Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

CTP-Based Tissue Outcome: Promising Tool to Prove the Beneficial Effect of Mechanical Recanalization in Acute Ischemic Stroke.

PURPOSE: To prove the tissue-protecting effect of mechanical recanalization, we assessed the CT perfusion-based tissue outcome ("TO") and correlated this imaging parameter with the 3-month clinical outcome ("CO"). MATERIALS AND METHODS: 159 patients with large intracranial artery occlusions revealing mechanical recanalization were investigated by CCT, CT angiography (CTA) and CT perfusion (CTP) upon admission. For the final infarct volume, native CCT was repeated after 24 h. The "TO" ("percentage mismatch loss" = %ML) was defined as the difference between initial penumbral tissue on CTP and final infarct volume on follow-up CCT. We monitored the three-month modified Rankin Scale (mRS), age, bleeding occurrence, time to recanalization, TICI score and collateralization grade, infarct growth and final infarct volume. Spearman's correlation and nominal regression analysis were used to evaluate the impact of these parameters on mRS.  RESULTS: Significant correlations were found for %ML and mRS (c = 0.48, p < 0.001), for final infarct volume and mRS (c = 0.52, p < 0.001), for TICI score and mRS (c = - 0.35, p < 0.001), for initial infarct core and mRS (c = 0.14, p = 0.039) as well as for age and mRS (c = 0.37, p < 0.001). According to the regression analysis, %ML predicted the classification of mRS correctly in 38.5 % of cases. The subclasses mRS 1 and 6 could be predicted by %ML with 86.4 % and 60.9 % reliability, respectively. No correlations were found for time to recanalization and mRS, for collateralization grade and mRS, and for post-interventional bleeding and mRS.  CONCLUSION: Better than the TICI score, CT-based TO predicts the clinical success of mechanical recanalization, showing that not recanalization, but reperfusion should be regarded as a surrogate parameter for stroke therapy. KEY POINTS: • %ML as well as the final infarct volume can make a direct point about the immediate effect of successful mechanical recanalization.• The clinical outcomes after mechanical recanalization are reliably predicted by %ML, reflecting the benefit of escalation therapy including interventional reopening of parent vessel occlusions.• Not recanalization but rather reperfusion should be regarded as a surrogate parameter for successful stroke therapy.

Discontinuous versus Continuous Weaning in Stroke Patients.

BACKGROUND: An increasing number of stroke patients have to be supported by mechanical ventilation in intensive care units (ICU), with a relevant proportion of them requiring gradual withdrawal from a respirator. To date, weaning studies have focused merely on mixed patient groups, COPD patients or patients after cardiac surgery. Therefore, the best weaning strategy for stroke patients remains to be determined. METHODS: Here, we designed a prospective randomized controlled study comparing adaptive support ventilation (ASV), a continuous weaning strategy, with biphasic positive airway pressure (BIPAP) in combination with spontaneous breathing trials, a discontinuous technique, in the treatment of stroke patients. The primary endpoint was the duration of the weaning process. RESULTS: Only the 40 (out of 54) patients failing in an initial spontaneous breathing trial (T-piece test) were included into the study; the failure proportion is considerably larger compared to previous studies. Eligible patients were pseudo-randomly assigned to one of the two weaning groups. Both groups did not differ regarding age, gender, and severity of stroke. The results showed that the median weaning duration was 10.7 days (±SD 7.0) in the discontinuous weaning group, and 8 days (±SD 4.5) in the continuous weaning group (p < 0.05). CONCLUSIONS: To the best of our knowledge, this is the first clinical study to show that continuous weaning is significantly more effective compared to discontinuous weaning in mechanically ventilated stroke patients. We suppose that the reason for the superiority of continuous weaning using ASV as well as the bad performance of our patients in the 2 h T-piece test is caused by the patients' compliance. Compared to patients on surgical and medical ICUs, neurological patients more often suffer from reduced vigilance, lack of adverse-effects reflexes, dysphagia, and cerebral dysfunction. Therefore, stroke patients may profit from a more gradual withdrawal of weaning.

