cover image European Journal of Neurology

European Journal of Neurology

2018 - Volume 25
Issue 5 | May 2018
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Original Article

Background and purpose

Many epidemiological studies of Guillain−Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends.

Method

Seventy‐one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined.

Results

The incidence rate of GBS was 0.42 cases per 100 000 person‐years and that of FS was 0.22 cases per 100 000 person‐years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients.

Conclusions

Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

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Authors:
N. Matsui, H. Nodera, D. Kuzume, N. Iwasa, Y. Unai, W. Sakai, Y. Miyazaki, H. Yamazaki, Y. Osaki, A. Mori, T. Furukawa, A. Tsukamoto‐Miyashiro, Y. Shimatani, M. Yamasaki, Y. Izumi, S. Kusunoki, K. Arisawa and R. Kaji
Article first published online:
01 Mar 2018 | DOI: 10.1111/ene.13569

Original Article

Background and purpose

The aim was to determine the predictors of focal hypoperfusion on computed tomography (CT) perfusion (CTP) in patients with acute posterior circulation stroke and its association with long‐term outcome.

Methods

Patients with posterior circulation stroke were selected from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) who underwent CTP within 24 h of stroke onset as part of the stroke imaging protocol. Hypoperfusion was defined as an area of visually well demarcated mean transit time prolongation corresponding to an arterial territory on standard reconstruction CTP imaging maps. Areas of hypoperfusion were assessed with the posterior circulation Acute Stroke Prognosis Early CT Score. Clinical and imaging associations with focal hypoperfusion were identified using multiple imputation analyses, and the adjusted functional outcome measured by the modified Rankin Scale at 3 and 12 months was determined.

Results

Of the 3595 consecutive patients from the ASTRAL registry between 2003 and 2014, 1070 (29.7%) had a posterior circulation stroke and 436 of these (40.7%) patients had a good quality baseline CTP. 23.1% had early ischaemic changes and 37.4% had focal hypoperfusion. In multiple imputation analysis, visual field deficits, reduced level of consciousness, cardiac and multiple stroke mechanisms, significant vessel pathology and ischaemic changes visible on plain CT were associated with focal hypoperfusion. Focal hypoperfusion was independently associated with outcome at 12 months (odds ratio 2.04, 95% confidence interval 1.22–3.42,  < 0.01).

Conclusions

In posterior circulation stroke patients undergoing acute CTP, multiple clinical, aetiological and radiological variables were associated with focal hypoperfusion. Patients with focal hypoperfusion had a worse 12‐month outcome.

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Authors:
L.‐P. Pallesen, D. Lambrou, A. Eskandari, J. Barlinn, K. Barlinn, H. Reichmann, V. Dunet, P. Maeder, V. Puetz and P. Michel
Article first published online:
13 Mar 2018 | DOI: 10.1111/ene.13578

CME Article

Background and purpose

Misdiagnosis of refractory epilepsy (rE) is common and such patients experience a long diagnostic delay. Our aim was to identify key clinical/laboratory factors in order to obtain an alternative diagnosis in patients referred for rE.

Methods

Between January 2010 and December 2015, 125 consecutive patients with a diagnosis of rE were prospectively enrolled. All patients underwent a comprehensive neurological, neuropsychiatric and cardiological evaluation, and had an observation time of at least 1 year after the study entry.

Results

Diagnosis of rE was confirmed in 104/125 (83.2%) patients (55 women, mean age 38.8 ± 14.3 years). Thirteen/125 patients (10.4%, seven women, mean age 50.8 ± 20.9) were diagnosed with syncope, which was cardiac/cardio inhibitory in 9/13 (69%). The remaining 8/125 patients (6.4%, six women, mean age 41.2 ± 14.6 years) were diagnosed with psychogenic non‐epileptic seizures. Age at onset had a high accuracy in differentiating patients with syncope from others, with the best cut‐off age at 35 years and above. Abnormal brain magnetic resonance imaging (MRI) had a significant yield of about 70% in rE. A diagnostic model including age at onset and brain MRI was highly accurate in differentiating patients with syncope from others. In patients with cardiac/cardio inhibitory syncope, the point score of historical features was ≥1 and falsely favoured the diagnosis of epileptic seizures.

Conclusions

This prospective cohort study identifies rE mimics who are at high risk of morbidity and mortality. rE starting in adulthood should raise a high suspicion of cardiac syncope. Brain MRI is accurate in differentiating rE from other conditions.

