cover image European Journal of Neurology

European Journal of Neurology

2017 - Volume 24
Issue 3 | March 2017
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Original Article

Background and purpose

Cerebrospinal fluid (CSF) removal improves clinical symptoms of many patients with idiopathic normal‐pressure hydrocephalus (iNPH). The aim of this study was to investigate the correlation of changes in the optic nerve sheath diameter (ONSD) with patient responses to CSF removal.

Methods

Transorbital ultrasonography was performed to obtain ONSD measurements in 31 patients with iNPH before and after lumbar puncture. Measurements were obtained while patients were supine and upright. Changes in the ONSD between supine and upright positions [ONSD variability (ONSD‐V)] were assessed and compared with those in 60 healthy volunteers. ONSD‐V was correlated with relative changes in a validated iNPH severity (Boon) score.

Results

Mean pre‐puncture ONSD‐V was significantly lower in healthy volunteers and patients with no response to CSF removal (Fisher test) [0.05 ± 0.14 mm (SD)] than in responsive patients [0.37 ± 0.20 mm (SD), < 0.001]. ONSD‐V predicted response to the spinal tap test (odds ratio, 0.30; 95% confidence interval, 0.12–0.75 mm, = 0.011). The higher the ONSD‐V, the better the therapeutic effect ( = 14.980, < 0.001). The post‐spinal tap test ONSD‐V correlated significantly with clinical severity in the motor portion of the Boon score [0.16 ± 0.23 mm (SD), = 0.003].

Conclusions

The ONSD‐V before and after spinal tap test correlated well with the clinical effects of CSF removal. Transorbital ultrasonography seems to be a reliable, safe add‐on to the Fisher test and may support selection of patients for shunt intervention.

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Authors:
M. Ertl, R. Aigner, M. Krost, Z. Karnasová, K. Müller, M. Naumann and F. Schlachetzki
Article first published online:
15 Dec 2016 | DOI: 10.1111/ene.13225

Original Article

Background and purpose

Evans index is an estimate of ventricular size used in the diagnosis of idiopathic normal‐pressure hydrocephalus (iNPH). Values >0.3 are considered pathological and are required by guidelines for the diagnosis of iNPH. However, there are no previous epidemiological studies on Evans index, and normal values in adults are thus not precisely known. We examined a representative sample to obtain reference values and descriptive data on Evans index.

Methods

A population‐based sample ( = 1235) of men and women aged ≥70 years was examined. The sample comprised people living in private households and residential care, systematically selected from the Swedish population register. Neuropsychiatric examinations, including head computed tomography, were performed between 1986 and 2000.

Results

Evans index ranged from 0.11 to 0.46. The mean value in the total sample was 0.28 (SD, 0.04) and 20.6% ( = 255) had values >0.3. Among men aged ≥80 years, the mean value of Evans index was 0.3 (SD, 0.03). Individuals with dementia had a mean value of Evans index of 0.31 (SD, 0.05) and those with radiological signs of iNPH had a mean value of 0.36 (SD, 0.04).

Conclusions

A substantial number of subjects had ventricular enlargement according to current criteria. Clinicians and researchers need to be aware of the range of values among older individuals.

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Authors:
D. Jaraj, K. Rabiei, T. Marlow, C. Jensen, I. Skoog and C. Wikkelsø
Article first published online:
04 Jan 2017 | DOI: 10.1111/ene.13226

Original Article

Background and purpose

Objective cognitive performance (OCP) is often impaired in patients post‐stroke but the consequences of OCP for patient‐reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post‐stroke OCP and SCC.

Methods

Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores.

Results

The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, = 0.003), which remained significant in multivariate adjusted models ( = 0.25, = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models ( = −0.34, < 0.001).

Conclusions

Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post‐stroke.

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Authors:
M. W. A. van Rijsbergen, R. E. Mark, W. J. Kop, P. L. M. de Kort and M. M. Sitskoorn
Article first published online:
21 Dec 2016 | DOI: 10.1111/ene.13227

Original Article

Background and purpose

Elderly patients exposed to drugs with anticholinergic or sedative properties may have an increased risk of adverse events. This study aimed to assess the relationship between patient characteristics and changes of exposure to anticholinergic and sedative medications during their hospital stay.

Methods

A multicentre longitudinal study was set up on hospitalized patients (aged ≥65 years) using at least one drug at admission. The primary outcome was change of exposure to anticholinergic and sedative drugs between admission and discharge. Sociodemographic characteristics of the patients, comorbidities, life habits and information about the hospital stay (origin of admission, reasons for hospitalization) were collected.

