cover image European Journal of Neurology

European Journal of Neurology

2014 - Volume 21
Issue 4 | April 2014
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Short Communication

Background and purpose

Mutations in the gene have been identified in patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many detailed clinico‐genetic correlations have been performed.

Methods

To investigate mutations in a mixed Asian PKD population and perform clinico‐genetic correlations, we recruited patients between 2002 and 2011 and administered a standardized questionnaire.

Results

Amongst 29 unrelated patients with PKD recruited, five mutations were present in 15 patients. Three mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs; c.697_698delAG/p.Ser233Trp fsX5). Clinico‐genetic correlations revealed that a history of seizures was more common in patients with mutations, although this did not reach statistical significance (= 0.08). A younger age of onset, non‐Chinese, and the presence of premonitory sensations were significantly associated with mutations in the univariate analysis. Multivariate logistic regression analysis demonstrated that age of onset [odds ratio (OR) = 0.59, = 0.025] and premonitory sensation (OR = 10.67, = 0.028) were independently associated with positive mutation.

Conclusions

mutations are common in patients with PKD, and a double mutation is reported for the first time. mutations are significantly associated with a younger age of onset and the presence of premonitory sensation in our population.

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Authors:
L. C. S. Tan, K. Methawasin, E. W. L. Teng, A. R. J. Ng, S. H. Seah, W. L. Au, J. J. Liu, J. N. Foo, Y. Zhao and E. K. Tan
Article first published online:
29 Mar 2013 | DOI: 10.1111/ene.12142

Original Article

Background and purpose

Oral anticoagulation (OAC) is an effective preventive therapy for ischemic stroke in atrial fibrillation (AF). The management of anticoagulation in AF patients with previous intracerebral hemorrhage (ICH) is challenging. The aim of this study was to determine the prevalence of AF after acute ICH in a consecutive monocenter cohort, and to document the subsequent management with respect to OAC.

Methods

Consecutive patients with spontaneous ICH were prospectively included within 19 months. Diagnosis of AF was based on medical history, 12‐lead electrocardiogram (ECG), 24‐h and continuous ECG monitoring. CHADS scores and patient medication were recorded at admission and after 3 months. Additionally, after 3 months mortality, the management of anticoagulation and a newly detected AF were assessed.

Results

In total, 206 ICH patients were eligible for data analysis. After 3 months, AF had been diagnosed in 64/206 ICH patients (31.1%). Mortality after 3 months was higher in patients with AF in univariate analysis (45.3% vs. 31.0%). After adjusting for comorbidities and OAC use, AF did not remain an independent predictor for mortality. In total, 35 patients with AF survived 3 months. Of these, CHADS score was 2 (2/3, median, interquartile range (IQR)) and 27/35 patients had an indication for OAC with respect to the CHADS score, but only 25.7% had been (re‐)started on OAC. No consistent factors for deciding whether to initiate OAC treatment could be identified.

Conclusions

Atrial fibrillation is a frequent comorbidity in patients suffering an ICH. Our findings underline the prevailing uncertainty regarding the anticoagulation management of AF after ICH.

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Authors:
S. Horstmann, T. Rizos, E. Jenetzky, C. Gumbinger, W. Hacke and R. Veltkamp
Article first published online:
12 Jun 2013 | DOI: 10.1111/ene.12215

Short Communication

Background and purpose

The etiological classification of patients with transient ischaemic attack (TIA) is a difficult endeavor and the use of serum biomarkers could improve the diagnostic accuracy. The aim of this study was to correlate atrial fibrillation, the main cardioembolic etiology (CE), with different serum biomarkers measured in consecutive TIA patients.

Methods

The concentrations of interleukin‐6 (IL‐6), tumor necrosis factor‐alpha, neuron‐specific enolase, high‐sensitivity C‐reactive protein, IL‐1‐α and the N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) were quantified in the serum of 140 patients with TIA and 44 non‐stroke subjects. Measurements were performed at different times throughout evolution: within 24 h of symptoms onset and at days 7 and 90.

