neurology (EAN) Scientific Panel on Coma and Chronic Disorders of Consciousness, representing 10 European countries, reviewed the scientific evidence for the evaluation of coma and other DoC using standard bibliographic measures. Recommendations followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The guideline was endorsed by the EAN.

Results

Besides a comprehensive neurological examination, the following suggestions are made: probe for voluntary eye movements using a mirror; repeat clinical assessments in the subacute and chronic setting, using the Coma Recovery Scale – Revised; use the Full Outline of Unresponsiveness score instead of the Glasgow Coma Scale in the acute setting; obtain clinical standard EEG; search for sleep patterns on EEG, particularly rapid eye movement sleep and slow‐wave sleep; and, whenever feasible, consider positron emission tomography, resting state functional magnetic resonance imaging (fMRI), active fMRI or EEG paradigms and quantitative analysis of high‐density EEG to complement behavioral assessment in patients without command following at the bedside.

Conclusions

Standardized clinical evaluation, EEG‐based techniques and functional neuroimaging should be integrated for multimodal evaluation of patients with DoC. The state of consciousness should be classified according to the highest level revealed by any of these three approaches.

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Authors:
D. Kondziella, A. Bender, K. Diserens, W. van Erp, A. Estraneo, R. Formisano, S. Laureys, L. Naccache, S. Ozturk, B. Rohaut, J. D. Sitt, J. Stender, M. Tiainen, A. O. Rossetti, O. Gosseries and C. Chatelle
Article first published online:
23 Feb 2020 | DOI: 10.1111/ene.14151

Original Article

Background and purpose

The aim was to investigate the relationship between the serum urate (UA) levels and patterns of striatal dopamine depletion in patients with Parkinson’s disease (PD).

Methods

In all, 167 PD patients who underwent F‐fluorinated ‐3‐fluoropropyl‐2‐beta‐carboxymethoxy‐3‐beta‐(4‐iodophenyl) nortropane positron emission tomography scans were enrolled. After quantifying dopamine transporter (DAT) availability in each striatal subregion, sex‐dependent patterns of striatal dopamine depletion were analysed by measuring (i) dopamine depletion in the other striatal subregions and posterior putamen (intersubregional ratio, ISR) and (ii) the interhemispheric asymmetry of dopamine depletion in the posterior putamen (asymmetric ratio, AR).

Results

The interaction analysis revealed a significant interaction effect of sex and serum UA levels on the ISR but not on the AR. The ISR was negatively correlated with the serum UA levels in all patients with PD ( = −0.156,  = 0.045), and this association was more prominent in male PD patients ( = −0.422,  < 0.001). However, no significant association between the AR and serum UA levels was found in any of the patients. In addition, serum UA levels were significantly associated with DAT availability in the posterior putamen on both the more affected side ( = 0.312,  = 0.005) and the less affected side ( = 0.312,  = 0.005) only in male PD patients.

Conclusions

The present study demonstrated the potentially close sex‐specific relationship between the serum UA levels and the anterior–posterior gradient of DAT patterns, suggesting a sex‐specific protective effect of UA on nigrostriatal dopaminergic neurons in PD.

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Authors:
K. Baik, S. J. Chung, H. S. Yoo, Y. H. Lee, J. H. Jung, Y. H. Sohn and P. H. Lee
Article first published online:
20 Feb 2020 | DOI: 10.1111/ene.14152

Original Article

Background and purpose

The purpose of this study was to evaluate the safety and effectiveness of mechanical thrombectomy (MT) in patients with acute ischaemic stroke related to isolated and primary posterior cerebral artery (PCA) occlusions amongst the patients enrolled in the multicentre post‐market Trevo Registry.

Method

Amongst the 2008 patients enrolled in the Trevo Registry with acute ischaemic stroke due to large vessel occlusion treated by MT, 22 patients (1.1%) [10 females (45.5%), mean age 66.2 ± 14.3 years (range 28–91)] had a PCA occlusion [17 P1 (77.3%) and five P2 occlusions (22.7%)]. Recanalization after the first Trevo (Stryker, Fremont, CA, USA) pass and at the end of the procedure was rated using the modified Thrombolysis in Cerebral Infarction (mTICI) score. Procedure‐related complications (i.e. groin puncture complication, perforation, symptomatic haemorrhage, embolus in a new territory) were also recorded. The modified Rankin Scale at 90 days was assessed.