Grasping multiple sclerosis: do quantitative motor assessments provide a link between structure and function?

Motor disability in MS is commonly assessed by the Expanded Disability Status Scale (EDSS). Categorical rating scales are limited by subjective error and inter-rater variability. Therefore, objective and quantitative measures of motor disability may be useful to supplement the EDSS in the setting of clinical trials. It was previously shown that grip-force-variability (GFV) is increased in MS. We hypothesized that GFV may be an objective measure of motor disability in MS. To investigate whether the increase in GFV in MS is correlated to the clinical disability as assessed by the EDSS and to microstructural changes in the brain as assessed by diffusion tensor imaging, GFV was recorded in a grasping and lifting task in 27 MS patients and 23 controls using a grip-device equipped with a force transducer. The EDSS was assessed by neurologists experienced in MS. Patients underwent diffusion tensor imaging at 3T to assess the fractional anisotropy (FA) of the cerebral white matter as a measure of microstructural brain integrity. GFV was increased in MS and correlated to changes in the FA of white matter in the vicinity of the somatosensory and visual cortex. GFV also correlated with the EDSS. GFV may be a useful objective measure of motor dysfunction in MS linked to disability and structural changes in the brain. Our data suggests that GFV should be further explored as an objective measure of motor dysfunction in MS. It could supplement the EDSS, e.g., in proof of concept studies.

Vascularization of carotid plaque in recently symptomatic patients is associated with the occurrence of transcranial microembolic signals.

BACKGROUND AND PURPOSE: Microembolic signals (MES) are detectable in the middle cerebral artery by transcranial ultrasound downstream to atherosclerotic lesions of the internal carotid artery (ICA) in patients with stroke or transient ischaemic attack. The occurrence of MES predicts future risk of stroke in patients with symptomatic and asymptomatic carotid stenosis. The detection of intra-plaque neo-vascularization by contrast-enhanced ultrasound (CEUS) in atherosclerotic plaques of the ICA is associated with future cardiovascular/cerebrovascular events. We investigated whether there is an association between both surrogate markers of future vascular events. METHODS: Forty-one patients with symptomatic atherosclerotic plaques underwent ipsilateral transcranial ultrasound MES detection for 30 min followed by a CEUS investigation of the plaque. The occurrence and number of MES was documented, and the degree of intra-plaque neo-vascularization was measured semi-quantitatively. RESULTS: During the 30 min investigation, 17 patients had MES and nine of them showed neo-vascularization of the atherosclerotic plaque. The remaining 24 patients did not have MES, and only in four patients of this group could plaque neo-vascularization be demonstrated (P = 0.020). CONCLUSIONS: We found an association between the occurrence of MES and the presence of neo-vascularization in patients with symptomatic atherosclerotic carotid plaque. Therefore, plaque neo-vascularization might also be a surrogate marker of future stroke risk.

[Regional and national stroke units in Germany: amended certification criteria]. / Regionale und überregionale Stroke-Units in Deutschland : Aktualisierte Zertifizierungskriterien.

Stroke units (SU) have been certified for many years by the German Stroke Society (DSG) and the German Stroke Aid Foundation (SDSH). Since 2009 this is now undertaken in the third generation by the LGA InterCert of the Technical Surveillance Society of Rhineland (TÜV Rheinland). This article presents the amended certification criteria which came into effect in 2012. Many criteria and definitions could be further defined and specified and residual grey areas and fields of conflict could be reduced. For the first time a distinction has been made between the minimum requirements relevant for certification and additional recommendations by the SU Commission of the DSG. In this manner the authors are aiming to motivate SU operators not just to align quality assurance measures to the minimum requirements but to deliberately go beyond them. There is a great deal of evidence to indicate that this will not only serve to increase the motivation of personnel and the quality of treatment but simultaneously the economic situation can also be improved.

