European Journal of Neurology

Editorials
Screening tools for fitness to drive after traumatic brain injury and stroke

CME Article

Prediction of on-road driving ability after traumatic brain injury and stroke

Review Article
Anaemia and cognitive performances in the elderly: a systematic review

Original Articles
Pregnancy outcome following use of levodopa, pramipexole, ropinirole, and rotigotine for restless legs syndrome during pregnancy: a case series

Background
Restless legs syndrome (RLS) is related to parity, and its symptoms may worsen during pregnancy. Treatment with levodopa or dopamine agonists is the first-line therapy for RLS; however, there are limited data on treatment in pregnancy. We therefore assessed the safety of levodopa, pramipexole, rotigotine, and ropinirole in pregnancy.

Methods
Prospective documentation of pregnancies exposed to levodopa, pramipexole, rotigotine, and ropinirole between 1998 and 2011 was evaluated as to their outcome (teratogenicity or fetotoxicity) by the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy.

Results
We were able to complete 59 pregnancy outcomes exposed to RLS pharmacotherapy. For specific treatments, the numbers of exposed pregnancies/live born children/spontaneous abortions/induced abortions/malformations were as follows: levodopa only: 38/29 (one pair of twins)/3/7/3; pramipexole only: 12/9/3/0/0; rotigotine only: 2/2/0/0/0; ropinirole only: 3/2/0/1/0; levodopa combined with pramipexole: 3/3/0/0/0; levodopa combined with ropinirole: 1/1/0/0/0. No major birth defects were found with any RLS treatment, and three infants exposed to levodopa had minor anomalies.

Conclusions
In our small prospective case series, there was no increased risk above baseline for major malformations or other adverse outcomes for levodopa and pramipexole. If necessary, levodopa treatment may be considered as an alternative to cabergoline, for which safety has been well documented in pregnancy.

Young adult ischaemic stroke related acute symptomatic and late seizures: risk factors

Background and purpose

After first-ever ischaemic stroke, to assess the risk and baseline factors associated with acute symptomatic seizure (ASS) (occurring within 7 days) and late post-stroke seizure (LPS) (>7 days).

Methods
All consecutive patients aged 1549 with first-ever ischaemic stroke between 1994 and 2007 treated at the Helsinki University Central Hospital were included, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (>6.1 mm) and hyponatremia (<137 mm), use of psychiatric medication, stroke severity (NIH Stroke Scale) and anatomical (Bamford criteria) and etiological (Trial of Org in Acute Stroke Treatment) stroke subtype.

Results
ASSs emerged in 35 (3.5%) patients. LPSs (n = 102) occurred at a cumulative rate of 6.1% at 1 year, 9.5% at 5 years and 11.5% at 10 years. In multivariate analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95% confidence interval 3.9146.14), moderate stroke severity (3.95, 1.868.41), cortical involvement (3.69, 1.668.18) and hyponatremia (3.26, 1.417.57) were independently associated with ASSs. Risk factors for LPSs were total anterior circulation infarct (15.94, 7.62 33.33), partial anterior circulation infarct (3.48, 1.527.93), history of ASS (3.94, 2.077.48), antidepressant use at the time of LPS (3.88, 2.466.11), hemorrhagic infarct (1.94, 1.193.15), male gender (1.79, 1.102.92) and hyperglycemia (1.62, 1.052.51).

Conclusions
In young ischaemic stroke patients, the magnitude of seizure risk and the major risk factors were similar to older ischaemic stroke patients but risk factors for ASSs and LPSs differed.

The association between asymptomatic coronary artery disease and CHADS2 and CHA2DS2VASc scores in patients with stroke (pages 12561263)

Background and purpose

CHADS2 and CHA2DS2-VASc scores are measurement tools that stratify thromboembolic risk in patients with non-valvular atrial fibrillation, and are predictive of cerebral atherosclerosis, fatal stroke and ischaemic heart disease. Patients with higher CHADS2 and CHA2DS2-VASc scores are more likely to have had an akinetic/hypokinetic left ventricular segment or a recent myocardial infarction, all of which are associated with coronary artery disease (CAD). Most of the CHADS2 score components are also risk factors for atherosclerosis. Thus, CHADS2 and CHA2DS2-VASc scores may be predictive of CAD.

