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European Journal of Neurology
2013 - Volume 20Issue 5 | May 2013
Article first published online:
22 Oct 2012 | DOI: 10.1111/ene.12007
22 Oct 2012 | DOI: 10.1111/ene.12007
Review Article
Betamethasone therapy in ataxia telangiectasia: unraveling the rationale of this serendipitous observation on the basis of the pathogenesis
Abstract
Ataxia telangiectasia (A‐T) is a rare autosomal recessive disorder characterized by progressive neurological dysfunction. To date, only supportive care aimed to halt the progressive neurodegeneration is available for the treatment. Recently, an improvement of neurological signs during short‐term treatment with betamethasone has been reported. To date, the molecular and biochemical mechanisms by which the steroid produces such effects have not yet been elucidated. Therefore, a review of the literature was carried out to define the potential molecular and functional targets of the steroid effects in A‐T. Glucocorticoids (GCs) are capable of diffusing into the CNS by crossing the blood–brain barrier (BBB) where they exert effects on the suppression of inflammation or as antioxidant. GCs have been shown to protect post‐mitotic neurons from apoptosis. Eventually, GCs may also modulate synaptic plasticity. A better understanding of the mechanisms of action of GCs in the brain is needed, because in A‐T during the initial phase of cell loss the neurological impairment may be rescued by interfering in the biochemical pathways. This would open a new window of intervention in this so far incurable disease.
Article first published online:
04 Nov 2012 | DOI: 10.1111/ene.12024
04 Nov 2012 | DOI: 10.1111/ene.12024
Original Article
Predictors of quality of life among multiple sclerosis patients: a comprehensive analysis
Background and purpose
Multiple sclerosis (MS) is a debilitating neurological disease of young people with substantial consequences on patients' quality of life (QOL). A variety of QOL instruments have been used to evaluate the efficacy of treatments. However, no study assessed the role of the different demographic, clinical, physical, social, economic and psychological parameters in the perception of patients with MS of their QOL.
Methods
Two‐hundred and one consecutive patients attending outpatient clinics were prospectively studied and objectively assessed using Expanded Disability Status Scale (EDSS), 8‐m walk test, and Symbol Digit Modality Test. Patients completed the following questionnaires: MS QOL‐54, Hamilton Depression Rating Scale, Fatigue Severity Scale, Brief Pain Inventory Average Pain Score, Drug Side‐Effects Severity Scale, Social Support, Religiosity, Physiotherapy and Exercise, and Socioeconomic Profile. Overall, QOL, physical (PHCS) and mental (MHCS) health composite scores were computed as outcome measures from MSQOL‐54.
Results
Depression, social support, religiosity, education years and living area predicted overall QOL by linear regression (= 0.43). Unemployment and absence of fatigue correlated with poor and good QOL, respectively. Fatigue, pain, depression, EDSS, social support, MS type and anti‐cholinergic treatment predicted PHCS (= 0.81). Fatigue, pain, depression, education years and social support predicted MHCS (= 0.70).
Conclusion
The QOL in patients with MS is not solely determined by physical disability, but rather by the level of social support, living area, depression, level of education, employment, fatigue and religiosity. Accordingly, we suggest that these should be evaluated in every patient with MS as they may be modified by targeted interventions.
Article first published online:
08 Jan 2013 | DOI: 10.1111/ene.12046
08 Jan 2013 | DOI: 10.1111/ene.12046
Original Article
Replication and meta‐analysis of common variants identifies a genome‐wide significant locus in migraine
Background and purpose
Genetic factors contribute to the aetiology of the prevalent form of migraine without aura (MO) and migraine with typical aura (MTA). Due to the complex inheritance of MO and MTA, the genetic background is still not fully established. In a population‐based genome‐wide association study by Chasman . ( 2011: 43: 695–698), three common variants were found to confer risk of migraine at a genome‐wide significant level (< 5 × 10). We aimed to evaluate the top association single nucleotide polymorphisms (SNPs) from the discovery set by Chasman . in a primarily clinic‐based Danish and Icelandic cohort.
Methods
The top association SNPs were assessed in 2523 cases and 38 170 controls, and a meta‐analysis was performed, combining the discovery set with all the follow‐up studies. Finally the confirmed SNPs were assessed in a genotype–phenotype analysis.