Results

The study included 337 patients (mean age, 85.4 years) with an average hospital stay of 30.1 ± 37.5 days. The drug burden index increased during the hospital stay among males ( = 0.03), patients for whom the reason for hospitalization was either a stroke ( = 0.001) or inability to stay in their own home ( = 0.001), and patients with diabetes mellitus ( = 0.009). In the adjusted model, drug burden index increased among patients hospitalized for stroke, inability to stay in their own home or post‐surgery, and for patients with diabetes mellitus or hypertension.

Conclusions

The drug management of elderly patients during hospital stays may increase exposure to anticholinergic and sedative drugs. Although the anticholinergic and sedative properties may be in relation to the therapeutic purpose, they also represent an unexpected risk. Physicians and clinical pharmacists should consider performing optimization of the drug prescriptions for patients at risk.

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Authors:
V. Dauphinot, R. Faure, L. Bourguignon, S. Goutelle, P. Krolak‐Salmon and C. Mouchoux
Article first published online:
27 Dec 2016 | DOI: 10.1111/ene.13228

Original Article

Background and purpose

The aim of this study was to investigate the correlation between the duration of the QTc interval and the brain lesion load at the level of the structures involved in superior autonomic control (insula, cingulate cortex and amygdala‐hippocampus) in multiple sclerosis (MS) patients.

Methods

Thirty‐one consecutive patients with relapsing−remitting MS were recruited. The QT interval was measured manually in all 12 leads by a single blinded observer, with the longest QT value adjusted for heart rate by using the Bazett's formula. All patients performed a brain magnetic resonance imaging (MRI) scan including three‐dimensional double inversion recovery and three volumetric fast‐field echo sequences. The following MRI measures were obtained: (i) global and regional cortical thickness (CTh); (ii) white matter lesion load volume; (iii) cortical damage blindly assessed by a trained observer who assigned, on the basis of the number of cortical lesions, a score from 0 to 5 for each of the brain areas analysed.

Results

In all, 16% of the patients had an increased QTc interval. The QTc interval was correlated with disease duration, cortical insular lesion volume and grey matter lesion volume in the three examined areas and inversely correlated with global and insular CTh.

Conclusions

An increased QTc interval in patients with MS may have a cerebral origin possibly driven by involvement of the insular cortex. With the recent introduction in clinical practice of treatments with potential cardiac effects such as fingolimod, the recognition of a long QTc interval could be clinically crucial and should encourage appropriate electrocardiographic monitoring in order to prevent the risk of malignant ventricular pro‐arrhythmia and iatrogenic sudden death.

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Authors:
G. Turri, M. Calabrese, E. Pancheri, S. Monaco, A. Gajofatto and V. Marafioti
Article first published online:
23 Jan 2017 | DOI: 10.1111/ene.13229

Original Article

Background and purpose

Respiratory disorders are a major cause of morbidity and mortality in multiple sclerosis (MS). Mainly reported in walking patients, they are poorly explored when walking is severely impaired. To characterize respiratory impairment in patients with advanced MS.

Methods

From 2012 to 2015, patients with MS with an Expanded Disability Status Scale (EDSS) score of ≥7 who were referred for functional and rehabilitation evaluation underwent pulmonary function tests to study lung volumes, cough efficacy and respiratory muscle pressures.

Results

Among 73 patients with a median EDSS score of 8 [7.5; 8.5], 72.6% had impaired respiratory function with a mean vital capacity (VC) of 57.9 ± 33.5% of theoretical value. Severe impairment (VC < 50%) was found for 34 (46.6%) patients. Cough was impaired in 45 (61.6%) patients, with a mean cough peak flow of 3.14 ± 1.9 L/s and severe impairment (cough peak flow < 2.67 L/s) in 27 (37.0%) patients. Overall, the results suggested predominant expiratory muscle dysfunction and non‐predominant diaphragm impairment. EDSS score was correlated with VC but not with any other clinical data.

Conclusion

Restrictive respiratory failure is frequent in severely impaired patients with MS, predominantly involves expiratory muscles, does not involve diaphragm weakness and is associated with cough impairments.

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Authors:
J. Levy, D. Bensmail, A. Brotier‐Chomienne, S. Butel, C. Joussain, C. Hugeron and H. Prigent
Article first published online:
03 Jan 2017 | DOI: 10.1111/ene.13231

CME Article

Background and purpose

Considered to be benign conditions, the common genetic generalized epilepsy (GGE) syndromes are now known to be frequently accompanied by cognitive dysfunction. However, unresolved issues impede clinical management of this common comorbidity, including which cognitive abilities are most affected, whether there are differences between syndromes and how seizure type and mood symptoms affect cognitive dysfunction. We provide a detailed description of cognitive ability and evaluate factors contributing to cognitive dysfunction.