Results

Median National Institutes of Health Stroke Scale at admission was 14 (interquartile range 8–16). Stroke aetiology was cardio‐embolic in 68.2% of cases. Half of the patients (11/22) received intravenous tissue plasminogen activator. 54.5% of the patients were treated under general anaesthesia. Reperfusion (i.e. mTICI 2b or 3) after first pass was obtained in 65% of cases. Final mTICI 2b–3 reperfusion was obtained in all cases. Only one (4.5%) procedure‐related complication was recorded (puncture site) that resolved after surgery. At 90‐day follow‐up, modified Rankin Scale 0–2 was obtained in 59% of the patients and 9.1% died within the first 3 months after MT.

Conclusion

Mechanical thrombectomy for PCA occlusions seems to be safe (<5% procedure‐related complications) and effective. Larger repository datasets are needed.

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Authors:
F. Clarençon, F. Baronnet, E. Shotar, V. Degos, C. Rolla‐Bigliani, B. Bartolini, E. Veznedaroglu, R. Budzik, J. English, B. Baxter, D. S. Liebeskind, A. Krajina, R. Gupta, S. Miralbes, A. Lüttich, R. G. Nogueira, Y. Samson, S. Alamowitch and N.‐A. Sourour
Article first published online:
21 Feb 2020 | DOI: 10.1111/ene.14154

Original Article

Background and purpose

In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) introduced a novel pooled cohort risk (PCR) model for atherosclerotic cardiovascular disease. In this study, we evaluated the relationship between the PCR score and cerebral large‐ and small‐vessel diseases (cLVD and cSVD) in a healthy population,

Methods

We assessed consecutive health check‐up volunteers from 2006 to 2013. We calculated the estimated 10‐year atherosclerotic cardiovascular disease risk as the PCR score based on the 2013 ACC/AHA guidelines. We evaluated both cSVD/cLVD, including the prevalence of cLVD, lacunes and cerebral microbleed (CMB), and the volume of white matter hyperintensity (WMH). In addition to PCR score, the risk factors that were associated with outcome variables at  < 0.10 in univariate analysis were included for further multivariable linear or regression analyses.

Results

A total of 2720 participants were evaluated (mean age, 57 years, male sex, 54%). In multivariable analysis, PCR score was associated with WMH volume [ = 0.361; 95% confidence interval (CI), 0.320–0.402,  < 0.001], cLVD [adjusted odds ratio (aOR), 1.66; 95% CI, 1.29–2.16,  < 0.001], lacunes (aOR, 1.80; 95% CI, 1.52–2.14,  < 0.001) and CMBs (aOR, 1.75; 95% CI, 1.40–2.19,  < 0.001). Furthermore, PCR score also showed dose‐response tendencies according to the burden of cLVD, WMH, lacunes and CMB.

Conclusions

A higher PCR score based on the ACC/AHA guidelines is closely associated with a higher prevalence and burden of cLVD and cSVD.

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Authors:
K.‐W. Nam, H.‐M. Kwon, H.‐Y. Jeong, J.‐H. Park, H. Kwon and S.‐M. Jeong
Article first published online:
14 Feb 2020 | DOI: 10.1111/ene.14155

Original Article

Background and purpose

The aim was to explore the risk of early stroke recurrence within 3 months after watershed infarction and to investigate whether early dual antiplatelet therapy is more effective in decreasing such risk.

Methods

Patients enrolled in the Clopidogrel in High‐risk Patients with Acute Non‐disabling Cerebrovascular Events (CHANCE) trial and who had acute infarction on diffusion‐weighted imaging were included in this subgroup analysis. All magnetic resonance images were read centrally by two neurologists who were blinded to the patients’ baseline and outcome information. The primary outcome was any stroke recurrence within 3 months. The hazard ratios were adjusted by known predictors of stroke recurrence.

Results

Of the 1089 patients with magnetic resonance imaging data enrolled in CHANCE, 834 (76.58%) patients had acute infarcts on diffusion‐weighted imaging. The median and range of duration from randomization to stroke recurrence was 1.5 (1–6) days. Patients with watershed infarction had higher risk of stroke recurrence than those without (17.20% vs. 6.34%) within the first week after initial stroke; the hazard ratio (95% confidence interval) was 2.799 (1.536–5.101) adjusted by age, sex, smoking, body mass index, medical history, time to randomization, open‐label aspirin dose at first day, single or dual antiplatelet therapy, National Institutes of Health Stroke Scale score at randomization, in‐hospital treatment and white matter lesions,  < 0.001. There was no interaction between antiplatelet therapy and the presence of watershed infarction ( = 0.544).

