cover image European Journal of Neurology

European Journal of Neurology

2015 - Volume 22
Issue 1 | January 2015
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Original Article

Background and purpose

Although Parkinson's disease (PD) is characterized by typical motor manifestations, non‐motor symptoms (NMS) are an outstanding part of the disease. At present, several specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Part I – Non‐Motor Aspects of Experiences of Daily Living (nM‐EDL) compared with the Non‐Motor Symptoms Scale (NMSS).

Methods

To this purpose, 434 consecutive patients with PD were included in an international, observational, cross‐sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin's Concordance Correlation Coefficient (LCCC) and Bland–Altman plot.

Results

As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (> 0.60). The total score correlation of the MDS‐UPDRS Part I with the NMSS was high (= 0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60–64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland–Altman plot; LCCC < 0.60 for severe patients).

Conclusions

(i) MDS‐UPDRS Part I (nM‐EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant.

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Authors:
P. Martinez‐Martin, K. R. Chaudhuri, J. M. Rojo‐Abuin, C. Rodriguez‐Blazquez, M. Alvarez‐Sanchez, T. Arakaki, A. Bergareche‐Yarza, A. Chade, N. Garretto, O. Gershanik, M. M. Kurtis, J. C. Martinez‐Castrillo, A. Mendoza‐Rodriguez, H. P. Moore, M. Rodriguez‐Violante, C. Singer, B. C. Tilley, J. Huang, G. T. Stebbins and C. G. Goetz
Article first published online:
22 Apr 2013 | DOI: 10.1111/ene.12165

Short Communication

Background and purpose

Detection of autoantibodies against neuronal surface antigens and their correlation with the pattern and severity of symptoms led to the definition of new autoimmune‐mediated forms of encephalitis and was essential for the initiation of immunotherapies including plasma exchange. The elimination of autoantibodies using selective immunoadsorption (IA) is a pathophysiologically guided therapeutic approach but has not yet been evaluated in a separate analysis.

Methods

A retrospective analysis was performed of patients with autoimmune encephalitis who were treated with tryptophan IA in six neurological clinics between 2009 and 2013. The modified Rankin scale (mRS) was used to evaluate neurological status before and after IA.

Results

Data on 13 patients were documented. Twelve patients were positive for specific autoantibodies (NMDA‐R, GABA, GAD, Lgl1). Patients received a series of a median of six IA treatments. Median mRS of all patients was 3.0 before IA and 2.0 after IA ( < 0.001). Eleven patients improved by at least one point in mRS after IA.

Conclusion

For autoimmune‐mediated forms of encephalitis rapid elimination of autoantibodies with selective IA seems to be an effective therapeutic option as part of multimodal immune therapy.

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Authors:
W. Köhler, S. Ehrlich, C. Dohmen, M. Haubitz, F. Hoffmann, S. Schmidt, R. Klingel, A. Kraft, T. Neumann‐Haefelin, H. Topka, O. Stich, A. Baumgartner and C. Fassbender
Article first published online:
03 Mar 2014 | DOI: 10.1111/ene.12389

Short Communication

Background and purpose

Olfactory dysfunction is common in Parkinson's disease (PD) and it is one of the earliest non‐motor symptoms. A few studies have suggested that deep brain stimulation of the subthalamic nucleus (STN‐DBS) could improve olfactory function. Our aim was to evaluate the acute effect of bilateral STN‐DBS on a commonly used smell test in PD patients.

Methods

Fifteen PD patients who underwent bilateral STN‐DBS and 15 controls were recruited. Patients and controls were tested for odor identification.

Results

No statistical differences were documented between ON and OFF STN‐DBS acute stimulation concerning olfaction. Controls presented a better performance for olfactory identification than patients.

Conclusions

Our exploratory study did not support that bilateral STN‐DBS could have an acute effect on olfactory function in PD patients.

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Authors:
M. Fabbri, L. C. Guedes, M. Coelho, D. Simão, D. Abreu, M. M. Rosa, L. Silveira‐Moriyama and J. J. Ferreira
Article first published online:
06 Mar 2014 | DOI: 10.1111/ene.12396

Short Communication

Background and purpose

Spastic paraplegia type 5 (SPG5) is an autosomal recessive (AR) hereditary spastic paraplegia (HSP) associated with pure or complicated phenotypes. This study aimed to screen SPG5 in Taiwanese HSP patients.

Methods

Sequencing of the SPG5 gene, , was performed in a cohort of 25 ethnic Han Taiwanese patients with AR or sporadic HSP. Clinical information and magnetic resonance imaging (MRI) were analyzed in confirmed SPG5 patients.

Results

One (33%) AR kindred and four (18%) sporadic cases had mutations. All of the SPG5 cases carried the mutation c.334 C>T (R112X). Haplotype analysis suggested a ‘founder effect’ in ethnic Hans for this mutation. The phenotype was either pure or complicated by cerebellar ataxia. For the primary HSP phenotype, there were profound dorsal column sensory deficits in all patients. Spine MRI showed thoraco‐lumbar cord atrophy in some patients.

Conclusions

Spastic paraplegia type 5 is a common cause of AR and sporadic HSPs that has a higher frequency in Taiwanese than in other ethnic groups. It is associated with a founder mutation and its phenotype is characterized by pronounced dorsal column sensory loss, with cerebellar ataxia in some patients.

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Authors:
M.‐Y. Lan, T.‐H. Yeh, Y.‐Y. Chang, H.‐C. Kuo, H. S. Sun, S.‐C. Lai and C.‐S. Lu
Article first published online:
18 Mar 2014 | DOI: 10.1111/ene.12407

Short Communication

Background and purpose

To evaluate whether cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels could predict the time to generalization (TTG) in amyotrophic lateral sclerosis (ALS).

Methods

Cerebrospinal fluid NFL levels of 37 cases of sporadic ALS were measured and the time of symptom spreading from spinal or bulbar localization to both (TTG) was evaluated in all patients.