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Authors:
A. Labate, L. Mumoli, A. Curcio, G. Tripepi, G. D'Arrigo, E. Ferlazzo, U. Aguglia, C. Indolfi, A. Quattrone and A. Gambardella
Article first published online:
01 Mar 2018 | DOI: 10.1111/ene.13579

Original Article

Background and purpose

The DAWN trial recently showed compelling evidence in treating late window and wake‐up stroke patients with thrombectomy using a clinical‐imaging mismatch. The aim was to evaluate the results of thrombectomy for unknown‐onset strokes (UOS) treated in our centres after a diffusion weighted imaging/fluid attenuated inversion recovery (DWI‐FLAIR) mismatch based selection.

Methods

A multicentre, cohort study was performed of consecutive UOS treated by thrombectomy between 2012 and 2016. UOS with proximal anterior circulation occlusion discovered beyond 6 h from ‘last seen normal’ were compared with known‐onset strokes (KOS) for whom thrombectomy was started within 6 h from onset. Time intervals were recorded from first time found abnormal. Results were adjusted for age, diabetes, hypertension, National Institutes of Health Stroke Scale, site of occlusion, DWI Alberta Stroke Programme Early CT Score, intravenous thrombolysis and use of general anaesthesia.

Results

Amongst 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a ‘last time seen well’ beyond 6 h and DWI‐FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 h. Favourable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, = 0.022). After pre‐specified adjustment, this difference was not significant (adjusted relative risk 0.91; 95% confidence interval 0.80–1.04; = 0.17). No differences were found in secondary outcomes. Time intervals from first found abnormal were significantly longer in UOS.

Conclusion

Thrombectomy of UOS with anterior circulation occlusion and DWI‐FLAIR mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h from onset. This pattern of imaging could be used for patient selection when time of onset is unknown.

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Authors:
S. Escalard, B. Gory, M. Kyheng, J.‐P. Desilles, H. Redjem, G. Ciccio, S. Smajda, J. Labreuche, M. Mazighi, M. Piotin, R. Blanc, B. Lapergue and R. Fahed
Article first published online:
01 Mar 2018 | DOI: 10.1111/ene.13580

Original Article

Background and purpose

The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management.

Methods

A steering committee of MS neurologists developed case‐ and practice‐based questions for two sequential surveys distributed to MS neurologists throughout Europe.

Results

Respondents generally favoured changing rather than stopping disease‐modifying treatment (DMT) in patients transitioning from relapsing−remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium‐enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice‐based questions and management are summarized.

Conclusions

Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence‐based recommendations and/or guidelines.

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Authors:
O. Fernández, M. Delvecchio, G. Edan, S. Fredrikson, G. Giovannoni, H.‐P. Hartung, E. Havrdova, L. Kappos, C. Pozzilli, P. S. Soerensen, B. Tackenberg, P. Vermersch and G. Comi
Article first published online:
28 Feb 2018 | DOI: 10.1111/ene.13581

Original Article

Background and purpose

Whereas intravenous thrombolysis (IVT) is allowed for acute ischaemic stroke in patients on vitamin K antagonists with international normalized ratio ≤1.7, there are no similar recommendations for patients on direct oral anticoagulants (DOACs), notably due to the lack of coagulation tests to assess the therapeutic effects. Although the literature is scarce, consisting of small case series and retrospective studies, considering the frequency of this situation the French Vascular Neurology Society and the French Study Group on Haemostasis and Thrombosis have worked on a joint position paper to provide a practical position regarding the emergency management of ischaemic stroke in patients on DOACs.

Method

Based on a review of the literature, the authors wrote a first text that was submitted to a broad panel of members from the two societies. The text was then amended by the authors to address experts’ comments and to reach a consensus.

Results

In patients with normal renal function and who stopped the DOAC for at least 48 h, the management should not differ from that in patients without oral anticoagulant. In patients who are still on DOACs, mechanical thrombectomy is encouraged preferentially when applicable in first line. Otherwise, when specific tests are available, values <50 ng/ml indicate that IVT is allowed. In the absence of specific tests, standard tests (thrombin time, prothrombin time and activated partial thromboplastin time) can be used for dabigatran and rivaroxaban, although interpretation of these tests may be less reliable. In some patients on dabigatran, idarucizumab may be used before IVT.

Conclusions

In this expert opinion paper, it is suggested that IVT can be performed in patients selected according to the time elapsed since the drug was last taken, renal function, type of hospital where the patient is admitted and plasma concentration of DOAC.

