cover image European Journal of Neurology

European Journal of Neurology

2017 - Volume 24
Issue 8 | August 2017
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Short Communication

Background and purpose

Motor recovery after stroke can be characterized into two different patterns. A majority of patients recover about 70% of initial impairment, whereas some patients with severe initial deficits show little or no improvement. Here, we investigated whether recovery from visuospatial neglect and aphasia is also separated into two different groups and whether similar proportions of recovery can be expected for the two cognitive functions.

Methods

We assessed 35 patients with neglect and 14 patients with aphasia at 3 weeks and 3 months after stroke using standardized tests. Recovery patterns were classified with hierarchical clustering and the proportion of recovery was estimated from initial impairment using a linear regression analysis.

Results

Patients were reliably clustered into two different groups. For patients in the first cluster ( = 40), recovery followed a linear model where improvement was proportional to initial impairment and achieved 71% of maximal possible recovery for both cognitive deficits. Patients in the second cluster ( = 9) exhibited poor recovery (<25% of initial impairment).

Conclusions

Our findings indicate that improvement from neglect or aphasia after stroke shows the same dichotomy and proportionality as observed in motor recovery. This is suggestive of common underlying principles of plasticity, which apply to motor and cognitive functions.

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Authors:
N. A. Marchi, R. Ptak, M. Di Pietro, A. Schnider and A. G. Guggisberg
Article first published online:
06 Jun 2017 | DOI: 10.1111/ene.13296

Original Article

Background and purpose

Migraine has greatly impacted the quality of life for migraineurs and was ranked as the seventh highest specific cause of disability worldwide in 2012. Because of the role of serotonin in migraine mechanisms, antidepressants have been used in the prevention of migraine. However, the role of antidepressants for migraine prophylaxis in adults has not been completely established. Our aim was systematically to assess the efficacy and feasibility of antidepressants for the prevention of migraine in adults based on currently available literature.

Methods

A comprehensive search of databases was conducted including the Cochrane, PubMed, Web of Science and Embase databases from inception to July 2016. Randomized controlled trials that assigned adults with a clinical diagnosis of migraine to antidepressant or placebo treatment were included. The primary outcome was the reduction of migraine frequency or index.

Results

Overall, 16 randomized controlled trials including 1082 participants were identified. Antidepressants had a significant advantage over placebo in reducing the migraine frequency or index of adults with a standardized mean difference of −0.79 [95% confidence interval (CI) −1.13 to −0.45, < 0.00001]. Patients receiving antidepressant therapy were more likely to experience an at least 50% reduction of headache burden than those receiving placebo (28.9% vs. 20.2%; risk ratio 1.40; 95% CI 0.97–2.02; = 0.07). However, antidepressants were less well tolerated than placebo because of some adverse events (risk ratio 1.74, 95% CI 1.05–2.89, = 0.03).

Conclusions

Antidepressants are effective in the prophylaxis of migraine in adults, but the level of evidence for antidepressants except for amitriptyline seems to be quite shaky.

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Authors:
X.‐M. Xu, C. Yang, Y. Liu, M.‐X. Dong, D.‐Z. Zou and Y.‐D. Wei
Article first published online:
29 May 2017 | DOI: 10.1111/ene.13320

CME Article

Background and purpose

The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti‐voltage‐gated potassium channels (VGKC)‐complex, anti‐leucine‐rich glioma‐inactivated 1 (LGI1) and anti‐contactin‐associated protein‐2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow‐up interviews in 2015 and 2016.

Methods

We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and F‐fluorodeoxyglucose positron emission tomography scans were re‐evaluated by experts in the field.

Results

A total of 28/192 patients tested positive for VGKC‐complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative ( = 4) or not tested ( = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain–Barré syndrome, Creutzfeldt–Jakob disease, neuromyotonia and anti‐‐methyl‐D‐aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1‐positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using F‐fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow‐up (median 3.2 years), the median modified Rankin Scale score of anti‐LGI1‐positive patients was 2 and only two patients reported seizures in the past year.

Conclusions

Patients diagnosed with anti‐LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti‐VGKC‐complex patients, all anti‐LGI1‐positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.

