The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide. METHODS: The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates. FINDINGS: In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5-23·9) in the EU and 41·1 million (36·7-45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09-1·14) in the EU and 1·97 million (1·95-2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3-17·1) of total DALYs and 19·5% (18·0-21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80-84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs. INTERPRETATION: Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries. FUNDING: European Academy of Neurology.

The influence of iron oxidation state on quantitative MRI parameters in post mortem human brain.

A variety of Magnetic Resonance Imaging (MRI) techniques are known to be sensitive to brain iron content. In principle, iron sensitive MRI techniques are based on local magnetic field variations caused by iron particles in tissue. The purpose of this study was to investigate the sensitivity of MR relaxation and magnetization transfer parameters to changes in iron oxidation state compared to changes in iron concentration. Therefore, quantitative MRI parameters including R1, R2, R2∗, quantitative susceptibility maps (QSM) and magnetization transfer ratio (MTR) of post mortem human brain tissue were acquired prior and after chemical iron reduction to change the iron oxidation state and chemical iron extraction to decrease the total iron concentration. All assessed parameters were shown to be sensitive to changes in iron concentration whereas only R2, R2∗ and QSM were also sensitive to changes in iron oxidation state. Mass spectrometry confirmed that iron accumulated in the extraction solution but not in the reduction solution. R2∗ and QSM are often used as markers for iron content. Changes in these parameters do not necessarily reflect variations in iron content but may also be a result of changes in the iron's oxygenation state from ferric towards more ferrous iron or vice versa.

Mean Platelet Volume Does Not Predict Restenosis After Carotid Artery Stenting in Whites.

Background and Purpose- Mean platelet volume (MPV) indicates platelet activity possibly affecting patient's risk for progressive atherosclerotic disease. A recent study identified elevated MPV as a predictor of in-stent restenosis (ISR) after carotid artery stenting (CAS) in a Chinese population. However, the role of MPV on the development of ISR following CAS in whites is yet unknown. Methods- We retrospectively identified all consecutive patients who underwent CAS for atherosclerotic disease at our center from 2005 to 2017. All patients were followed clinically and by duplex sonography at 1, 3, and 6 months and annually after CAS. ISR was defined as ≥50% stenosis (NASCET [North American Symptomatic Carotid Endarterectomy Trial] criteria) in the treated vessel. MPV was assessed before CAS, at last follow-up and at the time of ISR detection. Results- Of 392 patients with CAS (mean age 68.5±9.5 years, 26.8% women, 42.3% symptomatic stenosis), 54 had ISR after a mean follow-up time of 32 months. Baseline MPV was not different in ISR compared with non-ISR patients (10.7 versus 10.6 fL, P=0.316). MPV levels did also not change from baseline to ISR detection (P=0.310) and were not associated with recurrent stroke or vascular events (P>0.5). Multivariable analysis identified active smoking as the sole risk factor for carotid ISR (odds ratio, 2.53 [95% CI, 1.21-5.29]). Conclusions- We did not identify MPV as a risk factor for ISR after CAS in whites. Smoking cessation is an important target to avoid this complication.

White Matter Hyperintensities in Alzheimer's Disease: A Lesion Probability Mapping Study.

BACKGROUND/OBJECTIVE: Higher white matter hyperintensity (WMH) load has been reported in Alzheimer's disease (AD) patients in different brain regions when compared to controls. We aimed to assess possible differences of WMH spatial distribution between AD patients and age-matched controls by means of lesion probability maps. METHODS: The present study included MRI scans of 130 probable AD patients with a mean age of 73.4±8.2 years from the Prospective Dementia Registry Austria Study and 130 age-matched healthy controls (HC) from the Austrian Stroke Prevention Family Study. Risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and smoking were assessed. Manually segmented FLAIR WMH masks were non-linearly registered to a template and voxel-based probability mapping was performed. RESULTS: There were no significant between-group differences in cardiovascular risk factors and WMH volume. AD patients showed a significantly higher likelihood of having WMH in a bilateral periventricular distribution than controls before and after correcting for age, sex, cardiovascular risk factors, and ventricular volume (p≤0.05; threshold-free cluster enhancement corrected). There was no significant association between the periventricular WMH volume and cognitive decline of AD patients. CONCLUSION: In AD, WMH were preferentially found in a periventricular location but the volume of lesions was unrelated to cognitive decline in our study irrespective of lesion location.