Methods
In all, 1733 consecutive patients with acute ischaemic stroke who underwent multi-slice computed tomography coronary angiography were enrolled. The association of CHADS2 and CHA2DS2-VASc scores with the presence and severity of CAD was investigated.

Results
Of the 1733 patients, 1220 patients (70.4%) had any degree of CAD and 576 (33.3%) had significant CAD (50% stenosis in at least one coronary artery). As the CHADS2 and CHA2DS2-VASc scores increased, the presence of CAD also increased (P < 0.001). The severity of CAD was correlated with CHADS2 score (Spearman coefficient 0.229, P < 0.001) and CHA2DS2-VASc score (Spearman coefficient 0.261,P < 0.001). In multivariate analysis, after adjusting for confounding factors, CHADS 2 and CHA2DS2VASc scores 2 were independently associated with CAD. The CHA2DS2-VASc score was a better predictor of the presence of CAD than the CHADS2 score on area under the curve analysis.

Conclusion
CHADS2 and CHA2DS2-VASc scores were predictive of the presence and severity of CAD in patients with stroke. When a patient has high CHADS2 or CHA2DS2-VASc scores, physicians should consider coronary artery evaluation.

Cholesterol affects retinal nerve fiber layer thickness in patients with multiple sclerosis with optic neuritis

Background and purpose

To evaluate the associations between retinal nerve fiber layer (RNFL) thickness and lipid profiles in multiple sclerosis (MS).

Methods
This study enrolled 136 patients with MS (n = 272 eyes; 108 females, 28 males, mean age: 46.7 8.9 years); 45% had a history of optic neuritis (ON). Subjects received optical coherence tomography (OCT) testing to assess RNFL thickness and visual acuity testing with Snellen charts. A subset of 88 patients received pattern reversal visual-evoked potential (PRVEP) testing. Lipid profiles consisting of serum highdensity lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and total cholesterol (TC) levels were obtained within 6 months of OCT. Regression analyses were used to assess the associations between RNFL thickness and lipid profile variables.

Results
Low RNFL thickness (P = 0.008) and higher PRVEP latency (P = 0.017) were associated with high LDL cholesterol > 100 mg/dl status. Low RNFL thickness (P = 0.008) and higher PRVEP latency (P = 0.043) were associated with high HDL cholesterol levels. Low RNFL thickness was also associated with HDL

cholesterol > 60 mg/dl status (P = 0.001) and with TC > 200 mg/dl status (P = 0.015). The probability of average RNFL thickness in the lowest tertile ( 33rd percentile) was associated with interactions between TC > 200 mg/dl status (P = 0.001, odds ratio = 7.5, 95% confidence interval = 2.721) with affected/unaffected by ON status.

Conclusions
High cholesterol adversely affects RNFL thickness in patients with MS with ON.

Thymus histology and concomitant autoimmune diseases in Japanese patients with musclespecific receptor tyrosine kinase-antibody-positive myasthenia gravis(pages 12721276)

Impact of blood pressure changes and course on hematoma growth in acute intracerebral hemorrhage (pages 12771283)

Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke?(pages 1284 1291) Predicting multiple sclerosis following isolated optic neuritis in children (pages 12921296) Neuropsychological course of voltage-gated potassium channel and glutamic acid decarboxylase antibody related limbic encephalitis (pages 12971304) High resolution MRI difference between moyamoya disease and intracranial atherosclerosis (pages 13111318)

Short Communication
The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage Huntington's disease: a pilot study (pages 13251329)

Book Review
Proteopathic Seeds and Neurodegenerative Diseases (page e118)