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Authors:
M. Celicanin, M. Blaabjerg, C. Maersk‐Moller, S. Beniczky, L. Marner, C. Thomsen, F. W. Bach, D. Kondziella, H. Andersen, F. Somnier, Z. Illes and L. H. Pinborg
Article first published online:
25 May 2017 | DOI: 10.1111/ene.13324

Original Article

Background and purpose

Based on the data of several trials the Totaled Health Risks in Vascular Events (THRIVE) score has been shown to predict outcome after either intravenous thrombolysis (IVT) or endovascular therapy (ET) in acute stroke patients. It is unknown whether the THRIVE score can also predict outcome in everyday clinical practice. Using our prospectively obtained stroke database the utility of the THRIVE score to predict clinical and radiological outcome in everyday clinical practice was analysed.

Methods

The relationships between THRIVE and good outcome (modified Rankin Scale ≤ 2 at discharge), poor outcome (modified Rankin Scale 5–6), in‐hospital death, symptomatic intracranial haemorrhage (SICH) as well as infarct size were examined in patients with distal intracranial carotid artery, M1 and M2 occlusions after either IVT or ET.

Results

From January 2008 to October 2016 a total of 546 patients were treated with IVT and 492 patients received ET with stent retrievers (with or without IVT). In both treatment groups the THRIVE score predicted clinical outcome (Mantel−Haenszel chi‐squared tests for trend  < 0.001 for good outcome,  < 0.001 for poor outcome and  < 0.001 for in‐hospital death). In the ET group the THRIVE score remained an independent predictor of outcome after controlling for recanalization. The THRIVE score was associated with the infarct size after IVT or ET, whereas it did not predict SICH rates in either treatment group.

Conclusions

In everyday clinical practice the THRIVE score strongly predicts clinical outcome and the extent of ischaemia after ET or IVT in patients with anterior circulation large vessel occlusions.

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Authors:
A. Kastrup, F. Brunner, H. Hildebrandt, C. Roth, M. Winterhalter, C. Gießing and P. Papanagiotou
Article first published online:
29 May 2017 | DOI: 10.1111/ene.13328

Original Article

Background and purpose

Assessing survival is a critical issue in patients with amyotrophic lateral sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by magnetic resonance imaging (MRI) and disease progression. The aim of the study was to determine the predictive added value of multimodal SC MRI on survival.

Methods

Forty‐nine ALS patients were recruited and clinical data were collected. Patients were scored on the Revised ALS Functional Rating Scale and manual muscle testing. They were followed longitudinally to assess survival. The cervical SC was imaged using the 3 T MRI system. Cord volume and cross‐sectional area (CSA) at each vertebral level were computed. Diffusion tensor imaging metrics were measured. Imaging metrics and clinical variables were used as inputs for a multivariate Cox regression survival model.

Results

On building a multivariate Cox regression model with clinical and MRI parameters, fractional anisotropy, magnetization transfer ratio and CSA at C2–C3, C4–C5, C5–C6 and C6–C7 vertebral levels were significant. Moreover, the hazard ratio calculated for CSA at the C3–C4 and C5–C6 levels indicated an increased risk for patients with SC atrophy (respectively 0.66 and 0.68). In our cohort, MRI parameters seem to be more predictive than clinical variables, which had a hazard ratio very close to 1.

Conclusions

It is suggested that multimodal SC MRI could be a useful tool in survival prediction especially if used at the beginning of the disease and when combined with clinical variables. To validate it as a biomarker, confirmation of the results in bigger independent cohorts of patients is warranted.

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Authors:
G. Querin, M. M. El Mendili, T. Lenglet, S. Delphine, V. Marchand‐Pauvert, H. Benali and P.‐F. Pradat
Article first published online:
06 Jun 2017 | DOI: 10.1111/ene.13329

Original Article

Background and purpose

Randomized controlled trials have shown that bridging endovascular therapy (EVT) after intravenous thrombolysis (IVT) therapy improves outcome in patients with stroke with large‐artery anterior circulation stroke compared with IVT alone. It remains unknown whether IVT adds any benefit to EVT in these patients. The aim of this study was to assess recanalization rates and thrombus dislocation before initiation of EVT in patients receiving bridging therapy.

Methods

All patients in the Bernese stroke registry (2008–2015) in whom bridging therapy was considered were included in this analysis. Relevant recanalization before EVT, thrombus dislocation and increase in thrombus load between initial and control imaging were assessed retrospectively.