Nigral iron deposition in common tremor disorders.

OBJECTIVE: We investigated R2* relaxation rates as a marker of iron content in the substantia nigra in patients with common tremor disorders and explored their diagnostic properties. METHODS: Mean nigral R2* rates were measured in 40 patients with tremor-dominant Parkinson's disease (PD), 15 with tremor in dystonia, 25 with essential tremor, and 25 healthy controls. RESULTS: Tremor-dominant PD patients had significantly higher nigral R2* values (34.1 ± 5.7) than those with tremor in dystonia (30.0 ± 3.9), essential tremor (30.6 ± 4.8), and controls (30.0 ± 2.8). An R2* threshold of 31.15 separated tremor-dominant PD from controls with a sensitivity and specificity of 67.5% and 72%. The sensitivity and specificity for discrimination between PD and non-PD tremor patients was 67.5% and 60%. CONCLUSION: Iron content in the substantia nigra is significantly higher in tremor-dominant PD than in tremor in dystonia, essential tremor, and controls. Because of the considerable overlap, nigral R2* cannot be suggested as a useful diagnostic tool. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis.

BACKGROUND: Vascular risk factors (VRF) in multiple sclerosis (MS) patients have been associated with lower brain volumes. It is currently unknown if this association already exists in early MS and how it develops over time. METHODS: We identified 82 patients with clinically isolated syndrome (CIS) ( n = 61) or with early relapsing-remitting MS ( n = 21) and assessed their VRF including arterial hypertension, hyperlipidaemia, diabetes mellitus and smoking. We analysed T2-lesion load, normalized brain volume (NBV), cortical grey (cGMV) and white matter volumes (WMV), thalamic and basal ganglia volumes at baseline and follow-up magnetic resonance imaging (MRI) and assessed the percentage of brain volume change (PBVC) using SIENA. RESULTS: Patient mean age was 32.4 (±8.7) years and 54 (65%) were women. Median follow-up period was 42 (29-54) months. In total, 26 patients (31.7%) had one or more VRF (VRF+). At baseline, VRF+ patients had a lower NBV (1530.9 cm3 vs 1591.2 cm3, p = 0.001), a lower cGMV (628.5 cm3 vs 668.6 cm3, p = 0.002) and WMV (752.2 cm3 vs 783.9 cm3, p = 0.009) than VRF-negative patients. Similar results were obtained at follow-up. PBVC was comparable between patients with and without VRF. CONCLUSION: VRF are associated with lower brain volume already in early MS but do not lead to increased brain volume loss during 3.5 years of follow-up.

Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis.

In recent years, new antibodies have been discovered which mediate autoimmune encephalitis. This immunological response can be triggered by an infection or a tumor. Classical onconeuronal antibodies are directed against intracellular neuronal agents but recently, a novel group of antibodies to neuronal cell-surface and synaptic antigens associated with different CNS-syndromes, has been discovered. Interestingly, the syndromes in this group can be successfully treated with immunotherapy and frequently do not have underlying tumors. The aim of this review is to describe the current state of knowledge about autoimmune encephalitis, in order to provide clinicians with a concise, up-to-date overview. Thus, a comprehensive literature search was performed in medical databases. The literature was carefully studied and new findings focusing on the symptoms, diagnosis and treatment were summarized and interpreted. Even though it might be challenging in some cases, the awareness of certain symptom constellations and demographic information, in combination with laboratory- and MRI-results, allows clinicians to make the diagnosis of probable autoimmune encephalitis at an early stage. Treatment can therefore be initiated faster, which significantly improves the outcome. Further investigations could define the underlying pathogenic mechanisms. Randomized controlled trials, paired with increasing clinical experience, will be necessary to improve the identification of affected patients, treatment strategies, and outcomes in the years to come.

