cover image European Journal of Neurology

European Journal of Neurology

2016 - Volume 23
Issue 8 | August 2016
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Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.12863

Original Article

Background and purpose

Few studies exist on long‐term post‐stroke depressive symptoms and anxiety in young adults, although these young patients have a particular interest in their long‐term prognosis, given their usually long life expectancy and being in the midst of an active social, working and family life. The aims of this study were to investigate the prevalence of depressive symptoms and anxiety and their association with clinical and demographic variables and with functional outcome after stroke in young adults.

Methods and results

Long‐term prevalence of depressive symptoms and anxiety was calculated in 511 patients with a transient ischaemic attack or ischaemic stroke, aged 18–50 years, using the Hospital Anxiety and Depression scale, compared with 147 controls. Functional outcome was assessed with the modified Rankin Score (mRS) and the Instrumental Activities of Daily Living scale (IADL). 16.8% of patients had depressive symptoms and 23.0% had anxiety, versus 6.1% ( = 0.001) and 12.2% ( < 0.001) in controls. In ischaemic stroke patients, depressive symptoms and anxiety were associated with poor functional outcome (mRS > 2 or IADL < 8).

Conclusion

Even a decade after stroke at young age, depressive symptoms and anxiety were prevalent and associated with poor functional outcome. Therefore, even in the long term, treating physicians should be aware of the long‐term presence of these symptoms as their recognition may be the first step in improving long‐term functional independence.

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Authors:
N. A. M. M. Maaijwee, I. Tendolkar, L. C. A. Rutten‐Jacobs, R. M. Arntz, P. Schaapsmeerders, L. D. Dorresteijn, H. C. Schoonderwaldt, E. J. van Dijk and F.‐E. de Leeuw
Article first published online:
20 Apr 2016 | DOI: 10.1111/ene.13009

Original Article

Background and purpose

Aneurysmal subarachnoid hemorrhage (SAH) survivors often complain of fatigue, which is disabling. Fatigue is also a common symptom of pituitary dysfunction (PD), in particular in patients with growth hormone deficiency (GHD). A possible association between fatigue after SAH and long‐term pituitary deficiency in SAH survivors has not yet been established.

Methods

A single center observational study was conducted amongst 84 aneurysmal SAH survivors to study the relationship between PD and fatigue over time after SAH, using mixed model analysis. Fatigue was measured with the Fatigue Severity Scale and its relationships with other clinical variables were studied.

Results

Three‐quarters of respondents (76%) have pathological fatigue directly after SAH and almost two‐thirds (60%) of patients still have pathological levels of fatigue after 14 months. The severity of SAH measured with a World Federation of Neurosurgical Societies (WFNS) score higher than 1 ( = 0.008) was associated with long‐term fatigue. There is no statistically significant effect of PD ( = 0.8) or GHD ( = 0.23) on fatigue in SAH survivors over time.

Conclusions

Fatigue is a common symptom amongst SAH survivors. WFNS is a usable clinical determinant of fatigue in SAH survivors. Neither PD nor GHD has a significant effect on long‐term fatigue after SAH.

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Authors:
L. Khajeh, G. M. Ribbers, M. H. Heijenbrok‐Kal, K. Blijdorp, D. W. J. Dippel, E. M. Sneekes, H. J. G. van den Berg‐Emons, A. J. van der Lely, S. J. C. M. M. Neggers and F. van Kooten
Article first published online:
29 Apr 2016 | DOI: 10.1111/ene.13014

Original Article

Background and purpose

Night‐time sleep disturbances are important non‐motor symptoms and key determinants of health‐related quality of life (HRQoL) in patients with Parkinson's disease (PD). The Parkinson's KinetiGraph (PKG) can be used as an objective measure of different motor states and periods of immobility may reflect episodes of sleep. Our aim was to evaluate whether PKG can be used as an objective marker of disturbed night‐time sleep in PD.

