The role of intima-media-thickness, ankle-brachial-index and inflammatory biochemical parameters for stroke risk prediction: a systematic review.

BACKGROUND: Despite important advances in therapeutic approaches in stroke, the options of acute treatment are still limited. Primary prevention represents another potentially highly efficient strategy. For effective prevention the early detection of subjects at risk is of utmost importance. Coinciding with a change in current understanding of atherosclerosis as an inflammatory, cross-organ disease, new parameters to assess the individual risk are emerging. METHODS: Systematic review of the potential of selected parameters for prediction of cerebrovascular events beyond detection of traditional risk factors that might expand the repertoire of primary prevention programs in stroke. RESULTS: An absolute carotid intima-media thickness difference of 0.1 mm increases the future risk of stroke by 13-18%. An ankle-brachial index <0.9 was associated with a relative risk of 2.33 (95% CI 2.02-2.68) for stroke. In patients with acute stroke and ABI values < 0.9 the risk for a new vascular event is significantly increased (HR 2.1; 95% CI 1.6-2.8). Measurements of several molecular biomarkers may be used to predict future vascular events independently of traditional risk factors. CONCLUSIONS: Based on the data presented, there is clear evidence that measurement of the ankle-brachial index identifies subjects of increased stroke risk in primary and secondary care settings as well as of stroke recurrence in acute stroke.

Multimodal strategy in the successful implementation of a stroke unit in a community hospital.

OBJECTIVES: Thrombolysis in stroke remains underutilized in daily practice. We analyzed the impact of a multimodal strategy on the rate of thrombolysis and specific procedure times during the implementation of a community hospital stroke unit. MATERIAL AND METHODS: During a period of 2 years before and after implementation of a stroke unit, we prospectively recorded all patients with thrombolysis and specific procedure times. Calculated door-to-needle time (DNT), door-to-CT time (DCT) and CT-to-needle time (CNT) were analyzed. All structural changes before and after the implementation were analyzed. RESULTS: The number of patients with thrombolysis increased from 24 in 2005-2006 (4.8% of all admitted patients with ischemic stroke) to 95 in 2007-2008 (12.8%). DNT was significantly reduced from 62.2±36.1 to 38.5±22.2 min (P<0.001). DCT remained unchanged at 10.3±9.5 to 10.4±13.9 min (P=0.974), whereas CNT improved from 45.7±23.1 to 28.3±20.3 min (P=0.001). Several structural changes concerning staff, logistics, procedures and laboratory were identified which contributed to decreasing DNT. CONCLUSIONS: A multimodal strategy including several structural changes enables the successful implementation of a community hospital stroke unit offering rapid access to thrombolysis with a very short DNT.

Dynamics of intracranial venous flow patterns in patients with idiopathic intracranial hypertension.

OBJECTIVE: To examine the dynamics of intracranial venous flow patterns in patients with idiopathic intracranial hypertension (IIH). METHODS: Nonrandomized controlled trial analyzing the difference in cerebral perfusion in 13 IIH patients and 12 healthy controls using contrast-enhanced duplex sonography. In patients, an additional 3D gradient echo magnetic resonance venography (MRV) using a new technique was performed to quantify stenosis of the cerebral sinus. The cerebral perfusion parameters, including cerebral transit time (CTT) and time to peak (TTP), were analyzed. RESULTS: IIH patients had a higher BMI (29.3 [95% CI 26.4, 32.2] vs. 23.3 [95% CI 20.7, 25.9], p = 0.003) and an increased prevalence of headache, but all other clinical characteristics were comparable. The CTT did not differ significantly. The TTP was significantly longer in IIH patients compared to controls (8.5 [95% CI 7.6, 9.4] vs. 7.3 s [95% CI 6.3, 8.1], p = 0.04). Twelve of 13 (92%) IIH patients showed stenosis of the cerebral sinus. CONCLUSIONS: Our study is the first to report an altered cerebral venous flow in IIH patients compared to controls using a dynamic ultrasonographic technique. A simplified MRV technique confirms the high prevalence and reliable detection of venous stenosis in IIH patients.