Conclusions

Minor stroke with watershed infarction has high recurrent risk in the first week. Dual antiplatelet therapy may be safely implemented, yet watershed infarction mechanisms of hypoperfusion and emboli may not be addressed.

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Authors:
Y. Pu, X. Liu, Y. Wang, X. Meng, J. Jing, X. Zou, Y. Pan, A. Wang, X. Zhao, S. C. Johnston, Y. Wang, K. Atchaneeyasakul, D. S. Liebeskind and L. Liu
Article first published online:
03 Mar 2020 | DOI: 10.1111/ene.14156

Original Article

Background and purpose

Plaque neovascularization is a hallmark of carotid plaque vulnerability. With contrast‐enhanced ultrasound (CEUS) it is possible to visualize plaque neovessels . Our aim was to determine if CEUS‐detected neovessels were associated with stroke recurrences in patients with a recent stroke and carotid atherosclerosis.

Methods

We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the internal carotid artery on the side consistent with symptoms. All of our patients underwent a carotid ultrasound examination including a CEUS study. Neovascularization was graded into three categories according to the extent of neovessels. During the follow‐up, we recorded stroke recurrences. A multivariable Cox regression analysis was performed to evaluate predictors of recurrence.

Results

We included 78 patients whose mean age was 74.3 ± 10.4 years. There were 29 (37.2%) patients with a low‐grade stenosis (<50%). The remainder presented moderate (50%–69%) or high‐grade (≥70%) stenosis. CEUS was not interpretable in 35.9% of the patients, mainly due to calcium shadows. We detected neovascularization in 80% of the plaques. After a median follow‐up of 14.1 (interquartile range, 9.5‐19.6) months, there were 15 (19.2%) stroke recurrences. In the Cox regression analysis, CEUS‐detected neovascularization was independently associated with the risk of stroke recurrence, even after adjusting for the degree of stenosis (hazard ratio, 6.57; 95% confidence interval, 1.66–26.01).

Conclusion

In patients with an anterior circulation ischaemic stroke and carotid atherosclerosis, plaque neovascularization detected with CEUS was an independent predictor of stroke recurrence.

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Authors:
P. Camps‐Renom, L. Prats‐Sánchez, F. Casoni, J. M. González‐de‐Echávarri, P. Marrero‐González, I. Castrillón, R. Marín, E. Jiménez‐Xarrié, R. Delgado‐Mederos, A. Martínez‐Domeño, D. Guisado‐Alonso and J. Martí‐Fàbregas
Article first published online:
16 Feb 2020 | DOI: 10.1111/ene.14157

Original Article

Background and purpose

We investigated 952 subjects undergoing diagnostic lumbar puncture (LP) to study the effects of needle size, needle design and stylet reinsertion on the risk of post‐dural puncture headache (PDPH).

Methods

This randomized double‐blind study was performed at Umeå University Hospital in Sweden during 2013–2018. Subjects were randomly assigned one of three needles [22 gauge (G) atraumatic, 25G atraumatic and 25G cutting] and stylet reinsertion before needle withdrawal or not. The main outcome measure was PDPH assessed by standardized telephone interview(s) 5 days after the LP, repeated until headache cessation. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PDPH.

Results

The mean (SD) age was 51.1 (16.7) years and 53.6% were females. The smaller bore (25G) atraumatic needle incurred a lower risk of headache compared with the larger bore (22G) atraumatic needle [22.0% (69/314) vs. 30.2% (98/324); OR, 0.65; 95% CI, 0.45–0.93] and compared with the cutting needle [32.8% (103/314); OR, 0.58; 95% CI, 0.40–0.82]. Reinserting the stylet before needle withdrawal did not reduce the risk of headache.

Conclusions

These data suggest that a 25G atraumatic needle is superior to a larger atraumatic needle, and to a same‐sized cutting needle, in preventing PDPH after diagnostic LP. In contrast to one earlier report, this study did not find that stylet reinsertion was effective in preventing PDPH. This study provides class I evidence that a small atraumatic needle decreases the risk of PDPH and that stylet reinsertion does not influence PDPH risk.

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Authors:
J. Salzer, G. Granåsen, P. Sundström, M. Vågberg and A. Svenningsson
Article first published online:
20 Feb 2020 | DOI: 10.1111/ene.14158

Original Article

Background and purpose

Early neurological deterioration (END) occurs in 20%–30% of patients with lacunar stroke and challenges their clinical management. This retrospective cohort study analyzed clinical and neuroimaging risk factors predicting the occurrence of END, the functional outcome after END and potential benefit from dual antiplatelet therapy (DAPT) in patients with lacunar strokes.