Methods

In this prospective comparative study, data from PKG recordings over six consecutive 24 h periods are compared with Hauser diaries and scales focusing on motor state, sleep and HRQoL in PD patients. Thirty‐three ‘non‐sleepy’ PD patients (PD‐NS) were compared with 30 PD patients presenting with excessive daytime sleepiness (PD‐EDS). The groups were matched for age, gender and Hoehn and Yahr state.

Results

In the PD‐EDS group subjective sleep reports correlated with the PKG's parameters for quantity and quality night‐time sleep, but not in the PD‐NS group. There were no significant correlations of the night‐time sleep quantity parameters of the Hauser diary with subjective sleep perception, neither in the PD‐EDS nor in the PD‐NS group.

Conclusions

This first PKG based study of night‐time sleep in PD suggests that PKG could be used to provide an easy to use and rough evaluation of aspects of night‐time sleep and one that could flag patients where polysomnography may be required. In sleepy PD patients for instance, quantity and quality PKG parameters correlate with different aspects of sleep such as insomnia, parasomnia and restless legs syndrome.

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Authors:
L. Klingelhoefer, A. Rizos, A. Sauerbier, S. McGregor, P. Martinez‐Martin, H. Reichmann, M. Horne and K. R. Chaudhuri
Article first published online:
10 May 2016 | DOI: 10.1111/ene.13015

Original Article

Background and purpose

Investigation of the relationship between mitochondrial DNA (mtDNA) variants and Parkinson disease (PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking.

Methods

The index mtDNA variants and their defining mitochondrial haplogroup were determined in 725 PD patients and 744 non‐PD controls. Full‐length mtDNA sequences were also conducted in 110 cases harboring various haplogroups. Cybrid cellular models, composed by fusion of mitochondria‐depleted rho‐zero cells and donor mitochondria, were used for a rotenone‐induced PD simulation study.

Results

Multivariate logistic regression analysis revealed that subjects harboring the mitochondrial haplogroup B5 have resistance against PD (odds ratio 0.50, 95% confidence interval 0.32–0.78; = 0.002). Furthermore, a composite mtDNA variant group consisting of A10398G and G8584A at the coding region was found to have resistance against PD (odds ratio 0.50, 95% confidence interval 0.33–0.78; = 0.001). In cellular studies, B4 and B5 cybrids were selected according to their higher resistance to rotenone, in comparison with cybrids harboring other haplogroups. The B5 cybrid, containing G8584A/A10398G variants, showed more resistance to rotenone than the B4 cybrid not harboring these variants. This is supported by findings of low reactive oxygen species generation and a low apoptosis rate in the B5 cybrid, whereas a higher expression of autophagy was observed in the B4 cybrid particularly under medium dosage and longer treatment time with rotenone.

Conclusions

Our studies, offering positive results from clinical investigations and cybrid experiments, provide data supporting the role of variant mtDNA in the risk of PD.

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Authors:
C. W. Liou, J. H. Chuang, J. B. Chen, M. M. Tiao, P. W. Wang, S. T. Huang, T. L. Huang, W. C. Lee, S. W. Weng, P. H. Huang, S. D. Chen, R. S. Chen, C. S. Lu and T. K. Lin
Article first published online:
10 May 2016 | DOI: 10.1111/ene.13020

Original Article

Background and purpose

Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb‐kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger and hand movements, may contribute to impaired dexterity even more than bradykinesia . However, the impact of limb‐kinetic apraxia on ADL remains controversial. Our aim was to identify the strongest predictor of buttoning and unbuttoning in PD. It was hypothesized that coin rotation (a surrogate of limb‐kinetic apraxia) represents the most important determinant.

Methods

Sixty‐four right‐handed, early to moderate PD patients were recruited from three movement disorder centers (Hoehn andYahr stages 1–3). Buttoning, unbuttoning and coin rotation (right and left hand) represented the target tasks. Motor impairment was assessed according to the Unified Parkinson's Disease Rating Scale.

Results

Multiple linear regression analysis showed that coin rotation with the right hand was the only significant predictor of buttoning ( < 0.001) and unbuttoning ( = 0.002). Notably, measures of bradykinesia or overall motor impairment did not represent significant predictors.