Results

A total of 319 patients were included. Relevant recanalization before EVT occurred in 8.8% and thrombus dislocation in 7.2% of patients before EVT. Recanalization rates were significantly higher in distal compared with large and more proximal vessel occlusions of the anterior circulation (occlusion of internal carotid artery, 5.4%; middle cerebral artery segment M1, 8.1%; middle cerebral artery segment M2, 17.6%) and in drip‐and‐ship patients compared with mother‐ship patients. In multivariable regression analysis the occlusion site was the only independent predictor of relevant recanalization before EVT ( = 0.046).

Conclusions

Relevant recanalization after IVT and prior to EVT in patients receiving bridging therapy was highly dependent on the occlusion site. These findings suggest that future randomized controlled trials should consider occlusion site and treatment paradigm to specify patients who benefit most from bridging therapy in comparison to EVT or IVT alone.

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Authors:
L. Mueller, F. Pult, J. Meisterernst, M. R. Heldner, M.‐L. Mono, R. Kurmann, M. Buehlmann, U. Fischer, H. P. Mattle, M. Arnold, P. Mordasini, J. Gralla, G. Schroth, M. El‐Koussy and S. Jung
Article first published online:
25 Jun 2017 | DOI: 10.1111/ene.13330

Original Article

Background and purpose

Motoric cognitive risk (MCR) syndrome is a pre‐dementia syndrome. There is little information on the cognitive profile of individuals with MCR syndrome and its overlap with mild cognitive impairment (MCI) syndrome. This study aimed to examine and compare the cognitive performance of non‐demented older community dwellers with and without MCR and MCI syndromes.

Methods

A total of 291 non‐demented individuals were selected from the Gait and Alzheimer Interactions Tracking study, which is a cross‐sectional study. All participants were referred to a memory clinic. Individuals with and without MCR were separated into those with and without MCI. Cognitive performance was measured using the scores of the Mini Mental Status Examination, Frontal Assessment Battery, Free and Cued Selective Reminding Test, Trail Making Test part A and B, and Stroop test.

Results

The prevalence of MCI was 40.1% and that of MCR was 18.2%, with a higher prevalence of MCI in MCR group compared with the non‐MCR group (47.2% vs. 39.5%). Individuals with MCR and MCI syndromes had poorer cognitive performance in all domains compared with those without MCR ( < 0.005), except for the ratio part III: part I of the Stroop test ( = 0.345). The association between cognitive performance and MCR syndrome was worse on the Mini Mental Status Examination score [effect size, −0.57 (95% confidence interval, −1.02 to −0.12)] and Trail Making Test part B [effect size, 0.59 (95% confidence interval, 0.14–1.04)] in individuals with MCR and MCI syndromes.

Conclusions

Motoric cognitive risk syndrome is associated with low global cognitive performance. Association of MCR and MCI syndromes is characterized by a worse cognitive performance.

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Authors:
H. Sekhon, G. Allali, C. P. Launay, J. Chabot and O. Beauchet
Article first published online:
16 Jun 2017 | DOI: 10.1111/ene.13331

Letter to the Editor

Anti‐‐methyl‐‐aspartate receptor encephalitis and Epstein‐Barr virus: another tale on autoimmunity?

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Authors:
D. Danieli, A. C. M. Moraes, M. P. Alves, L. A. Dutra, R. Höftberger, O. G. P. Barsottini and M. R. Masruha
Article first published online:
14 Jul 2017 | DOI: 10.1111/ene.13332

Original Article

Background and purpose

A 1988 pilot study in Peru suggested an association between migraine and chronic exposure to high altitude. This study provides epidemiological evidence corroborating this.

Methods

In a cross‐sectional nationwide population‐based study, a representative sample of Nepali‐speaking adults were recruited through stratified multistage cluster sampling. They were visited at home by trained interviewers using a culturally adapted questionnaire. The altitude of dwelling of each participant was recorded.