Methods

A total of 76 adults with GGE were assessed with the Woodcock Johnson III Tests of Cognitive Abilities.

Results

Scores on tests of overall cognitive ability, acquired knowledge, long‐term retrieval and speed of information processing were significantly below the normative mean. Long‐term retrieval was a pronounced weakness with a large reduction in scores ( = 0.84). GGE syndrome, seizure type and the presence of recent psychopathology symptoms were not significantly associated with cognitive function.

Conclusions

This study confirms previous meta‐analytic findings with a prospective study, offers new insights into the cognitive comorbidity of these common epilepsy syndromes and reinforces the need for cognitive interventions in people with GGE.

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Authors:
A. Loughman, S. C. Bowden and W. J. D'Souza
Article first published online:
27 Dec 2016 | DOI: 10.1111/ene.13232

Original Article

Background and purpose

For patients with acute ischaemic stroke due to large‐vessel occlusion, it has recently been shown that mechanical thrombectomy (MT) with stent retrievers is better than medical treatment alone. However, few hospitals can provide MT 24 h/day 365 days/year, and it remains unclear whether selected patients with acute stroke should be directly transferred to the nearest MT‐providing hospital to prevent treatment delays. Clinical scales such as Rapid Arterial Occlusion Evaluation (RACE) have been developed to predict large‐vessel occlusion at a pre‐hospital level, but their predictive value for MT is low. We propose new criteria to identify patients eligible for MT, with higher accuracy.

Methods

The Direct Referral to Endovascular Center criteria were defined based on a retrospective cohort of 317 patients admitted to a stroke center. The association of age, sex, RACE scale score and blood pressure with the likelihood of receiving MT were analyzed. Cut‐off points with the highest association were thereafter evaluated in a prospective cohort of 153 patients from nine stroke units comprising the Madrid Stroke Network.

Results

Patients with a RACE scale score ≥ 5, systolic blood pressure <190 mmHg and age <81 years showed a significantly higher probability of undergoing MT (odds ratio, 33.38; 95% confidence interval, 12–92.9). This outcome was confirmed in the prospective cohort, with 68% sensitivity, 84% specificity, 42% positive and 94% negative predictive values for MT, ruling out 83% of hemorrhagic strokes.

Conclusions

The Direct Referral to Endovascular Center criteria could be useful for identifying patients suitable for MT.

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Authors:
J. Rodríguez‐Pardo, B. Fuentes, M. Alonso de Leciñana, Á. Ximénez‐Carrillo, G. Zapata‐Wainberg, J. Álvarez‐Fraga, F. J. Barriga, L. Castillo, J. Carneado‐Ruiz, J. Díaz‐Guzman, J. Egido‐Herrero, A. de Felipe, J. Fernández‐Ferro, L. Frade‐Pardo, Á. García‐Gallardo, A. García‐Pastor, A. Gil‐Núñez, C. Gómez‐Escalonilla, M. Guillán, Y. Herrero‐Infante, J. Masjuan‐Vallejo, M. Á. Ortega‐Casarrubios, J. Vivancos‐Mora and E. Díez‐Tejedor
Article first published online:
19 Jan 2017 | DOI: 10.1111/ene.13233

Original Article

Background and purpose

Cancer patients with cryptogenic stroke often have high plasma D‐dimer levels and lesions in multiple vascular regions. Hence, if patients with cryptogenic stroke display such characteristics, occult cancer could be predicted. This study aimed to investigate the clinical characteristics of cryptogenic stroke as the first manifestation of occult cancer and to determine whether plasma D‐dimer levels and lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke.

Methods

Between January 2006 and October 2015, data on 1225 patients with acute ischaemic stroke were extracted from the stroke database of Osaka University Hospital. Among them, 184 patients were classified as having cryptogenic stroke, and 120 patients without a diagnosis of cancer at stroke onset were identified. Clinical variables were analyzed between cryptogenic stroke patients with and without occult cancer.

Results

Among 120 cryptogenic stroke patients without a diagnosis of cancer, 12 patients had occult cancer. The body mass index, hemoglobin levels and albumin levels were lower; plasma D‐dimer and high‐sensitivity C‐reactive protein levels were higher; and lesions in multiple vascular regions were more common in patients with than in those without occult cancer. Multiple logistic regression analysis revealed that plasma D‐dimer levels (odds ratio, 3.48; 95% confidence interval, 1.68–8.33; = 0.002) and lesions in multiple vascular regions (odds ratio, 7.40; 95% confidence interval, 1.70–39.45; = 0.01) independently predicted occult cancer.

