cover image European Journal of Neurology

European Journal of Neurology

2015 - Volume 22
Issue 9 | September 2015
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Original Article

Background and purpose

Low serum levels of vitamin D have been associated with depression in non‐stroke subjects. Our aim was to examine the possible association between serum vitamin D levels and the development of post‐stroke depression (PSD).

Methods

In total, 189 patients with acute ischaemic stroke were consecutively recruited. Serum levels of 25‐hydroxyvitamin D [25(OH)D] were measured by competitive protein‐binding assay within 24 h after admission. The 17‐item Hamilton Depression Scale was used for screening for the existence of depressive symptoms at 1 month after stroke. Patients with a Hamilton Depression Scale score of ≥7 were given the Structured Clinical Interview of the , 4th edition, for diagnosis of PSD. Meanwhile, 100 healthy control subjects were also recruited and underwent measurement of 25(OH)D.

Results

Fifty‐five patients (29.1%) were diagnosed as having PSD at 1 month. Serum vitamin D levels within 24 h after admission were significantly lower in both non‐PSD patients and PSD patients than in normal controls. PSD patients had significantly lower vitamin D than non‐PSD patients. Serum vitamin D levels (≤37.1 and ≥64.1 nmol/l) were independently associated with the development of PSD (odds ratio 8.824, 95% confidence interval 2.011–38.720, =0.004, and odds ratio 0.127, 95% confidence interval 0.022–0.718, =0.020, respectively).

Conclusions

Serum vitamin D levels within 24 h after admission are found to be associated with PSD and may predict its development at 1 month post‐stroke.

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Authors:
B. Han, Y. Lyu, H. Sun, Y. Wei and J. He
Article first published online:
02 Dec 2014 | DOI: 10.1111/ene.12607

Review Article

Abstract

Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous stimulation. Infection is the most serious implantation‐associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation‐associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non‐invasive VNS delivery systems do not require surgery and permit patient‐administered stimulation on demand. These non‐invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.

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Authors:
E. Ben‐Menachem, D. Revesz, B. J. Simon and S. Silberstein
Article first published online:
23 Jan 2015 | DOI: 10.1111/ene.12629

Editorial

Abstract

Click to view the accompanying paper in this issue.

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Authors:
Y. Béjot
Article first published online:
05 Jan 2015 | DOI: 10.1111/ene.12635

Letter to the Editor

Response to Elia . ‘Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis’

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Authors:
M. Michaud, C. Gauchet and C. Dray
Article first published online:
17 Aug 2015 | DOI: 10.1111/ene.12729

Original Article

Background and purpose

Information about metabolic comorbidities in patients with multiple sclerosis (MS) is scarce. Our aim was to examine the prevalence of the metabolic syndrome (MetS) and its components in patients with long duration of MS and significant disability.

Methods

Demographic and clinical data, weight, height, waist circumference, blood pressure, and levels of fasting glucose, triglycerides and high density lipoprotein cholesterol (HDL‐C) were obtained from 130 MS patients with Extended Disability Status Scale (EDSS) score ≥3.0.

Results

Seventy‐two percent were female, mean ± SD age 55.8 ± 6.0, range 45–65 years, disease duration 18.2 ± 10.1 years, EDSS 5.5 ± 1.0. Obesity [body mass index (BMI) ≥ 30 kg/m] was present in 18.5% and overweight (BMI 25.0–29.9 kg/m) in 34.6%. The prevalence of the MetS was 30% with no gender difference. Fifty‐six percent had central obesity by waist circumference, 28% treated hypertension, 45.8% elevated blood pressure, 11% type 2 diabetes mellitus, 31.4% treated dyslipidemia, 28.8% elevated triglyceride levels and 31.4% had low HDL‐C. MS patients with MetS were significantly older (59.0 ± 5.5 vs. 53.8 ± 5.5,  < 0.0001) and heavier (BMI 29.0 ± 6.9 vs. 25.1 ± 4.7,  = 0.0009). There were no differences between the groups in neurological disability by the EDSS (5.7 ± 1.0 vs. 5.4 ± 1.0), disease duration (18.4 ± 9.9 vs. 18.2 ± 10.2 years) and number of steroid courses received (6.6 ± 9.5 vs. 6.3 ± 8.4).

Conclusions

Compared to the general population, adult disabled MS patients had lower rates of obesity and overweight, as assessed by BMI. Despite these reduced rates, the prevalence of the MetS was similar to the general population. Specifically higher rates of increased waist circumference were found, suggesting that the lower BMI may be misleading in terms of health risk.

