Internal carotid artery blood flow and pulsatility index in cognitively impaired people with chronic heart failure.

AIMS: Mild cognitive impairment and dementia are common and serious co-morbidities in people with chronic heart failure (HF) as they increase hospitalization rates, mortality and health care costs. Upon other factors, dysregulated cerebral perfusion might contribute to brain pathology. We aimed to evaluate the association of non-invasively measured blood flow (BF) and pulsatility index (PI) of the internal carotid artery (ICA) with (i) chronic HF parameters, (ii) brain morphologic measures and (iii) cognitive impairment. METHODS AND RESULTS: This post-hoc analysis of the observational, prospective Cognition.Matters-HF study included 107 chronic HF patients without atrial fibrillation or carotid artery stenosis (aged 63 ± 10 years; 19% women). Using extracranial sonography, we measured ICA-BF and ICA-PI 1.5 cm distal of the carotid bifurcation. Brain magnetic resonance imaging was performed on a 3-Tesla scanner to quantify cerebral atrophy, hippocampal atrophy and white matter hyperintensities. Extensive neuropsychological testing tested the cognitive domains intensity of attention, visual/verbal memory and executive function (including its subdomains selectivity of attention, visual/verbal fluency and working memory) using a comprehensive test battery. (i) Neither ICA-BF (median 630 (quartiles 570, 700) mL/min) nor ICA-PI (1.05 (0.96. 1.23)) related to left ventricular ejection fraction, left atrial volume index or NT-proBNP. (ii) Higher ICA-PI (r = 0.25; P = 0.011), but not ICA-BF (r = 0.08; P = 0.409), associated with increased volume of white matter hyperintensities beyond ageing, while neither ICA-PI nor ICA-BF related to cerebral or hippocampal atrophy indices. (iii) ICA-BF, but not ICA-PI, positively correlated with age-adjusted T-scores of executive function (r = 0.38; P < 0.001) and its subdomains working memory (r = 0.32; P < 0.001) and visual/verbal fluency (r = 0.32; P < 0.001). In a multivariate linear model of executive function, only ICA-BF (T = 3.79; P < 0.001), but not HF or magnetic resonance imaging parameters, remained a significant correlate of executive function. CONCLUSIONS: ICA-BF and ICA-PI, measured in broadly available extracranial sonography, independently related to measures of functional and structural brain changes in people with chronic HF, respectively. Due to limitations of this cross-sectional approach without a healthy control group, larger controlled longitudinal studies are needed to further elucidate the role of ICA-BF dysregulation and its implication for clinical care in this vulnerable cohort.

Reduced midbrain raphe echogenicity in patients with fibromyalgia syndrome.

OBJECTIVES: The pathogenesis of fibromyalgia syndrome (FMS) is unclear. Transcranial ultrasonography revealed anechoic alteration of midbrain raphe in depression and anxiety disorders, suggesting affection of the central serotonergic system. Here, we assessed midbrain raphe echogenicity in FMS. METHODS: Sixty-six patients underwent transcranial sonography, of whom 53 were patients with FMS (27 women, 26 men), 13 patients with major depression and physical pain (all women), and 14 healthy controls (11 women, 3 men). Raphe echogenicity was graded visually as normal or hypoechogenic, and quantified by digitized image analysis, each by investigators blinded to the clinical diagnosis. RESULTS: Quantitative midbrain raphe echogenicity was lower in patients with FMS compared to healthy controls (p<0.05), but not different from that of patients with depression and accompanying physical pain. Pain and FMS symptom burden did not correlate with midbrain raphe echogenicity as well as the presence and severity of depressive symptoms. CONCLUSION: We found reduced echogenicity of the midbrain raphe area in patients with FMS and in patients with depression and physical pain, independent of the presence or severity of pain, FMS, and depressive symptoms. Further exploration of this sonographic finding is necessary before this objective technique may enter diagnostic algorithms in FMS and depression.

Red flags for a concomitant giant cell arteritis in patients with vertebrobasilar stroke: a cross-sectional study and systematic review.