Results

With the exception of IL‐6, all biomarkers were higher in TIA patients than in controls. NT‐proBNP was significantly related to the presence or new diagnosis of AF at all time points analyzed. Furthermore, the baseline NT‐proBNP level was significantly higher than values at the 7‐day and 90‐day follow‐up. For this reason, different cut‐off values were obtained at different times: 313 pg/ml at baseline [odds ratio (OR) = 18.99,  < 0.001], 181 pg/ml at 7 days (OR = 11.4,  = 0.001) and 174 pg/ml (OR = 8.46,  < 0.001) at 90 days.

Conclusion

High levels of NT‐proBNP determined during the first 3 months after a TIA were associated with AF. Consequently, this biomarker may be useful to reclassify undetermined TIA patients as having disease of CE.

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Authors:
F. Purroy, I. Suárez‐Luis, G. Mauri‐Capdevila, S. Cambray, J. Farré, J. Sanahuja, G. Piñol‐Ripoll, A. Quílez, C. González‐Mingot, R. Begué, M. I. Gil, E. Fernández and I. Benabdelhak
Article first published online:
25 Jun 2013 | DOI: 10.1111/ene.12222

Editorial

Abstract

Click to view the accompanying paper in this issue.

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Authors:
A. Charidimou and D. J. Werring
Article first published online:
07 Sep 2013 | DOI: 10.1111/ene.12258

Original Article

Background and purpose

Trochlear headaches are a recently recognized cause of headache, of which both primary and inflammatory subtypes are recognized. The clinical features, long‐term prognosis and optimal treatment strategy have not been well defined.

Methods

A cohort of 25 patients with trochlear headache seen at the Mayo Clinic between 10 July 2007 and 28 June 2012 were identified.

Results

The diagnosis of trochlear headache was not recognized by the referring neurologist or ophthalmologist in any case. Patients most often presented with a new daily from onset headache ( = 22, 88%). The most characteristic headache syndrome was reported as continuous, achy, periorbital pain associated with photophobia and aggravation by eye movement, especially reading. Individuals with a prior history of migraine were likely to have associated nausea and experience trochlear migraine. Amongst individuals with trochleitis, 5/12 (41.6%) had an identified secondary mechanism. Treatment responses were generally, but not invariably, favorable to dexamethasone/lidocaine injections near the trochlea. At a median follow‐up of 34 months (range 0–68), 10/25 (40%) of the cohort had experienced complete remission.

Conclusions

Trochlear headaches are poorly recognized, have characteristic clinical features, and often require serial injections to optimize the treatment outcome. The identification of trochleitis should prompt neuroimaging to look for a secondary cause.

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Authors:
J. H. Smith, J. A. Garrity and C. J. Boes
Article first published online:
22 Nov 2013 | DOI: 10.1111/ene.12312

Review Article

Abstract

Dementia is more common in older age but a number of people develop symptoms at a younger age and are said to have early onset dementia (EOD). Those with EOD face different challenges to those with onset later in life. It has been difficult to quantify this disease burden. This is a systematic review of papers reporting on the prevalence of EOD. A search of Medline and Embase was performed. This was followed by a hand search of the references of these papers. Eleven suitable studies were included. All of the data was from more economically developed countries. The studies were heterogeneous in their design hindering direct comparison. The majority of the papers looked at all types of dementia although many gave a breakdown of the prevalence of different subgroups. A variety of diagnostic criteria was employed. Figures of 38 to 260 per 100 000 are quoted by papers looking at various different types of dementia together with an onset of between 30 and 64 or up to 420 per 100 000 for those aged 55–64. Prevalence rises as age approaches 65. Epidemiological data for prevalence rates for EOD are sparse. EOD remains a rare condition with low case numbers. Assimilation and comparison of results from existing studies is difficult due to methodological heterogeneity. Cross‐national standardization of methodology should be a priority for future research in this area.

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Authors:
M. A. Lambert, H. Bickel, M. Prince, L. Fratiglioni, E. Von Strauss, D. Frydecka, A. Kiejna, J. Georges and E. L. Reynish
Article first published online:
13 Jan 2014 | DOI: 10.1111/ene.12325

EFNS/ENS GUIDELINES/CME Article

Background and objectives

The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer‐reviewed evidence‐based guideline for clinical neurologists and other specialist physicians responsible for the care of patients with ataxia.