Results
Two out of three SNPs that showed genome‐wide significant associations in the previous study: rs10166942 (near ) and rs11172113 (in ) were significantly associated with migraine in the present study. The meta‐analysis confirmed the previous three genome‐wide significant associated SNPs (rs2651899, rs10166942 and rs11172113) to confer risk of migraine. In addition, the C‐allele of rs2078371 (near ) also reached genome‐wide significance for association with migraine [OR = 1.14; CI = (1.09–1.20); = 2.55 × 10].
Conclusion
encodes an integral membrane protein involved in oligodendrogenesis. This new finding supports the plausible implication of neuroglia in the pathophysiology of MO and MTA.
Article first published online:
07 Jan 2013 | DOI: 10.1111/ene.12055
07 Jan 2013 | DOI: 10.1111/ene.12055
Original Article
Long‐term MRI findings in neuromyelitis optica: seropositive versus seronegative patients
Background and purpose
Neuromyelitis optica (NMO) is a severe demyelinating inflammatory disorder associated with serum antibodies against aquaporin 4 (AQP4‐Ab). A significant number of patients with NMO remain seronegative over time. Long‐term observational magnetic resonance imaging (MRI) studies of the CNS in patients with NMO are rare or of limited duration. The objective of this study is to determine long‐term MRI characteristics of seropositive and seronegative patients, and assess possible overlap with multiple sclerosis (MS).
Methods
Clinical and radiological characteristics of 28 patients with NMO at onset and of 17 patients after an average follow‐up time of 9 years were recorded. Fifty percent of patients were seropositive for AQP4‐Ab. Onset and final brain/spinal MRI scans were retrospectively analysed and compared.
Results
Significantly more patients in the seronegative group had brain lesions at onset. Spinal lesions of seropositive patients were longer and showed increased cord swelling at onset MRI scans. After the follow‐up time the differences between both groups disappeared. Patients in the seropositive group tended to develop brain lesions over time. No patient fulfilled Barkhof's or McDonald's radiological criteria for MS at onset or over time.
Conclusion
Brain MRI features show differences between seropositive and seronegative patients at time of onset in NMO, but differences between groups vanish over time. None of the AQP4‐negative patients fulfill radiological MS criteria on a long‐term basis, suggesting that seronegative NMO constitutes an independent entity.
Article first published online:
25 Dec 2012 | DOI: 10.1111/ene.12058
25 Dec 2012 | DOI: 10.1111/ene.12058
Original Article
Advanced age and liability to oxaliplatin‐induced peripheral neuropathy: analysis of a prospective study
Background and purpose
The aim of this analysis of data extracted from a prospective, multicenter study is to test in a large homogenous population of chemotherapy‐naïve patients with colorectal cancer (CRC) treated with oxaliplatin (OXA)‐based chemotherapy whether advanced age increases the risk of developing OXA‐induced peripheral neuropathy (OXAIPN).
Methods
One‐hundred and forty‐five patients with CRC, without other significant co‐morbidities predisposing to peripheral neuropathy, were divided according to their age into two groups: patients aged between 50 and 68 years (group I, = 75); and patients aged ≥ 69 years (group II,= 70). Patients were prospectively monitored at baseline and followed‐up during chemotherapy using the motor and neurosensory National Cancer Institute Common Toxicity criteria, the clinical version of the Total Neuropathy Score and neurophysiology. The incidence and severity of both the acute and cumulative OXAIPN was thoroughly determined and then compared between age groups.
Results
No statistically significant difference was observed in the incidence of both the acute (= 64/75 vs. 56/70; = 0.510) and cumulative OXAIPN (= 51/75 vs. 49/70; = 0.858) between age groups. The severity of OXAIPN was also similar between age groups. In line with the clinical data, the neurophysiological results between age groups were also comparable.
Conclusion
The results of this study indicate that advanced age does not seem to represent a significant risk factor of OXAIPN in patients with CRC without any other significant co‐morbidities.
Article first published online:
17 Dec 2012 | DOI: 10.1111/ene.12061
17 Dec 2012 | DOI: 10.1111/ene.12061
Original Article
Cost‐effectiveness of onabotulinumtoxinA for the treatment of wrist and hand disability due to upper‐limb post‐stroke spasticity in Scotland
Background and purpose
The objective was to evaluate the cost‐effectiveness of treating upper‐limb post‐stroke spasticity (ULPSS) with usual care (UC) plus onabotulinumtoxinA versus UC alone in Scotland.