Stroke Referrals from Nursing Homes: High Rate of Mimics and Late Presentation.

BACKGROUND: Stroke has become a treatable condition with increasing evidence of treatment benefits in older people. However, stroke mimics in geriatric patients are especially prevalent, causing incorrect suspicion and consecutive burden to patients and emergency room resources. We therefore examined the dimension of this problem by investigating emergency room admissions from nursing homes for suspected stroke. METHODS: We performed a retrospective cohort study of all nursing home residents who were admitted to the neurological emergency room of our primary and tertiary care university hospital between 2013 and 2015. Patients were further divided into those with confirmed stroke and stroke mimics after diagnostic stroke work-up. RESULTS: Of 419 nursing home patients referred to the emergency room, nearly one third had suspected stroke (n = 126; mean age: 78 ± 14 years, polypharmacy rate: 77%). Of those, 43 (34%) had a confirmed stroke (ischaemic: n = 34; haemorrhagic: n = 9) and 83 (66%) had stroke mimics after diagnostic work-up. Only one patient underwent intravenous thrombolysis, followed by mechanical thrombectomy for middle cerebral artery occlusion. Prehospital delay (47%) and multimorbidity-associated contraindications (27%) were the main reasons for withholding recanalization therapy. Among the stroke-mimicking conditions, infectious diseases (24%) and epileptic seizures (20%) were the most frequent. Multivariate analysis identified focal deficits (OR 16.6, 95% CI 4.3-64.0), atrial fibrillation (OR 3.9, 95% CI 1.5-10.5) and previous stroke (OR 3.2, 95% CI 1.2-8.9) as indicators that were associated with stroke. CONCLUSIONS: In our region, nursing home referrals for suspected stroke have a high false positive rate and occur delayed, which most often precludes specific stroke treatment in addition to multimorbidity. Such problems may also exist in other centres and highlight the need for targeted educational and organizational efforts. Simple indicators as identified in this study may help to sort out patients with true stroke more efficiently.

Increased middle cerebral artery mean blood flow velocity index after stroke thrombectomy indicates increased risk for intracranial hemorrhage.

BACKGROUND AND PURPOSE: Cerebral hyperperfusion has been related to the risk of intracranial hemorrhage (ICH) in stroke patients after vessel recanalization therapy. We hypothesized that after successful mechanical thrombectomy for acute anterior circulation stroke, hemodynamics detectable by transcranial Duplex (TCD) sonography would vary, and that increased blood flow velocities would be associated with ICH. METHODS: We retrospectively identified all ischemic stroke patients with successful endovascular recanalization for anterior circulation vessel occlusion (Thrombolysis in Cerebral Infarction 2b-3) between 2010 and 2017. We reviewed their postinterventional TCD examinations for mean blood flow (MBF) velocities of the recanalized and contralateral middle cerebral artery (MCA) and searched for an association with postinterventional ICH and clinical outcome. RESULTS: 123 stroke patients (mean age 63±14 years, 40% women) with successful anterior circulation thrombectomy were analyzed. Of those, 18 patients had postinterventional ICH. ICH patients had an increased MCA MBF velocity index (=MBF velocity of the recanalized divided by the contralateral MCA) compared with non-ICH patients (1.32±0.39 vs 1.02±0.32, P<0.001). In multivariate analysis, a higher MCA MBF velocity index was associated with postinterventional ICH and poor 90 day outcome. CONCLUSIONS: A high MCA MBF velocity index on TCD after successful recanalization therapy for anterior circulation stroke indicates a risk for postinterventional ICH and worse prognosis.

Early Dysphagia Screening by Trained Nurses Reduces Pneumonia Rate in Stroke Patients: A Clinical Intervention Study.