Methods

This guideline is based on systematic evaluations of the relevant literature and on three consensus meetings of the task force.

Diagnosis

If acquired causes are ruled out, and if the disease course is rather slowly progressive, a (heredo)degenerative disease is likely. A positive family history gives much guidance. In the case of a dominant family history, first line genetic screening is recommended for spinocerebellar ataxia (SCA) 1, 2, 3, 6, 7 and 17 (level B), and in Asian patients also for dentatorubral‐pallidoluysian atrophy (DRPLA). In the case of recessive disease, a stepwise diagnostic work‐up is recommended, including both biochemical markers and targeted genetic testing, particularly aimed at Friedreich's ataxia, ataxia telangiectasia, ataxia due to vitamin E deficiency, polymerase gamma gene (POLG gene, various mutations), autosomal recessive spastic ataxia of Charlevoix−Saguenay (ARSACS) and ataxia with oculomotor apraxia (AOA) types 1 and 2. If family history is negative, we still advise to screen for the more common dominant and recessive ataxias. In addition, if onset is below 45 years we recommend the full work‐up for recessive ataxias; if onset is above 45 years we recommend to screen for fragile X mental retardation 1 premutations (good practice points). In sporadic cases with an onset after 30 years, a diagnosis of multiple system atrophy should be considered (good practice point). In particular the genetic work‐up will change over the upcoming years due to the diagnostic utility of new techniques such as gene panel diagnostics based on next generation sequencing for routine work‐up, or even whole exome and genome sequencing for selected cases.

Treatment

Some of the rare recessive ataxias are treatable, but for most of the heredodegenerative ataxias treatment is purely symptomatic. Idebenone is not effective in Friedreich's ataxia (level A). Riluzole (level B) and amantadine (level C) might provide symptomatic relief, irrespective of exact etiology. Also, varenicline for SCA3 patients (level B) can be considered. There is level Class II evidence to recommend physiotherapy, and Class III data to support occupational therapy.

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Authors:
B. P. C. van de Warrenburg, J. van Gaalen, S. Boesch, J.‐M. Burgunder, A. Dürr, P. Giunti, T. Klockgether, C. Mariotti, M. Pandolfo and O. Riess
Article first published online:
13 Jan 2014 | DOI: 10.1111/ene.12341

Original Article

Background and purpose

Diaphragms of the internal carotid and vertebral arteries as a cause of ischaemic stroke are reported and stenting of diaphragms as a therapeutic option in stroke secondary prevention is described.

Methods

Five patients were cared for in our institution from 2000 to 2011 for recurrent ischaemic strokes which were classified to be of undetermined aetiology after completion of the usual investigations. Because the patients had already had ischaemic strokes in the territory of the same artery, a conventional digital subtracted angiography was performed. A diaphragm was identified on the artery that supplied the territory in which the stroke occurred. The stroke was therefore attributed to the diaphragm. Clinical and radiological data, treatment and the clinical course of the patients was retrospectively reviewed.

Results

The diaphragm was located in the vertebral artery in three cases and in the bulb of the internal carotid artery in two. In all cases cerebral MR showed ischaemic strokes of different ages downstream of the diaphragm. Stenting was performed in four cases. No patient had a symptomatic recurrent ischaemic event after stenting.

Conclusions

Diaphragms are a rare cause of recurrent embolic strokes which are often not detected with non‐invasive imaging. Stenting appears to be a therapeutic option in stroke secondary prevention. These observations suggest that conventional angiography should be performed in cases of recurrent ischaemic strokes in the territory of a single artery and in cases of ischaemic stroke of undetermined aetiology in young adults when the usual investigations are negative.

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Authors:
S. Lenck, M.‐A. Labeyrie, J.‐P. Saint‐Maurice, N. Tarlov and E. Houdart
Article first published online:
21 Jan 2014 | DOI: 10.1111/ene.12343

Original Article

Background and purpose

The occurrence of amyotrophic lateral sclerosis (ALS) during pregnancy is uncommon and the effect of one on the other is not well described.