Results

Kaplan−Meier analysis showed a short TTG in patients with high NFL levels (log‐rank test chi‐squared = 19.4, <0.0001). In a multivariate regression model patients with NFL levels above the median had an eight‐fold higher risk of generalization (adjusted hazard ratio 7.9, 95% confidence interval 2.9–21.4, <0.0001) compared with those with NFL levels below the median.

Conclusions

This study shows that in sporadic ALS NFL, a marker of neurodegeneration, is correlated with TTG, a clinical intermediate parameter of survivorship.

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Authors:
R. Tortelli, M. Copetti, M. Ruggieri, R. Cortese, R. Capozzo, A. Leo, E. D'Errico, M. Mastrapasqua, S. Zoccolella, F. Pellegrini, I. L. Simone and G. Logroscino
Article first published online:
22 Apr 2014 | DOI: 10.1111/ene.12421

Original Article

Background and purpose

White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) have been linked to small‐vessel disease, but the precise pathogenesis underlying WMHs remains unclear. Studies about an association of WMHs with extracranial atherosclerotic stenosis (ECAS) showed conflicting results and the relationship of WMHs with intracranial atherosclerotic stenosis (ICAS) is uncertain.

Methods

A cross‐sectional study of 679 consecutive Korean patients with acute ischaemic stroke (mean age 67.8 ± 12.6; 395 males) who underwent brain MRI/MR angiography was conducted. Severity of deep WMHs (d‐WMHs,  = 560) and periventricular WMHs (p‐WMHs,  = 590) was rated separately and compared across three groups: ICAS ( = 318), ECAS ( = 71) and no cerebral atherosclerotic stenosis (NCAS) ( = 290).

Results

The ICAS group showed a higher d‐WMH/p‐WMH score (1.62 ± 0.85/1.65 ± 0.79) than both the ECAS (1.25 ± 0.87/1.23 ± 0.78) and NCAS (1.19 ± 0.92/1.24 ± 0.81) groups (<0.001 for all). Patients with a greater number of ICAS were more likely to have higher scores of d‐WMH/p‐WMH (<0.001 for all). Patients with higher scores of d‐WMH/p‐WMH had a higher incidence of ICAS (<0.001 for all), but not of ECAS or NCAS. In multivariable analysis, a dose−response relationship was observed between the extent of ICAS versus WMHs. Compared with one ICAS lesion, for d‐WMHs the odds ratio (OR) = 2.61 [95% confidence interval (CI) 0.95–7.20] for two ICAS lesions and OR = 3.37 (1.10–10.32) for ≥3 ICAS lesions; whilst for p‐WMHs (score ≥2) OR = 1.70 (95% CI 0.96–2.98) for two ICAS lesions and OR = 2.02 (1.15–3.55) for ≥3 ICAS lesions.

Conclusion

ICAS is independently associated with progressively greater WMH burden. The association of ICAS with WMH severity appears to be stronger than that of ECAS/NCAS in the Korean (Asian) stroke population.

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Authors:
J.‐H. Park, H.‐M. Kwon, J. Lee, D.‐S. Kim and B. Ovbiagele
Article first published online:
09 Apr 2014 | DOI: 10.1111/ene.12431

Editorial

Abstract

Click to view the accompanying paper in this issue.

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Authors:
A. H. V. Schapira
Article first published online:
21 Jul 2014 | DOI: 10.1111/ene.12523

Original Article

Background and purpose

To investigate resource use and burden associated with spina bifida (SB) in Germany.

Methods

A questionnaire was used to obtain information on SB‐related healthcare resource use and assistive technologies used for the last 1 and 10 years. Individuals with SB were recruited at a tertiary specialist clinic. To participate, persons with SB required the cognitive ability to respond or a caregiver to answer questions on their behalf. They could use personal medical charts or other records to answer. The analyses included assessment of frequency and extent of resource use for both time frames.

Results

Data on 88 persons with a diagnosis of SB were collected (44% female). During the last year, 88.6% ( = 78) reported at least one visit to a general practitioner's (GP's) office, 77.3% ( = 68) to a urologist and 69.3% ( = 61) to a physiotherapist. The annual average number of visits was 7.6 GP, 3.6 urologist and 65.3 physiotherapist visits. Amongst those hospitalized, a single hospitalization lasted 7.3 days on average, whereas the average annual number of hospital days was 14.8 days. During the previous 10 years, 67.0% ( = 59) of responders used a wheelchair, 64.7% ( = 57) used glasses and 59.1% ( = 52) used orthopaedic shoes, with an average of 2.5, 2.8 and 6.1 new items used, respectively.

Conclusions

The results indicate that persons with SB require a substantial amount of interaction with healthcare providers, as well as other healthcare‐related resource use, both in the shorter and longer terms.

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Authors:
F. E. van Nooten, R. Winnette, R. Stein, M. Kissner, A. Schröder, M. Jöckel, M. Raluy‐Callado, D. Lambrelli, M. Meinhardt and R. Wasiak
Article first published online:
07 Aug 2014 | DOI: 10.1111/ene.12524

Original Article

Background and purpose

Myasthenia gravis (MG) is an autoimmune disease but certain genetic factors predispose its development. Since susceptibility to different forms of MG is linked to a number of allelic variants, the aim of this study was to explore the human leukocyte antigen (HLA) profile of our patients with muscle‐specific tyrosine kinase (MuSK) MG.

Methods

Human leukocyte antigen (HLA) typing was performed in our cohort of 31 MuSK MG patients available for the study. The allele groups of DRB1* and DQB1* loci were typed with sequence‐specific oligonucleotide probes and high resolution typing for DQB1* was performed using sequence‐specific primers. HLA frequencies were compared with unrelated healthy bone marrow donors.

Results

Significant association of MuSK MG with alleles DRB1*14 [odds ratio (OR) 3.8], DRB1*16 (OR 3.3) ( < 0.01) and DQB1*05 (OR 2.2) ( < 0.05) was found. In our patients the most frequent DQB1* allele was DQB1*05:02. An absolute absence of DRB1*13 in our cohort of MuSK MG patients was also found, whilst this allele was present in 25% (495/1992) of control subjects (OR 0) ( < 0.01). The HLA DRB1*16−DQB1*05 (OR 2.9) haplotype was found to be associated with MuSK MG ( < 0.05).