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Authors:
E. Touzé, Y. Gruel, I. Gouin‐Thibault, E. De Maistre, S. Susen, P. Sie and L. Derex
Article first published online:
09 Mar 2018 | DOI: 10.1111/ene.13582

Original Article

Background and purpose

The analysis of the spatial distribution of cases could give important cues on putative environmental causes of a disease. Our aim was to perform a spatial analysis of an amyotrophic lateral sclerosis (ALS) cohort from the Piedmont and Aosta Valley ALS register (PARALS) over a 20‐year period.

Methods

The address at the moment of diagnosis was considered for each ALS case. Municipalities’ and census divisions’ resident populations during the 1995–2014 period were obtained. A cluster analysis was performed adopting both Moran's index and the Kulldorff spatial scan statistic.

Results

A total of 2702 ALS patients were identified. An address was retrieved for 2671 (99%) patients. Moran's index was −0.01 ( value 0.83), thus revealing no clusters. SaTScan identified no statistically significant clusters. When census divisions were considered, Moran's index was 0.13 ( value 0.45); SaTScan revealed one statistically significant small cluster in the province of Alessandria. Here, 0.0099 cases were expected and three cases were observed (relative risk 304.60; 95% confidence interval 109.83–845.88, value 0.03).

Discussion

Our study showed a substantial homogeneous distribution of ALS cases in Piedmont and Aosta Valley. The population‐based setting and the adoption of proper statistical analyses strengthen the validity of our results. Such a finding further suggests the involvement of multiple environmental and genetic factors in ALS pathogenesis.

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Authors:
R. Vasta, A. Calvo, C. Moglia, S. Cammarosano, U. Manera, A. Canosa, F. D'Ovidio, L. Mazzini and A. Chiò
Article first published online:
25 Mar 2018 | DOI: 10.1111/ene.13586

Editorial

Abstract

Click to view the accompanying paper in this volume.

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Authors:
Z. T. Kincses and L. Vécsei
Article first published online:
27 Mar 2018 | DOI: 10.1111/ene.13591

Short Communication

Background and purpose

Acute onset of amnestic syndrome may represent a challenging diagnostic issue. In addition to non‐vascular etiology, thalamic strokes or infarction involving several temporal lobe structures have been reported.

Methods

We describe three patients in whom an isolated bilateral anterior fornix infarction presented with an acute amnestic syndrome. Clinical presentation, differential diagnosis and magnetic resonance images are discussed for each patient and vascular anatomy of the involved brain regions is also considered.

Results

Bilateral anterior columns of the fornix showed cytotoxic edema and bilateral narrowing of anterior cerebral artery was demonstrated.

Conclusions

We suggest that bilateral fornix infarction should always be considered in the diagnostic work‐up of an amnestic syndrome with acute onset.

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Authors:
A. Salvalaggio, A. Cagnin, L. Nardetto, R. Manara and C. Briani
Article first published online:
06 Mar 2018 | DOI: 10.1111/ene.13592

Editorial

Abstract

Click to view the accompanying paper in this volume.

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Authors:
A. I. Tröster
Article first published online:
06 Mar 2018 | DOI: 10.1111/ene.13593

Original Article

Background and purpose

In 2011, fingolimod was approved in Switzerland for the treatment of relapsing‐remitting multiple sclerosis (RRMS). The aim of the present study was to assess the effectiveness and retention of fingolimod in a real‐life Swiss setting, in which patients can receive fingolimod as both first‐ and second‐line treatment for RRMS.

Methods

This cross‐sectional, observational study with retrospective data collection was performed at 19 sites that comprised both hospitals and office‐based physicians across Switzerland. Sites were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 274 consenting adult patients with RRMS who had received treatment with fingolimod were analyzed.

Results

Mean treatment duration with fingolimod was 32 months. Under fingolimod, 77.7% of patients remained free from relapses and 90.3% did not experience disability progression. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was 72.1%. A total of 28.5% of patients had been RRMS treatment‐naïve prior to fingolimod therapy. High long‐term treatment retention rates ranging between 95.7% at 24 months and 87.8% at 36 months were observed.

Conclusion

In this Swiss cohort of naïve and pre‐treated subjects with RRMS, the majority of patients under fingolimod treatment showed freedom from relapses and disability progression. In addition, treatment retention rate over 2 and 3 years was high, irrespective of previous treatment.