Conclusions

Constituting the novel key finding, limb‐kinetic apraxia seems to be particularly relevant for ADL requiring dexterity skills in PD, even at early to moderate disease stages. Our results prompt research into the pathophysiological background and therapeutic options to treat limb‐kinetic apraxia. The simple coin rotation test provides valuable information about ADL‐related dexterity skills.

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Authors:
T. Foki, T. Vanbellingen, C. Lungu, W. Pirker, S. Bohlhalter, T. Nyffeler, J. Kraemmer, D. Haubenberger, F. Ph. S. Fischmeister, E. Auff, M. Hallett and R. Beisteiner
Article first published online:
01 May 2016 | DOI: 10.1111/ene.13021

Original Article

Background and purpose

Alterations in the gut microbial community composition may be influential in neurological disease. Microbial community profiles were compared between early onset pediatric multiple sclerosis (MS) and control children similar for age and sex.

Methods

Children ≤18 years old within 2 years of MS onset or controls without autoimmune disorders attending a University of California, San Francisco, USA, pediatric clinic were examined for fecal bacterial community composition and predicted function by 16S ribosomal RNA sequencing and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. Associations between subject characteristics and the microbiota, including beta diversity and taxa abundance, were identified using non‐parametric tests, permutational multivariate analysis of variance and negative binomial regression.

Results

Eighteen relapsing−remitting MS cases and 17 controls (mean age 13 years; range 4–18) were studied. Cases had a short disease duration (mean 11 months; range 2–24) and half were immunomodulatory drug (IMD) naïve. Whilst overall gut bacterial beta diversity was not significantly related to MS status, IMD exposure was (Canberra, < 0.02). However, relative to controls, MS cases had a significant enrichment in relative abundance for members of the (, and ) and depletion in and (all and < 0.000005). Microbial genes predicted as enriched in MS versus controls included those involved in glutathione metabolism (Mann−Whitney, = 0.017), findings that were consistent regardless of IMD exposure.

Conclusions

In recent onset pediatric MS, perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration. Findings were suggestive of a pro‐inflammatory milieu.

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Authors:
H. Tremlett, D. W. Fadrosh, A. A. Faruqi, F. Zhu, J. Hart, S. Roalstad, J. Graves, S. Lynch, E. Waubant, Greg Aaen, Anita Belman, Leslie Benson, T. Charles Casper, Tanuja Chitnis, Mark Gorman, Yolanda Harris, Lauren Krupp, Tim E Lotze, Jayne Ness, Cody Olsen, Moses Rodriguez, John Rose, Timothy C Simmons, Jan‐Mendelt Tillema and Bianca Weinstock‐Guttman
Article first published online:
13 May 2016 | DOI: 10.1111/ene.13026

Original Article

Background and purpose

Transcranial sonography (TCS) of the brain parenchyma is used to visualize alterations in the substantia nigra (SN) and it is applied for early diagnosis of Parkinson's disease. Our aim was to explore specific echogenic alterations of the SN in dementia with Lewy bodies (DLB) compared to Alzheimer's disease (AD).

Methods

Seventy‐one subjects underwent TCS: 22 DLB, 28 AD and 21 healthy elderly controls. Cognitive impairment, extrapyramidal signs, visual hallucinations, fluctuations and rapid eye movement sleep behaviour symptoms were investigated. TCS assessed SN hyperechogenicity and symmetry.

Results

Transcranial sonography revealed SN hyperechogenicity in 100% of DLB compared to 50% of AD and 30% of controls. Mean SN echogenic area (cm) was 0.22 ± 0.03 in DLB, 0.15 ± 0.03 in AD and 0.14 ± 0.03 in controls ( < 0.0001). More than 50% of DLB presented a marked hyperechogenicity (cutoff value >0.22 cm) compared to only 10% of AD ( < 0.0003). DLB had symmetrical SN enlargement, whereas AD were mostly asymmetrical ( = 0.015). A combination of SN echogenic area and asymmetry index had a sensitivity of 88.9% and a specificity of 81.2% in discriminating DLB from AD (positive predictive value 85.7%, negative predictive value 85.7%). No association was found between SN hyperechogenicity and Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination or the presence of visual hallucinations.