A brief review of Susac syndrome.

Susac syndrome was named after J.O. Susac who first described the syndrome in 1979. It is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. It mainly occurs in young women. This underdiagnosed disease needs to be considered in the differential diagnosis of a broad variety of disorders. In Susac syndrome, autoimmune processes leading to damage and inflammation-related occlusion of the microvessels in brain, retina, and inner ear are thought to play a causal role. The diagnosis is based primarily on the clinical presentation, the documentation of branch retinal artery occlusion by fluorescence angiography, and characteristic findings on cerebral MRI, that help in distinguishing Susac syndrome from other inflammatory entities, like multiple sclerosis. Antiendothelial cell antibodies could be detected in some patients. Patients are successfully treated with immunosuppression, however, the best regimen still needs to be defined. As a result of the rarity of the disease, controlled therapeutic trials are missing so far. In this review, we want to demonstrate the clinical features, natural history, treatment, and clinical course of Susac syndrome, illustrated by a typical case history.

[Concept for allocation of acute stroke patients: evaluation of the quality of diagnosis reached by the emergency medical services of Münster]. / Zuweisungskonzept bei akutem Schlaganfall : Untersuchung der rettungsdienstlichen Diagnosequalität in der Stadt Münster.

BACKGROUND: Acute stroke is a time- and expertise-critical emergency. An immediate and correct diagnosis by emergency medical services (EMS) in the prehospital phase and patient transfer to the nearest adequate hospital with a stroke unit is required for early treatment of acute stroke. PATIENTS AND METHODS: We evaluated all patients who were admitted by the EMS of Münster to one of the two stroke units in the town between October 2008 and December 2010 with a diagnosis of acute stroke. Furthermore all patients were critically analyzed who were admitted without a diagnosis of acute stroke by the EMS but nonetheless had a stroke and the correct diagnosis was not found until examination in the neurological department. RESULTS: We analyzed 615 patients who were admitted to the stroke units with the diagnosis of acute stroke. In 561 cases (91%) this diagnosis could be confirmed, but in 54 patients (9%) the diagnosis by the EMS was incorrect. Epileptic seizure was the most frequent false-positive diagnosis in this group of patients (39%; n = 21). Although the acute symptoms were caused by a stroke, the correct diagnosis was not defined by the EMS in 127 patients. This accounted for 18% of all patients admitted to the emergency departments by the EMS where ultimately a stroke was diagnosed. In 24% of these cases (n = 30) the emergency doctor missed the correct diagnosis, which meant 4% of all patients admitted by the EMS, finally diagnosed with an acute stroke. In all other cases in the group with a false-negative diagnosis (76% or 97 patients) an emergency doctor was not involved in the referral by the EMS. CONCLUSION: Emergency medical services should be involved in the establishment of admission programs for acute stroke patients to provide the fastest means of transportation to a stroke unit. Coma, symptoms of posterior cerebral circulation and epileptic seizures cause difficulties in ensuring an immediate and correct diagnosis. Sending an emergency doctor to the scene increases diagnostic certainty which is essential to initiate early treatment.

Reperfusion by combined thrombolysis and mechanical thrombectomy in acute stroke: effect of collateralization, mismatch, and time to and grade of recanalization on clinical and tissue outcome.