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Authors:
O. Pinhas‐Hamiel, M. Livne, G. Harari and A. Achiron
Article first published online:
14 May 2015 | DOI: 10.1111/ene.12738

Original Article

Background and purpose

Anxiety is potentially a pre‐motor symptom of Parkinson's disease (PD). Our aim was to investigate the association between anxiety and subsequent PD risk in a population‐based sample.

Methods

A total of 174 776 participants, who were free of prior PD, dementia and stroke, were enrolled from Taiwan National Health Insurance Research Database between 1 January 2005 and 31 December 2005. The association between anxiety at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities, especially depression, and concomitant medication use was adjusted in the proportional hazards models.

Results

Over an average follow‐up of 5.5 years, 2258 incident PD cases were diagnosed. After adjusting for age, sex, comorbidities and concomitant medication use, patients with anxiety were more likely to develop PD than subjects without anxiety [adjusted hazard ratio (HR) 1.38; 95% confidence interval (CI) 1.26–1.51]. Anxiety severity was dose‐dependently associated with increased likelihood of PD: crude HR 1.27 (95% CI 1.11–1.44) for mild anxiety, 1.35 (95% CI 1.19–1.53) for moderate anxiety and 2.36 (95% CI 2.13–2.62) for severe anxiety (<0.0001). Results were similar after adjustment for age, sex, comorbid depression and other PD risk factors, and in the sensitivity analyses excluding participants with comorbid depression or with a PD diagnosis <3 years after anxiety diagnosis, and controlling for Charlson's scores.

Conclusions

The likelihood of developing PD was greater amongst patients with anxiety than patients without anxiety, and the severity of anxiety correlated with risk of PD.

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Authors:
C.‐H. Lin, J.‐W. Lin, Y.‐C. Liu, C.‐H. Chang and R.‐M. Wu
Article first published online:
29 May 2015 | DOI: 10.1111/ene.12740

Original Article

Background and purpose

Cognitive impairment is common after stroke, but the prevalence and long‐term significance of the diverse neuropsychological deficits on functional outcome are still not well known. The frequency and prognostic value of domain‐specific cognitive impairments were investigated in a large cohort of ischaemic stroke patients.

Methods

Consecutive patients (= 409), aged 55–85 years, from the acute stroke unit of the Helsinki University Hospital, Finland, were evaluated with extensive clinical and neuropsychological assessments 3 months post‐stroke. Impairments within nine cognitive domains were determined according to age‐appropriate normative data from a random healthy population. Functional disability was evaluated with the modified Rankin scale (mRS) 3 and 15 months post‐stroke.

Results

In all, 83% patients showed impairment in at least one cognitive domain, whereas 50% patients were impaired in multiple (≥3) domains. In cases with excellent clinical recovery at 3 months (mRS = 0–1, no disability), the occurrence of any cognitive impairment was 71%. Memory, visuoconstructional and executive functions were most commonly impaired. A substantially smaller proportion of patients scored below the conventional or more stringent cut‐offs in the Mini‐Mental State Examination (MMSE). Domain‐specific cognitive impairments were associated with functional dependence at 15 months regardless of stroke severity and other confounders.

Conclusions

Cognitive impairment as evaluated with a comprehensive neuropsychological assessment is prevalent in stroke survivors even with successful clinical recovery. Typically multiple domains and complex cognitive abilities are affected. MMSE is not sensitive in detecting these symptoms. Post‐stroke cognitive impairment is strongly related to poor functional outcome.

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Authors:
H. Jokinen, S. Melkas, R. Ylikoski, T. Pohjasvaara, M. Kaste, T. Erkinjuntti and M. Hietanen
Article first published online:
04 Jun 2015 | DOI: 10.1111/ene.12743

CME Article

Background and purpose

Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence‐based clinical recommendations in a systematic review.

Methods

A systematic literature search of Medline, EMBASE, the Cochrane Library and three trial registries was performed. Randomized controlled trials (RCTs) and non‐randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools. The primary outcome was ‘residual neurological symptoms’ whilst the secondary outcomes were disability, quality of life, pain, fatigue, depression, cognition, sleep, adverse events and cerebrospinal fluid pleocytosis. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

After screening 5779 records, eight RCTs and eight NRS were included. Risk of bias was generally high. No statistically significant difference was found between doxycycline and beta‐lactam antibiotics in a meta‐analysis regarding residual neurological symptoms at 4–12 months [risk ratio (RR) 1.27, 95% confidence interval (CI) 0.98–1.63,  = 0.07] or adverse events (RR 0.82, 95% CI 0.54–1.25,  = 0.35). Significantly fewer neurological symptoms for cefotaxime compared with penicillin were found (RR 1.81, 95% CI 1.10–2.97,  = 0.02). Adverse events were significantly fewer for penicillin (RR 0.56, 95% CI 0.38–0.84,  = 0.005).