Carotid- intima media thickness is independently associated with cognitive decline. The INVADE study.

OBJECTIVES: Increased carotid intima-media thickness (C-IMT) is a non-invasive marker of atherosclerosis and predicts vascular events. Moreover, increasing evidence suggests an association between carotid atherosclerosis and cognitive decline. The purpose of this study is to investigate the relationship between C-IMT and the development of cognitive impairment in a large population-based sample. METHODS: This study was based on the data of the participants of the INVADE (Intervention project on cerebrovascular diseases and dementia in the district of Ebersberg, Bavaria) project. Vascular risk factors, Geriatric depression scale (GDS) and "6 Item Cognitive Impairment Test" (6CIT) were evaluated at baseline and after 2 years. The relationship between C-IMT and cognitive impairment was analysed using multivariate logistic regression. RESULTS: Complete baseline data were available in 3386 subjects (mean age 67.7 [95% confidence interval (CI): 67.5, 68.0] years, 41% male). During follow-up, 174 subjects developed a new cognitive impairment. In the subgroup without cognitive impairment at baseline a significant association between cognitive decline after 2 years and elevated C-IMT at baseline could be detected with a significantly higher baseline C-IMT in those with cognitive decline (0.87 mm vs. 0.78 mm; p < 0.0001). After adjustment for various risk factors only age, GDS baseline 6CIT and C-IMT were independently associated with the development of a new cognitive impairment. CONCLUSIONS: Our data indicate that an increased carotid intima-media thickness predicts a cognitive decline in an elderly population without prevalent cognitive impairment.

[Somatic factors in cognitive impairment]. / Somatische Faktoren bei leichten kognitiven Störungen.

Mild cognitive impairment describes a cognitive decline greater than expected for an individual's age and education level that does not interfere significantly with activities of daily life. In the recent years concepts of "mild cognitive impairment" with divergent definitions have been discussed as potential preclinical forms of dementia. The etiology of cognitive impairment is heterogeneous and it can be promoted or caused by numerous somatic factors. Relevant somatic factors include hypertension, diabetes mellitus, heart failure, chronic obstructive airways disease and bronchial asthma. Cognitive impairment may be facilitated by hypercholesterolemia, chronic renal failure, hypothyroidism, testosterone deficiency, minimal hepatic encephalopathy, HIV- and hepatitis C-infection. Knowledge and diagnosis of these somatic factors is essential in cognitive impairment, as diligent treatment may lead to improve cognitive performance and postpone the manifestation of dementia.

[Secondary prevention of stroke according to PRoFESS and SPARCL]. / Sekundärprophylaxe des Schlaganfalls nach PRoFESS und SPARCL.

Stroke is still the leading cause of long-term major disability in developed countries, although several improvements have been achieved in acute stroke therapy (e.g. thrombolysis, stroke-unit treatment,etc.). Therefore, an effective secondary prevention - guided by the etiology and risk factors of stroke - is of particular importance to reduce stroke morbidity. Recently, two important studies (SPARCL and PRoFESS) analyzed the significance of statin therapy as well as the efficacy of different antiplatelet therapies for secondary stroke prevention. In this review we summarize the results and discuss the implications of these findings - including the most recent data - for stroke prevention.

Bilateral grey-matter increase in the putamen in primary blepharospasm.