Methods

Factors associated with END and benefit from DAPT were retrospectively analyzed in 308 patients with lacunar stroke symptoms and detected lacunar infarction by magnetic resonance imaging. END was defined by deterioration of ≥3 total National Institutes of Health Stroke Scale (NIHSS) points, ≥2 NIHSS points for limb paresis or documented deterioration within 5 days after admission. Patients were treated with DAPT according to in‐house standards. The primary efficacy end‐point for functional outcome was fulfilled if NIHSS at discharge improved after END at least to the score at admission.

Results

Male gender [odds ratio (OR) 2.08; 95% confidence interval (CI) 1.09–4.00], higher age (OR = 1.65 per 10 years; 95% CI 1.18–2.31), motor paresis (OR = 18.89, 95% CI 4.66–76.57) and infarction of the internal capsule or basal ganglia (OR = 3.58, 95% CI 1.26–10.14) were associated with an increased risk for END. A larger diameter of infarction (OR = 0.85, 95% CI 0.76–0.95), more microangiopathic lesions (OR = 0.75, 95% CI 0.57–0.99) and pontine localization (OR = 0.29, 95% CI 0.12–0.65) were factors associated with unfavorable functional outcome after END occurred. Localization in the internal capsule or basal ganglia was identified as a significant predictive factor for a benefit from DAPT after END.

Conclusions

Identified clinical and neuroimaging factors predicting END occurrence, functional outcome after END and potential benefit from DAPT might improve the clinical management of patients with lacunar strokes.

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Authors:
A. Berberich, C. Schneider, C. Herweh, T. Hielscher, T. Reiff, M. Bendszus, C. Gumbinger and P. Ringleb
Article first published online:
18 Feb 2020 | DOI: 10.1111/ene.14159

Original Article

Background and purpose

The purpose was to determine the test–retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self‐administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression‐based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example.

Methods

Substudy 1 assessed test–retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples.

Results

The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician‐administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample.

Conclusions

The self‐administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting.

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Authors:
S. M. Rao, R. Galioto, M. Sokolowski, M. McGinley, J. Freiburger, M. Weber, T. Dey, L. Mourany, D. Schindler, C. Reece, D. M. Miller, F. Bethoux, R. A. Bermel, J. R. Williams, N. Levitt, G. A. Phillips, J. K. Rhodes, J. Alberts and R. A. Rudick
Article first published online:
02 Mar 2020 | DOI: 10.1111/ene.14162

Original Article

Background and purpose

Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia lasting up to 24 h. One major differential for TGA is transient epileptic amnesia, which typically lasts < 1 h. However, TGA can also be short in duration and little is known about the time trends, characteristics and prognosis of TGA cases lasting < 1 h.

Methods

We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK [Oxford cohort 1977–1987 versus Oxford Vascular Study (OXVASC) 2002–2018] to determine the time trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy [Northern Umbria TGA registry (NU) 2002–2018]. We compared the risk factors, clinical features and long‐term prognosis (major cardiovascular events, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting < 1 h versus those lasting ≥ 1 h.

Results

Overall, 639 patients with TGA were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared with the original Oxford cohort, there were more cases with TGA lasting < 1 h in OXVASC [32 (32.0%) vs. 9 (8.8%)] and NU (11.8% vs. 8.8% in Oxford cohort). In both OXVASC and NU, patient age, vascular risk factors and clinical features were largely similar between those with TGA lasting < 1 h versus those lasting ≥ 1 h. Moreover, there was no difference in the long‐term risk of seizure/epilepsy or major cardiovascular events between TGA lasting < 1 h versus TGA lasting ≥ 1 h.

Conclusions

Short‐duration TGA episodes (<1 h) were not uncommon and were more frequent than in earlier studies. The clinical features and long‐term prognosis of short‐duration TGA did not differ from more typical episodes lasting ≥ 1 h.

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Authors:
M. Romoli, M. A. Tuna, L. Li, M. Paciaroni, D. Giannandrea, F. Tordo Caprioli, A. Lotti, P. Eusebi, M. G. Mosconi, M. Pellizzaro Venti, N. Salvadori, A. Gili, S. Ricci, F. Stracci, P. Sarchielli, L. Parnetti, P. M. Rothwell and P. Calabresi
Article first published online:
26 Feb 2020 | DOI: 10.1111/ene.14163

Original Article

Background and purpose

There is no clear consensus among current guidelines on the preferred admission ward [i.e. intensive care unit (ICU) or stroke unit (SU)] for patients with intracerebral hemorrhage. Based on expert opinion, the American Heart Association and European Stroke Organization recommend treatment in neurological/neuroscience ICUs (NICUs) or SUs. The European Stroke Organization guideline states that there are no studies available directly comparing outcomes between ICUs and SUs.