Results

Of 2100 participants, over half [1100 (52.4%)] were resident above 1000 m and almost one quarter [470 (22.4%)] at ≥2000 m. Age‐ and gender‐standardized migraine prevalence increased from 27.9% to 45.5% with altitude between 0 and 2499 m and thereafter decreased to 37.9% at ≥2500 m. The likelihood of having migraine was greater (odds ratio, 1.5–2.2; ≤ 0.007) at all higher altitudes compared with <500 m. In addition, all symptom indices increased with altitude across the range <500 m to 2000–2499 m, i.e. median attack frequency from 1.3 to 3.0 days/month ( < 0.001), median duration from 9 to 24 h ( < 0.001) and pain intensity [the proportion reporting ‘bad pain’ (highest intensity)] from 35.5% to 56.9% ( = 0.011). Each of these showed a downward trend above 2500 m.

Conclusions

Dwelling at high altitudes increases not only migraine prevalence but also the severity of its symptoms.

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Authors:
M. Linde, L. Edvinsson, K. Manandhar, A. Risal and T. J. Steiner
Article first published online:
29 May 2017 | DOI: 10.1111/ene.13334

Original Article

Background and purpose

Aseptic infections of the central nervous system (CNS) are frequently observed in Germany. However, no study has systematically addressed the spectrum of aseptic CNS infections in Germany.

Methods

Data on 191 adult patients diagnosed from January 2007 to December 2014 with aseptic meningitis or encephalitis/meningoencephalitis at our hospital were collected by chart review and analyzed for demographic, clinical and laboratory findings. Patients were stratified according to the causative virus and findings were compared between groups.

Results

In our cohort, meningitis was caused in 36% by enterovirus (EV), 15% by herpes simplex virus (HSV), 12% by varicella zoster virus (VZV) and 5% by tick borne encephalitis (TBE). Encephalitis/meningoencephalitis was caused in 13% by HSV, 13% by VZV, and three out of 11 tested patients were positive for TBE. The highest incidence of EV infections was between 25 and 35 years and of HSV infections between 30 and 60 years. VZV infections had a bimodal distribution peaking below 30 and above 70 years. VZV and EV infections were more frequently observed during summer, whereas HSV infections showed no seasonal preference. Inflammatory changes in cerebrospinal fluid (CSF) were highest in HSV and lowest in EV infections.

Conclusions

Polymerase chain reaction tests for HSV, VZV and EV in CSF and TBE serology determined the causative virus in over 60% of tested patients. The age of affected patients, seasonal distribution, disease course and inflammatory changes in CSF differ between groups of patients affected by the most common viral infections.

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Authors:
M. Kaminski, V. Grummel, D. Hoffmann, A. Berthele and B. Hemmer
Article first published online:
21 Jun 2017 | DOI: 10.1111/ene.13335

Original Article

Background and purpose

Trial discontinuation and non‐publication represent major sources of research waste in clinical medicine. No previous studies have investigated non‐dissemination bias in clinical trials of neurodegenerative diseases.

Methods

ClinicalTrials.gov was searched for all randomized, interventional, phase II–IV trials that were registered between 1 January 2000 and 31 December 2009 and included adults with Alzheimer's disease, motor neurone disease, multiple sclerosis or Parkinson's disease. Publications from these trials were identified by extensive online searching and contact with authors, and multiple logistic regression analysis was performed to identify characteristics associated with trial discontinuation and non‐publication.

Results

In all, 362 eligible trials were identified, of which 12% (42/362) were discontinued. 28% (91/320) of completed trials remained unpublished after 5 years. Trial discontinuation was independently associated with number of patients ( = 0.015; more likely in trials with ≤100 patients; odds ratio 2.65, 95% confidence interval 1.21–5.78) and phase of trial ( = 0.009; more likely in phase IV than phase III trials; odds ratio 3.90, 95% confidence interval 1.41–10.83). Trial non‐publication was independently associated with blinding status ( = 0.005; more likely in single‐blind than double‐blind trials; odds ratio 5.63, 95% confidence interval 1.70–18.71), number of centres ( = 0.010; more likely in single‐centre than multi‐centre trials; odds ratio 2.49, 95% confidence interval 1.25–4.99), phase of trial ( = 0.041; more likely in phase II than phase IV trials; odds ratio 2.88, 95% confidence interval 1.04–7.93) and sponsor category ( = 0.001; more likely in industry‐sponsored than university‐sponsored trials; odds ratio 5.05, 95% confidence interval 1.87–13.63).