Giant cell arteritis (GCA) may affect the brain-supplying arteries, resulting in ischemic stroke, whereby the vertebrobasilar territory is most often involved. Since etiology is unknown in 25% of stroke patients and GCA is hardly considered as a cause, we examined in a pilot study, whether screening for GCA after vertebrobasilar stroke might unmask an otherwise missed disease. Consecutive patients with vertebrobasilar stroke were prospectively screened for GCA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, and halo sign of the temporal and vertebral artery on ultrasound. Furthermore, we conducted a systematic literature review for relevant studies. Sixty-five patients were included, and two patients (3.1%) were diagnosed with GCA. Patients with GCA were older in age (median 85 versus 69 years, p = 0.02). ESR and CRP were significantly increased and hemoglobin was significantly lower in GCA patients compared to non-GCA patients (median, 75 versus 11 mm in 1 h, p = 0.001; 3.84 versus 0.25 mg/dl, p = 0.01, 10.4 versus 14.6 mg/dl, p = 0.003, respectively). Multiple stenoses/occlusions in the vertebrobasilar territory affected our two GCA patients (100%), but only five (7.9%) non-GCA patients (p = 0.01). Our literature review identified 13 articles with 136 stroke patients with concomitant GCA. Those were old in age. Headache, increased inflammatory markers, and anemia were frequently reported. Multiple stenoses/occlusions in the vertebrobasilar territory affected around 70% of stroke patients with GCA. Increased inflammatory markers, older age, anemia, and multiple stenoses/occlusions in the vertebrobasilar territory may be regarded as red flags for GCA among patients with vertebrobasilar stroke.

Corrigendum: Are Cerebral White Matter Lesions Related to the Presence of Bilateral Internal Carotid Artery Stenosis or to the Length of Stenosis Among Patients With Ischemic Cerebrovascular Events?

[This corrects the article DOI: 10.3389/fneur.2019.00919.].

Symptomatic vs. Asymptomatic 20-40% Internal Carotid Artery Stenosis: Does the Plaque Size Matter?

Background: Around 9-15% of ischemic strokes are related to internal carotid artery (ICA)-stenosis ≥50%. However, the extent to which ICA-stenosis <50% causes ischemic cerebrovascular events is uncertain. We examined the relation between plaque cross-sectional area and length and the risk of ischemic stroke or TIA among patients with ICA-stenosis of 20-40%. Methods: We retrospectively identified patients admitted to the Department of Neurology, University Hospital of Würzburg, from January 2011 until September 2016 with ischemic stroke or TIA and concomitant ICA-stenosis of 20-40%, either symptomatic or asymptomatic. Plaque length and cross-sectional area were assessed on ultrasound scans. Results: We identified 41 patients with ischemic stroke or TIA and ICA-stenosis of 20-40%; 14 symptomatic and 27 asymptomatic. The plaque cross-sectional area was significantly larger among symptomatic than asymptomatic ICA-stenosis; median values (IQR) were 0.45 (0.21-0.69) cm2 and 0.27 (0.21-0.38) cm2, p = 0.03, respectively. A plaque cross-sectional area ≥0.36 cm2 had a sensitivity of 71% and a specificity of 76% for symptomatic compared with asymptomatic ICA-stenosis. In a sex-adjusted multivariate logistic regression, a plaque cross-sectional area ≥0.36 cm2 and a plaque length ≥1.65 cm were associated with an OR (95% CI) of 5.54 (1.2-25.6), p = 0.028 and 1.78 (0.36-8.73), p = 0.48, respectively, for symptomatic ICA-stenosis. Conclusion: Large plaques might increase the risk of ischemic stroke or TIA among patients with low-grade ICA-stenosis of 20-40%. Sufficiently powered prospective longitudinal cohort studies are needed to definitively test the stroke risk stratification value of carotid plaque length and cross-sectional area in the setting of current optimal medical treatment.

Are Cerebral White Matter Lesions Related to the Presence of Bilateral Internal Carotid Artery Stenosis or to the Length of Stenosis Among Patients With Ischemic Cerebrovascular Events?