Methods
We developed a model to simulate costs and quality‐adjusted life years (QALYs) gained from treating ULPSS. Efficacy data and health utilities were taken from clinical trials. Unit costs were taken from published Scottish sources. We compared UC plus onabotulinumtoxinA and UC alone in three scenarios: (i) a scenario from the National Health Service perspective, which included differences in onabotulinumtoxinA use, specialist visits and day‐hospital visits; (ii) a scenario that only included differences in onabotulinumtoxinA use and specialist visits; and (iii) a scenario from a societal perspective that included differences in onabotulinumtoxinA use, specialist visits and caregiver burden.
Results
In the first scenario, the model predicted that UC plus onabotulinumtoxinA produced 0.107 QALYs at an additional cost of £1099 compared with UC alone over 5 years, resulting in an incremental cost‐effectiveness ratio (ICER) of £10 271/QALY. In the second scenario, the ICER increased to £27 134/QALY. In the third scenario (societal perspective), UC plus onabotulinumtoxinA produced lower total cost and higher QALYs, and therefore was superior to UC alone.
Conclusions
Based on a model, UC plus onabotulinumtoxinA improved disability, which translated into greater QALYs but also increased direct medical costs compared with UC alone; however, the resulting ICER can be considered cost‐effective. Moreover, UC plus onabotulinumtoxinA can be cost‐saving if reduction in caregiver burden was included. OnabotulinumtoxinA offers value for money in the management of ULPSS in Scotland.
Article first published online:
24 Dec 2012 | DOI: 10.1111/ene.12062
24 Dec 2012 | DOI: 10.1111/ene.12062
Original Article
Collateral circulation on perfusion‐computed tomography‐source images predicts the response to stroke intravenous thrombolysis
Background and purpose
Perfusion‐computed tomography‐source images (PCT‐SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT‐SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis.
Methods
We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color‐coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT‐SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2–3) vs. poor (scores 0–1) collaterals. The predetermined primary end‐point was a good 3‐month functional outcome, while early neurological recovery, transcranial duplex‐assessed 24‐h MCA recanalization, 24‐h hypodensity volume and hemorrhagic transformation were considered secondary end‐points.
Results
Fifty‐four patients were included (55.5% women, median NIHSS 10), and 4‐13‐23‐14 patients had LMC score (LMCs) of 0‐1‐2‐3, respectively. The probability of a good long‐term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, = 0.004. Good‐LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23–197.75), = 0.008]. Patients with good LMCs had better early neurological recovery (= 0.001), smaller hypodensity volumes (< 0.001) and a clear trend towards a higher recanalization rate.
Conclusions
A higher degree of LMC assessed by PCT‐SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients.
Article first published online:
24 Dec 2012 | DOI: 10.1111/ene.12063
24 Dec 2012 | DOI: 10.1111/ene.12063
Original Article
Characterization of patients with recurrent ischaemic stroke using the ASCO classification
Background and purpose
The ASCO score has the advantage of allowing a more comprehensive characterization of ischaemic stroke patients and their risk factors, as reflected in different grades of evidence of atherosclerotic changes (A), small vessel disease (S), potential cardiac (C) or other (O) sources. It might also help to characterize patients with recurrent ischaemic stroke and document the etiology of stroke recurrence as well as the further development of risk factor constellations.
Methods
We prospectively screened our stroke database for patients with recurrent ischaemic stroke between 2004 and 2011, and classified each stroke using ASCO. The distribution of etiologies was analysed, and changes in the ASCO score were documented for each patient.
Results
We identified 131 patients with recurrence of ischaemic stroke. At the first event, the distribution of etiologies and their grade of evidence was 97 grade 1 (A = 18/S = 32/C = 44/O = 3), six grade 2 (A = 2/S = 1/C = 3/O = 0), 199 grade 3 (A = 85/S = 83/C = 23/O = 8), 204 grade 0 (A = 26/S = 14/C = 44/O = 120) and 18 grade 9 (A = 0/S = 1/C = 17/O = 0). At stroke recurrence, 98 grade 1 (A = 16/S = 24/C = 55/O = 3), 11 grade 2 (A = 2/S = 5/C = 4/O = 0), 210 grade 3 (A = 94/S = 92/C = 13/O = 11), 171 grade 0 (A = 16/S = 9/C = 26/O = 117) and 34 grade 9 (A = 0/S = 1/C = 33/O = 0) were identified. Analysis of each individual showed a modification of the score in 85 patients (64.9%).