BACKGROUND AND PURPOSE: Dysphagia is a common stroke symptom and leads to serious complications such as aspiration and pneumonia. Early dysphagia screening can reduce these complications. In many hospitals, dysphagia screening is performed by speech-language therapists who are often not available on weekends/holidays, which results in delayed dysphagia assessment. METHODS: We trained the nurses of our neurological department to perform formal dysphagia screening in every acute stroke patient by using the Gugging Swallowing Screen. The impact of a 24/7 dysphagia screening (intervention) over swallowing assessment by speech-language therapists during regular working hours only was compared in two 5-month periods with time to dysphagia screening, pneumonia rate, and length of hospitalization as outcome variables. RESULTS: Overall, 384 patients (mean age, 72.3±13.7 years; median National Institutes of Health Stroke Scale score of 3) were included in the study. Both groups (pre-intervention, n=198 versus post-intervention, n=186) were comparable regarding age, sex, and stroke severity. Time to dysphagia screening was significantly reduced in the intervention group (median, 7 hours; range, 1-69 hours) compared with the control group (median, 20 hours; range, 1-183; P=0.001). Patients in the intervention group had a lower rate of pneumonia (3.8% versus 11.6%; P=0.004) and also a reduced length of hospital stay (median, 8 days; range, 2-40 versus median, 9 days; range, 1-61 days; P=0.033). CONCLUSIONS: 24/7 dysphagia screening can be effectively performed by nurses and leads to reduced pneumonia rates. Therefore, empowering nurses to do a formal bedside screening for swallowing dysfunction in stroke patients timely after admission is warranted whenever speech-language therapists are not available.

Mucosal biopsy shows immunologic changes of the colon in patients with early MS.

OBJECTIVE: To investigate immune cells of the colonic mucosa and fecal short-chain fatty acids (SCFAs) in treatment-naive patients with a clinically isolated syndrome (CIS) or early relapsing MS. METHODS: In this cross-sectional proof-of-concept study, we obtained mucosal specimens during ileocolonoscopy from 15 untreated patients with CIS/MS and 10 controls. Mucosal immune cells were analyzed by FACS, and gas chromatography-mass spectrometry measurements of stool samples served to determine SCFA. RESULTS: The number of total dendritic cells (DCs), CD103+ tolerogenic DCs, and CD4+25+127-regulatory T cells (Tregs) was significantly reduced in the distal colon of patients with CIS/MS compared with controls, whereas we found no differences in the proximal colon. The patients' fecal samples also showed a substantially lower content of SCFA and especially lower levels of butyrate and acetate. CONCLUSIONS: Our findings indicate a disturbed homeostasis of colonic DCs and Tregs in patients with MS which could be associated with colonic SCFA depletion. Although not implying causality, these findings confirm parallel abnormalities of the gut in MS and warrant further research if modulation of the colonic SCFA profile or the colonic Treg pool can serve to modify the course of MS.

Iron Mapping in Multiple Sclerosis.

Increased iron deposition in cerebral deep gray matter has been considered a global marker for neurodegeneration in multiple sclerosis (MS); it scales with disease duration and severity. Iron accumulation in white matter and MS lesions might be more directly related to disease activity and has been discussed as a contributor to the inflammatory and neurodegenerative cascade. New insights into iron and MS are expected from MR imaging. We discuss findings from MR iron mapping proposed. Because of the confounding magnetic properties of myelin, iron mapping in white matter remains an unresolved issue.

Symmetry of the arcuate fasciculus and its impact on language performance of patients with brain tumors in the language-dominant hemisphere.