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Authors:
C. Zecca, S. Roth, O. Findling, G. Perriard, V. Bachmann, M. L. Pless, A. Baumann, C. P. Kamm, P. H. Lalive and A. Czaplinski
Article first published online:
06 Mar 2018 | DOI: 10.1111/ene.13594

Original Article

Background and purpose

In‐hospital complications after stroke represent barriers to optimal recovery and are even potentially life‐threatening. Anemia is common in stroke patients and is related to poor outcome after stroke. Less is known, however, of the association of anemia with complications. We aimed to investigate the impact of anemia on a series of in‐hospital complications after ischemic stroke.

Methods

Consecutive patients with ischemic stroke within 7 days were included. Anemia on admission and its severity were defined according to World Health Organization criteria. Eight pre‐specified complications, such as pneumonia, gastrointestinal bleeding (GIB) and hemorrhagic transformation, were recorded during hospitalization.

Results

A total of 2647 patients were included. Anemia was present in 648 patients (24.5%), and 883 patients (33.4%) experienced at least one complication. Patients with anemia were more likely to experience one or more complications, pneumonia, GIB and thromboembolism (all <0.001) than patients without anemia. After adjustment for the confounders, patients with anemia had an adjusted odds ratio for at least one complication of 1.539 [95% confidence interval (CI), 1.232–1.923], for pneumonia of 1.707 (95% CI, 1.345–2.167), for GIB of 2.245 (95% CI, 1.215–4.148) and for thromboembolism of 3.443 (95% CI, 1.668–7.108). The risk of at least one complication, pneumonia, GIB and thromboembolism increased with anemia severity (all <0.05). There was no significant association between anemia and urinary tract infection, hemorrhagic transformation, seizures and brain herniation.

Conclusion

Anemia is an independent predictor of in‐hospital complications following stroke, especially for pneumonia, GIB and thromboembolism. It remains to be studied whether prophylaxis and treatment of anemia would prevent in‐hospital complications.

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Authors:
C.‐C. Wei, S.‐T. Zhang, G. Tan, S.‐H. Zhang and M. Liu
Article first published online:
09 Mar 2018 | DOI: 10.1111/ene.13595

Letter to the Editor

The dawn of unknown‐onset strokes

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Authors:
J. Li, S. Feng and Z. Xia
Article first published online:
17 Apr 2018 | DOI: 10.1111/ene.13597

Short Communication

Background and purpose

The aim was to determine the genetic background of unknown muscular dystrophy in five French families.

Methods

Twelve patients with limb girdle muscular dystrophy or distal myopathy were clinically evaluated. Gene mutations were identified using targeted exon sequencing and mutated DNAJB6 was tested .

Results

Five patients presented with distal lower limb weakness whilst others had proximal presentation with a variable rate of progression starting at the mean age of 38.5 years. Two novel mutations (c.284A>T, p.Asn95Ile, two families; and c.293_295delATG, p.Asp98del, one family) as well as the previously reported c.279C>G (p.Phe93Leu, two families) mutation in were identified. All showed a reduced capacity to prevent protein aggregation.

Conclusions

The mutational and phenotypical spectrum of ‐caused muscle disease is larger than previously reported, including also dysphagia. The originally reported c.279C>G (p.Phe93Leu) mutation is now identified in four different populations and appears to be a mutational hotspot. Our report confirms that some mutations cause distal‐onset myopathy and hence defects should be considered broadly in dominant muscular dystrophy families.

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Authors:
P. H. Jonson, J. Palmio, M. Johari, S. Penttilä, A. Evilä, I. Nelson, G. Bonne, N. Wiart, V. Meyer, A. Boland, J.‐F. Deleuze, C. Masson, T. Stojkovic, F. Chapon, N. B. Romero, G. Solé, X. Ferrer, A. Ferreiro, P. Hackman, I. Richard and B. Udd
Article first published online:
30 Mar 2018 | DOI: 10.1111/ene.13598

Editorial

Abstract

Click to view the accompanying paper in this volume.

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Authors:
W. Grisold
Article first published online:
13 Mar 2018 | DOI: 10.1111/ene.13599

Letter to the Editor

Heterozygous KIDINS220 mutation leads to spastic paraplegia and obesity in an Asian girl

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Authors:
L. Yang, W. Zhang, J. Peng and F. Yin
Article first published online:
17 Apr 2018 | DOI: 10.1111/ene.13600

Original Article

Background and purpose

Magnetic resonance imaging is part of the diagnostic criteria for Alzheimer's disease (AD) through the evaluation of hippocampal atrophy. The objective of this study was to evaluate which sequence of T1‐weighted (T1WI) and T2‐weighted (T2WI) imaging allowed the best visual evaluation of hippocampal atrophy.