Conclusions
Recurrent ischaemic stroke does not always have the same etiology as the previous one(s). Among variable changes of grade 1 etiologies, an increasing prevalence of cardioembolism – often insufficiently treated – at stroke recurrence was a major finding. ASCO proved to be highly useful to monitor risk factor constellations.
Article first published online:
08 Jan 2013 | DOI: 10.1111/ene.12068
08 Jan 2013 | DOI: 10.1111/ene.12068
Original Article
Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis
Background and purpose
Optical coherence tomography (OCT) has shown thinning of the retinal nerve fibre layer (RNFL) and total macular volume (TMV) in multiple sclerosis (MS) patients. Measures of retinal atrophy are associated with the brain parenchymal fraction (BPF) assessed by magnetic resonance imaging (MRI). However, in MS, data on the relation of OCT measures and grey and white matter volumes are contradictory. We performed a prospective cross‐sectional study with a statistically pre‐defined endpoint to test our hypothesis that OCT measures of neuro‐axonal degeneration are related to global and partial brain atrophy in early forms of MS.
Methods and results
Forty‐four patients with clinically isolated syndrome (= 10) or relapsing–remitting MS (= 34; mean disease duration = 3.2 years, median EDSS = 1.5) were enrolled in the study. Peripapillary‐ and volumetric OCT scans of the macula were performed using latest spectral‐domain OCT technology. BPF as well as white and grey matter fractions (WMF/GMF) were assessed by 1.5 Tesla MRI scans. Generalized estimating equation models adjusted for age and linear regression statistics were used to assess the association between OCT and MRI measures. RNFL thickness, TMV and age were significantly associated with BPF. RNFL thickness and TMV independently predicted WMF (= 0.003 and = 0.032) but not GMF (= 0.717 and = 0.357) when corrected for age. In contrast, age was strongly associated with GMF (< 0.001) but not WMF.
Conclusion
Our study suggests that, in early MS, OCT measures of retinal atrophy are related to volumetric changes in the white but not grey matter compartment as assessed by MRI. It further substantiates the association of retinal thinning and brain tissue loss in MS.
Article first published online:
31 Jan 2013 | DOI: 10.1111/ene.12070
31 Jan 2013 | DOI: 10.1111/ene.12070
Original Article
Ischaemic stroke at a young age is a serious event – final results of a population‐based long‐term follow‐up in Western Norway
Background and purpose
Our population‐based long‐term follow‐up of young ischaemic stroke patients and controls showed 10‐fold increased mortality and fivefold increased arterial event rate nearly 12 years after study inclusion. We now assess memory, anxiety, depression and sleep in relation to employment and functional outcome, treatment goals and results from a last alive–dead survey.
Methods
Patients ( = 232) ≤ 49 years with an index‐stroke between 1988 and 1997 were retrospectively selected and compared with age‐ and sex‐matched controls (= 453). At follow‐up from 2004 to 2005, 144 (77%) of 187 patients were clinically examined. Self‐assessment information about memory problems, anxiety, depression, sleeping problems, education and employment was compared with answers from standardized questionnaires from 167 controls. Functional outcome was measured by the modified Rankin Scale (mRS).
Results
Patients compared with controls had more memory problems (41.0% vs. 5.4%, < 0.001), anxiety (19.4% vs. 9%, = 0.009), depression (29.2% vs. 13.2%, = 0.001) and sleeping problems (36.1% vs. 19.2%, = 0.001). In the multiple regression analysis male gender (OR 9.3, 95%CI 0.10–0.61, = 0.002), normal memory (OR 12.7, 95%CI 0.07–0.47, < 0.001) and mRS 0–1 (OR 15.7, 95%CI 0.002–0.12, < 0.001) were factors for full‐time employment. Blood pressure was < 140/90 mmHg in 39% of patients, 49% stopped smoking and 38.2% used statins. After a mean observation time of 18.3 years, 63 (27.2%) of 232 patients were dead.
Conclusions
Our data show a heterogeneous prognosis and high mortality even for long‐time survivors of ischaemic stroke at a young age. Prospective studies of young stroke patients and controls are necessary for direct comparison.