Methods

We performed an observational study comparing outcomes of 10 811 consecutive non‐comatose patients with intracerebral hemorrhage according to admission ward [ICUs, SUs and normal wards (NWs)]. Primary outcomes were the modified Rankin Scale score at discharge and intrahospital mortality. An additional analysis compared NICUs with SUs.

Results

Treatment outside an SU was associated with higher odds for an unfavorable outcome [ICU vs. SU: odds ratio (OR), 1.27; 95% confidence interval (CI), 1.09–1.46; NW vs. SU: OR, 1.28; 95% CI, 1.08–1.52] and higher odds for intrahospital mortality (ICU vs. SU: OR, 2.11; 95% CI, 1.75–2.55; NW vs. SU: OR, 1.52; 95% CI, 1.23–1.89). A subgroup analysis of severely affected patients treated in dedicated NICUs (vs. SUs) showed that they had a lower risk of a poor outcome (OR, 0.45; 95% CI, 0.26–0.79).

Conclusions

Treatment in SUs was associated with better functional outcome and reduced mortality compared with ICUs and NWs. Our findings support the current guideline recommendations to treat patients with intracerebral hemorrhage in SUs or NICUs and suggest that some patients may further benefit from NICU treatment.

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Authors:
M. N. Ungerer, P. Ringleb, B. Reuter, C. Stock, F. Ippen, S. Hyrenbach, I. Bruder, P Martus, C. Gumbinger, Martin Schabet, Karin Schoser, Michael Daffertshofer, Stephan Neumaier, Rita Sorge, Elke Drewitz and Sonja Hyrenbach
Article first published online:
06 Mar 2020 | DOI: 10.1111/ene.14164

Editorial Commentary

Diagnosing consciousness

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Authors:
V. De Herdt
Article first published online:
06 Mar 2020 | DOI: 10.1111/ene.14165

Original Article

Background and purpose

Subjective cognitive decline (SCD) is a self‐experienced decline in cognitive capacity with normal performance on standardized cognitive tests and has been shown to increase the risk of Alzheimer’s disease (AD). SCD could also be related to other conditions such as normal aging, psychiatric, neurological or medical disorders. The SCD Initiative proposed a set of features (SCD‐plus) that increase the likelihood of preclinical AD in individuals with SCD. Our aim was to assess the effect of these features on the risk of conversion from SCD to AD.

Methods

In total 150 SCD subjects who underwent extensive neuropsychological investigation, assessment of cognitive complaints and apolipoprotein E (ApoE) genotyping at baseline and clinical‐neuropsychological follow‐up for a mean time of 11 years were included.

Results

During the follow‐up, 20 subjects developed AD. Considering SCD‐plus features, age at onset ≥60 years and ApoE ε4 significantly increased the risk of conversion from SCD to AD. When our sample was stratified into three groups (no risk factor, one risk factor, two risk factors), the proportion of conversion was statistically significantly different between the three groups.

Conclusions

Our model allows the risk of AD to be stratified in patients experiencing SCD according to age at onset and ApoE genotype.

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Authors:
S. Mazzeo, S. Padiglioni, S. Bagnoli, M. Carraro, I. Piaceri, L. Bracco, B. Nacmias, S. Sorbi and V. Bessi
Article first published online:
08 Mar 2020 | DOI: 10.1111/ene.14167

Letters to the Editor

Response to ‘Do different treatment strategies of galcanezumab have similar effect on migraine?’

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Authors:
P. J. Goadsby, G. M. Terwindt, D. D. Ruff, J. H. Ford, A. Tockhorn‐Heidenreich, V. L. Stauffer, S. Govindan and S. K. Aurora
Article first published online:
02 Mar 2020 | DOI: 10.1111/ene.14168

Original Article

Background and purpose

It remains unclear whether smoking status has an impact on platelet reactivity and clinical outcomes of ticagrelor versus clopidogrel in patients with acute minor stroke or transient ischaemic attack (TIA).