OBJECTIVE Cerebral damage in frontal, parietal, and temporal brain areas and, probably more importantly, their interconnections can lead to deficits in language. However, neural plasticity and repair allow the brain to partly compensate for neural injury, mediated by both functional and structural changes. In this study, the authors sought to systematically investigate the relationship between language performance in brain tumor patients and structural perisylvian pathways (i.e., the arcuate fasciculus [AF]) using probabilistic fiber tracking on diffusion tensor imaging. The authors used a previously proposed model in which the AF is divided into anterior, long, and posterior segments. The authors hypothesized that right-handed patients with gliomas in the language-dominant (left) hemisphere would benefit from a more symmetrical or right-lateralized language pathway in terms of better preservation of language abilities. Furthermore, they investigated to what extent specific tumor characteristics, including proximity to the AF, affect language outcome in such patients. METHODS Twenty-seven right-handed patients (12 males and 15 females; mean age 52 ± 16 years) with 11 low-grade and 16 high-grade gliomas of the left hemisphere underwent 3-T diffusion-weighted MRI (30 directions) and language assessment as part of presurgical planning. For a systematic quantitative evaluation of the AF, probabilistic fiber tracking with a 2 regions of interest approach was carried out. Volumes of the 3 segments of both hemispheric AFs were evaluated by quantifying normalized and thresholded pathways. Resulting values served to generate the laterality index of the AFs. RESULTS Patients without language deficits tended to have an AF that was symmetric or lateralized to the right, whereas patients with deficits in language significantly more often demonstrated a left-lateralized posterior segment of the AF. Patients with high-grade gliomas had more severe language deficits than those with low-grade gliomas. Backward logistic regression revealed the laterality index of the posterior AF segment and tumor grade as the only independent statistically significant predictors for language deficits in this cohort. CONCLUSIONS In addition to the well-known fact that tumor entity influences behavioral outcome, the authors' findings suggest that the right homologs of structural language-associated pathways could be supportive for language function and facilitate compensation mechanisms after brain damage in functionally eloquent areas. This further indicates that knowledge about preoperative functional redistribution (identified by neurofunctional imaging) increases the chance for total or near-total resections of tumors in eloquent areas. In the future, longitudinal studies with larger groups are mandatory to overcome the methodological limitations of this cross-sectional study and to map neuroplastic changes associated with language performance and rehabilitation in brain tumor patients.

Posterior versus Anterior Circulation Stroke in Young Adults: A Comparative Study of Stroke Aetiologies and Risk Factors in Stroke among Young Fabry Patients (sifap1).

BACKGROUND: Although 20-30% of all strokes occur in the posterior circulation, few studies have explored the characteristics of patients with strokes in the posterior compared to the anterior circulation so far. Especially data on young patients is missing. METHODS: In this secondary analysis of data of the prospective multi-centre European sifap1 study that investigated stroke and transient ischemic attack (TIA) patients aged 18-55 years, we compared vascular risk factors, stroke aetiology, presence of white matter hyperintensities (WMH) and cerebral microbleeds (CMB) between patients with ischaemic posterior circulation stroke (PCS) and those having suffered from anterior circulation stroke (ACS) based on cerebral MRI. RESULTS: We diagnosed PCS in 612 patients (29.1%, 407 men, 205 women) and ACS in 1,489 patients (70.9%). Their age (median 46 vs. 47 years, p = 0.205) and stroke severity (modified Rankin Scale: both 2, p = 0.375, Barthel Index 90 vs. 85, p = 0.412) were similar. PCS was found to be more frequent among the male gender (66.5 vs. 60.1% with ACS, p = 0.003). Vertebral artery (VA) dissection was more often the cause of PCS (16.8%) than was carotid artery dissection of ACS (7.9%, p < 0.001). Likewise, small vessel disease (Trial of Org 10172 in Acute Stroke Treatment [TOAST] = 3, PCS: 14.7%, ACS: 11.8%) and stroke of other determined aetiology (TOAST = 4, PCS: 24.5%, ACS: 16.0%) were more frequent in those with PCS. Furthermore, patent foramen ovale (PFO; PCS: 31.1%, ACS: 25.4%, p = 0.029) was more often detected in patients with PCS. In contrast, large-artery atherosclerosis (TOAST = 1, PCS: 15.4%, ACS: 22.2%) and cardio-embolic stroke (TOAST = 2, PCS: 15.6%, ACS: 18.0%) were less frequent in those with PCS (p < 0.001) as were preceding cerebrovascular events (10.1 vs. 14.1%, p = 0.014), TIA (4.8 vs. 7.7%, p = 0.016) and smoking (53.2 vs. 61.0%, p = 0.001). The presence, extent, and location of WMH and CMB did not differ between the 2 groups. CONCLUSIONS: Our data suggested a different pattern of aetiology and risk factors in young patients with PCS compared to those with ACS. These findings especially call for a higher awareness of VA dissection and potentially for more weight of a PFO as a risk factor in young patients with PCS. Clinical trial registration-URL: http://www.clinicaltrials.gov; NCT00414583.