Conclusions

Transcranial sonography may be a valid supportive tool in the diagnostic workup of neurodegenerative dementia helping clinicians to distinguish DLB from AD even at the early stages.

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Authors:
S. Favaretto, U. Walter, C. Baracchini, S. Pompanin, C. Bussè, G. Zorzi, M. Ermani and A. Cagnin
Article first published online:
01 May 2016 | DOI: 10.1111/ene.13028

Original Article

Background and purpose

Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated. The relation between education level and suicidality has not been investigated in MS patients. Our objective was to estimate attempted suicide and completed suicide risks amongst MS patients.

Methods

A total of 29 617 Swedish MS patients were identified through the Swedish Patient Register and matched with 296 164 people without MS from the general population. Cox regression analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education and calendar period.

Results

The adjusted HR for attempted suicide amongst MS patients is 2.18 (95% CI 1.97–2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (95% CI 1.53–2.30). In both groups women are at higher risk of attempting suicide, whilst men are at higher risk of completing suicide. Education level is inversely associated with completed suicide amongst the non‐MS cohort (0.68, 0.51–0.91), but not amongst MS patients (1.10, 0.60–2.04).

Conclusion

Multiple sclerosis patients are at higher risk of both attempted and completed suicide. No evidence was found of an inverse association between educational level and risk of completed suicide amongst MS patients.

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Authors:
P. Brenner, S. Burkill, J. Jokinen, J. Hillert, S. Bahmanyar and S. Montgomery
Article first published online:
27 Apr 2016 | DOI: 10.1111/ene.13029

Original Article

Background and purpose

The association between the presence of cerebral microbleeds (CMBs) and serum vascular endothelial growth factor (VEGF) levels in patients with Alzheimer's disease (AD) was investigated.

Methods

Consecutive AD patients who underwent magnetic resonance examination with susceptibility‐weighted imaging (SWI) were prospectively examined. The presence of CMBs on SWI was independently interpreted. The number and location of microbleeds were assessed. Demographics including age, sex and risk factors were obtained. Serum VEGF levels were measured with an enzyme‐linked immunosorbent assay.

Results

Of the 146 AD patients included, 47 (32.2%) patients had CMBs on SWI. The CMBs were most commonly located in strictly lobar locations (29/47, 61.7%). The mean VEGF levels were higher in the patients with CMBs than in those without (336.72 ± 15.18 vs. 192.37 ± 11.34 pg/ml). Multivariate logistic regression analyses showed that, for each 10 pg/ml increase of VEGF levels, there was a significant increase in the presence of CMBs after adjusting for age and sex, and after additional adjustment for cardiovascular risk factors, silent lacunar infarction and white matter hyperintensity in patients with AD (odds ratio 2.37; 95% confidence interval 1.53−4.02, = 0.004).

Conclusion

Serum VEGF levels are associated with the presence of CMBs in patients with AD.

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Authors:
J. B. Zhang, M. F. Li, H. X. Zhang, Z. G. Li, H. R. Sun, J. S. Zhang and P. F. Wang
Article first published online:
29 Apr 2016 | DOI: 10.1111/ene.13030

Original Article

Background and purpose

Charcot−Marie−Tooth (CMT) disease is the most common inherited neuropathy, but therapeutic options have been limited to symptom management. Past pharmacological trials have failed, possibly due to insensitive outcome measures (OMs). The aim of the current study was to evaluate the validity and reliability of the 6‐min walk test (6MWT) and StepWatch Activity Monitoring (SAM) with other previously validated OMs in CMT disease.

Methods

A prospective multicenter study was performed, consecutively enrolling 168 CMT patients (104 with CMT1A, 27 with CMT1B, 37 with X‐linked CMT) from Italian centers specializing in CMT care.