Conclusions

Evidence regarding pharmacological treatment of acute Lyme neuroborreliosis is scarce and therefore insufficient to recommend preference of beta‐lactam antibiotics over doxycycline or vice versa. However, due to considerable imprecision, relevant differences between treatments cannot be excluded. No evidence suggesting benefits of extended antibiotic treatments could be identified. Further well‐designed trials are needed. Individual treatment decisions should address patients' preferences and individual conditions like prior allergic reactions.

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Authors:
R. Dersch, M. H. Freitag, S. Schmidt, H. Sommer, S. Rauer and J. J. Meerpohl
Article first published online:
08 Jun 2015 | DOI: 10.1111/ene.12744

Original Article

Background and purpose

Converging research in patients with multiple sclerosis (MS) has shown increased rates of alexithymia and disturbances in social cognition, including empathy and theory of mind. Moral judgment is one of the most complex spheres of human cognition, relying on intricate neural circuits related to many other affective, social, cognitive and behavioral processes.

Methods

Relapsing−remitting MS patients (=38) and age‐, gender‐ and education‐matched controls (=38) completed a measure of alexithymia (Toronto Alexithymia Scale), a measure of empathy (Interpersonal Reactivity Index) and a series of moral dilemmas, for which measures of moral permissibility, emotional reactivity and moral relativity (the perception of how one's moral attitudes compare to the attitudes of the rest of the people) were derived.

Results

Relative to controls, patients exhibited decreased levels of other‐oriented empathy [empathic concern (<0.01) and fantasy (<0.01)], increased levels of self‐oriented personal distress (<0.01), as well as higher rates of alexithymia (<0.001). Moral permissibility was significantly reduced in patients with MS (=0.038), who also showed higher levels of emotional reactivity (<0.01). Additionally, a significantly higher number of patients than controls considered that respondents would deliver similar judgments to the same moral scenarios (<0.001).

Discussion

Understanding such complex interactions between individual dispositions and moral cognition has the potential to contribute to the development of better assessment and intervention strategies for MS patients, enhancing quality of life by achieving better social participation.

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Authors:
E. Gleichgerrcht, B. Tomashitis and V. Sinay
Article first published online:
11 Jun 2015 | DOI: 10.1111/ene.12745

Original Article

Background and purpose

Despite surgery, radiotherapy (RT) and temozolomide (TMZ), the prognosis of glioblastoma (GBM) patients remains dismal. Normally prescribed with the aim to lower blood pressure, angiotensin‐II (Ang‐II) inhibitors were reported to reduce angiogenesis and tumour growth in several tumour models including one glioma. Thus whether treatment with Ang‐II inhibitors could be associated with a better clinical outcome in GBM patients was investigated.

Methods

A series of 81 consecutive patients, homogeneously treated with RT and TMZ for a newly diagnosed, supratentorial GBM, were analysed. The objective of this retrospective study was to assess the impact of angiotensin‐converting enzyme inhibitors (ACEIs) and Ang‐II receptor 1 blockers (ARBs) on functional independence, progression‐free survival (PFS) and overall survival (OS).

Results

Amongst the 81 GBM patients analysed, 26 were already treated for high blood pressure (seven with ACEIs and 19 with ARBs). The number of patients who remained functionally independent at 6 months after RT was higher in the group of patients treated with Ang‐II inhibitors compared to the other patients (85% vs. 56%,  = 0.01). In patients treated with Ang‐II inhibitors, PFS was 8.7 months (vs. 7.2 months in the other patients) and OS was 16.7 months (vs. 12.9 months). The use of Ang‐II inhibitors was a significant prognostic factor for both PFS ( = 0.04) and OS ( = 0.04) in multivariate analysis.

Conclusion

Treatment with Ang‐II inhibitors in combination with RT and TMZ might improve clinical outcome in GBMs. Prospective trials are needed to test this hypothesis.

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Authors:
E. Januel, R. Ursu, A. Alkhafaji, A. Marantidou, J. Doridam, C. Belin, C. Levy‐Piedbois and A. F. Carpentier
Article first published online:
04 Jun 2015 | DOI: 10.1111/ene.12746

Original Article

Background and purpose

Medial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE‐HS) is the most frequent form of surgical temporal lobe epilepsy. In this study, it was aimed to determine whether different types of aura represent a cardinal and characteristic feature of MTLE‐HS and might provide a diagnostic complement to help identify patients who will be seizure‐free after surgery.

