cover image European Journal of Neurology

European Journal of Neurology

2015 - Volume 22
Issue 11 | November 2015
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Original Article

Background and purpose

Energy metabolism is altered in patients with amyotrophic lateral sclerosis (ALS) but the role of diabetes is largely unknown.

Methods

A population‐based case−control study was conducted of 5108 ALS cases and 25 540 individually matched population controls during 1991–2010. Information on ALS and pre‐existing diabetes was retrieved from the Swedish Patient Register to explore the association of ALS with diabetes overall and with insulin‐dependent or non‐insulin‐dependent diabetes specifically. Variation of the association by diabetes duration and age was also studied.

Results

In total, 224 ALS cases (4.39%) and 1437 controls (5.63%) had diabetes before the index date, leading to an overall inverse association between diabetes and ALS risk [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.68–0.91]. The association was strong for non‐insulin‐dependent diabetes (OR 0.66, 95% CI 0.53–0.81) but not for insulin‐dependent diabetes (OR 0.83, 95% CI 0.60–1.15) and varied as a function of diabetes duration, with the strongest association observed around 6 years after first ascertainment of diabetes. The association was age‐specific; the inverse association was noted only amongst individuals aged 70 or older. In contrast, for younger individuals (<50 years), pre‐existing insulin‐dependent diabetes was associated with a higher ALS risk (OR 5.38, 95% CI 1.87–15.51).

Conclusions

Our study suggests that there is an association between diabetes and ALS, and highlights the importance of taking into account age, insulin dependence and diabetes duration. Future studies should explore whether the association is independent of body mass index.

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Authors:
D. Mariosa, F. Kamel, R. Bellocco, W. Ye and F. Fang
Article first published online:
19 Jan 2015 | DOI: 10.1111/ene.12632

Editorial

Abstract

Click to view the accompanying paper in this issue.

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Authors:
A. Jawaid, J. A. Brown and P. E. Schulz
Article first published online:
18 Jan 2015 | DOI: 10.1111/ene.12660

Original Article

Background and purpose

Pain affects around two‐thirds of people with Multiple Sclerosis (pwMS). Biomedical treatments show limited efficacy. A recently developed cognitive‐behavioural model of Multiple Sclerosis (MS) pain suggests several psychosocial factors may worsen pain and related disability. The current study investigated whether psychosocial factors drawn from this model explain significant amounts of the variance in pain severity and interference over and above measures of disease severity and pain subtype.

Methods

Six hundred and twelve pwMS experiencing pain completed a UK wide cross‐sectional survey including valid and reliable psychometric questionnaires. Hierarchical regressions determined the relative contribution of disease severity and psychosocial factors to predicting pain severity and interference.

Results

All psychosocial factors including distress, negative beliefs about pain and its consequences, and avoidance of activity, were related to pain outcomes, explaining a further 24% and 30% of the variance in pain severity and interference after controlling for demographic and disease variables. Findings were similar for neuropathic and non‐neuropathic pain subgroups.

Conclusions

All pwMS reported significant pain and associated disability even though over 90% were taking pain medication. Psychosocial factors identified as important in predicting pain severity and, to a greater extent, pain interference are potentially modifiable and may be important treatment targets for both pain subtypes.

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Authors:
A. M. Harrison, E. Silber, L. M. McCracken and R. Moss‐Morris
Article first published online:
14 Jul 2015 | DOI: 10.1111/ene.12763

Original Article

Background and purpose

The prognostic value of contrast accumulation from non‐contrast brain computed tomography taken immediately after endovascular reperfusion treatment in acute ischaemic stroke patients to predict symptomatic hemorrhage was studied.

Methods

Between July 2007 and August 2014, acute anterior circulation ischaemic stroke patients who were treated by intra‐arterial thrombolysis or thrombectomy were included. Contrast accumulation was defined as a high attenuation area from non‐contrast brain computed tomography immediately taken after endovascular reperfusion treatment, and patients were categorized into three groups according to the presence and location of contrast: (i) negative, (ii) cortical involvement and (iii) non‐cortical involvement. The rates of symptomatic hemorrhage after 24 h and functional outcome at discharge were compared between patients with and without cortical involvement.

Results

Of 64 patients who were treated by endovascular intervention, contrast accumulation was detected in 56, including 33 patients with cortical involvement and 23 patients without cortical involvement. The cortical involvement pattern was more frequently associated with symptomatic hemorrhage (13 vs. 1 patient,  = 0.003) and with grave outcome at discharge with modified Rankin Scale 5 or 6 (14 vs. 4,  = 0.048) than the non‐cortical involvement group. Multivariate logistic regression analysis including initial collateral status and occlusion site disclosed that cortical involvement pattern independently predicted symptomatic hemorrhage after endovascular treatment (odds ratio 19.0, confidence interval 1.6–227.6,  = 0.020).