Methods

The clinical and genetic features of five cases of ALS are reported with an onset during pregnancy or within 1 month from delivery. Charts from 239 women with a diagnosis of ALS attending the neuromuscular clinics at the Neuromuscular Omnicentre (NEMO) and at IRCCS Policlinico San Donato from 2008 to 2011 were reviewed.

Results

Of these, 12.8% of the women in child‐bearing age had a diagnosis of ALS during pregnancy or immediately after delivery. Genetic screening of the major causative genes revealed two mutations in superoxide dismutase 1 (SOD1) gene; the analysis of vascular endothelial growth factor (VEGF) promoter variation showed a segregation of the haplotype CA/AG (−2578C/A; −1190A/G) in patients developing ALS related to pregnancy. No effects on foetal development or neonatal course were observed.

Conclusions

Pregnancy may unmask ALS but whether this is coincidental is unclear. Hormonal and inflammatory modifications might trigger ALS in subjects with increased susceptibility to oxidative stress related to the toxic function of SOD1 or in subjects with a reduction of neuroprotective molecules such as VEGF.

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Authors:
C. Lunetta, V. A. Sansone, S. Penco, L. Mosca, C. Tarlarini, F. Avemaria, E. Maestri, M. G. Melazzini, G. Meola and M. Corbo
Article first published online:
28 Jan 2014 | DOI: 10.1111/ene.12345

Letter to the Editor

C9ORF72 familial motor neuron disease − frontotemporal dementia associated with lung adenocarcinoma and anti‐Ma2/Ta antibodies: a chance association?

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Authors:
N. Geevasinga, J. R. Burrell, M. Hibbert, S. Vucic and K. Ng
Article first published online:
13 Mar 2014 | DOI: 10.1111/ene.12347

Original Article

Background and purpose

To compare the course of treatment in patients with symptomatic Wilson's disease (WD) receiving either D‐penicillamine (DPA) or zinc sulfate (ZS) as first‐line therapy.

Methods

In all, 143 consecutive patients diagnosed with symptomatic WD from January 2005 to December 2009, followed until December 2010, were included. The decision about first‐line therapy was made individually after discussion with the patient. Physicians had no clear preference of one drug over the other. Data were analyzed in subgroups with predominantly neurological (DPA, 35; ZS, 21) and hepatic (DPA, 36; ZS, 51) presentation of WD.

Results

According to Kaplan–Meier analysis, neurological WD patients scheduled for DPA had a similar probability of not remaining on first‐line therapy as patients receiving ZS (20% vs. 24% at the end of follow‐up), with adjusted odds ratio (OR) of 0.9 (95% CI 0.2–3.5). In patients with hepatic WD, this probability was significantly higher for DPA (31% vs. 12%; adjusted OR 3.0, 95% CI 0.9–9.9), especially in the first 6 months. Early worsening occurred only in neurological WD patients, with no differences between both treatment groups (35% vs. 19%; OR 2.8, 95% CI 0.7–10.8). Neurological improvement and decrease of liver enzymes were achieved with similar frequency. Compliance with DPA was better in hepatic (97% vs. 80%) but not in neurological patients (91% vs. 81%). Drug adverse effects were more common on DPA (15% vs. 3%).

Conclusions

DPA and ZS are effective in the majority of WD patients. Neither therapy appears to be clearly superior. Therefore ZS may be considered a reasonable alternative to DPA as a first‐line therapy.

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Authors:
A. Członkowska, T. Litwin, M. Karliński, K. Dziezyc, G. Chabik and M. Czerska
Article first published online:
21 Jan 2014 | DOI: 10.1111/ene.12348

Original Article

Background and purpose

To assess, through systematic review, distinctive or common clinical signs of autosomal dominant cerebellar ataxias (ADCAs), also referred to as spinocerebellar ataxias (SCAs) in genetic nomenclature.

Methods

This was a structured search of electronic databases up to September 2012 conducted by two independent reviewers. Publications containing proportions or descriptions of ADCA clinical features written in several languages were selected. Gray literature was included and a back‐search was conducted of retrieved publication reference lists. Initial selection was based on title and abstract screening, followed by full‐text reading of potentially relevant publications. Clinical findings and demographic data from genetically confirmed patients were extracted. Data were analyzed using the chi‐squared test and controlled for alpha‐error inflation by applying the Holms step‐down procedure.