Conclusions

The strong association of MuSK MG with DQB1*05 alleles observed in patient series from other countries was confirmed. The novel finding in our cohort of MuSK MG patients was the absolute absence of DRB1*13 allele, which might have a protective role in the development of MuSK MG, at least in our population.

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Authors:
A. V. Nikolic, Z. P. Andric, R. B. Simonovic, V. M. Rakocevic Stojanovic, I. Z. Basta, S. D. Bojic and D. V. Lavrnic
Article first published online:
29 Jul 2014 | DOI: 10.1111/ene.12525

Original Article

Background and purpose

Chronic kidney disease (CKD) is associated with a higher risk of stroke and atrial fibrillation (AF). There are limited data on the comorbidity of renal dysfunction and AF in stroke patients. Our aim was to determine the frequency of kidney dysfunction in ischaemic stroke patients with and without AF.

Methods

In a prospectively collected, single center cohort of acute ischaemic stroke and transient ischaemic attack (TIA) patients, glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease equation on admission. Renal function was graded into five categories (cat.): cat. 1, eGRF ≥90 ml/min/1.73 m; cat. 2, 60–89; cat. 3, 30–59; cat. 4, 15–29; cat. 5, <15. The diagnosis of AF was based on medical history, a 12‐lead electrocardiogram (ECG) and 24‐h Holter or continuous ECG monitoring.

Results

In total, 2274 patients (1727 stroke, 547 TIA; median age 71.0) were included. Median eGFR was 78.6 ml/min/1.73 m (interquartile range 61/95); 21.1% were in cat. 3, 2.1% in cat. 4, 0.7% in cat. 5. In all, 535 patients (23.5%) suffered from AF; 28.0% of these were in cat. 3, 2.6% and 0.8% in cat. 4 and cat. 5, respectively. In multivariable analysis, age [odds ratio (OR) 1.1], diabetes (OR 1.8), heart failure (OR 1.7) and AF (OR 1.4) were independently associated with kidney dysfunction (eGFR < 60).

Conclusions

Renal dysfunction is far more common in stroke patients than in the general population and more common in AF‐related stroke. These findings may have implications for the choice of anticoagulants.

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Authors:
M. Laible, S. Horstmann, T. Rizos, G. Rauch, M. Zorn and R. Veltkamp
Article first published online:
04 Aug 2014 | DOI: 10.1111/ene.12528

Original Article

Background and purpose

The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of ‘autoimmune epilepsy’. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy.

Methods

Eighty‐one patients and 75 age‐ and sex‐matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED‐resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell‐based assays and a radioimmunoassay. Patients with AED‐resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency.

Results

Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED‐resistant epilepsy group (= 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency.

Conclusions

A significant proportion of patients with AED‐resistant epilepsy harbor neural‐specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.

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Authors:
R. Iorio, G. Assenza, M. Tombini, G. Colicchio, G. Della Marca, A. Benvenga, V. Damato, P. M. Rossini, C. Vollono, D. Plantone, A. Marti, A. P. Batocchi and A. Evoli
Article first published online:
12 Aug 2014 | DOI: 10.1111/ene.12529

Original Article

Background and purpose

Status epilepticus (SE) refractory to first‐ and second‐line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE) – an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults.

Methods

Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed.

Results

In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01–4.07; OR 4.83, 95% CI 2.42–9.68; OR 2.45, 95% CI 1.16–5.16]. The prediction model showed good measures of calibration (Hosmer–Lemesow goodness‐of‐fit test  = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set ‐ results that were similar in the validation data set (Hosmer–Lemeshow  = 0.24; area under the receiver operating characteristic curve 0.73).

Conclusions

This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.

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Authors:
R. Sutter, P. W. Kaplan, S. Marsch, E. M. Hammel, S. Rüegg and W. C. Ziai
Article first published online:
07 Aug 2014 | DOI: 10.1111/ene.12531

Original Article

Background and purpose

Some 3%−10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years (‘early’ onset MS, EOMS). Optical coherence tomography is a non‐invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age‐ or disease‐duration‐matched later onset MS (LOMS) and healthy controls (HCs).

Methods

In this observational cross‐sectional study at two German academic MS centres, RNFLT and TMV were measured by spectral‐domain optical coherence tomography in 32 HCs, 36 EOMS (mean age at onset 15.5 ± 2.0 years) and 58 LOMS patients.

Results

In comparison with HCs, EOMS patients displayed a significant reduction of RNFLT and TMV independently of a history of optic neuritis. In particular, RNFLT loss in EOMS was similar to that in LOMS and TMV loss was slightly higher compared with disease‐duration‐matched LOMS. In a generalized estimating model, the EOMS group also displayed a similar correlation between disease duration and RNFLT or TMV loss to LOMS patients.

Conclusions

These data argue for a significant amount of axonal and neuronal damage in the retina of EOMS patients and may provide a structural basis for the observation that EOMS patients reach states of irreversible disability at a younger age than patients with LOMS.

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Authors:
K. Huhn, R. Lämmer, T. Oberwahrenbrock, A. Lämmer, A. Waschbisch, D. Gosar, A. Brandt, F. Paul, R. A. Linker and D.‐H. Lee
Article first published online:
07 Aug 2014 | DOI: 10.1111/ene.12532

Original Article

Background and purpose

Uric acid (UA) has been studied extensively as a valuable biomarker of Parkinson's disease (PD), but its relationship with non‐motor symptoms (NMS) in PD has been poorly investigated. Our aim was to evaluate the usefulness of baseline serum UA as a marker of NMS progression in newly diagnosed PD.

Methods

Sixty‐nine newly diagnosed PD patients were enrolled. At baseline, all patients completed the NMS questionnaire (NMSQuest), and serum UA levels were measured. After 2 years, the NMSQuest was completed again and patients were categorized into four groups: NMS improvement (domain involvement at baseline but not at 2‐year follow‐up visit), NMS absence (domain not involved at baseline or 2‐year follow‐up visits), NMS presence (domain involvement both at baseline and 2‐year follow‐up visits) and NMS worsening (domain not involved at baseline but involved at 2‐year follow‐up).