Conclusion

Our study provides evidence that the cortical involvement of contrast accumulation is associated with symptomatic hemorrhage after endovascular reperfusion treatment.

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Authors:
J.‐M. Kim, K.‐Y. Park, W. J. Lee, J. S. Byun, J. K. Kim, M.‐S. Park, S.‐W. Ahn and H.‐W. Shin
Article first published online:
01 Jul 2015 | DOI: 10.1111/ene.12764

Original Article

Background and purpose

To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post‐stroke epilepsy.

Methods

This nationwide cohort study was conducted by using data from 2004 to 2008 on new occurrence of post‐stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ) and new AEDs. Recurrent seizures requiring either emergency room (ER) visits or hospitalization were used to measure the efficacy of seizure control. The Kaplan−Meier failure curve and Cox proportional hazard regression analyses were used to compare the risk of seizure recurrence in patients taking various AEDs.

Results

In all, 3622 late‐onset post‐stroke epilepsy patients were selected. Overall, 1.05 and 0.70 recurrent seizure incidences occurred per 100 person‐months based on ER visits [95% confidence interval (CI) 0.95–1.15] and hospitalizations (95% CI 0.62–0.78), respectively. The incidences of ER visits for patients using different AEDs were 1.26, 0.70, 0.43 and 0.38 per 100 person‐months for PHT, VPA, CBZ and new AEDs, respectively. Compared with patients using PHT, the adjusted hazard ratios for ER visits were 0.56 (95% CI 0.42–0.74; < 0.001), 0.37 (95% CI 0.18–0.75;  = 0.006) and 0.28 (95% CI 0.15–0.52; < 0.001) for patients using VPA, CBZ and new AEDs, respectively. The adjusted hazard ratios of hospitalizations for seizure recurrence yielded similar results.

Conclusions

This large nationwide, population‐based study demonstrated that late‐onset post‐stroke epilepsy patients using VPA and new AEDs have better seizure control than those using PHT as demonstrated by lower risks of ER visits and hospitalization.

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Authors:
Y.‐H. Huang, N.‐F. Chi, Y.‐C. Kuan, L. Chan, C.‐J. Hu, H.‐Y. Chiou and L.‐N. Chien
Article first published online:
06 Jul 2015 | DOI: 10.1111/ene.12766

Original Article

Background and Purpose

Chronic inflammatory demyelinating polyneuropathy (CIDP) may have variable evolution profiles, which have not been compared between cohorts. The relationship of disease status with motor strength, function and electrophysiology is uncertain.

Methods

Disease status was studied with a simplified proposed scale in two patient cohorts totalling 72 subjects from Leicester, UK, and Angers, France. Clinical and electrophysiological records were analysed.

Results

Independent ascertainment of disease status in each cohort revealed similar rates of remission ( = 0.23), stable/improving disease ( = 0.34) and unstable/active disease ( = 1). No correlation was ascertained with strength or function. Median nerve compound muscle action potential was the only independent electrophysiological predictor of disease status ascertained ( = 0.046).

Conclusions

Disease status distribution may represent an important comparative indicator for management of CIDP cohorts and could be useful for benchmarking service and treatment provision. Degree of upper limb motor axonal loss may represent a useful electrophysiological marker of disease status in CIDP.

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Authors:
Y. A. Rajabally, J. Cassereau, A. Robbe and G. Nicolas
Article first published online:
14 Jul 2015 | DOI: 10.1111/ene.12767

Original Article

Background and purpose

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Approximately 5%–10% of cases are familial (FALS) and the remaining are sporadic (SALS). To date FUS mutations are responsible for 4%–6% of familial cases as well as 0.7%–1.8% of sporadic cases.

Methods

The frequency of FUS mutations was investigated in an Italian cohort of 500 SALS and 40 FALS patients through direct sequencing of exons 5, 6, 13, 14 and 15.

Results

Eight FUS mutation carriers were identified in five SALS (1%) and three FALS (7.5%), five already known and three new mutations: a mutation was identified in a sporadic subject as well as the co‐presence of FUS/C9ORF72 mutations in a FALS subject. The molecular and clinical details of the three patients harbouring a novel mutation (G245V, G509D and R491C) are presented here. Moreover the co‐presence of the R491C mutation and C9ORF72 pathological expansion was found according to the oligogenic disease model.

Conclusions

In conclusion our results revealed a higher frequency of FUS mutation carriers (7.5%) in FALS compared to literature data together with a higher presence of female gender.

