Pattern of Activated Pathways and Quality of Collateral Status in Patients with Symptomatic Internal Carotid Artery Occlusion.

BACKGROUND: Internal carotid artery occlusion (ICAO) is an important risk factor for stroke. Cerebral hemodynamics in patients with ICAO depends on the individual capacity to activate sufficient collateral pathways. Therefore, the assessment of intracranial collaterals is essential for the acute and long-term management of these patients and accurate estimation of further stroke risk. METHODS: Acute stroke patients with unilateral ICAO were prospectively enrolled. We assessed the following collaterals by transcranial color-coded sonography (TCCS): the anterior and posterior communicating artery (ACoA, PCoA), the ophthalmic artery (OA), and leptomeningeal collaterals of the posterior cerebral artery (LMC). We subdivided the flow pattern of the Doppler spectrum in the middle cerebral artery (MCA) into 3 categories: (1) good, (2) moderate, and (3) bad according to the hemodynamic effects on the ipsilateral MCA flow. Finally, we compared the individual TCCS results with the stroke pattern detected on CT or MRI scan. RESULTS: One hundred thirteen patients (age 66 ± 12 years; -female 24) were included. The collateral status was good, moderate, and bad in 59 (52%), 37 (33%), and 17 (15%) patients, respectively. The ACoA collateral was most frequently activated (81%), followed by the OA (63%), the PCoA (53%), and the LMC (22%). The quality of the collateral status was determined by the type (p = 0.0003) but not by the number (p = 0.19) of activated collateral pathways. Good collateral function was highly associated with primary collaterals (ACoA > PCoA). Best parameter for a good collateral status was an antegrade flow in the OA, indicating a high blood supply via the communicating arteries. CONCLUSIONS: TCCS allows the assessment of intracranial collaterals and their hemodynamic capacity. Prevalence of collateral sufficiency in ICAO seems to be higher than previously reported. ACoA cross flow is essential for the optimal hemodynamic compensation of ICAO. Antegrade OA flow indicates good collateral status.

Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders. METHODS: At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications. RESULTS: Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine. CONCLUSIONS: US and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.

Long-chain omega-3 fatty acids improve brain function and structure in older adults.

Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.

Effect of fingolimod (FTY720) on cerebral blood flow, platelet function and macular thickness in healthy volunteers.

AIM: Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers. METHODS: The study included 88 healthy volunteers who received fingolimod 0.5 mg or 1.25 mg or matched placebo over a period of 4 weeks. Transcranial colour coded sonography was performed to measure mean blood flow velocities, the platelet function was measured by the PFA-100® assay using a collagen/epinephrine cartridge and macular thickness was measured using optical coherence tomography. An assessment of non-inferiority of fingolimod vs. placebo was performed against a reference value (20% of the overall baseline value). RESULTS: All 88 randomized participants completed the study. At day 28 compared with baseline value, for 0.5 mg, 1.25 mg and placebo treatments, the mean middle cerebral artery blood flow velocity decreased by 4, 1 and 3.7 cm s(-1), respectively. The platelet function analyzer closure time increase was not significant (7.8, 7.5 and 10.4 s, respectively). The mean percentage change in the central foveal thickness from baseline for both eyes was below 3% for all groups. The safety profile of fingolimod in this study was found consistent with the previous reports. CONCLUSIONS: In healthy volunteers, the changes seen with both fingolimod doses were found to be within normal variability, non-inferior and comparable with those observed with placebo for all the pharmacodynamic parameters assessed.

Feasibility of a patient-oriented navigation programme for patients with lung cancer or stroke in Germany: Protocol of the CoreNAVI study.

BACKGROUND: Patient navigation programmes were introduced in the United States and recently gained interest in Germany, where the health care system is fragmented. Navigation programmes aim to decrease barriers to care for patients with age-associated diseases and complex care paths. Here we describe a feasibility study to evaluate a patient-oriented navigation model that was developed in a first project phase by integrating data about barriers to care, vulnerable patient populations and existing support services. METHODS: We designed a mixed-methods feasibility study that consists of two two-arm randomized controlled trials aligned with observational cohorts. The intervention group of the RCTs gets support by personal navigators for 12 months. The control group receives a brochure with regional support offers for patients and caregivers. The feasibility of the patient-oriented navigation model for two prototypic age-associated diseases, lung cancer and stroke, is evaluated with regard to its acceptance, demand, practicality and efficacy. This investigation includes process evaluation measures with detailed documentation of the screening and recruitment process, questionnaires about satisfaction with navigation, observant participation and qualitative interviews. Estimates of efficacy for patient-reported outcomes are obtained at three follow-up time points including satisfaction with care and health-related quality of life. Furthermore, we analyze health insurance data from patients of the RCT insured at a large German health insurance (AOK Nordost) to investigate heath care utilization, costs and cost effectiveness. TRIAL REGISTRATION: The study is registered at the German Clinical Trial Register (DRKS-ID: DRKS00025476).