Results

with Bonferroni correction showed that patients with NMS absence presented significantly higher UA values than patients with NMS presence with regard to the attention/memory (= 0.023), depression/anxiety (= 0.028) and cardiovascular domains (= 0.002), whilst no differences were found with regard to both the NMS improvement and worsening groups. In addition, multinomial regression analysis showed that the lowest tertile of NMS progression presented higher UA levels (= 0.023; odds ratio 0.488) compared with patients with greater NMS progression.

Conclusions

This is the first report of a relationship between serum UA and presence/progression of multiple NMS in PD, providing additional evidence of the reliability of UA as a biomarker of PD and opening new insights on PD neuroprotection.

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Authors:
M. Moccia, M. Picillo, R. Erro, C. Vitale, K. Longo, M. Amboni, G. Santangelo, R. Palladino, G. Capo, G. Orefice, P. Barone and M. T. Pellecchia
Article first published online:
07 Aug 2014 | DOI: 10.1111/ene.12533

Original Article

Background and purpose

Subdural hematoma (SDH) is associated with a high mortality rate. However, the risk of SDH in diabetic patients has not been well studied. The aim of the study was to examine the risk of SDH in incident diabetic patients.

Methods

From a universal insurance claims database of Taiwan, a cohort of 28 045 incident diabetic patients from 2000 to 2005 and a control cohort of 56 090 subjects without diabetes were identified. The incidence and hazard ratio of SDH were measured by the end of 2010.

Results

The mean follow‐up years were 7.24 years in the diabetes cohort and 7.44 years in the non‐diabetes cohort. The incidence of SDH was 1.57‐fold higher in the diabetes cohort than in the non‐diabetes cohort (2.04 vs. 1.30 per 1000 person‐years), with an adjusted hazard ratio of 1.63 [95% confidence interval (CI) 1.43–1.85]. The stratified data showed that adjusted hazard ratios were 1.51 (95% CI 1.28–1.77) for traumatic SDH and 1.89 (95% CI 1.52–2.36) for non‐traumatic SDH. The 30‐day mortality rate for those who developed SDH in the diabetes cohort was 8.94%.

Conclusions

This study demonstrates that incident diabetic patients are at higher risk of SDH than individuals without diabetes. Proper intervention for diabetic patients is necessary for preventing the devastating disorder.

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Authors:
I.‐K. Wang, H.‐J. Chen, Y.‐K. Cheng, Y.‐Y. Wu, S.‐Y. Lin, C.‐Y. Chou, C.‐T. Chang, T.‐H. Yen, F.‐R. Chuang, F.‐C. Sung and C. Y. Hsu
Article first published online:
27 Aug 2014 | DOI: 10.1111/ene.12538

Original Article

Background and purpose

Studies investigating the association between 25‐hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking.

Methods

Cross‐sectional (baseline) and prospective data (up to 3 years follow‐up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini‐Mental State Examination) and attention‐specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season‐specific 25(OH)D quartiles.

Results

Those in the lowest and highest season‐specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06–2.60, =0.03; 1.62, 95% confidence interval 1.02–2.59, =0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log‐transformed) attention reaction times for Choice Reaction Time (lowest, = 0.023, =0.01; highest, = 0.021, =0.02), Digit Vigilance Task (lowest, = 0.009, =0.05; highest, = 0.01, =0.02) and Power of Attention (lowest, = 0.017, =0.02; highest, = 0.022, =0.002) and greater Reaction Time Variability (lowest, = 0.021, =0.02; highest, = 0.02, =0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non‐users of vitamin D supplements/medication.

Conclusion

Low and high season‐specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention‐specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.

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Authors:
A. Granic, T. R. Hill, T. B. L. Kirkwood, K. Davies, J. Collerton, C. Martin‐Ruiz, T. von Zglinicki, B. K. Saxby, K. A. Wesnes, D. Collerton, J. C. Mathers and C. Jagger
Article first published online:
13 Aug 2014 | DOI: 10.1111/ene.12539

Original Article

Background and purpose

Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis.

Methods

A retrospective cohort study was conducted on adult patients with encephalitis admitted to the medical intensive care unit (ICU) of a university hospital over a 20‐year period. Patients' characteristics and outcomes were compared between two 10‐year periods: (i) 1991–2001 and (ii) 2002–2012. Multivariate logistic regression was used to analyze factors associated with a poor outcome, as defined by a modified Rankin scale (mRS) score of 4–6 (severe disability or death) 90 days after admission.

Results

A total of 279 patients were studied. Causes of encephalitis were infections ( = 149, 53%), immune‐mediated causes ( = 41, 15%) and undetermined causes ( = 89, 32%). The distribution of causes differed significantly between the two periods, with an increase in the proportion of encephalitis recognized to be of immune‐mediated causes. At day 90, 208 (75%) patients had an mRS = 0–3 and 71 (25%) had an mRS = 4–6. After adjustment for functional status before admission, the following parameters were independently associated with a poor outcome: coma [odds ratio (OR) 7.09, 95% confidence interval (95% CI) 3.06–17.03], aspiration pneumonia (OR 4.02, 95% CI 1.47–11.03), a lower body temperature (per 1 degree, OR 0.72, 95% CI 0.53–0.97), elevated cerebrospinal fluid protein levels (per 1 g/l, OR 1.55, 95% CI 1.17–2.11) and delayed ICU admission (per 1 day, OR 1.04, 95% CI 1.01–1.07).

Conclusions

Indicators of outcome in adult patients with severe encephalitis reflect both the severity of illness and systemic complications. Our data suggest that patients with acute encephalitis may benefit from early ICU admission.

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Authors:
R. Sonneville, N. Gault, E. de Montmollin, I. F. Klein, E. Mariotte, S. Chemam, F. Tubach, B. Mourvillier, J. F. Timsit, M. Wolff and L. Bouadma
Article first published online:
01 Sep 2014 | DOI: 10.1111/ene.12541

Original Article

Background and purpose

Patients with myotonic dystrophy type 1 (DM1) have an increased incidence of endocrine dysfunction. In this study, the temporal evolution of endocrine dysfunction in patients with DM1 was investigated.