Article first published online:
07 Jan 2013 | DOI: 10.1111/ene.12073
07 Jan 2013 | DOI: 10.1111/ene.12073
Original Article
Vertebrobasilar dolichoectasia as a risk factor for cerebral microbleeds
Background
Both vertebrobasilar dolichoectasia (VBD) and cerebral microbleeds (CMBs) are related with the risk of intracerebral hemorrhage. We aimed to examine the relationship between the VBD and CMB in ischaemic stroke patients.
Methods
A consecutive series of 182 patients hospitalized because of ischaemic stroke or transient ischaemic attack (TIA), and who underwent gradient echo brain magnetic resonance imaging were retrospectively recruited from a prospective stroke registry. CMB locations were categorized into anterior and posterior circulation. Ectasia was defined as basilar artery (BA) diameter > 4.5 mm, and dolichosis, as either BA bifurcation above the suprasellar cistern or lateral to the margin of the clivus or dorsum sellae. Whether VBD is associated with CMB anywhere in the brain or in anterior or posterior circulation territories was analysed using binary and multinomial logistic regression models.
Results
Twenty‐four subjects (13.2%) had VBD and 48 (26.4%) had CMBs. CMBs were more frequently observed in patients with VBD than without (66.7% vs. 20.3%, < 0.001). VBD was significantly associated with CMBs in any location (crude odds ratio, 7.88; 95% confidence interval, 3.10–20.02), in the posterior circulation territory only (9.63; 2.60–34.94), and in both territories (9.25; 3.40–26.29), but not in the anterior circulation only (1.14; 0.009–11.20). These associations remained unchanged after adjusting for age, gender, hypertension, leukoaraiosis and stroke subtype.
Conclusions
VBD in patients with ischaemic stroke or TIA is independently associated with CMBs, especially in the posterior circulation territory.
Article first published online:
08 Jan 2013 | DOI: 10.1111/ene.12075
08 Jan 2013 | DOI: 10.1111/ene.12075
Original Article
Stroke recurrence in patients with recently symptomatic carotid stenosis and scheduled for carotid revascularization
Background and purpose
Patients with symptomatic carotid stenosis (sCS) have a higher risk of stroke recurrence following the first ischaemic event. Guidelines recommend that patients undergo carotid revascularization (CR), preferably within 2 weeks of the event. We aimed to determine the rate of stroke recurrence during hospitalization in patients who were admitted to the hospital with an acute ischaemic event and who underwent CR for recently sCS.
Methods
As part of the stroke registry in Schleswig‐Holstein, Germany (QugSS2; Qualitätsgemeinschaft Schlaganfallversorgung in Schleswig‐Holstein), over a 4.5‐year period (starting 2007) all patients (= 15 797) who were admitted to the hospital with an acute cerebral ischaemic event were included and prospectively evaluated.
Results
A total of 597 (3.8%) patients (mean age, 71 ± 10 years; 30% women) underwent a CR. The median time between symptom onset and admission to hospitals was 6 h. During the mean hospitalization of 10 days, 30 patients (5%) suffered a stroke. The rates of stroke recurrence were higher, albeit non‐significantly, in men compared with women (6% vs. 2.3%, respectively; = 0.059), and in patients admitted with ischaemic stroke compared with patients admitted with transient ischaemic attack (6.1% vs. 2%, respectively; = 0.052). The risk of stroke recurrence did not show any association with the other demographic and clinical parameters.
Conclusion
The rate of stroke recurrence was 5% in patients with recently sCS who scheduled for CR. This suggests that CR should be performed immediately after presenting event to prevent stroke recurrence.
Article first published online:
11 Jan 2013 | DOI: 10.1111/ene.12078
11 Jan 2013 | DOI: 10.1111/ene.12078
Original Article
Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy
Background and purpose
We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength.
Methods
Thirty patients with motor involvement in maintenance therapy with intravenous immunoglobulin (IVIG) fulfilling the EFNS/PNS criteria for CIDP, aged 18–80 years, were randomized either to SCIG at a dose corresponding to their pre‐study IVIG dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start and end of the trial as well as 2 weeks before (−2, 0, 10, 12 weeks), isokinetic strength performance of four predetermined and weakened muscle groups was measured. Also, an Overall Disability Sum Score (ODSS), 40‐m‐walking test (40‐MWT), nine‐hole‐peg test, Neurological Impairment Score (NIS), Medical Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated.