BACKGROUND AND PURPOSE: Our research focuses on interventional neuroradiology (stroke treatment including imaging methods) and general neuroimaging with an emphasis on functional MR imaging. Our aim was to determine the efficacy of revascularization (TIMI) of middle cerebral and/or carotid artery occlusion by means of mechanical recanalization techniques and to evaluate the impact of collateralization, mismatch in perfusion CT, time to revascularization, grade of revascularization on tissue, and clinical outcome in patients with acute ischemic stroke. MATERIALS AND METHODS: Thirty-one patients with MCA and/or ICA occlusion were included. Ischemic stroke was diagnosed by NECT, CTA, and volume PCT for grading collateralization and mismatch. Time to recanalization was measured from the onset of stroke to the time point of DSA-proved mechanical recanalization. Tissue outcome was calculated by segmentation of infarct size between pre- and postinterventional CT and percentage mismatch lost. Clinical outcome was determined by the mRS. RESULTS: Twenty-one of 31 patients (61.8%) presented with MCA and 10/31 patients (38.2%), with distal ICA occlusions. Sufficient recanalization (TIMI 2 and 3) was achieved in 23/31 (75%). Clinical evaluation revealed an mRS score of ≤2 in 25.5%. Age (r = 0.439, P = .038) and TIMI (r = 0.544, P = .002) showed the strongest correlation with clinical outcome. Time to recanalization, TIMI score, and mismatch were associated with a good tissue outcome in ANOVA. CONCLUSIONS: Favorable outcome after mechanical recanalization of acute MCA and ICA occlusion depends on time to and grade of recanalization, mismatch, and collateralization. These results indicate that multimodal stroke imaging is helpful to guide therapy decisions and to indicate patients amenable for mechanical recanalization.

[Silent brain infarcts]. / Klinisch stumme Hirninfarkte.

Silent brain infarctions are frequently found by modern cerebral imaging. Up to 30% of persons without a clinical history of stroke were found to have silent brain infarction in epidemiological studies. "Silent" refers to ischemic brain lesions for which no matching clinical syndrome can be found based on history or clinical investigation. Age, education, and ethnic background have a strong impact on noticing and reporting stroke symptoms. The current clinical definition of stroke is insensitive for cognitive deficits which can also be caused by brain infarctions. The majority of silent brain infarctions are localized in the subcortical white matter of the brain; however, about 10% of silent brain infarctions are cortical. Silent brain infarctions are strongly associated with stroke risk factors and comorbidities that are known to cause clinically overt stroke. Silent brain infarctions are 5 to 10 times more frequent than clinically overt strokes. Silent brain infarctions as defined by DWI lesions on MRI imaging are a frequent finding during operative or interventional procedures and their monitoring may help improve the respective techniques in order to decrease the risk of periprocedural stroke.

[Susac syndrome: an interdisciplinary challenge]. / Susac-Syndrom : Eine interdisziplinäre Herausforderung.

Susac syndrome, named after John Susac, the first to describe this condition, is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. Although certainly a rare disease, Susac syndrome needs to be considered in the differential diagnosis of a broad variety of diseases. The pathogenesis is not yet clear. Autoimmune processes leading to damage and inflammation-related occlusion of the microvessels in brain, retina, and inner ear are thought to play a causal role. The diagnosis is based primarily on the clinical presentation, the documentation of branch retinal artery occlusion by fluorescence angiography, and characteristic findings on cerebral MRI. Usually, immunosuppressive therapy is required, though controlled therapy trials are missing so far. The intention of this review article is to raise awareness of this disease among neurologists, psychiatrists, ophthalmologists, and ENT specialists as a high number of unreported cases probably exists. Accordingly, the focus is on the clinical presentation and the diagnostic approach.

An unusual case of neuralgic amyotrophy presenting with bilateral phrenic nerve and vocal cord paresis.