Methods

Endocrine function was assessed in 68 patients with DM1, in whom endocrine function had been followed, on average, for 8 years. The endocrine function was assessed by measuring the concentration of hormones and metabolites in blood and by validating libido with questionnaires.

Results

At baseline, 30 of the 68 patients presented with at least one hormonal dysfunction. When re‐evaluated after 8 years, 57 of 68 patients had endocrine dysfunction. Diabetic patients had increased from one to four. At follow‐up, hyperparathyroidism occurred in 25% and abnormal thyroid‐stimulating hormone in 21%, compared with 14% and 9% at baseline. Sixteen of 33 men had increased luteinizing hormone levels compared with seven at baseline.

Conclusions

Our findings show that endocrine abnormalities amongst patients with DM1 increase over time. Based on these findings it is suggested that correctable endocrine abnormalities should be monitored periodically in this patient group.

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Authors:
J. R. Dahlqvist, M. C. Ørngreen, N. Witting and J. Vissing
Article first published online:
25 Aug 2014 | DOI: 10.1111/ene.12542

Original Article

Background and purpose

Intracerebral hemorrhage (ICH) is a common and severe form of stroke but is scarcely studied in young adults. Our aim was to study risk factors, clinical presentation and early mortality of ICH in the young and compare these features with older patients.

Methods

All consecutive patients aged between 16 and 49 diagnosed with a first‐ever ICH at the Departments of Neurology or Neurosurgery of the Helsinki University Central Hospital between January 2000 and March 2010 ( = 336) were analyzed retrospectively. Comparisons were performed amongst demographic subgroups and with patients over 49 years of age enrolled between January 2005 and March 2010 ( = 921).

Results

In the young patients, median age was 42 years (interquartile range 34–47), 59.5% were male, and annual incidence was 4.9 (95% confidence interval 4.5–5.3) per 100 000. The most prevalent risk factors were hypertension (29.8%) and smoking (22.3%). Compared with older patients hypertensive microangiopathy was less common (25.0% vs. 34.3%,  = 0.002) and structural lesions more common (25.0% vs. 4.9%,  < 0.001) assumed etiologies of ICH. The cause remained elusive in 32.1% of all young patients and in 22.5% of those who underwent magnetic resonance imaging and any angiography ( = 89,  = 0.023). Three‐month mortality rate was lower in young patients compared with older ones (17.0% vs. 32.7%,  < 0.001). Hematoma volumes were similar across all ages ( = 0.324) and independently predicted mortality in older patients but not in the young.

Conclusions

Intracerebral hemorrhage (ICH) in the young appears less fatal and has a different spectrum of causes and factors associated with short‐term mortality than for the elderly.

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Authors:
R.‐J. Koivunen, J. Satopää, A. Meretoja, D. Strbian, E. Haapaniemi, M. Niemelä, T. Tatlisumak and J. Putaala
Article first published online:
21 Aug 2014 | DOI: 10.1111/ene.12543

Original Article

Background and purpose

Move for Change is an online pan‐European patient survey based on the European Parkinson's Disease Association (EPDA) Charter for People with Parkinson's Disease (PD), which states that all PD patients have the right to: be referred to a doctor with a specialist interest in PD; receive an accurate diagnosis; have access to support services; receive continuous care; and take part in managing their illness.

Methods

This part of the survey focuses on the final two elements of the Charter. It was administered online through the EPDA website and through affiliated patient associations’ websites. A total of 1591 questionnaires were received and 1546 were analysed (97.2%).

Results

Approximately half of the patients (53.0%) consulted a neurologist regularly (every 4–6 months). Consultations were usually arranged as part of a follow‐up process (65.5%) and lasted for 15–30 min (63.2%), with 16.1% lasting <10 min and 17.9% lasting >30 min. Patients were largely satisfied with the attention they received (63.2%) but just 11.6% of patients were involved in treatment decisions, and 39.1% prepared a list of symptom changes for discussion. Two hundred caregivers also took part in the survey, and 71.4% felt included in the treatment plan by the doctor.

Conclusions

These results highlight that PD disease‐management is driven by the clinician; he/she arranges consultations and makes the majority of management decisions, rather than patients being included in the process. This survey can be used to raise awareness for PD patients, encouraging greater involvement in the management of PD.

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Authors:
B. R. Bloem and F. Stocchi
Article first published online:
08 Sep 2014 | DOI: 10.1111/ene.12544

Original Article

Background and purpose

Earlier studies suggested an association between idiopathic restless legs syndrome (RLS) and cardiovascular diseases. However, the risk of cardiovascular events in patients with secondary RLS due to end‐stage renal disease (ESRD) is unclear. Our aim was to examine whether ESRD patients with RLS had an increased risk of cardio/cerebrovascular events and mortality.

Methods

In all, 1093 ESRD patients were recruited between 2009 and 2010. The diagnosis and severity of RLS were assessed in a face‐to‐face interview. The occurrence of cardio/cerebrovascular events and death were confirmed by medical record review. The association between RLS and the outcomes of interest was examined using an adjusted multivariate Cox regression model.

Results

After a mean follow‐up period of 3.7 ± 0.8 years, ESRD patients with RLS had a significantly higher risk of developing cardiovascular events and strokes [adjusted hazard ratio (aHR) 2.82, 95% confidence interval (CI) 2.02–4.11, and aHR 2.41, 95% CI 1.55–3.75, respectively] compared with patients without RLS. Increasing RLS severity was associated with an increasing likelihood of cardiovascular events [mild RLS severity, aHR 1.71 (95% CI 1.02–2.87); moderate, 2.79 (1.64–4.66); severe, 2.85 (1.99–4.46)] and strokes [mild, 1.89 (0.87–4.16); moderate, 2.42 (1.50–3.90); severe, 2.64 (1.49–4.91)] in a dose‐dependent manner. RLS also increased the risk of total mortality in patients with ESRD [aHR 1.53 (95% CI 1.07–2.18), =0.02]; this association attenuated slightly after stratification by individual RLS severity category [mild RLS severity, aHR 1.44 (95% CI 0.78–2.67); moderate, 1.49 (0.98–2.55); severe, 2.03 (0.93–4.45)].