BACKGROUND: Primary blepharospasm is a focal dystonia characterised by excessive involuntary closure of the eyelids. The pathophysiology of primary blepharospasm is unresolved. AIM: To pinpoint grey-matter changes that are associated with primary blepharospasm. METHODS: 16 right-handed patients with primary blepharospasm (mean age 67.4 (SD 4.3) years; 12 women) were compared with 16 healthy volunteers matched for sex and age. High-resolution T1-weighted magnetic resonance imaging of each participant was obtained and analysed by voxel-based morphometry, a method to detect regionally specific differences in grey matter between patients and control group. To evaluate whether the identified grey-matter changes were correlated with the duration of primary blepharospasm or botulinum neurotoxin treatment (BoNT), separate regression analyses were carried out. RESULTS: In patients with primary blepharospasm, grey-matter increase in the putamina was observed, whereas regression analyses did not indicate a correlation between grey-matter increases and the duration of primary blepharospasm or BoNT. Grey-matter decrease was detected in the left inferior parietal lobule; here regression analyses of grey-matter decrease showed a significant (p = 0.013) correlation of grey-matter decrease with the duration of BoNT. CONCLUSIONS: The data suggest structural changes in primary blepharospasm and point to a crucial role of the putamen for the pathophysiology of this focal dystonia.

Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity.

BACKGROUND: Chlamydia pneumoniae (Cp) infection has been associated with atherosclerosis and has been proposed as a possible additional cardiovascular risk factor. However, the relationship between Cp seropositivity and the progression of early carotid atherosclerosis is not unequivocally clarified. METHODS AND RESULTS: We evaluated the association between serological detection of Cp IgG and/or IgA antibodies and the progression of the intima-media thickness (IMT) of the common carotid artery using duplex ultrasonography in a prospective study with a follow-up of 3 years in 272 consecutive patients with cerebrovascular disease. Cp-seropositive patients showed a significantly enhanced progression of the IMT even after adjustment for other cardiovascular risk factors (0.12 mm/y [95% CI 0.11 to 0.14] versus 0.07 mm/y [0.05 to 0.09]; P:<0.005). Patients with increased C-reactive protein (>/=0.5 mg/dL) and Cp seropositivity showed the most pronounced IMT progression. Multivariate regression analysis revealed Cp seropositivity to be an independent risk factor for progression of early carotid atherosclerosis. Cox proportional-hazard regression analysis demonstrated a significantly increased rate of cerebrovascular and cardiovascular events in patients with Cp seropositivity, particularly in patients with increased C-reactive protein levels. CONCLUSIONS: Our data support the importance of chronic inflammation and infection for the early stages of atherosclerotic development.

Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke.

OBJECTIVE: To evaluate the prognostic impact of early pathologic sympathetic activation after stroke. METHODS: The authors examined 112 consecutive patients (mean age, 69 years; 60 men) with their first brain infarction. A pathologic sympathetic activation was presumed if the initial norepinephrine level exceeds 300 pg/mL. In addition, involvement of the insular cortex, nighttime blood pressure changes, and several cardiovascular risk factors were determined. One-year outcome measures were mortality rate, cardiovascular and cerebrovascular events, and activities of daily living (Barthel index and Rankin score). RESULTS: Norepinephrine levels greater than 300 pg/mL, nighttime blood pressure increases, and insular involvement were associated with a lower Barthel index (p < 0.005) at the 1-year follow-up. By stepwise logistic regression analysis, insular infarction, serum norepinephrine concentration, right-sided infarction, and nighttime blood pressure increase were significant and independent predictors of an unfavorable functional outcome. Cox regression analysis showed a higher rate of cardiovascular and cerebrovascular events (hazard ratio, 2.9; 95% CI, 1.07; 6.83; p < 0.04) in patients with initially increased norepinephrine concentrations. CONCLUSIONS: The involvement of the insular cortex, the occurrence of a pathologic nighttime blood pressure increase, and an initially increased serum norepinephrine concentration are independent predictors of poor long-term outcome.

Cardiac troponin I plasma levels for diagnosis and quantitation of perioperative myocardial damage in patients undergoing coronary artery bypass surgery.