Results

In all, 1062 publications reviewing 12 141 patients (52% male) from 30 SCAs were analyzed. Mean age at onset was 35 ± 11 years. Onset symptoms in 3945 patients revealed gait ataxia as the most frequent sign (68%), whereas overall non‐ataxia symptom frequency was 50%. Some ADCAs often presented non‐ataxia symptoms at onset, such as SCA7 (visual impairment), SCA14 (myoclonus) and SCA17 (parkinsonism). Therefore a categorization into two groups was established: pure ataxia and mainly non‐ataxia forms. During overall disease course, dysarthria (90%) and saccadic eye movement alterations (69%) were the most prevalent non‐ataxia findings. Some ADCAs were clinically restricted to cerebellar dysfunction, whilst others presented additional features.

Conclusions

Autosomal dominant cerebellar ataxias encompass a broad spectrum of clinical features with high prevalence of non‐ataxia symptoms. Certain features distinguish different genetic subtypes. A new algorithm for ADCA classification at disease onset is proposed.

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Authors:
M. Rossi, S. Perez‐Lloret, L. Doldan, D. Cerquetti, J. Balej, P. Millar Vernetti, M. Hawkes, A. Cammarota and M. Merello
Article first published online:
12 Feb 2014 | DOI: 10.1111/ene.12350

Original Article

Background and purpose

Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulation (OAC). Our aim was to investigate the impact of the international normalized ratio (INR) level on mortality in OAC‐associated ICH compared with non‐OAC‐associated ICH.

Methods

A retrospective chart review of consecutive ICH patients treated at the Helsinki University Central Hospital from January 2005 to March 2010 ( = 1013) was performed. An ICH was considered to be OAC‐associated if the patient was on warfarin at ICH onset. The association of INR with 3‐month mortality was adjusted in a multivariable logistic regression model for factors influencing the crude odds ratios (ORs) in bivariable logistic regression by more than 5%.

Results

One in eight ICHs was OAC‐associated ( = 132). Of these, 50% had therapeutic INR (2.0–3.0), 7% had INR <2.0 and 43% had high INR (>3.0) on admission. Patients on OAC were older (median 76 vs. 66 years;  < 0.001) with more severe symptoms (median National Institutes of Health Stroke Scale 14 vs. 10;  < 0.001) and larger hematomas (median 11.4 vs. 9.7 ml;  < 0.001) on admission than patients not on OAC. After adjustment for confounders, 3‐month mortality in the whole cohort was associated with higher baseline INR (OR 1.06; CI 1.03–1.09 per 0.1 increment). Mortality was higher with both therapeutic (51% at 3 months; OR 3.59; CI 1.50–8.60) and high (61%; OR 5.26; CI 1.94–14.27) INR values compared with non‐OAC‐associated ICH (29%).

Conclusions

Patients with OAC‐associated ICH had more severe strokes and higher mortality compared with patients with ICH not related to OAC. Higher baseline INR was associated with increased 3‐month mortality.

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Authors:
S. Curtze, D. Strbian, A. Meretoja, J. Putaala, H. Eriksson, E. Haapaniemi, S. Mustanoja, T. Sairanen, J. Satopää, H. Silvennoinen, M. Niemelä, M. Kaste and T. Tatlisumak
Article first published online:
21 Jan 2014 | DOI: 10.1111/ene.12352

Original Article

Background and purpose

Chemotherapy‐induced peripheral neuropathy negatively affects the quality of life for many patients treated with oxaliplatin or docetaxel for gastrointestinal cancer or breast cancer. Symptoms can persist long after treatment and often include neuropathic pain. Our objective was to characterize the neuropathies with regard to symptoms, neurological signs and objective evidence of damage to the structure and function of the peripheral nerves. Furthermore, the diagnostic values of skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS) were compared.