Conclusions

ESRD patients with RLS demonstrated an increased likelihood of cardio/cerebrovascular events and mortality.

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Authors:
C.‐H. Lin, H.‐N. Sy, H.‐W. Chang, H.‐H. Liou, C.‐Y. Lin, V.‐C. Wu, S.‐L. Wu, C.‐C. Chang, P.‐F. Chiu, W.‐Y. Li, S.‐Y. Lin, K.‐D. Wu, Y.‐M. Chen and R.‐M. Wu
Article first published online:
21 Aug 2014 | DOI: 10.1111/ene.12545

Original Article

Background and purpose

Whilst there is evidence implicating small vessel cerebrovascular disease in the pathogenesis of Alzheimer's disease (AD), its specific contribution to the pathophysiology of AD remains unclear. The burden of small vessel cerebrovascular disease visualized as white matter hyperintensity (WMH) and its association with medial temporal atrophy (MTA) at different stages of AD was studied.

Methods

One hundred and sixty‐five cognitively normal (CN) community controls, 103 mild cognitive impairment (MCI) patients, 141 mild AD patients and 68 moderate−severe AD patients were studied. Clinical, cognitive and risk factor data were collected, and WMH and MTA were quantified by trained raters. The Jonckheere−Terpstra test for ordered alternatives was used to study the association between WMH and MTA in different stages of AD.

Results

The burden of total WMH increased significantly with increasing severity of AD, even after correcting for confounders. The proportion of CN, MCI, mild AD and moderate−severe AD subjects with severe burden of WMH was 6.7%, 9.7%, 28.4%, and 39.7%, respectively. A strong positive association between WMH severity and MTA was evident amongst MCI ( = 0.011) and mild AD ( = 0.003) subjects, but not in CN ( = 0.953) and moderate−severe AD subjects ( = 0.301).

Conclusions

The burden of WMH increased significantly from the stage of CN to MCI to AD. The association between WMH and MTA was greatest at the stage of MCI and mild AD. This has implications on the strategy to slow the progression of AD, where measures to reduce WMH, including control of vascular risk factors, need to be optimized at the stage of MCI and mild AD.

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Authors:
N. Kandiah, R. J. Chander, A. Ng, M. C. Wen, A. R. Cenina and P. N. Assam
Article first published online:
21 Aug 2014 | DOI: 10.1111/ene.12546

Original Article

Background and purpose

During the past decade, several population‐based studies have found an inverse association between blood pressure (BP) and headache. However, most of them have a cross‐sectional design or lack a validated definition of a headache‐free population at baseline. Therefore, additional population‐based studies using a clearly defined headache‐free population and a prospective design are warranted.

Methods

Data from two large epidemiological studies, the Nord‐Trondelag Health Survey 1995–1997 (HUNT 2) and 2006–2008 (HUNT 3), were used to evaluate the association between BP (systolic, diastolic and pulse pressure) at baseline and headache (migraine and tension type headache) at follow‐up.

Results

An inverse relationship was found between all three BP measures at baseline in HUNT 2 and any headache in HUNT 3, more evident for systolic BP [odds ratio (OR) 0.90 per 10 mmHg increase in systolic BP, 95% confidence interval (CI) 0.87–0.93, < 0.001] and pulse pressure (OR 0.84 per 10 mmHg increase in pulse pressure, 95% CI 0.80–0.89, < 0.001) than for diastolic BP (OR 0.92 per 10 mmHg increase in diastolic BP, 95% CI 0.87–1.00, = 0.036). The most robust finding, evident for both sexes, was that increased pulse pressure was linked to decreased prevalence of both migraine and tension type headache.

Conclusion

An inverse relationship between BP and subsequent development of headache was confirmed in this large‐scale population‐based cohort study. Nevertheless, further research is needed to investigate the underlying mechanisms explaining these findings.

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Authors:
C. F. Fagernæs, I. Heuch, J.‐A. Zwart, B. S. Winsvold, M. Linde and K. Hagen
Article first published online:
25 Aug 2014 | DOI: 10.1111/ene.12547

Original Article

Background and purpose

There are concerns that systemic thrombolysis might not achieve clinically important outcome amongst chronic heart failure (CHF) patients with acute ischaemic stroke. Our aim was to investigate the relevance of CHF on the outcome of acute stroke patients who received thrombolysis.

Methods

A non‐randomized cohort analysis was conducted using data obtained from the Virtual International Stroke Trials Archive. The association of outcome amongst CHF patients with thrombolysis treatment was described using the modified Rankin scale (mRS) distribution at day 90, stratified by the presence of atrial fibrillation. Dichotomized outcomes were considered as a secondary end‐point.

Results

5677 patients were identified, of whom 2366 (41.7%) received thombolysis. Five hundred and three (8.9%) patients had CHF, of whom 209 (41.6%) received thrombolysis. The presence of CHF was associated with a negative impact on overall stroke outcome [odds ratio (OR) 0.73 (95% confidence interval (CI) 0.62–0.87),  < 0.001]. However, thrombolysis treatment was associated with favourable functional outcome using ordinal mRS, irrespective of CHF status, after adjustment for age and baseline National Institutes of Health Stroke Scale [OR 1.44 (95% CI 1.04–2.01,  = 0.029) for CHF patients versus OR 1.50 (95% CI 1.36–1.66,  < 0.001) for non‐CHF patients]. CHF patients had higher mortality at day 90 than non‐CHF patients. There was no significant difference for recurrent stroke or symptomatic intracerebral haemorrhage within 7 days of the initial stroke between CHF and thrombolysis groups.

Conclusions

Chronic heart failure was associated with a worse outcome with or without thrombolysis. However, acute stroke patients who received thrombolysis had more favourable outcome regardless of CHF status, compared with their untreated peers. Our findings should reassure clinicians considering systemic thrombolysis treatment in hyperacute ischaemic stroke patients with CHF.