Methods

A subgroup analysis of a randomized controlled trial was conducted. Patients with minor stroke or TIA were randomized for treatment with ticagrelor plus aspirin or clopidogrel plus aspirin. Platelet reactivity was assessed by VerifyNow P2Y12 assay at baseline, 7 + 2 days and 90 ± 7 days. High on‐treatment platelet reactivity (HOPR) was defined as P2Y12 reaction units >208. Clinical outcomes included any stroke, composite clinical vascular events and bleeding events at 90 days. Patients who smoked one or more cigarettes per day for at least 1 year in their lives were defined as smokers.

Results

Of 675 patients enrolled in the trial, 370 patients (54.8%) were smokers. At 7 + 2 days, the proportion of HOPR in ticagrelor versus clopidogrel was significantly lower in smokers (5.2% vs. 21.8%) and non‐smokers (2.3% vs. 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR ( = 0.058). At 90 ± 7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers: 7.0% vs. 4.9%; hazard ratio, 1.57; 95% confidence interval, 0.65–3.79;  = 0.39; non‐smokers: 5.3% vs. 13.5%; hazard ratio, 0.39; 95% confidence interval, 0.17–0.91;  = 0.01; for interaction = 0.02).

Conclusions

Among patients with minor stroke or TIA, ticagrelor was superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of new stroke, particularly for non‐smokers.

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Authors:
Y. Yang, W. Chen, X. Meng, L. Liu, Y. Wang, Y. Pan and Y. Wang
Article first published online:
08 Mar 2020 | DOI: 10.1111/ene.14171

Original Article

Background and purpose

Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated.

Methods

Trial participation required a recent embolic stroke of undetermined source. Patients’ history of cancer was recorded at the time of study entry. During a mean follow‐up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all‐cause mortality were compared between patients with cancer and patients without cancer.

Results

Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non‐cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78–1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71–2.87). Amongst cancer patients, the annual rate of major bleeds was non‐significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67–9.96; for interaction 0.95). All‐cause mortality was similar in both groups.

Conclusions

Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all‐cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. (NCT02313909).

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Authors:
N. Martinez‐Majander, G. Ntaios, Y. Y. Liu, P. Ylikotila, H. Joensuu, J. Saarinen, K. S. Perera, J. Marti‐Fabregas, A. Chamorro, S. Rudilosso, L. Prats‐Sanchez, S. D. Berkowitz, H. Mundl, E. Themeles, M. Tiainen, A. Demchuk, S. E. Kasner, R. G Hart and T. Tatlisumak
Article first published online:
11 Mar 2020 | DOI: 10.1111/ene.14172

Short Communication

Background and purpose

We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation.

Methods

The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K‐ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence.

Results

Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHADS‐VASc score were not significantly different between patients with and without recurrent stroke.

Conclusions

A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

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Authors:
J.‐M. Kim, K.‐Y. Park, I.‐W. Yu, T.‐J. Song, Y.‐J. Kim, B. J. Kim, S. H. Heo, J.‐M. Jung, K.‐M. Oh, C. K. Kim, S. Yu, J.‐H. Park, J. C. Choi, M.‐S. Park, J.‐T. Kim, K.‐H. Choi, Y.‐H. Hwang, J.‐W. Chung, O. Y. Bang, G.‐M. Kim and W.‐K. Seo
Article first published online:
13 Mar 2020 | DOI: 10.1111/ene.14175

Original Article

Background and purpose

The aim was to investigate whether probable rapid eye movement sleep behavior disorder (pRBD) is associated with impulse control disorders (ICDs) in drug‐naïve patients with Parkinson’s disease (PD) and whether baseline pRBD is associated with a higher incidence of ICDs during follow‐up.

Methods

The Parkinson’s Progression Markers Initiative is an international, multicenter, prospective cohort study to identify biomarkers of PD progression. In all, 423 drug‐naïve patients with early‐stage PD were included in the cross‐sectional analysis, and 320 patients who screened negative for any ICDs or related behaviors at baseline were included in the longitudinal analysis.

Results

In the cross‐sectional analysis, a significant correlation was found between pRBD and ICDs in drug‐naïve patients whilst controlling for potential confounders [odds ratio 2.56, 95% confidence interval (CI) 1.38–4.76,  = 0.003]. In the longitudinal analysis, baseline pRBD was an independent predictor of ICD development over time [hazard ratio (HR) 1.648, 95% CI 1.054–2.576;  = 0.028]. Other significant predictors of ICDs included younger age of onset (HR = 0.973, 95% CI = 0.950–0.997;  = 0.026) and greater State‐Trait Anxiety Inventory score (HR = 1.040, 95% CI = 1.020–1.061;  < 0.001).