Results
SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side‐effects at the injection site. In the SCIG group there was an increase of isokinetic muscle strength of 5.5 ± 9.5% (< 0.05) as compared with a decline of 14.4 ± 20.3% (< 0.05) in the placebo group; the difference between the two groups being significant (< 0.01). ODSS, NIS, MRC, grip strength and 40‐MWT improved following SCIG versus saline.
Conclusions
SCIG treatment in CIDP is feasible, safe and effective, and seems an attractive alternative to IVIG.
Article first published online:
07 Jan 2013 | DOI: 10.1111/ene.12080
07 Jan 2013 | DOI: 10.1111/ene.12080
Original Article
Spinal cord injury: association with axonal peripheral neuropathy in severely paralysed limbs
Background and purpose
Pressure sores are a major health problem in spinal cord injury (SCI). In this population pressure damage to peripheral nerves was not thoroughly investigated so far. However, intact peripheral nerves and innervated muscles are a prerequisite for the effectiveness of supportive therapies like functional electrical stimulation (FES).
Methods
We assessed electroneurographic (ENG) data of lower limbs in SCI individuals admitted to our hospital due to severe pressure sores. Our centers prospectively acquired ENG data of the European Multicenter study about SCI (EMSCI) patients served as early control.
Results
In the pressure sore cohort (= 15) all patients were sensory‐motor complete (American Spinal Cord Injury Association Impairment Scale A). Most patients (10/15) suffered from a severe axonal sensory‐motor polyneuropathy in paralysed legs with absent compound muscle action potentials (CMAPs) of tibial/peroneal nerves as well as absent sensory nerve action potentials of sural nerves. The onset of this polyneuropathy dates within the first year after incident SCI and was mainly associated with increasing sensory‐motor completeness as demonstrated by a significant CMAP drop of our centers EMSCI‐ENG data on serial tibial nerve recordings in 275 patients.
Conclusions
Severe SCI is associated with an early‐onset axonal polyneuropathy in paralysed limbs to which pressure damage might contribute. Because intact peripheral nerves are required for: (i) maintenance of motor function in centrally impaired muscles; and (ii) effectiveness of supportive therapies like FES, ENG‐monitoring could serve as a low invasive screening method for peripheral nerve integrity in patients with SCI to initiate pressure relief procedures early enough.
Article first published online:
11 Jan 2013 | DOI: 10.1111/ene.12082
11 Jan 2013 | DOI: 10.1111/ene.12082
Original Article
Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single Center retrospective series
Background and purpose
Epileptic seizures account for 24–40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs).
Methods
We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's ‐test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for < 0.05.
Results
About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs > 4 cm (= 0.001) and those fed by dilated arterial feeders (= 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; < 0.001 and 48.9% vs. 23.5%; = 0.002, respectively). No lobar predisposition was observed. A nidus > 4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26–6.31; = 0.009) at logistic regression analysis.
Conclusions
AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography.
Article first published online:
11 Jan 2013 | DOI: 10.1111/ene.12085
11 Jan 2013 | DOI: 10.1111/ene.12085
Letter to the Editor
A novel familial prion disease causing pan‐autonomic‐sensory neuropathy and cognitive impairment
Article first published online:
11 Apr 2013 | DOI: 10.1111/ene.12089
11 Apr 2013 | DOI: 10.1111/ene.12089
CME Article
Exposure to anaesthetic agents does not affect multiple sclerosis risk
Background and purpose
It has been hypothesized that exposure to anaesthetic agents, some of which are chemically related to organic solvents, may affect the risk of developing multiple sclerosis (MS). The aim of this study was to estimate the influence of occupational exposure to anaesthetic agents on the risk for MS. We further aimed to investigate the impact of general anaesthesia and usage of nitrous oxide.
Methods
This report is based on two population‐based, case–control studies, one with incident cases (1798 cases, 3907 controls) and one with prevalent cases (5216 cases, 4701 controls). Using logistic regression, the occurrence of MS among subjects who have been exposed to anaesthetic agents was compared with that of those who have never been exposed by calculating the odds ratio with a 95% confidence interval.
Results
No association was found between occupational exposure to anaesthetic agents and risk of developing MS, also general anaesthesia or usage of nitrous oxide had no impact on MS risk.
Conclusions
Neither occupational exposure to anaesthetic agents, nor general anaesthesia or usage of nitrous oxide has any impact on MS risk and is safe also for people with a genetic susceptibility to the disease. However, further studies would be valuable in order to clarify whether other forms of organic solvents contribute to the triggering of MS.