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Authors:
A. H. Abdul‐Rahim, R. L. Fulton, B. Frank, J. J. V. McMurray, K. R. Lees, A. V. Alexandrov, P. W. Bath, E. Bluhmki, L. Claesson, J. Curram, S. M. Davis, G. Donnan, H. C. Diener, M. Fisher, B. Gregson, J. Grotta, W. Hacke, M. G. Hennerici, M. Hommel, M. Kaste, K. R. Lees, P. Lyden, J. Marler, K. Muir, R. Sacco, A. Shuaib, P. Teal, N. G. Wahlgren, S. Warach and C. Weimar
Article first published online:
25 Aug 2014 | DOI: 10.1111/ene.12548

Original Article

Background and purpose

Ketogenesis is a physiological phenomenon due to starvation or a ketogenic diet (KD), a drastic restricted carbohydrate dietary regimen that induces lipid metabolism and ketone body synthesis. Two patients whose migraines disappeared only during, and not outside, cycles of very‐low‐calorie KD performed to reduce their weight were recently observed. To confirm our observation, in a dietitian clinical setting two parallel groups of migraineurs, one receiving a 1‐month very‐low‐calorie KD prescription followed by a 5‐month standard low‐calorie diet (SD) and the other a 6‐month SD, were followed.

Methods

Ninety‐six overweight female migraineurs were enrolled in a diet clinic and blindly received a KD (= 45) or an SD (= 51) prescription. Mean monthly attack frequency, number of days with headaches and tablet intake were assessed before and 1, 2, 3 and 6 months after diet initiation.

Results

In the KD group, the baseline attack frequency (2.9 attacks per month), number of days with headaches (5.11 days per month) and tablet intake (4.91 doses per month) were significantly reduced after the first month of diet (respectively 0.71, 0.91, 0.51; overall, KD versus baseline, < 0.0001). During the transition period (first versus second month), the KD group showed a transient worsening of each clinical headache variable (respectively 2.60, 3.60, 3.07), despite being improved compared with baseline, with continuous improvement up to month 6 (respectively 2.16, 2.78, 3.71). In the SD group, significant decreases in the number of days with headaches and tablet intake were observed only from month 3 ( < 0.0001), and in attack frequency at month 6 ( < 0.0001).

Conclusions

The underlying mechanisms of KD efficacy could be related to its ability to enhance mitochondrial energy metabolism and counteract neural inflammation.

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Authors:
C. Di Lorenzo, G. Coppola, G. Sirianni, G. Di Lorenzo, M. Bracaglia, D. Di Lenola, A. Siracusano, P. Rossi and F. Pierelli
Article first published online:
25 Aug 2014 | DOI: 10.1111/ene.12550

Editorial

Abstract

Click to view the accompanying paper in this issue.

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Authors:
R. Topakian
Article first published online:
25 Aug 2014 | DOI: 10.1111/ene.12551

Original Article

Background and purpose

Mutations in the gene are causative of ‐associated neurodegeneration (PLAN), a spectrum of neurodegenerative conditions including infantile, childhood and adult onset forms.

Methods

Seventeen North African patients with a clinical suspicion of infantile‐onset PLAN underwent clinical, neurophysiological and neuroimaging examinations, and sequencing. Haplotype analysis was performed to date the identified founder mutation.

Results

All patients carried biallelic mutations in . Sixteen children had the commonest form of infantile‐onset PLAN, with early onset of psychomotor regression, hypotonia, pyramidal and cerebellar signs, and abnormal ocular movements. The phenotype was highly homogeneous, with rapid development of severe spastic tetraparesis, cognitive impairment and optic atrophy. Neuroimaging showed cerebellar atrophy and claval hypertrophy to be the commonest and earliest signs, whilst cerebellar cortex hyperintensity and pallidal iron deposition were later findings. Motor or sensory‐motor neuropathy and electroencephalogram fast rhythms were also frequent. Nine patients from six families shared the same founder mutation (p.V691del) which probably arose by the late seventeenth century. Only one patient fitted the diagnosis of the much rarer childhood‐onset PLAN. Despite the early onset (18 months), clinical progression was slower, with behavioral disturbances and dystonia. Typical features of infantile‐onset PLAN such as hypotonia, nystagmus/strabismus, optic atrophy, electroencephalogram fast rhythms and motor neuropathy were absent. Cerebellar atrophy, claval hypertrophy and pallidal hypointensity were evident at brain magnetic resonance imaging. This patient carried a missense variant predicted to be less deleterious.

Conclusions

The PLAN‐associated phenotypes and the challenges of diagnosing the childhood‐onset form are delineated, and a common North African founder mutation is identifed.

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Authors:
M. Romani, I. Kraoua, A. Micalizzi, H. Klaa, H. Benrhouma, C. Drissi, I. Turki, S. Castellana, T. Mazza, E. M. Valente and N. Gouider‐Khouja
Article first published online:
27 Aug 2014 | DOI: 10.1111/ene.12552

Original Article

Background and purpose

The association between vascular risk factors and dementia is of interest. Several studies have shown that cerebral small vessel disease (SVD) is associated with dementia. However, the association between cerebral large vessel disease (LVD) and dementia has not been thoroughly examined.

Methods

The Osaka Follow‐up Study for Carotid Atherosclerosis, Part 2, was a prospective cohort study of cardiovascular events and dementia in which patients ( = 1106) with vascular risk factors underwent carotid ultrasound. Of these patients, 600 who had normal cognitive function were included and underwent brain magnetic resonance imaging. The presence of lacunar infarction and carotid stenosis served as markers for SVD and LVD, respectively.

Results

Amongst 600 patients (mean 68 years, 57% men), 261 (44%) showed lacunar infarction and 94 (16%) showed carotid stenosis. During the follow‐up period (median 8.0 years), 57 patients had incident dementia. Patients with carotid stenosis and lacunar infarction were significantly more likely to be diagnosed with dementia (log‐rank test,  = 0.037 and 0.001, respectively). The association between lacunar infarction and dementia remained significant after adjusting for risk factors including stroke history, apolipoprotein E genotype and years of education (hazard ratio 2.64, 95% confidence interval 1.22–6.09). However, the presence of carotid stenosis was not associated with incident dementia after adjusting for age and sex ( =0.477).