OBJECTIVE: The definition of a reliable and generally accepted diagnostic standard for perioperative myocardial damage is desirable. Cardiac troponin I (cTnI) is highly specific for myocardial tissue and can be measured rapidly. The aim of our study was to evaluate the diagnostic potential of cTnI for myocardial lesions in patients undergoing coronary artery bypass surgery (CABG). METHODS: A total of 119 patients with diffuse coronary artery disease were operated on using blood cardioplegia. Serial blood samples drawn before and after surgery were analyzed for the activity of creatine kinase MB isoenzyme (CKMB) and the concentrations of CKMB mass, cardiac troponins T and I. On the basis of the biochemical results (except cTnI) and the findings of electrocardiography/echocardiography, patients were classified and cTnI was studied for each group separately: group I, minor myocardial damage; group II, non-transmural infarction; group III, transmural infarction; and group IV, preoperative non-transmural infarction. RESULTS: In 87 patients of group I (73.1%) cTnI levels remained low; 19 patients (16.0%) were assigned to group II, 8 patients (6.7%) to group III, and 5 patients (4.2%) to group IV. For discrimination of patients without and with perioperative myocardial infarction (PMI) by one cTnI determination, the use of cutoff values of 6.5 ng/ml at 8 h, 9.8 ng/ml at 12 h, and 11.6 ng/ml at 24 h after aortic unclamping resulted in a diagnostic efficiency of 88, 94 and 98%). Especially, a cTnI value at 24 h had a sensitivity of 100% and a specificity of 97%. Cardiac troponin levels at 24 h were found to correlate closely with the well-recognized 2-48 h area-under-the-curve (P < 0.0001; R = 0.993), making serial determinations unnecessary. CONCLUSIONS: cTnI qualifies as a marker for diagnosis of PMI and quantitation of the amount of myocardial damage, because of the availability of a quick diagnostic test with high specificity, the high diagnostic efficiency, and especially the sufficient information gained by a single determination 24 h after aortic unclamping.

Voxel-based morphometry in individual patients: a pilot study in early Huntington disease.

BACKGROUND AND PURPOSE: Voxel-based morphometry (VBM) has proved a powerful method to detect subtle changes of gray matter (GM) at the group level but the role of VBM for the detection of GM changes in single subjects, especially in those with suspected neurodegenerative disorder, remains uncertain. Here, we performed single subject analyses in 22 patients in early stages of Huntington disease (HD), a neurodegenerative disorder with a well-known and characteristic pattern of GM loss. MATERIALS AND METHODS: We applied an ANCOVA with age and gender as covariates and corrected for multiple statistical tests by false discovery rate (P < 0.05). Each patient was compared to 133 healthy controls. The same procedure was applied to 22 of the controls matched for age and gender in a pair-wise manner. RESULTS: Our analyses yielded biologically plausible results in HD patients in which GM decrease within the caudate nucleus could be identified in 15 of the 16 most affected patients while GM decrease was found in only 1 control subject. Lowering the size of the control group yielded comparable results with 99 and 66 control subjects whereas sensitivity decreased with 33 control subjects. CONCLUSIONS: Our pilot study demonstrates a potential role of VBM for the detection of cerebral GM changes in single subjects with suspected neurodegenerative disorder.

Structural brain changes in tinnitus.

Tinnitus is a common but poorly understood disorder characterized by ringing or buzzing in the ear. Central mechanisms must play a crucial role in generating this auditory phantom sensation as it persists in most cases after severing the auditory nerve. One hypothesis states that tinnitus is caused by a reorganization of tonotopic maps in the auditory cortex, which leads to an overrepresentation of tinnitus frequencies. Moreover, the participation of the limbic system in generating tinnitus has been postulated. Here we aimed at identifying brain areas that display structural change in tinnitus. We compared tinnitus sufferers with healthy controls by using high-resolution magnetic resonance imaging and voxel-based morphometry. Within the auditory pathways, we found gray-matter increases only at the thalamic level. Outside the auditory system, gray-matter decrease was found in the subcallosal region including the nucleus accumbens. Our results suggest that reciprocal involvement of both sensory and emotional areas are essential in the generation of tinnitus.