Methods

Patients complaining of neuropathy symptoms at least 3 months after completion of treatment with oxaliplatin ( = 20) or docetaxel ( = 20) were recruited from the Department of Oncology or using hospital records. Neuropathy scores were determined along with the intraepidermal nerve fibre density in skin biopsies from the proximal and distal parts of the leg, QST and NCS.

Results

Clinically only sensory functions were affected. In general, neuropathy scores were higher in the oxaliplatin‐treated group. Both sensory and motor fibres were affected in the NCS, showing predominantly signs of axonal damage. Mechanical detection threshold was most often affected in the QST. NCS, QTS and skin biopsy were abnormal in 11, 13 and 17 and 7, 11 and 15 of the oxaliplatin‐treated patients and docetaxel‐treated patients, respectively.

Conclusions

Chemotherapy‐induced peripheral neuropathy after oxaliplatin or docetaxel treatment is a clinically sensory, axonal neuropathy affecting only small nerve fibres in some patients. NCS are often normal, whereas QST and skin biopsy have a higher diagnostic sensitivity.

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Authors:
T. Krøigård, H. D. Schrøder, C. Qvortrup, L. Eckhoff, P. Pfeiffer, D. Gaist and S. H. Sindrup
Article first published online:
25 Jan 2014 | DOI: 10.1111/ene.12353

Original Article

Background and purpose

High‐dose steroid administration is the usual treatment of multiple sclerosis (MS) relapse, but it remains to determine whether this treatment may act by changing the excitability of cortical circuitry.

Methods

The functional cortical effects of high‐dose steroids in 21 MS patients before and after 3 days of intravenous administration of methylprednisolone (1 g/day) for the treatment of MS relapse were studied. Investigations included various clinical scales [Kurtzke Functional System Scale (KFSS), Expanded Disability Status Scale and Fatigue Severity Scale, 10‐m walk] and transcranial magnetic stimulation (TMS) tests of cortical excitability [resting motor threshold, recruitment curve of motor evoked potentials, short‐interval intracortical inhibition (SICI) and intracortical facilitation (ICF) at various interstimuli intervals (ISIs), cortical silent period and interhemispheric inhibition].

Results

Following steroid administration, clinical improvement was significant for the KFSS pyramidal (motor) and total scores, whilst TMS showed a reduction of SICI (mean and maximum values) and an increase of ICF at 10 ms ISI.

Conclusions

Very rapid functional changes in the excitability of cortical circuits involved in motor control can be induced by steroids, before any process of remyelination or axonal regeneration has time to occur. The net effect of steroids on the balance between intracortical GABAergic inhibition and glutamatergic facilitation was in favour of weaker inhibition or stronger facilitation, which could lead to improving the motor performance in MS patients.

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Authors:
S. S. Ayache, A. Créange, W. H. Farhat, H. G. Zouari, V. Mylius, R. Ahdab, M. Abdellaoui and J.‐P. Lefaucheur
Article first published online:
28 Jan 2014 | DOI: 10.1111/ene.12356

Letter to the Editor

SPG31 presenting with orthostatic tremor

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Authors:
R. Erro, C. Cordivari and K. P. Bhatia
Article first published online:
13 Mar 2014 | DOI: 10.1111/ene.12360

Letters to the Editor

Diffusion tensor imaging before, during and after progressive multifocal leukoencephalopathy

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Authors:
D. Ontaneda, K. Sakaie, J. Lin, M. J. Lowe, M. D. Phillips and R. J. Fox
Article first published online:
13 Mar 2014 | DOI: 10.1111/ene.12361

Original Article

Background and purpose

Huntington's disease is due to a CAG triplet repeat elongation in the huntingtin gene. Boundaries in CAG numbers have been found between healthy people with and without risk to pass the disorder to the next generation, and between people without, with a mild, or with a fully penetrant phenotype. These data have been generated in western populations and it is not clear whether they are also valid amongst Chinese.

Methods

In order to establish normative data in the huntingtin gene for Chinese people, 966 chromosomes from normal controls were tested. Further, the range of CAG repeats was examined in a cohort from six centres and a total of 368 patients with the disease were included.