Results

Statistical analysis showed that the 6MWT was highly related with all previously used OMs. Some, but not all, SAM parameters were related to commonly used OMs but may provide more information about quality of life.

Conclusions

The current study demonstrated the validity and reliability of the 6MWT and SAM as OMs for CMT. Moreover, SAM provides data that correlate better with quality of life measures, making it useful in future rehabilitation trials.

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Authors:
L. Padua, C. Pazzaglia, D. Pareyson, A. Schenone, A. Aiello, G. M. Fabrizi, T. Cavallaro, L. Santoro, F. Manganelli, F. Gemignani, F. Vitetta, A. Quattrone, A. Mazzeo, M. Russo, G. Vita, L. Gentile, S. Messina, C Stancanelli, G.L. Vita, C. Iacovelli, D. Figliolia, S. Silipo, I. Cabrini, C. Pisciotta, S. Tozza and M. Contini
Article first published online:
10 May 2016 | DOI: 10.1111/ene.13033

CME Article

Background and purpose

Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated primarily with dopamine agonist (DA) use. Comparative surveys of clinical occurrence of impulse control behaviours on longer acting/transdermal DA therapy across age ranges are lacking. The aim of this study was to assess the occurrence of ICDs in PD patients across several European centres treated with short‐ or long‐acting [ropinirole (ROP); pramipexole (PPX)] and transdermal [rotigotine skin patch (RTG)] DAs, based on clinical survey as part of routine clinical care.

Methods

A survey based on medical records and clinical interviews of patients initiating or initiated on DA treatment (both short‐ and long‐acting, and transdermal) across a broad range of disease stages and age groups was performed.

Results

Four hundred and twenty‐five cases were included [mean age 68.3 years (range 37–90), mean duration of disease 7.5 years (range 0–37)]. ICD frequencies (as assessed by clinical interview) were significantly lower with RTG (4.9%; < 0.05) compared with any other assessed DAs except for prolonged release PPX (PPX‐PR). The rate of ICDs for PPX‐PR (6.6%) was significantly lower than for immediate release PPX (PPX‐IR) (19.0%; < 0.05). Discontinuation rates of DA therapy due to ICDs were low.

Conclusion

Our data suggest a relatively low rate of ICDs with long‐acting or transdermal DAs, however these preliminary observational data need to be confirmed with prospective studies controlling for possible confounding factors.

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Authors:
A. Rizos, A. Sauerbier, A. Antonini, D. Weintraub, P. Martinez‐Martin, B. Kessel, T. Henriksen, C. Falup‐Pecurariu, M. Silverdale, G. Durner, K. Røkenes Karlsen, M. Grilo, P. Odin and K. Ray Chaudhuri
Article first published online:
11 May 2016 | DOI: 10.1111/ene.13034

Original Article

Background and purpose

Emerging research suggests the use of self‐regulation (SR) for improving functional regain in patients post stroke. SR is proposed to produce an added effect to effective modified constraint‐induced movement therapy (mCIMT). This study aimed to examine the effect of a self‐regulated mCIMT programme (SR‐mCIMT) for functional regain in patients with sub‐acute stroke.

Methods

Eighty‐six patients completed the trial: SR‐mCIMT, = 29; mCIMT, = 31; or conventional functional rehabilitation, = 26. All interventions were 2‐week therapist‐guided training. Outcome measurements, taken by a blinded assessor, examined arm function [Action Research Arm Test (ARAT), Fugl‐Meyer Assessment (FMA)], daily task performance [Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)] and self‐perceived arm use in functional tasks [Motor Activity Log (MAL)].

Results

Significant differences were found with the SR‐mCIMT outperforming the other groups after the intervention (ARAT, = 0.006; FMA, Lawton IADL and MAL, all s < 0.001). In terms of the carry‐over effect, the SR‐mCIMT group outperformed in the hand and coordination subscales of ARAT and FMA ( = 0.012–0.013) and the self‐perceived quality of arm use ( = 0.002).

Conclusion

A combination of SR and mCIMT could produce an added effect in functional regain in patients post stroke.