Background and purpose: Previous studies delivered contradicting results regarding the relation between the presence of an internal carotid artery stenosis (ICAS) and the occurence of white matter lesions (WMLs). We hypothesize that special characteristics related to the ICAS might be related to the WMLs. We examined the relation between the presence of bilateral ICAS, the degree and length of stenosis and ipsi-, contralateral as well as mean white matter lesion load (MWMLL). Methods: In a retrospective cohort, patients with ischemic stroke or transient ischemic attack (TIA) as well as ipsi- and/or contralateral ICAS were identified. The length and degree of ICAS, as well as plaque morphology (hypoechoic, mixed or echogenic), were assessed on ultrasound scans and, if available, the length was also measured on magnetic resonance angiography (MRA) scans, and/or digital subtraction angiography (DSA). The WMLs were assessed in 4 areas separately, (periventricular and deep WMLs on each hemispherer), using the Fazekas scale. The MWMLL was calculated as the mean of these four values. Results: 136 patients with 177 ICAS were identified. A significant correlation between age and MWMLL was observed (Spearman correlation coefficient, ρ = 0.41, p < 0.001). Before adjusting for other risk factors, a significantly positive relation was found between the presence of bilateral ICAS and MWMLL (p = 0.039). The length but not the degree of ICAS showed a very slight trend toward association with ipsilateral WMLs and with MWMLL. In an age-adjusted multivariate logistic regression with MWMLL ≥2 as the outcome measure, atrial fibrillation (OR 3.54, 95% CI 1.12-11.18, p = 0.03), female sex (OR 3.11, 95% CI 1.19-8.11, p = 0.02) and diabetes mellitus (OR 2.76, 95% CI 1.16-6.53, p = 0.02) were significantly related to WMLs, whereas the presence of bilateral stenosis showed a trend toward significance (OR 2.25, 95% CI 0.93-5.45, p = 0.074). No relation was found between plaque morphology and MWMLL, periventricular, or deep WMLs. Conclusion: We have shown a slight correlation between the length of stenosis and the presence of WMLs which might be due to microembolisation originating from the carotid plaque. However, the presence of bilateral ICAS seems also to be related to WMLs which may point to common underlying vascular risk factors contributing to the occurrence of WML.

Atypical presentation of giant cell arteritis in a patient with vertebrobasilar stroke: A case report.

RATIONALE: Giant cell arteritis (GCA) is known to present with typical manifestations like temporal headache and visual abnormalities. However, several cases with atypical manifestations were reported. Stroke occurs in 3% to 7% of patients with GCA. PATIENT CONCERNS: A 67-year-old male patient with known hypertension presented with somnolence, disorientation and mild bilateral limb ataxia. The magnetic resonance imaging showed multiple acute infarctions in the territory of the vertebrobasilar system with occlusion of the left vertebral artery. DIAGNOSIS: Ten months later, during a routine neurovascular follow-up, recanalization of the left vertebral artery was observed and a hypoechoic concentric "halo" sign around both vertebral arteries, mainly on the left side was evident. On further examination of the superficial temporal artery, a hypoechoic concentric "halo" sign was also found, which-along with increased inflammatory markers-raised suspicion about GCA. Classical GCA features like headache, temporal tenderness or amaurosis fugax were not present. Repeated in-depth diagnostic work-up including 48 hours Holter-ECG did not reveal another stroke etiology. INTERVENTIONS: Intravenous Methylprednisolone 250 mg/d was immediately started and after 6 days the dose was tapered to 80 mg/d. The patient was discharged on a tapering scheme with the recommendation to start azathioprine. Additionally, we placed the patient on acetylsalicylic acid 100 mg/d and clopidogrel 75 mg/d. However, the patient was not compliant to treatment; he stopped prednisolone early and did not start azathioprine. OUTCOMES: The inflammatory markers were markedly reduced at the beginning of the treatment. After stopping the immunosuppressive medications, the inflammatory markers were once again increased. Three months later, the patient developed bilateral middle cerebral artery and right occipital lobe infarctions. LESSONS: In patients with cryptogenic vertebrobasilar strokes, GCA may be considered in the differential diagnosis, especially if the inflammatory markers are increased.

Structural abnormality of the substantia nigra in children with attention-deficit hyperactivity disorder.

BACKGROUND: Structural abnormality of the substantia nigra can be detected by transcranial sonography in neuropsychiatric disorders such as Parkinson disease and restless legs syndrome. We investigated echogenicity of the substantia nigra as a potential structural marker for dysfunction of the nigrostriatal dopamine system in children with attention-deficit hyperactivity disorder (ADHD). METHODS: We used a blinded design and determined echogenicity of the substantia nigra by use of transcranial sonography in 22 children with ADHD and 22 healthy controls matched for age and sex. RESULTS: The echogenic substantia nigra area was significantly larger in ADHD patients than in healthy controls (F(1,42) = 9.298, p = 0.004, effect size = 0.92). We found no effects of age or sex. LIMITATIONS: Owing to a lack of dimensional assessment, we could not analyze the correlation between echogenicity and clinical symptoms. CONCLUSION: Our results support the hypothesis that the nigrostriatal dopaminergic system is abnormal in children with ADHD.