Conclusion

Our data suggest that identifying baseline pRBD in early‐stage PD may help clinicians to choose a better therapeutic strategy so as to prevent or limit neuropsychiatric complications.

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Authors:
R. Cao, X. Chen, F. Xing, C. Xie, P. Hu and K. Wang
Article first published online:
16 Mar 2020 | DOI: 10.1111/ene.14177

Original Article

Background and purpose

The aim was to investigate the clinical impact of the duration of artificial ventilation in stroke patients receiving mechanical thrombectomy (MT) under general anaesthesia.

Methods

All consecutive ischaemic stroke patients who had been treated at our centre with MT for anterior circulation large vessel occlusion under general anaesthesia were identified over an 8‐year period. Ventilation time was analysed as a continuous variable and patients were grouped into extubation within 6 h (‘early’), 6–24 h (‘delayed’) and >24 h (‘late’). Favourable outcome was defined as modified Rankin Scale scores of 0–2 at 3 months post‐stroke. Pneumonia rate and reasons for prolonged ventilation were also assessed.

Results

Amongst 447 MT patients (mean age 69.1 ± 13.3 years, 50.1% female), the median ventilation time was 3 h. 188 (42.6%) patients had a favourable 3‐month outcome, which correlated with shorter ventilation time (Spearman’s rho 0.39,  < 0.001). In patients extubated within 24 h, early compared to delayed extubation was associated with improved outcome (odds ratio 2.40, 95% confidence interval 1.53–3.76,  < 0.001). This was confirmed in multivariable analysis ( = 0.01). A longer ventilation time was associated with a higher rate of pneumonia during neurointensive care unit/stroke unit stay (early/delayed/late extubation: 9.6%/20.6%/27.7%,  < 0.01). Whilst stroke‐associated complications represented the most common reasons for late extubation (>24 h), delayed extubation (6–24 h) was associated with admission outside of core working hours ( < 0.001).

Conclusions

Prolonged ventilation time after stroke thrombectomy independently predicts unfavourable outcome at 3 months and is associated with increased pneumonia rates. Therefore, extubation should be performed as early as safely possible.

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Authors:
S. Fandler‐Höfler, S. Heschl, M. Kneihsl, P. Argüelles‐Delgado, K. Niederkorn, A. Pichler, H. Deutschmann, F. Fazekas, A. Berghold, C. Enzinger and T. Gattringer
Article first published online:
17 Mar 2020 | DOI: 10.1111/ene.14178

Original Article

Background and purpose

Several studies have indicated that altered serotonergic neurotransmission may contribute to non‐motor features commonly associated with Parkinson's disease (PD) such as apathy and depression. 5‐hydroxytryptophan (5‐HTP) is the intermediate metabolite of L‐tryptophan in the production of serotonin. To date, there has been inconsistent research on the use of 5‐HTP in PD. The purpose of this study was to compare the effects of 5‐HTP with those of placebo on apathy and depressive symptoms in patients with PD.

Methods

A single‐center, randomized, double‐blind placebo‐controlled cross‐over trial was employed; 25 individuals were subsequently enrolled into the study. Patients received placebo and 50 mg of 5‐HTP daily over a period of 4 weeks. For the assessment of efficacy on depressive and apathy symptoms the Beck Depression Inventory‐II (BDI‐II), Hamilton Depression Rating Scale (HDRS) and Apathy Scale (AS) were respectively administered at screening, baseline and weeks 4, 8, 12 and 16. Primary efficacy outcomes were the comparison of 5‐HTP to placebo in mean change from baseline to weeks 4, 8, 12 and 16 in total score on the AS, BDI‐II and HDRS.

Results

Repeated‐measures analysis revealed a significant improvement of depressive symptoms during the 50‐mg 5‐HTP treatment compared with placebo as assessed by the HDRS. No effect of 5‐HTP was seen on apathy symptoms assessed by the AS.

Conclusions

This study provides preliminary evidence of clinical benefit of 5‐HTP for treating depressive symptoms in PD. Larger studies with a longer treatment duration are needed to corroborate these early findings.

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Authors:
M. Meloni, M. Puligheddu, M. Carta, A. Cannas, M. Figorilli and G. Defazio
Article first published online:
13 Mar 2020 | DOI: 10.1111/ene.14179

Original Article

Background and purpose

Among patients with an acute ischaemic stroke secondary to large‐vessel occlusion, the hypoperfusion intensity ratio (HIR) [time to maximum (TMax) > 10 volume/TMax > 6 volume] is a strong predictor of infarct growth. We studied the correlation between HIR and collaterals assessed with digital subtraction angiography (DSA) before thrombectomy.