Diagnosis of multiple sclerosis: progress and challenges.

The diagnosis of multiple sclerosis is based on neurological symptoms and signs, alongside evidence of dissemination of CNS lesions in space and time. MRI is often sufficient to confirm the diagnosis when characteristic lesions accompany a typical clinical syndrome, but in some patients, further supportive information is obtained from cerebrospinal fluid examination and neurophysiological testing. Differentiation is important from other diseases in which demyelination is a feature (eg, neuromyelitis optica spectrum disorder and acute disseminated encephalomyelitis) and from non-demyelinating disorders such as chronic small vessel disease and other inflammatory, granulomatous, infective, metabolic, and genetic causes that can mimic multiple sclerosis. Advances in MRI and serological and genetic testing have greatly increased accuracy in distinguishing multiple sclerosis from these disorders, but misdiagnosis can occur. In this Series paper we explore the progress and challenges in the diagnosis of multiple sclerosis with reference to diagnostic criteria, important differential diagnoses, controversies and uncertainties, and future prospects.

Patent Foramen Ovale and Cryptogenic Strokes in the Stroke in Young Fabry Patients Study.

BACKGROUND AND PURPOSE: A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO. METHODS: We investigated the PFO prevalence in 3497 transient ischemic attack and ischemic stroke patients aged 18 to 55 years in the prospective multicenter SIFAP1 study (Stroke in Young Fabry Patients 1) using the ASCO classification. Patients without an obvious cause for transient ischemic attack/stroke (ASCO 0) were divided into subgroups with and without vascular risk factors (ASCO 0+ and 0-). In addition, we looked for PFO-related magnetic resonance imaging lesion patterns. RESULTS: PFO was identified in 25% of patients. Twenty percent of patients with a definite or probable cause of transient ischemic attack/stroke (≥1 grade 1 or 2 ASCO criterion; n=1769) had a PFO compared with 29% of cryptogenic stroke patients (ASCO 0 and 3; n=1728; P<0,001); subdivision of cryptogenic strokes revealed a PFO in 24% of 978 ASCO 3 patients (n.s. versus ASCO 1 and 2) and a higher prevalence of 36% in 750 ASCO 0 cases (P<0.001 versus ASCO 3 and versus ASCO 1 and 2). PFO was more commonly observed in ASCO 0- (n=271) than in ASCO 0+ patients (n=479; 48 versus 29%; P<0.001). There was no PFO-associated magnetic resonance imaging lesion pattern. CONCLUSIONS: Cryptogenic stroke patients demonstrate a heterogeneous PFO prevalence. Even in case of less conclusive diseases like nonstenotic arteriosclerosis, patients should preferentially be considered to have a non-PFO-mediated stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.

No evidence for increased brain iron deposition in patients with ischemic white matter disease.

Besides specific iron accumulation in some neurodegenerative disorders, increased iron deposition in cerebral deep gray matter (DGM) is found in multiple sclerosis. As this is considered largely a white matter (WM) disease, we speculated that patients with more severe ischemic WM hyperintensities (WMH) might also have an increased iron concentration in DGM structures and tested this assumption by using magnetic resonance imaging-based quantitative R2* relaxometry. WMH severity was measured in 61 patients with acute transient neurological symptoms (mean age: 71.5 ± 8.3 years) undergoing 3-Tesla magnetic resonance imaging. Despite a 6-year higher age of patients with more severe (i.e., early confluent or confluent) WMH, their DGM R2* rates did not differ from patients with punctate or no WMH. In the globus pallidum, R2* rates were even lower in patients with severe WMH. WMH volume was not correlated with R2* levels in any of the analyzed DGM structures. These findings argue against WM damage per se causing increased DGM iron deposition in multiple sclerosis and suggest no role of iron accumulation in ischemic small vessel disease.