Conclusions

This study demonstrated that carotid stenosis had little association with dementia, but lacunar infarction had a significant association. The impact of SVD on dementia could be much greater than that of LVD.

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Authors:
K. Kitagawa, K. Miwa, Y. Yagita, S. Okazaki, M. Sakaguchi and H. Mochizuki
Article first published online:
27 Aug 2014 | DOI: 10.1111/ene.12553

Original Article

Background and purpose

No systematic nerve ultrasound (US) studies on patients with neuropathy and anti‐myelin‐associated glycoprotein (anti‐MAG) antibodies are available.

Patients and methods

Twenty‐eight patients (18 men, 10 women, mean age 69.2 ± 10.9 years; mean disease duration 6.9 years) with anti‐MAG neuropathy underwent nerve US. Echotexture, nerve cross‐sectional area (CSA) and intra‐nerve and inter‐nerve CSA variability were assessed. The frequency (number of nerves with enlarged CSA, ‘enlarged nerves sum score’) and distribution (proximal versus distal, arms versus legs, symmetry) of US abnormalities were considered. Controls included two groups: four patients with immunoglobulin M (IgM) paraproteinaemic neuropathy without anti‐MAG antibodies and five with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with IgM paraprotein.

Results

In all, 26/28 patients had increased CSA (23 with at least one nerve outside entrapment sites). Intra‐nerve CSA variability was abnormal in 21/28 patients (in 14 for increased nerve CSA outside entrapment sites). Inter‐nerve CSA variability was abnormal in 16 patients (of whom half for CSA increase out of entrapment sites). The enlarged nerves sum score in anti‐MAG neuropathy patients was greater than in MAG‐negative paraproteinaemic neuropathies and lower than in CIDP. Intra‐nerve variability appeared instead similar in anti‐MAG and controls. No correlation was found between US findings and Inflammatory Neuropathy Cause and Treatment Group (INCAT) disability score or disease duration.

Discussion

Amongst the different measures to assess the US pattern (symmetry/asymmetry, proximal/distal distribution and sum score), the enlarged nerves sum score was the most useful for differentiating the three groups of patients with demyelinating neuropathies and may contribute to diagnosis in a typical cases.

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Authors:
M. Lucchetta, L. Padua, G. Granata, M. Luigetti, M. Campagnolo, C. Dalla Torre, D. Coraci, M. Sabatelli and C. Briani
Article first published online:
01 Sep 2014 | DOI: 10.1111/ene.12554

Letter to the Editor

Why is mesial temporal lobe epilepsy with Ammon's horn sclerosis becoming less common?

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Authors:
T. A. Butler, P. Dugan and J. French
Article first published online:
13 Dec 2014 | DOI: 10.1111/ene.12570

Invited Review

Abstract

Myasthenia gravis (MG) is an autoimmune disorder leading to skeletal muscle weakness and fatigability. MG subgroups are defined according to pathogenetic autoantibody (against acetylcholine receptor, muscle‐specific tyrosine kinase or lipoprotein receptor‐related protein 4), thymus pathology and clinical manifestations. MG patients have an increased risk for concordant autoimmune disease, in particular with early onset MG. Most common comorbidities are thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. Cardiomyositis and subclinical heart dysfunction have been described in patients with thymoma MG and late onset MG but represent no major threat. A thymic lymphoepithelioma implies an increased risk for another cancer. Autoimmune MG represents no distinct cancer risk factor, although lymphomas and a few other cancer types have been reported with slightly increased frequency. Severe MG‐related muscle weakness means a risk for respiratory failure and respiratory tract infection. Drug MG treatment can lead to side‐effects. Thymectomy is regarded as a safe procedure both short and long term. Non‐MG‐related comorbidity represents a diagnostic and therapeutic challenge, especially in elderly patients. Diagnostic accuracy and optimal follow‐up is necessary to identify and treat all types of coexisting disease in MG.

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Authors:
N. E. Gilhus, A. Nacu, J. B. Andersen and J. F. Owe
Article first published online:
30 Oct 2014 | DOI: 10.1111/ene.12599

Invited Review

Abstract

As captured by the proposed new definition, epilepsy is increasingly recognized as a disorder characterized not only by an enduring predisposition to recurrent seizures but explicitly also by the neurobiological, cognitive, psychological and social consequences of this condition. Further, both in the estimated 15 million people worldwide who have ongoing seizures despite optimal management and in a substantial proportion of those in remission, the consequences and comorbidities of epilepsy are the major determinants of quality of life. These include mood disorders such as anxiety and depression, dose related and longer term effects of antiepileptic drugs, including on prenatal development and bone health, and neurobehavioural effects. Whilst separating those that are part of an underlying condition or have unrelated contributors from those that are potentially remediable can be difficult, given the range of tools now available to assist with screening and management there is no excuse for not at least trying as part of standard care for people with epilepsy. Managing epilepsy well is about much more than controlling seizures and this needs to be recognized in planning and delivering services, as well as in prioritizing research.

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Authors:
M. Mula and H. R. Cock
Article first published online:
04 Nov 2014 | DOI: 10.1111/ene.12603

Invited Review

Abstract

Statins intolerance is mainly due to their side effects on the neuromuscular system (primarily muscle). It has become an important issue because of the major cardiovascular risk reduction of this class of drugs. However, the facts related to these side effects are sometimes under‐recognized or controversial. A literature review of the recent developments in the field is given. The clinical definition of statin myopathy and its presentation are not suitable for the myology field. Management and prevention are not validated. More genetic risk factors need to be established. Neurologists should become more involved in statin intolerance evaluation and management.

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Authors:
Z. Argov
Article first published online:
13 Dec 2014 | DOI: 10.1111/ene.12604

Introduction

Introduction

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Authors:
Article first published online:
13 Dec 2014 | DOI: 10.1111/ene.12628

Calendar

Calendar

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Authors:
Article first published online:
13 Dec 2014 | DOI: 10.1111/ene.12655