Conclusions

High plasma D‐dimer levels and lesions in multiple vascular regions can be used to predict occult cancer in patients with cryptogenic stroke.

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Authors:
Y. Gon, M. Sakaguchi, J. Takasugi, T. Kawano, H. Kanki, A. Watanabe, N. Oyama, Y. Terasaki, T. Sasaki and H. Mochizuki
Article first published online:
27 Dec 2016 | DOI: 10.1111/ene.13234

Original Article

Background and purpose

Up‐to‐date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease‐modifying therapies and recommendations for monitoring disease activity into their clinical practice.

Methods

A steering committee of MS neurologists used a modified Delphi process to develop case‐ and practice‐based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case‐based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing−remitting MS (RRMS) and RRMS with breakthrough disease.

Results

Multiple sclerosis neurologists from 11 European countries responded to survey 1 ( = 233) and survey 2 ( = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first‐line injectables and oral treatments for mild RRMS, and moved to second‐line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented.

Conclusions

Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.

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Authors:
O. Fernández, M. Delvecchio, G. Edan, S. Fredrikson, G. Gionvannoni, H.‐P. Hartung, E. Havrdova, L. Kappos, C. Pozzilli, P. S. Soerensen, B. Tackenberg, P. Vermersch and G. Comi
Article first published online:
31 Jan 2017 | DOI: 10.1111/ene.13236

Editorial

The European Federation of Neurological Associations patients’ survey: what insights for neurologists?

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Authors:
M. Leonardi, C. Scaratti, A. Little, D. Walsh, H. Clarke, A. Craven, R. Ayadi, L. De Torres and A. Raggi
Article first published online:
23 Jan 2017 | DOI: 10.1111/ene.13237

Original Article

Background and purpose

Falls are common in people with Parkinson's disease (PD) but few data exist on fall‐related hospitalizations in this group. This population‐based study compared fall‐related hospital admissions, injury rates and consequences in people with and without PD, and determined whether PD was an independent predictor of fall‐related hospital length of stay.

Methods

This was a retrospective study using probabilistic linkage of hospital data in people aged ≥65 years hospitalized for a fall between 1 July 2005 and 31 December 2013 in New South Wales, Australia. Rates of hospital admissions and injuries per person admitted over the study period were compared between people with and without PD using Poisson or negative binomial regression. Multilevel linear modelling was used to analyse length of stay by clustering individuals and adjusting for possible confounders.

Results

There were 342 265 fall‐related hospital admissions in people aged ≥65 years during the study period, of which 8487 (2.5%) were for people with PD. Sixty‐seven per cent of fall‐related PD admissions were associated with injury and 35% were associated with fracture. People with PD had higher rate ratios for fall admissions (1.63, 95% confidence interval 1.59–1.67) and injury (1.47, 95% confidence interval 1.43–1.51) and longer median length of stay [9 (interquartile range 1–27) vs. 6 (interquartile range 1–20) days in people without PD; < 0.001]. PD remained associated with increased length of stay after controlling for comorbidity, age, sex and injury ( < 0.001).

Conclusions

This study provides important benchmark data for hospitalizations for falls and fall injuries for older people with PD, which may be used to monitor the effect of fall prevention programmes.

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Authors:
S. S. Paul, L. Harvey, C. G. Canning, S. Boufous, S. R. Lord, J. C. T. Close and C. Sherrington
Article first published online:
24 Jan 2017 | DOI: 10.1111/ene.13238

Original Article

Background and purpose

Charcot−Marie−Tooth (CMT) 1C due to mutations in is a rare subtype amongst the autosomal dominant demyelinating forms of CMT. Our objective was to report the clinical and electrophysiological characteristics of 18 CMT1C patients and compare them to 20 patients with mutations: 10 CMT1A patients and 10 patients with hereditary neuropathy with liability to pressure palsies (HNPP).

Methods

Charcot−Marie−Tooth 1C patients were followed‐up in referral centres for neuromuscular diseases or were identified by familial survey. All CMT1A and HNPP patients were recruited at the referral centre for neuromuscular diseases of Pitié‐Salpêtrière Hospital.