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Authors:
C. Tarlarini, C. Lunetta, L. Mosca, F. Avemaria, N. Riva, V. Mantero, E. Maestri, A. Quattrini, M. Corbo, M. G. Melazzini and S. Penco
Article first published online:
15 Jul 2015 | DOI: 10.1111/ene.12772

CME Article

Background and purpose

There is limited primary‐care‐based evidence about a potential association between anti‐inflammatory therapy and dementia subtypes. The present study addressed this limitation by using electronic health records from a large primary care database.

Method

A case–control study was implemented using electronic medical records. Cases had a diagnosis of dementia between 1992 and 2014. Up to four controls matched on age, gender, family practice and index date were selected for each case. Use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and glucocorticoid drugs represented the exposure variables. Primary outcome measures included all‐cause dementia and main dementia subtypes, including Alzheimer disease (AD), vascular dementia (VaD) and Lewy body dementia (LBD). Data were analysed using conditional logistic regression.

Results

The study identified 31 083 patients with AD, 23 465 with VaD and 1694 with LBD. Ever‐used NSAIDs were associated with a modest increase in the risk of all‐cause dementia (odds ratio 1.04, 95% confidence interval 1.02–1.05,  < 0.006), whilst no association was apparent for ever‐used glucocorticoids (0.98, 0.96–1.01,  = 0.152). There was no evidence for an association between NSAIDs and AD (1.03, 0.99–1.06,  = 0.07) or LBD (1.13, 0.99–1.29,  = 0.08). However, a significant increase in the risk for VaD (1.33, 1.29–1.38,  < 0.001) was observed. Similar patterns emerged for glucocorticoid therapy.

Conclusion

In a large primary care population, there was no robust evidence for a potential association between anti‐inflammatory drugs and risk of AD or LBD. NSAIDs and glucocorticoid drugs were associated with higher risk of VaD.

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Authors:
A. Dregan, P. Chowienczyk and D. Armstrong
Article first published online:
14 Jul 2015 | DOI: 10.1111/ene.12774

Original Article

Background and purpose

Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep−wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24‐h activity rhythms.

Methods

This study was conducted in the Rotterdam Study. A total of 970 community‐dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty‐four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses.

Results

Higher white matter lesion volume ( = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds ( = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24‐h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality.

Conclusions

White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24‐h activity rhythm.

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Authors:
L. A. Zuurbier, M. A. Ikram, A. I. Luik, A. Hofman, E. J. W. Van Someren, M. W. Vernooij and H. Tiemeier
Article first published online:
24 Jul 2015 | DOI: 10.1111/ene.12775

Invited Review

Abstract

Myofibrillar myopathies are a genetically diverse group of skeletal muscle disorders, with distinctive muscle histopathology. Causative mutations have been identified in the genes ,,,,,,,, and , which encode proteins which either reside in the Z‐disc or associate with the Z‐disc. Mitochondrial abnormalities have been described in muscle from patients with a myofibrillar myopathy. We reviewed the literature to determine the extent of mitochondrial dysfunction in each of the myofibrillar myopathy subtypes. Abnormal mitochondrial distribution is a frequent finding in each of the subtypes, but a high frequency of COX‐negative or ragged red fibres, a characteristic finding in some of the conventional mitochondrial myopathies, is a rare finding. Few studies of mitochondrial function have been performed in affected patients.

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Authors:
S. Jackson, J. Schaefer, M. Meinhardt and H. Reichmann
Article first published online:
23 Jul 2015 | DOI: 10.1111/ene.12814

Short Communication

Background and purpose

Although the genetic contribution to stroke risk is well known, it remains unclear if young‐onset stroke has a stronger genetic contribution than old‐onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole‐genome array data in population‐based samples.

Methods

This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young‐onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole‐genome array data using a mixed linear model. Heritability was estimated separately for young‐onset stroke and old‐onset stroke (age ≥ 55 years).

Results

Heritabilities for young‐onset stroke and old‐onset stroke were estimated at 42% (±8%,  < 0.001) and 34% (±10%,  < 0.001), respectively.

Conclusions

Our data suggest that the genetic contribution to the risk of stroke may be higher in young‐onset ischaemic stroke, although the difference was not statistically significant.

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Authors:
A. Bluher, W. J. Devan, E. G. Holliday, M. Nalls, S. Parolo, S. Bione, A.‐K. Giese, G. B. Boncoraglio, J. M. Maguire, M. Müller‐Nurasyid, C. Gieger, J. F. Meschia, J. Rosand, A. Rolfs, S. J. Kittner, B. D. Mitchell, J. R. O'Connell and Y.‐C. Cheng
Article first published online:
02 Sep 2015 | DOI: 10.1111/ene.12827

Calendar

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Authors:
Article first published online:
08 Oct 2015 | DOI: 10.1111/ene.12892