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Authors:
K. P. Y. Liu, K. Balderi, T. L. F. Leung, A. S. Y. Yue, N. C. W. Lam, J. T. Y. Cheung, S. S. M. Fong, C. M. W. Sum, M. Bissett, R. Rye and V. C. T. Mok
Article first published online:
19 May 2016 | DOI: 10.1111/ene.13037

Original Article

Background and purpose

Magnetic resonance diffusivity indices have been repeatedly proposed as biomarkers of neurodegeneration in amyotrophic lateral sclerosis (ALS), but no consensus exists as to which diffusivity parameter is the most sensitive to identify early degenerative changes. Despite numerous studies, surprisingly little is known of the segmental vulnerability of the corticospinal tracts and corpus callosum. Our objective was to characterize the core three‐dimensional white matter signature of ALS, to describe phenotype‐specific patterns of white matter degeneration and to evaluate the diffusivity profile of individual patients and controls in specific white matter segments.

Methods

A large neuroimaging study was undertaken with 62 patients and 55 age‐matched healthy controls. White matter alterations were explored based on fractional anisotropy and radial, mean and axial diffusivity indices. Atlas‐based region of interest analyses were carried out in the corona radiata, internal capsules, cerebral peduncles, and in the splenium, body and genu of the corpus callosum. Percentage change and receiver operating characteristic (ROC) curves were used to characterize disease‐state discriminating diffusivity measures and white matter regions.

Results

Bulbar onset patients exhibit extensive corticobulbar tract involvement in the genu of the internal capsule and in the lateral fibres of the corona radiata subjacent to the bulbar representation of the motor homunculus. Spinal onset patients show predominantly posterior internal capsule involvement and medial corona radiata pathology. ROC curve analyses revealed that diffusivity measures of the cerebral crura best discriminate patients and controls (area under the curve 80.1%).

Conclusions

Amyotrophic lateral sclerosis is associated with a core, disease‐specific three‐dimensional white matter signature which is best demonstrated by radial diffusivity measurements. The main ALS motor phenotypes are manifestations of the relatively selective involvement of corticospinal and corticobulbar fibres.

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Authors:
C. Schuster, M. Elamin, O. Hardiman and P. Bede
Article first published online:
21 May 2016 | DOI: 10.1111/ene.13038

Letter to the Editor

Long sleep duration: an epiphenomenon or a risk for stroke?

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Authors:
M. Nagai, K. Dote, M. Kato, S. Sasaki and N. Oda
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13039

Original Article

Background and purpose

Glucocorticoids (GCs) are the mainstay treatment of myasthenia gravis (MG). However, wide inter‐individual variability exists in the response to GCs.

Methods

A Chinese cohort of 257 MG patients treated with GCs was evaluated for the association between 19 single nucleotide polymorphisms in the gene and clinical response to the initial 3 month GC therapy. A quantitative MG score decreasing by ≥3 units or becoming zero was defined as sensitivity to GCs.

Results

The rs17209237* G allele was less frequent in the GC insensitive group compared with the GC sensitive group [ = 0.013, odds ratio (OR) 0.119]. The rs9324921* A allele was more frequent in the GC insensitive group than in the GC sensitive group ( = 0.046, OR 1.94). Carriers of the rs17209237 G allele were less frequent in the GC insensitive group than in the GC sensitive group (dominant model, = 0.009). Carriers of the rs9324921 A allele were more frequent in the GC insensitive group than in the GC sensitive group (dominant model, = 0.037). Multivariate logistic regression revealed that the rs17209237 G allele carrier ( = 0.037, OR 0.12) and disease duration before GC treatment ( = 0.011, OR 3.45) were independent factors that contributed to GC efficacy.

Conclusion

rs17209237 in the gene was identified as an independent factor that contributes to GC efficacy in MG patients. The genetic variations of the gene may play a role in predicting response to GC treatment.