BACKGROUND: Neuralgic amyotrophy (brachial plexus neuropathy, brachial plexus neuritis, or Parsonage-Turner syndrome) is an uncommon inflammatory condition typically characterized by acute and severe shoulder pain followed by paresis with muscle weakness and atrophy of the upper limb or shoulder girdle. We report an unusual clinical manifestation of neuralgic amyotrophy, namely bilateral phrenic nerve palsy with concomitant laryngeal paresis. CASE REPORT: A 55-year-old male presented with orthopnea and aphonia after an episode of bilateral shoulder pain preceded by an upper respiratory tract infection. Spirometry, chest X-ray and videolaryngoscopy revealed bilateral and simultaneous paresis of the diaphragm and the vocal cords. Clinical examination at admission and at the 2-month follow-up did not show upper limb weakness or atrophy, except for a mild atrophy of the right supraspinatus muscle. An electromyography of the upper limb muscles and nerve conduction studies did not reveal signs of denervation. Analysis of the cerebrospinal fluid and an MRI of the neuraxis were unremarkable. After treatment with prednisolone, vocal cord function markedly improved within 8 weeks, whereas paresis of the diaphragm persisted. CONCLUSION: Shoulder pain followed by diaphragmatic paralysis with dyspnea and hoarseness may be a manifestation of neuralgic amyotrophy even if upper limb or shoulder girdle palsies are absent.

The outer arterial wall layers are primarily affected in spontaneous cervical artery dissection.

OBJECTIVE: To evaluate the macroscopic and microscopic phenotype of the distal superficial temporal artery (STA) in patients with spontaneous cervical artery dissection (sCAD, n = 14). Arteries of accident victims, free of clinically apparent vascular disease, served as reference samples (n = 9). METHODS: Specimens of distal STA branches were obtained by biopsy or at autopsy. Their fine and ultrafine structure was documented by close-up photography of native STA branches, light microscopy, and electron microscopy in a case-control study. RESULTS: STA specimens from patients with sCAD revealed pathologic changes mainly in the adventitial and medial layers. In these areas, vacuolar degeneration and fissuring were associated with neoangiogenesis of capillaries and microscopic erythrocyte extravasation into the connective tissue. In addition, some specimens showed overt microhematomas close to the medial/adventitial border visible at low magnification. The reference arteries showed virtually no pathologic changes in the outer arterial layers. CONCLUSION: Bearing in mind that the STA is only a surrogate for the cervical arteries affected by sCAD, we propose the following pathogenetic model. We hypothesize that sCAD affects primarily the outer arterial layers. The process starts with degenerative changes at the medial-adventitial border associated with neoangiogenesis of capillary vessels branching from vasa vasorum in the adventitia. Leakage of neoangiogenetic capillaries releases blood cells into the connective tissue and leads to formation of microhematomas along the medial/adventitial border, as well as disintegration of the medial and adventitial texture. Microhematomas might then cause successive rupture of multiple neoangiogenetic capillaries and vasa vasorum, ultimately resulting in dissection.

[Comprehensive stroke unit]. / Erweiterte Stroke-Unit.

The concept of a "comprehensive stroke unit" (in German: Erweiterte Stroke-Unit) is an additional structural option for those stroke units already certified in Germany. Its aim is to complement the semi-intensive management of stroke unit patients in Germany by early mobilisation and neuropsychological rehab procedures. This concept is recommended in many European countries as well. It is based on the proof of efficacy of the combined treatment package in several randomised controlled trials. According to the Helsingborg Declaration, every stroke patient in Europe should have access to a chain of care best provided by a comprehensive stroke unit. Both early mobilisation and rehabilitation treatment can be integrated and continued without creating an interface between the acute stroke unit and the general neurological or medical ward. The monitoring beds of the acute stroke unit and the non-monitoring "enhanced care" beds are located within the same geographical area of the hospital and are run as a comprehensive stroke care entity. Continuous management of the acute stroke patients by the same team on the same unit means an increase in quality of care, better usage of staff resources and an additional gain in time. The scientific background of the advantages of a comprehensive stroke unit is described as are the structural and staff requirements. The clientel particularly benefiting from treatment on wards with enhanced care beds is described, and the spectrum of treatment services is defined. This concept will be used as the basis for an add-on qualification of already certified German stroke units. An important step was to fit the requirements of the comprehensive stroke unit to the already existing facilities and their infrastructures. From an economic point of view, the comprehensive stroke unit is expected to be cost-effective, either balanced or even positive.