Conclusions

There is evidence of non‐dissemination bias in randomized trials of interventions for neurodegenerative diseases. Associations with trial discontinuation and non‐publication were similar to findings in other diseases. These biases may distort the therapeutic information available to inform clinical practice.

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Authors:
J. D. Stefaniak, T. C. H. Lam, N. E. Sim, R. Al‐Shahi Salman and D. P. Breen
Article first published online:
21 Jun 2017 | DOI: 10.1111/ene.13336

Review Article

Abstract

The aim of the present study was to perform a meta‐analysis of published data to determine the significance of clinical factors and exposures to the risk of perinatal arterial ischaemic stroke (PAIS) and provide guidance for clinical diagnosis and treatment. A comprehensive literature search of the PubMed, Embase, MEDLINE and Cochrane Library databases for relevant observational studies (cohort/case−control) from March 1984 to March 2016 was undertaken. Two review authors independently examined the full text records to determine which studies met the inclusion criteria and evaluated risk factors for PAIS. Risk ratios, odds ratios and 95% confidence intervals were estimated. A total of 11 studies were included in the analyses. Intrapartum fever >38°C, pre‐eclampsia, oligohydramnios, primiparity, forceps delivery, vacuum delivery, fetal heart rate abnormalities, abnormal cardiotocography tracing, cord abnormalities, birth asphyxia, emergency caesarean section, tight nuchal cord, meconium‐stained amniotic fluid, umbilical arterial pH <7.10, Apgar score at 5 min <7, resuscitation at birth, hypoglycaemia, male gender and small for gestational age were identified as risk factors for PAIS. This systemic review and meta‐analysis provides a preliminary evidence‐based assessment of the risk factors for PAIS. Patients with any of the risk factors identified in this analysis should be given careful consideration to ensure the prevention of PAIS. Future studies focusing on the combined effects of multiple prenatal, perinatal and neonatal risk factors for PAIS are warranted.

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Authors:
C. Li, J. K. Miao, Y. Xu, Y. Y. Hua, Q. Ma, L. L. Zhou, H. J. Liu and Q. X. Chen
Article first published online:
24 Jun 2017 | DOI: 10.1111/ene.13337

Letter to the Editor

Prognosis of status epilepticus in adults: recent advances and future directions

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Authors:
A. Vogrig and G. Pauletto
Article first published online:
14 Jul 2017 | DOI: 10.1111/ene.13342

Letter to the Editor

Response to comments on: ‘Respiratory impairment in multiple sclerosis: a study of respiratory function in wheelchair‐bound patients’

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Authors:
J. Levy, D. Bensmail and H. Prigent
Article first published online:
14 Jul 2017 | DOI: 10.1111/ene.13343

Original Article

Background and purpose

Clusters of acute limb weakness in paediatric patients have been linked to outbreaks of non‐polio enteroviruses, termed acute flaccid myelitis (AFM). Outside these clusters, in countries where polio is not endemic, this poliomyelitic‐like illness is rare in childhood and its natural history is not well defined. We describe presenting features, investigation findings and long‐term outcome of a series of children with AFM.

Methods

This was a retrospective cohort study.

Results

Eight children (six females) aged 3 months to 8 years (median age 5 years) met case criteria. Initial symptoms were pain ( = 7) followed by limb weakness with hypotonia ( = 8). Flaccid paralysis occurred in only three patients. Two had cranial nerve dysfunction. Magnetic resonance imaging of the spinal cord demonstrated grey matter involvement particularly affecting the anterior cord, with longitudinally extensive changes in three children. Cerebrospinal fluid examination showed pleocytosis in six children with raised cerebrospinal fluid protein in five. Nerve conduction and electromyography findings were consistent with a motor neuronopathy. Residual deficits were common, with moderate to severe weakness seen in five patients. Median follow‐up was 28 months (range 17–108 months, 30.4 patient years in total).

Conclusions

Acute flaccid myelitis is an uncommon condition in childhood with a high rate of significant long‐term morbidity. AFM should be considered in children presenting with acute limb pain and weakness.

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Authors:
E. W. Andersen, A. J. Kornberg, J. L. Freeman, R. J. Leventer and M. M. Ryan
Article first published online:
22 Jun 2017 | DOI: 10.1111/ene.13345

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Article first published online:
14 Jul 2017 | DOI: 10.1111/ene.13382