DWI in transient global amnesia and TIA: proposal for an ischaemic origin of TGA.

There are conflicting reports concerning signal intensity changes in transient global amnesia (TGA) using diffusion weighted imaging (DWI). We prospectively analysed DWI signal intensity changes in TIA and TGA patients, and compared the clinical characteristics and risk factors of both groups. Using DWI and conventional T1 and T2 weighted turbo spin echo sequences, 28 patients with acute TGA (13 men, mean age 61.5 years) and 74 TIA patients (47 men, mean age 62.4 years) were studied within 48 hours after symptom onset. Every patient underwent an intensive diagnostic investigation. In 10/28 (36%) of the TGA patients and 21/74 (28%) of the TIA patients, DWI signal intensity changes occurred. The time to DWI and the duration of symptoms were comparable in TIA and TGA patients. Overall, TIA patients showed an increased prevalence of vascular risk factors compared with TGA patients. In the TGA group, patients with abnormal DWI showed carotid atherosclerosis significantly more frequently. Based on our data, we suggest that the aetiology of TGA could be explained by an ischaemic event; due to arterial thrombembolic ischaemia in one subgroup, particularly in those patients with increased vascular risk factors, and due to venous ischaemia in another subgroup with valsalva-like activities before symptom onset.

[Doppler sonography suggesting fulminant aortic dissection in initial middle cerebral artery infarction]. / Dopplersonographie mit Hinweis auf fulminante Aortendissektion bei initialem Mediainfarkt.

Acute aortic dissection is a cardiovascular emergency with a wide spectrum of clinical symptoms making the diagnosis difficult if the leading symptom of thoracic pain is not present. In up to 10% of cases an ischemic stroke may be the first clinical sign. We report a patient with a middle cerebral artery infarction in whom an abnormal signal in the extracranial Doppler sonography revealed the first hint of an aortic dissection. Before the diagnosis could be verified, the patient died due to electromechanical decoupling; autopsy showed an extensive aortic dissection with cardiac tamponade. Based on this case report, we review special problems of diagnosis and therapy in aortic dissection with primary cerebrovascular manifestation.

[Fugue and suicide]. / Fugue und Suizid.

The existence of dissociative fugue is doubted by many psychiatrists. We describe a 22-year-old patient who traveled about 600 km to Munich during a dissociative fugue and then exhibited an irreversible amnesia for a period of 24 h. There was a severe, clearly understandable conflict in the sense of a subjective stalemate situation which has been described as typical for dissociative fugue. The patient had a labile personality structure with insufficient coping strategies. It was possible to rule out other psychiatric or neurological disorders with sufficient certainty, and simulation was very unlikely. The conflict could not be satisfactorily solved, and the patient committed suicide 5 months later by jumping off a bridge.

Disturbance of venous flow patterns in patients with transient global amnesia.

Transient global amnesia (TGA) is an inability to form new memories. The pathophysiology and cause of TGA have not been defined. We examined the changes of internal jugular venous flow patterns in 21 patients with TGA and 21 age-matched and sex-matched controls using duplex ultrasonography during two Valsalva manoeuvres (blocking venous return through the superior vena cava). During both manoeuvres a retrograde flow component was seen significantly more frequently in the TGA group than in the controls. Ten patients reported Valsalva-like activities preceding TGA. In these patients a retrograde flow component took place more frequently than in those who did not report preceding Valsalva-like activities. Our results lend support to the hypothesis that TGA may be attributable to venous congestion, and consequent venous ischaemia to bilateral diencephalic or hippocampal structures.

Obstacles in the diagnosis and treatment of syphilitic amyotrophy.

The authors describe a case of syphilitic amyotrophy in a 37-year-old man presenting with subacute progressive painless weakness in the right arm. Syphilitic amyotrophy is still an existing differential diagnosis of painless and progressive weakness. The authors explore potential obstacles in the diagnostic workup and finding of adequate therapy.