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Authors:
Y. Xie, Y. Meng, H.‐F. Li, Y. Hong, L. Sun, X. Zhu, Y.‐X. Yue, X. Gao, S. Wang, Y. Li, L. L. Kusner and H. J. Kaminski
Article first published online:
17 May 2016 | DOI: 10.1111/ene.13040

Letter to the Editor

Beevor's sign: a potential clinical marker for myopathy

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Authors:
V. Preethish‐Kumar, O. Pogoryelova, K. Polavarapu, N. Gayathri, V. Seena, J. Hudson, I. Nishino, C. Prasad, H. Lochmüller and A. Nalini
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13041

Original Article

Background and purpose

The impact of intravenous recombinant tissue plasminogen activator (IV‐rtPA) in patients with acute ischaemic stroke (AIS) but no arterial occlusion is currently a matter of debate. This study aimed to assess functional outcome of such patients with respect to IV‐rtPA use.

Methods

A retrospective case−control analysis was performed comparing the outcome of AIS patients without arterial occlusion with or without IV‐rtPA use. Patients were selected from prospective consecutive observational registries of five European university hospitals. The primary study outcome was excellent outcome at 3 months after stroke, as defined by a modified Rankin Scale (mRS) 0–1.

Results

A total of 488 patients without arterial occlusion documented by angiography were included in the present study; 300 received IV‐rtPA and 188 did not. No between‐group difference was found for excellent outcome before and after adjustment for baseline characteristics (adjusted odds ratio for no IV‐rtPA use 0.79, 95% confidence interval 0.51–1.24, = 0.31). Similar results were found for favourable outcome (defined as a 90‐day mRS of 0–2) whereas a higher rate of early neurological improvement was found in IV‐rtPA‐treated patients (adjusted odds ratio 1.99; 95% confidence interval 1.29–3.07, = 0.002). Sensitivity analyses yielded similar results.

Conclusions

Our study suggests that AIS patients without visible arterial occlusion treated with IV‐rtPA may have no better outcome at 3 months than those untreated. However, only a randomized controlled trial would provide a definitive answer about the impact of rtPA in acute stroke patients without occlusion. Until then, these patients should be treated by rtPA as recommended.

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Authors:
N. Ajili, J. P. Decroix, C. Preda, J. Labreuche, D. Lopez, Y. Bejot, P. Michel, M. Sévin‐Allouet, I. Sibon, S. Vergnet, A. Wang, N. Sanda, M. Mazighi, F. Bourdain and B. Lapergue
Article first published online:
24 May 2016 | DOI: 10.1111/ene.13042

Letter to the Editor

European Association of Young Neurologists and Trainees in 2016: the year of changes and the introduction of the Residents and Research Fellows section of the European Academy of Neurology

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Authors:
V. Papp, P. Balicza, A. Sauerbier, L. Klingelhöfer, P. Zis, O. Gyorfi and A. Macerollo
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13044

Letter to the Editor

Response to the letter on ‘Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta‐analyses’

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Authors:
S. Bisenius, J. Neumann and M. L. Schroeter
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13046

Letter to the Editor

Response to the comment ‘Long sleep duration: an epiphenomenon or a risk for stroke?’

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Authors:
T. J. Kim, S.‐B. Ko and B.‐W. Yoon
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13047

Letter to the Editor

Antecedent ADHD and risk of dementia: is there a role for air pollution exposures? A reply to Golimstok . (2011)

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Authors:
K. Fluegge
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13048

Letter to the Editor

Mitochondrial neuropathy: considerations on pathogenesis

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Authors:
M. Luigetti, D. Sauchelli, G. Primiano, C. Cuccagna, D. Bernardo, M. Lo Monaco and S. Servidei
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13049

Letter to the Editor

Dantrolene as a possible prophylactic treatment for ‐related rhabdomyolysis

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Authors:
R. S. Scalco, N. C. Voermans, R. J. Piercy, H. Jungbluth and R. Quinlivan
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13051

Letter to the Editor

Hitting two birds with one stone: daily scheduled opioids in preventing migraine and migraine‐related epilepsy (migralepsy)

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Authors:
I. Derakhshan
Article first published online:
19 Jul 2016 | DOI: 10.1111/ene.13058