Methods

Visual qualitative ratings of the hippocampus of 100 patients with mild cognitive impairment (MCI) and 50 patients with AD were made independently by four operators according to the medial temporal lobe atrophy score based either on T1WI or T2WI. These two evaluations were compared in terms of interobserver reproducibility, concordance with a quantitative volumetric measure, discrimination power between AD and MCI groups, and correlation with several neuropsychological tests.

Results

The medial temporal lobe atrophy score evaluated on either T1WI or T2WI exhibited similar interobserver variability and accordance with quantitative volumetric evaluation. However, the visual evaluation on T2WI seemed to provide better discrimination power between AD and MCI groups for both left (T1WI, = 0.0001; T2WI, = 7.072 × 10) and right (T1WI, = 0.008; T2WI, = 0.001) hippocampus, and a higher overall correlation with neuropsychological tests.

Conclusions

The present study suggests that T2WI provides a more adequate visual rating of hippocampal atrophy.

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Authors:
C. Fischbach‐Boulanger, A. Fitsiori, V. Noblet, S. Baloglu, H. Oesterle, S. Draghici, N. Philippi, E. Duron, O. Hanon, J.‐L. Dietemann, F. Blanc and S. Kremer
Article first published online:
09 Mar 2018 | DOI: 10.1111/ene.13601

Original Article

Background and purpose

Acute disseminated encephalomyelitis followed by optic neuritis (ADEM‐ON) is a rare demyelinating syndrome that is different from multiple sclerosis and neuromyelitis optica spectrum disorder. The aim of this study was to describe the disease course, treatment response and outcome of children with ADEM‐ON.

Methods

Children of <18 years of age were identified from six countries of the EU Paediatric Demyelinating Disease Consortium. Patients fulfilled the diagnostic criteria for ADEM followed by at least one ON. Anti‐myelin oligodendrocyte glycoprotein (MOG) antibodies were tested in all patients.

Results

In this study of 17 patients (nine boys) with ADEM‐ON, anti‐myelin oligodendrocyte glycoprotein (MOG) antibodies were identified in 16 patients. Age at onset was 6.1 years (interquartile range, 5.1–9.2 years). Twelve patients received oral prednisolone and 10 received maintenance immunosuppression (e.g. azathioprine, intravenous immunoglobulins, Rituximab). During a follow‐up of 5.3 years (interquartile range, 1.8–10.2 years), 54 relapses occurred with a median of 3 relapses per patient (range, 1–9 per patient). Patients relapsed on all treatments but no relapses occurred on a prednisolone dose >10 mg/day. Visual and cognitive residual deficits were common in this group.

Conclusions

Acute disseminated encephalomyelitis followed by optic neuritis is an anti‐MOG antibody‐associated relapsing disorder that can have a heterogeneous disease course. Patients were refractory for maintenance immunosuppression and appeared to be corticosteroid‐dependent. Further international collaborations are now required to unify guidelines in this difficult‐to‐manage group of patients.

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Authors:
Y. Y. M. Wong, Y. Hacohen, T. Armangue, E. Wassmer, H. Verhelst, C. Hemingway, E. D. van Pelt, C. E. Catsman‐Berrevoets, R. Q. Hintzen, K. Deiva, M. J. Lim, K. Rostásy and R. F. Neuteboom
Article first published online:
09 Mar 2018 | DOI: 10.1111/ene.13602

Letter to the Editor

Unilateral flapping tremor associated with internal carotid artery stenosis

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Authors:
T. Obayashi, T. Takeda, M. Iijima, Y. Shimizu, H. Yoshizawa and K. Kitagawa
Article first published online:
17 Apr 2018 | DOI: 10.1111/ene.13604

Letter to the Editor

Atrial fibrillation after acute intracerebral hemorrhage: how would the insular cortex damage interact?

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Authors:
M. Nagai, K. Dote, M. Kato and N. Oda
Article first published online:
17 Apr 2018 | DOI: 10.1111/ene.13605

Letter to the Editor

Ondine's curse and temporal lobe seizures: anti‐Hu‐ and Zic4‐associated paraneoplastic brainstem and limbic encephalitis

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Authors:
L. Kay, S. Bauer, A. R. Koczulla, D. Librizzi, D. Vadasz, S. Knake, F. Rosenow and A. Strzelczyk
Article first published online:
17 Apr 2018 | DOI: 10.1111/ene.13629

Calendar

Calendar

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Article first published online:
17 Apr 2018 | DOI: 10.1111/ene.13654