Methods

Between January 2014 and March 2018, consecutive patients with an acute ischaemic stroke and an M1 middle cerebral artery (MCA) occlusion who underwent perfusion imaging and endovascular treatment at our center were screened. Ischaemic core (mL), HIR and perfusion mismatch (TMax > 6 s minus core volume) were assessed through magnetic resonance imaging or computed tomography perfusion. Collaterals were assessed on pre‐intervention DSA using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale. Baseline clinical and perfusion characteristics were compared between patients with good (ASITN/SIR score 3–4) and those with poor (ASITN/SIR score 0–2) DSA collaterals. Correlation between HIR and ASITN/SIR scores was evaluated using Pearson’s correlation. Receiver operating characteristic analysis was performed to determine the optimal HIR threshold for the prediction of good DSA collaterals.

Results

A total of 98 patients were included; 49% (48/98) had good DSA collaterals and these patients had significantly smaller hypoperfusion volumes (TMax > 6 s, 89 vs. 125 mL;  = 0.007) and perfusion mismatch volumes (72 vs. 89 mL;  = 0.016). HIR was significantly correlated with DSA collaterals (−0.327; 95% confidence interval, −0.494 to −0.138;  = 0.01). An HIR cut‐off of <0.4 best predicted good DSA collaterals with an odds ratio of 4.3 (95% confidence interval, 1.8–10.1) (sensitivity, 0.792; specificity, 0.560; area under curve, 0.708).

Conclusion

The HIR is a robust indicator of angiographic collaterals and might be used as a surrogate of collateral assessment in patients undergoing magnetic resonance imaging. HIR <0.4 best predicted good DSA collaterals.

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Authors:
A. Guenego, R. Fahed, G. W. Albers, G. Kuraitis, E. S. Sussman, B. W. Martin, D. G. Marcellus, J.‐M. Olivot, M. P. Marks, M. G. Lansberg, M. Wintermark and J. J. Heit
Article first published online:
13 Mar 2020 | DOI: 10.1111/ene.14181

Original Article

Background and purpose

The p.R4810K variant was identified as a strong susceptibility in patients with Moyamoya disease (MMD). The aim of this study was to investigate the angiographic characteristics in MMD with the p.R4810K variant.

Methods

Angiographic characteristics were compared between patients with wild‐type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching, including Suzuki stage, collateral circulation and external carotid artery (ECA) collateral. Collateral circulation was graded with scores ranging from 0 to 12: posterior collateral circulation from the posterior cerebral artery to the middle cerebral artery and anterior cerebral artery was scored from 0 to 6; anterior collateral circulation was scored as 6 to 0 corresponding to Suzuki stages 0 to 6.

Results

A total of 489 patients were screened; 133 pairs were obtained after 1:1 propensity score matching. Compared with the patients in the GA group, unilateral MMD was more frequent in the GG group ( = 0.026). Hemispheres in the GA group (86/266) had more posterior cerebral artery involvement than hemispheres in the GG group (48/266) ( < 0.001). Hemispheres in the GA group had a lower grade in collateral circulation than hemispheres in the GG group ( = 0.011), but ECA collateral was more frequently observed in the GA group than in the GG group (53.4% vs. 39.8%,  = 0.002). Superficial temporal artery and occipital artery collateral was more frequently observed in the GA group than in the GG group ( < 0.05).

Conclusions

Patients in the GA group had lower grades in collateral circulation than patients in the GG group, but ECA collateral was more frequently observed in the GA group than in the GG group.

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Authors:
P. Ge, Q. Zhang, X. Ye, X. Liu, X. Deng, J. Wang, R. Wang, Y. Zhang, D. Zhang and J. Zhao
Article first published online:
16 Mar 2020 | DOI: 10.1111/ene.14184

Editorial Commentary

For how long is memory lost in transient global amnesia?

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Authors:
P. Caramelli
Article first published online:
16 Mar 2020 | DOI: 10.1111/ene.14187

Editorial Commentary

Oral anticoagulant interruption and stroke: are we doing our best?

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Authors:
P. A. Kowacs
Article first published online:
08 Apr 2020 | DOI: 10.1111/ene.14218

Issue Information

Issue Information

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Authors:
Article first published online:
20 Apr 2020 | DOI: 10.1111/ene.14232