Results

The CAG triplet repeat range in normal controls was between 9 and 35 (mean 18.9, SD 2.57). Triplets in the range between 26 and 35 were found in 2.5%. In the patient cohort, triplet repeats in the shorter allele were between 8 and 37 (mean 17.7, SD 1.6). In the longer allele, a range between 36 and 120 was found. There was a negative correlation (−0.65,  = 0.42) between age at onset and the number of triplet repeats in the larger allele. The mean age at onset was 38 years, with a range between 2 and 70 years. In 23 patients (6%) a childhood or juvenile onset was noted.

Conclusion

These data show comparable ranges of huntingtin gene CAG triplet repeats in normal people and in patients with Huntington's disease as in western populations.

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Authors:
H. Jiang, Y. M. Sun, Y. Hao, Y. P. Yan, K. Chen, S. H. Xin, Y. P. Tang, X. H. Li, T. Jun, Y. Y. Chen, Z. J. Liu, C. R. Wang, H. Li, Z. Pei, H. F. Shang, B. R. Zhang, W. H. Gu, Z. Y. Wu, B. S. Tang and J.‐M. Burgunder
Article first published online:
28 Jan 2014 | DOI: 10.1111/ene.12366

Original Article

Background and purpose

The endothelium is crucial in maintaining the haemostatic balance between pro‐ and anti‐thrombotic factors. In this pilot study, the association of endothelial biomarkers with arterial recanalization and clinical outcome in the setting of acute ischaemic stroke (AIS) was evaluated amongst patients treated with recombinant tissue plasminogen activator (rt‐PA).

Methods

Sixty‐four AIS patients treated with rt‐PA were prospectively recruited. Blood was collected before thrombolysis and analysed for von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble endothelial protein C receptor (sEPCR). Complete recanalization was defined by a Thrombolysis in Myocardial Infarction Score of 3. Favourable clinical outcome was defined by a modified Rankin Score of 0–2 at 90 days.

Results

Amongst the 64 patients, 31 had no documented occlusion, 19 had persistent occlusion and 14 had complete recanalization. After adjustment for confounding factors, these patients presented lower sTM and sEPCR levels than patients with persistent occlusion (median sTM, 21 vs. 48 ng/ml,  = 0.008; median sEPCR, 78 vs. 114 ng/ml,  = 0.018), but similar levels compared with patients without occlusion. vWF levels did not differ between groups. None of these biomarkers was significantly associated with favourable outcome.

Conclusions

Recanalization after thrombolytic therapy is associated with low sTM and sEPCR levels but not with vWF levels. If corroborated in further larger studies, these findings could be helpful in the identification of patients resistant to rt‐PA thrombolysis who could benefit from a modified recanalization therapy.

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Authors:
D. Faille, J. Labreuche, E. Meseguer, M.‐G. Huisse, N. Ajzenberg and M. Mazighi
Article first published online:
04 Feb 2014 | DOI: 10.1111/ene.12369

Original Article

Background and purpose

Urinary symptoms associated with multiple sclerosis (MS) are common and negatively impact on quality of life, representing a considerable psychosocial and economic burden, often requiring care and hospitalization. Although the importance of identifying and adequately treating urinary symptoms in MS is now well recognized, there is no information, to date, about the real prevalence and impact of bladder symptoms in patients with clinically isolated syndromes (CISs) suggestive of MS.

Methods

The aim of the present study was to investigate, in a cohort of patients with a diagnosis of CIS suggestive of MS, the prevalence of urinary tract symptoms, their impact on quality of life measures and their association with functional urodynamic dysfunctions. Patients underwent a complete neurological and urological visit, urodynamic investigation and the MSQoL‐54 questionnaire.

Results

Twenty‐eight consecutive patients presenting with CISs were enrolled in the study; 53.6% of CIS patients reported urinary symptoms, 46.7% reporting irritative symptoms, 33.3% both irritative and obstructive symptoms and 20% obstructive symptoms alone. Urodynamic abnormalities were observed in 57.1% of the CIS patients. In 17.9% of the CIS patients urodynamic dysfunctions were asymptomatic. The presence of urinary symptoms was associated with lower scores on specific quality of life domains, particularly in women with obstructive symptoms.