Results

Two phenotypes were identified amongst 18 CMT1C patients: the classical CMT form (‘CMT‐like’, 11 cases) and a predominantly sensory form (‘sensory form’, seven cases). The mean CMT neuropathy score was 4.45 in CMT1C patients. Motor nerve conduction velocities in the upper limbs were significantly more reduced in CMT1A than in CMT1C patients. On the other hand, the motor nerve conduction velocity of the median nerve was significantly lower in CMT1C compared to the HNPP group. Distal motor latency was significantly more prolonged in CMT1A patients compared to the CMT1C and HNPP groups, the latter two groups having similar distal motor latency values. Molecular analysis revealed five new mutations (Ala111Thr, Gly112Ala, Trp116Arg, Pro135Leu, Arg160Cys).

Conclusions

Our study delineates CMT1C as mostly a mild form of neuropathy, and gives clinical and electrophysiological clues differentiating CMT1C from CMT1A and HNPP. Delineating phenotypes in CMT subtypes is important to orient molecular diagnosis and to help to interpret complex molecular findings.

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Authors:
R. Guimarães‐Costa, R. Iancu Ferfoglia, S. Leonard‐Louis, F. Ziegler, L. Magy, E. Fournier, O. Dubourg, P. Bouche, T. Maisonobe, A. Lacour, A. Moerman, P. Latour and T. Stojkovic
Article first published online:
16 Feb 2017 | DOI: 10.1111/ene.13239

Letter to the Editor

The right insular cortex infarction: a critical factor for mortality?

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Authors:
M. Nagai, K. Dote, M. Kato, S. Sasaki and N. Oda
Article first published online:
16 Feb 2017 | DOI: 10.1111/ene.13240

Letter to the Editor

Comment on ‘Myasthenia gravis: descriptive analysis of life‐threatening events in a recent nationwide registry’

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Authors:
Z. Su, B. Wang, J. Ni, Y. Hu, Y. Weng and X. Zhang
Article first published online:
16 Feb 2017 | DOI: 10.1111/ene.13248

Letter to the Editor

Targeted exomes reveal simultaneous and mutations in a severe Charcot‐Marie‐Tooth disease type 2 phenotype

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Authors:
C. Anghelescu, B. Francou, R. Cardas, A. Guiochon‐Mantel, P. Aubourg, L. Servais and T. Gidaro
Article first published online:
16 Feb 2017 | DOI: 10.1111/ene.13250

Letter to the Editor

Screening for Fabry disease in patients with ischaemic stroke at young age: the Italian Project on Stroke in Young Adults

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Authors:
L. Poli, M. Zedde, A. Zini, M. Del Sette, C. Lodigiani, A. Spalloni, F. Di Lisi, A. Toriello, V. Piras, C. Stilo, G. Tomelleri, L. Tancredi, M. Paciaroni, G. Silvestrelli, A. Adami, P. Costa, A. Morotti, V. De Giuli, F. Caria, M. Gamba, G. Malferrari, A. M. Simone, R. Musolino, E. Giorli, E. Banfi, S. Marcheselli, M. Rasura, N. Pugliese, M. Melis, P. Bovi, A. Padovani, A. Burlina, A. Pezzini, Elisabetta Del Zotto, Alessia Giossi, Maria Sessa, Nicola Gilberti, Mauro Magoni, Paola Ferrazzi, Luca Librè, Lidia Luciana Rota, Rosalba Patella, Filomena Di Liso, Rocco Salvatore Calabrò, Placido Bramanti, Paolo La Spina, Cinzia Finocchi, Maurizio Balestrino, Chiara Bruno, Davide Massucco, Carlo Gandolfo, Elisabetta Traverso, Maria Luisa DeLodovici, Elena Pinuccia Verrengia, Federico Carimati, Giorgio Bono, Maria Luisa Dell'Acqua, Guido Bigliardi, Laura Vandelli, Paolo Frigio Nichelli, Monica Carletti, Paolo Cerrato, Licia Iacoviello, Augusto Di Castelnuovo, Giovanni de Gaetano, Mario Grassi, Giampiero Locatelli, Valeria Caso, Cataldo D'Amore, Giancarlo Agnelli, Nicoletta Checcarelli, Mario Guidotti, Marco Arnaboldi, Giacomo Giacalone, Elisa Zanoli, Anna Cavallini, Alessandra Persico, Giuseppe Micieli, Alberto Chiti, Giovanni Orlandi, Piernicola Marchi, Alessia Lanari, Alfonso Ciccone, Laura Cucurachi, Marco Domenico Bonifati and Norina Marcello
Article first published online:
16 Feb 2017 | DOI: 10.1111/ene.13254

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Article first published online:
16 Feb 2017 | DOI: 10.1111/ene.13270