Neuroimaging in Susac's syndrome: focus on DTI.

BACKGROUND: Susac's syndrome is an underdiagnosed disease that is thought to occur mainly in young women. It is characterized by the triad of hearing loss, branch retinal artery occlusions, and encephalopathy with predominantly cognitive and psychiatric symptoms. Treatment consists of immunosuppressive therapy. Focal ischemic lesions in the central portion of the corpus callosum detectable by conventional MRI ("snowballs") are a typical feature of Susac's syndrome. The appearance of these lesions is not, however, correlated with the type and severity of the neuropsychological deficits. METHODS: Nine patients with Susac's syndrome, four men and five women, were investigated using Diffusion Tensor Imaging (DTI), a non-invasive technique for the detection of macro- and microstructural impairment of fiber integrity on the basis of normal values for the fractional anisotropy (FA). Patients were compared to a group of 83 healthy controls on a voxel-by-voxel basis. Several regions of interest were defined. RESULTS: Impairment of fiber integrity was found in every patient. As compared to the controls, every patient showed disruption of fiber integrity in the genu of the corpus callosum. Reduction of FA was found particularly in the prefrontal white matter. CONCLUSION: The type and severity of the encephalopathic symptoms in Susac's syndrome are much better represented by the prefrontal FA reductions detected by DTI than by the mostly sparse white matter abnormalities seen on conventional MRI. The fiber damage in the genu seems to be specific for patients with Susac's syndrome.

[Clinical relevance of normal and enlarged Virchow-Robin spaces]. / Klinische Bedeutung normaler und erweiterter Virchow-Robin-Räume.

Virchow-Robin spaces ensheathe the penetrating vessels of the brain. They communicate with the subpial space, are filled with interstitial fluid and contain a specific population of macrophages.Virchow-Robin spaces are a common finding in both CT and MR imaging. Recent radiologic studies have led to a concise definition of Virchow-Robin spaces.Virchow-Robin spaces appear isointense to cerebrospinal fluid on all imaging sequences. They are typically localised in the basal ganglia, subcortically or in the midbrain and pons. Enlarged Virchow-Robin spaces may appear as a single or multiple lesion(s). They may cause hydrocephalus in rare cases. Some studies indicate that enlarged Virchow-Robin spaces occur more frequently in elderly patients, in patients with arterial hypertension or CADASIL.In this review we illustrate the diagnostic criteria of normal and enlarged Virchow-Robin spaces and discuss their clinical relevance. Furthermore, we present an overview of the current knowledge on the anatomy, physiology and pathology of Virchow-Robin spaces.

Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function.

OBJECTIVE: C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). METHODS: We cross-sectionally examined 447 community-dwelling and stroke-free individuals from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study (mean age 63 years, 248 female). High-field MRI was performed in 321 of these subjects. Imaging measures included fluid-attenuated inversion recovery sequences for assessment of white matter hyperintensities, automated quantification of brain parenchyma volumes, and diffusion tensor imaging for calculation of global and regional white matter integrity, quantified by fractional anisotropy (FA). Psychometric analyses covered verbal memory, word fluency, and executive functions. RESULTS: Higher levels of hs-CRP were associated with worse performance in executive function after adjustment for age, gender, education, and cardiovascular risk factors in multiple regression analysis (beta = -0.095, p = 0.02). Moreover, higher hs-CRP was related to reduced global fractional anisotropy (beta = -0.237, p < 0.001), as well as regional FA scores of the frontal lobes (beta = -0.246, p < 0.001), the corona radiata (beta = -0.222, p < 0.001), and the corpus callosum (beta = -0.141, p = 0.016), in particular the genu (beta = -0.174, p = 0.004). We did not observe a significant association of hs-CRP with measures of white matter hyperintensities or brain atrophy. CONCLUSION: These data suggest that low-grade inflammation as assessed by high-sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function.