Conclusions

A high prevalence of urinary symptoms and urodynamic dysfunctions in patients with CISs and an association of urinary symptoms with quality of life measures were found. These results highlight the importance of identifying and optimally treating urinary symptoms also at the very early stages of MS.

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Authors:
M. Di Filippo, S. Proietti, L. Gaetani, M. Gubbiotti, M. Di Gregorio, P. Eusebi, P. Calabresi, P. Sarchielli and A. Giannantoni
Article first published online:
28 Jan 2014 | DOI: 10.1111/ene.12370

Original Article

Background and purpose

Pediatric multiple sclerosis (MS) clinical and incidence data have been reported for several countries but valid age dependent incidence data are not yet available. The true incidence of pediatric MS in Germany was estimated and the clinical characteristics at diagnosis according to the 2005 McDonald criteria are described.

Methods

Between 2009 and 2011 active prospective nationwide surveillance for MS in children and adolescents ≤15 years included all pediatric hospitals, MS centers and private practices specialized in MS. Data were adjusted for under‐reporting by capture−recapture from an independent second source.

Results

The estimated incidence of pediatric MS was 0.64 per 100 000 person‐years with clear increase from age group ≤10 (0.09/100 000) to 2.64 per 100 000 in age group 14−15 years. All had relapsing−remitting disease with polysymptomatic onset in half of the cases. Spinal MRI with positive findings in two‐thirds of patients contributed to diagnosis.

Conclusion

Using an active prospective surveillance system and the McDonald criteria for first MS diagnosis the age‐related incidence of pediatric MS in Germany was uncovered and is more common than in previous estimates. Thorough application of McDonald criteria and inclusion of spinal MRI data allowed for early diagnosis in almost 90% of cases.

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Authors:
K. Reinhardt, S. Weiss, J. Rosenbauer, J. Gärtner and R. von Kries
Article first published online:
28 Jan 2014 | DOI: 10.1111/ene.12371

Original Article

Background and purpose

Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case–control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome.

Methods

From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed.

Results

The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98–33.08], alcohol abuse (OR = 3.65, 95% CI 1.25–10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39–5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01–4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16–5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27–25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs).

Conclusions

Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death.

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Authors:
R. Sutter and P. W. Kaplan
Article first published online:
10 Feb 2014 | DOI: 10.1111/ene.12372

Original Article

Background and purpose

Obesity is associated with the risk of coronary artery disease and stroke. Visceral fat plays a significant role in the atherogenic effects of obesity. Whether visceral fat accumulation, as measured by computed tomography (CT), is an independent risk factor for the presence of cerebral small vessel disease (SVD) was investigated.

Methods

This study comprised 506 Japanese subjects 35–74 years of age (mean 55.3 years) without a history of symptomatic cerebrovascular disease who underwent health screening tests, including brain magnetic resonance imaging, carotid echography and measurements of the visceral fat area (VFA) and subcutaneous fat area (SFA) on abdominal CT. Visceral fat accumulation was defined as VFA ≥ 100 cm. Logistic regression analysis was performed to examine the associations between visceral fat accumulation and cerebral SVD such as white matter lesions (WMLs) and silent lacunar infarction (SLI).

Results

The prevalence of WMLs and SLI but not carotid plaque were significantly higher in subjects with VFA ≥ 100 cm than those with VFA < 100 cm. A VFA ≥ 100 cm was associated with WMLs and SLI independent of age, cardiovascular risk factors and other measurements of obesity, such as waist circumference and body mass index. A large waist circumference was independently associated with SLI. SFA, the combination of VFA and SFA, and body mass index were not associated with WMLs or SLI.

Conclusions

Visceral fat accumulation was independently associated with the presence of cerebral SVD in subjects without a history of symptomatic cerebrovascular disease.

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Authors:
K. Yamashiro, R. Tanaka, Y. Tanaka, N. Miyamoto, Y. Shimada, Y. Ueno, T. Urabe and N. Hattori
Article first published online:
05 Feb 2014 | DOI: 10.1111/ene.12374

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Article first published online:
13 Mar 2014 | DOI: 10.1111/ene.12417