Article first published online:
24 Jan 2013 | DOI: 10.1111/ene.12098
24 Jan 2013 | DOI: 10.1111/ene.12098
Letter to the Editor
Non‐invasive positive‐pressure ventilation in patients with amyotrophic lateral sclerosis: spinal versus bulbar form
Article first published online:
11 Apr 2013 | DOI: 10.1111/ene.12105
11 Apr 2013 | DOI: 10.1111/ene.12105
Letter to the Editor
Respiratory function deterioration and the effect of non‐invasive mechanical ventilation in amyotrophic lateral sclerosis: the crucial importance of bulbar muscle involvement
Article first published online:
11 Apr 2013 | DOI: 10.1111/ene.12106
11 Apr 2013 | DOI: 10.1111/ene.12106
Letter to the Editor
Rare neurological presentation of human granulocytic anaplasmosis
Article first published online:
11 Apr 2013 | DOI: 10.1111/ene.12110
11 Apr 2013 | DOI: 10.1111/ene.12110
Letter to the Editor
Sporadic Creutzfeldt–Jakob disease presenting as spastic paraparesis
Article first published online:
11 Apr 2013 | DOI: 10.1111/ene.12116
11 Apr 2013 | DOI: 10.1111/ene.12116
Book Review
Article first published online:
20 Feb 2013 | DOI: 10.1111/ene.12118
20 Feb 2013 | DOI: 10.1111/ene.12118
Miscellaneous
Calendar
Article first published online:
11 Apr 2013 | DOI: 10.1111/ene.12173
11 Apr 2013 | DOI: 10.1111/ene.12173
Original Article
Vigorimeter grip strength in CIDP: a responsive tool that rapidly measures the effect of IVIG – the ICE study
Background and purpose
In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more improvement in patients receiving immune globulin (IGIV‐C) intravenously than in those receiving placebo.
Methods
We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP.
Results
A randomized double‐blind trial was undertaken in 117 CIDP patients who received IGIV‐C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut‐off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV‐C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV‐C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV‐C group (37.5%–50.9%) than in the placebo group (21.1%–25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1‐point deterioration) findings.
Conclusions
Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.
Article first published online:
14 Aug 2012 | DOI: 10.1111/j.1468-1331.2012.03851.x
14 Aug 2012 | DOI: 10.1111/j.1468-1331.2012.03851.x
Short Communication
Early‐onset absence epilepsy: gene analysis and treatment evolution
Background and purposes
To determine the prevalence of mutations in children with early‐onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure‐free with anti‐epileptic drug (AED) monotherapy (group I) and those who needed add‐on treatment of a second AED (group II).
Methods
We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of was performed in each patient.
Results
Eighty‐four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first‐degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6‐month follow‐up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II ( = 0.008).
Conclusions
We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure‐free with add‐on treatment of a second AED.
Article first published online:
30 Sep 2012 | DOI: 10.1111/j.1468-1331.2012.03871.x
30 Sep 2012 | DOI: 10.1111/j.1468-1331.2012.03871.x
Short Communication
Association of Chr17q25 with cerebral white matter hyperintensities and cognitive impairment: the J‐SHIPP study
Background and purpose
A recent genome‐wide association study has successfully identified several genetic variations in the Chr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non‐European origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function.
Methods
Study subjects were 1190 general Japanese persons (66.0 ± 8.9 years old). Asymptomatic cerebrovascular damage, including lacunar infarctions, microbleeds, periventricular hyperintensity and deep and subcortical white matter hyperintensity (DSWMH), was evaluated by brain magnetic resonance imaging.
Results
A polymorphism rs3744028 was significantly associated with DSWMH grade ( = 0.015) but not periventricular hyperintensity, lacunar infarction, and microbleeds. Although age, hypertension, insulin resistance, B‐type natriuretic peptide, and carotid atherosclerosis were also correlated with DSWMH, association of the genotype was independent of these environmental risk factors. In contrast, the risk allele had a protective effect against reduced cognitive function.
Conclusion
Susceptibility of the 17q25 locus may be conserved beyond ethnic differences. Genetic variants may have bipolar effects on brain histological and functional changes.
Article first published online:
30 Sep 2012 | DOI: 10.1111/j.1468-1331.2012.03879.x
30 Sep 2012 | DOI: 10.1111/j.1468-1331.2012.03879.x