Substantia nigra echogenicity: A structural correlate of functional impairment of the dopaminergic striatal projection in Parkinson's disease.

Transcranial sonography (TCS) reveals abnormal spatial extension of substantia nigra (SN) echogenicity in a high proportion of patients with Parkinson's disease (PD). It has been proposed that this abnormality represents a structural trait that is mechanistically distinct from degeneration of dopaminergic nigrostriatal projection neurons. We sought to clarify the relationship between sonographic abnormalities of SN and dysfunction of striatal dopaminergic neurotransmission. We studied 50 patients with PD. The spatial extension of the echogenic SN area was compared with the activity of presynaptic striatal dopamine reuptake transporters, assessed in the same patients by I-123-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT) single-photon emission computed tomography (SPECT). Extension of echogenic SN area correlated (inversely) with striatal activity of presynaptic dopamine reuptake transporter in PD patients (R = -0.417; P = 0.003) and with the equivalent levodopa dose (R = 0.380; P = 0.006; linear regression analysis). Findings support the hypothesis that in PD abnormal extension of echogenic SN area provides a direct structural marker of degeneration of SN neurons. Therefore, in PD, TCS and beta-CIT assess pathophysiologically related phenomena.

Determination of ventricular diameters in multiple sclerosis patients with transcranial sonography (TCS)--a two year follow-up study.

CONTEXT: Brain atrophy is an indicator of diffuse brain pathology that appears even in the early stages of multiple sclerosis (MS). Magnetic resonance imaging (MRI) techniques used in clinical trials suggest a correlation between ventricular enlargement and axonal pathology and clinical disability in MS. OBJECTIVE: To evaluate by transcranial sonography (TCS) and MRI ventricular diameters in order to assess prospectively the development of brain atrophy in MS. SETTING: MS outpatient clinic of a university hospital. PATIENTS AND METHODS: 38 MS patients (27 females, 11 males) were followed up for 2 years. Ventricular diameters (third ventricle, right and left lateral ventricle) were determined by TCS at baseline, 12 and 24 months and correlated with clinical disability (Expanded Disability Status Scale, EDSS), and the Multiple Sclerosis Functional Composite Score (MSFC). MRI was performed at study entry and after two years. MAIN OUTCOME MEASURE: Correlation of ventricular diameters measured by TCS and MRI with assessment of clinical disability in MS patients at baseline and after two years. RESULTS: TCS and MRI measurements especially of third ventricle diameter matched closely at study entry and after two years (r = 0.9; p < 0.0001). At all time points the width of the third ventricle was significantly correlated with clinical disability (EDSS: r = 0.6, p < 0.01; MSFC: r = -0.6, p < 0.02). In the follow-up over 2 years there was an increase of the width of the third ventricle in comparison with study entry (p < 0.002). Increase of third ventricular width at study entry was associated with higher EDSS levels after 2 years (p = 0.01). CONCLUSION: Assessment of ventricular diameters by TCS is a reliable tool with which to monitor brain atrophy in the longitudinal follow-up of MS patients. Because TCS is a simple, inexpensive, non-invasive and generally available bedside-test it may be used in clinical practice as well as in therapeutic trials to assess brain atrophy.

Prognostic and diagnostic value of global cerebral blood flow volume and cerebral transit time in acute stroke.

Conventional duplex sonography is a well-established method for the assessment of the brain-supplying arteries in acute stroke. However, ultrasound (US) remains inconclusive in a significant number of stroke patients. Recently, two new US parameters, the cerebral transit time (cTT) and the global cerebral blood flow volume (CBF), have been introduced. In the present study, we investigated the diagnostic and prognostic value of both parameters in stroke patients. Conventional duplex examinations of the extra- and intracranial brain-supplying arteries and measurement of cTT and CBF were performed in 50 consecutive stroke patients within 24 h after symptom onset and compared with US findings in 22 age-matched healthy controls. Neurological deficits and the degree of disability were graded using several stroke scores, and were re-evaluated for outcome measure after 1 year. CBF and cTT were not assessable in 26% and 20% of the patients, respectively. Compared with the healthy control group, stroke patients showed a significant reduction of CBF and prolongation of cTT. More than 50% of patients with otherwise normal routine duplex examination had abnormal CBF or cTT findings. Furthermore, there was a strong correlation between the reduction of global CBF and the outcome after 1 year. Sonographic assessment of the CBF and cTT are additional parameters that might increase the diagnostic sensitivity of US in stroke patients, and may have prognostic relevance.