Methods

All types of auras and associations of auras reported by 400 MTLE‐HS patients referred for surgery were retrospectively collected and their statistical correlation with the postoperative outcome was examined in a subgroup of 305 patients who underwent surgery.

Results

A total of 876 auras were collected, classified into 12 categories. Globally, MTLE‐HS patients reported widely variable auras and groupings of auras. Most common were autonomic and abdominal visceral auras, followed by psychoaffective and experiential auras; less common, but seen in 10%–15% of patients, were non‐specific auras, somatosensory auras and visual auras, and least common, reported by less than 10% of patients, were auditory, gustatory, vestibular, olfactory and intellectual auras. No auras were reported in 10% of patients. 65% of patients experienced more than one type of aura (two to seven). No specific groupings of aura type were apparent. No evidence was found for correlation between postoperative outcome and (i) any category of aura, (ii) the number of categories of aura per patient and (iii) any association of categories of auras.

Conclusion

Auras and association of auras vary widely in MTLE‐HS and provide no useful insight into surgical outcome.

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Authors:
S. Dupont, Y. Samson, V.‐H. Nguyen‐Michel, C. Zavanone, S. Clémenceau, R. Miles, M. Baulac and C. Adam
Article first published online:
13 Jun 2015 | DOI: 10.1111/ene.12747

Original Article

Background and purpose

Corticobasal syndrome (CBS) is a clinical entity characterized by higher cortical dysfunctions associated with asymmetric onset of levodopa‐resistant parkinsonism, dystonia and myoclonus. One of the most typical and distressful features of CBS is limb apraxia, which affects patients in their everyday life. Transcranial direct current stimulation (tDCS) is a non‐invasive procedure of cortical stimulation, which represents a promising tool for cognitive enhancement and neurorehabilitation. The present study investigated whether anodal tDCS over the parietal cortex (PARC), would improve ideomotor upper limb apraxia in CBS patients.

Methods

Fourteen patients with possible CBS and upper limb apraxia were enrolled. Each patient underwent two sessions of anodal tDCS (left and right PARC) and one session of placebo tDCS. Ideomotor upper limb apraxia was assessed using the De Renzi ideomotor apraxia test that is performed only on imitation.

Results

A significant improvement of the De Renzi ideomotor apraxia test scores (post‐stimulation versus pre‐stimulation) after active anodal stimulation over the left PARC was observed ( = 17.6,  = 0.0005), whilst no significant effect was noticed after active anodal stimulation over the right PARC ( = 7.2,  = 0.07). A analysis revealed a selective improvement in the De Renzi ideomotor apraxia score after active anodal stimulation over the left PARC compared with placebo stimulation considering both right ( = 0.03) and left upper limbs ( = 0.01).

Conclusions

These findings indicate that tDCS to the PARC improves the performance of an ideomotor apraxia test in CBS patients and might represent a promising tool for future rehabilitation approaches.

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Authors:
M. Bianchi, M. Cosseddu, M. Cotelli, R. Manenti, M. Brambilla, M. C. Rizzetti, A. Padovani and B. Borroni
Article first published online:
13 Jun 2015 | DOI: 10.1111/ene.12748

Letter to the Editor

Reply to Dr Michaud .

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Authors:
A. E. Elia, C. Viscomi, V. La Bella, G. Tedeschi and A. Albanese
Article first published online:
17 Aug 2015 | DOI: 10.1111/ene.12756

Short Communication

Background

Recently, a novel mutation in exon 24 of gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi‐incident Mennonite family.

Methods

In the present study the mutation containing exon of the gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD).

Results

Our sequence analysis did not identify any coding variants in exon 24 of . Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed.

Conclusion

Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.

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Authors:
O. Lorenzo‐Betancor, K. Ogaki, A. I. Soto‐Ortolaza, C. Labbe, R. L. Walton, A. J. Strongosky, J. A. van Gerpen, R. J. Uitti, P. J. McLean, W. Springer, J. Siuda, G. Opala, A. Krygowska‐Wajs, M. Barcikowska, K. Czyzewski, A. McCarthy, T. Lynch, A. Puschmann, I. Rektorova, Y. Sanotsky, C. Vilariño‐Güell, M. J. Farrer, T. J. Ferman, B. F. Boeve, R. C. Petersen, J. E. Parisi, N. R. Graff‐Radford, D. W. Dickson, Z. K. Wszolek and O. A. Ross
Article first published online:
17 Aug 2015 | DOI: 10.1111/ene.12770

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Article first published online:
17 Aug 2015 | DOI: 10.1111/ene.12828