No correlation of substantia nigra echogenicity and nigrostriatal degradation in Parkinson's disease.

BACKGROUND: Substantia nigra hyperechogenicity assessed by transcranial sonography is a typical finding in up to 90% of patients with idiopathic Parkinson's disease, although its value as a surrogate marker for disease progression in Parkinson's disease is controversial. (123) I-FP-CIT-single photon emission computed tomography (SPECT) represents an established paraclinical surrogate marker to quantify the nigrostriatal dopaminergic deficit in Parkinson's disease. Whereas most studies found no correlation between extent of substantia nigra echogenicity and the putaminal FP-CIT binding ratio, a more recent analysis reported opposite results. METHODS: In 92 patients with Parkinson's disease the substantia nigra echogenicity was compared with the putaminal FP-CIT binding ratio using an investigator-independent SPECT analysis protocol and with several clinical parameters. RESULTS: No correlation was found between the substantia nigra hyperechogenicity and the FP-CIT binding ratio or the disease severity. CONCLUSIONS: Substantia nigra hyperechogenicity does not reflect the degree of the nigrostriatal degeneration or the clinical state of the disease progression.

No cerebrocervical venous congestion in patients with multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is characterized by demyelination centered around cerebral veins. Recent studies suggested this topographic pattern may be caused by venous congestion, a condition termed chronic cerebrospinal venous insufficiency (CCSVI). Published sonographic criteria of CCSVI include reflux in the deep cerebral veins and/or the internal jugular and vertebral veins (IJVs and VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural response of the cerebral venous drainage. METHODS: We performed an extended extra- and transcranial color-coded sonography study including analysis of extracranial venous blood volume flow (BVF), cross-sectional areas, IJV flow analysis during Valsalva maneuver (VM), and CCSVI criteria. Fifty-six MS patients and 20 controls were studied. RESULTS: Except for 1 patient, blood flow direction in the IJVs and VVs was normal in all subjects. In none of the subjects was IJV stenosis detected. IJV and VV BVF in both groups was equal in the supine body position. The decrease of total jugular BVF on turning into the upright position was less pronounced in patients (173 +/- 235 vs 362 +/- 150 ml/min, p < 0.001), leading to higher BVF in the latter position (318 ml/min +/- 242 vs 123 +/- 109 ml/min; p < 0.001). No differences between groups were seen in intracranial veins and during VM. None of the subjects investigated in this study fulfilled >1 criterion for CCSVI. INTERPRETATION: Our results challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS. Future studies should elucidate the difference between patients and healthy subjects in BVF regulation.

Classification of Intracranial Stenoses: Discrepancies between Transcranial Duplex Sonography and Computed Tomography Angiography.

Transcranial color-coded duplex sonography (TCCS) and computed tomography angiography (CTA) are widely used to identify intracranial stenoses (ISs). We assessed concordance of IS grading between TCCS and CTA and proposed new TCCS criteria for severe IS ≥70%. One hundred two stroke patients (70 ± 13 y) with TCCS-identified IS were included. TCCS and CTA were performed within 24 h after admission. TCCS peak systolic velocity cutoffs for <50%/50%-69% stenoses were ≥155/≥220 cm/s (middle cerebral artery [MCA]-M1), ≥100/≥140 cm/s (MCA-M2), ≥120/≥155 cm/s (anterior cerebral artery [ACA]-A1), ≥100/≥145 cm/s (posterior cerebral artery [PCA]-P1 and PCA-P2), ≥90/≥120 cm/s (vertebral artery [VA]-V4) and ≥100/≥140 cm/s (basilar artery [BA]). Criteria for ≥70% stenoses were, despite variable flow velocities, post-stenotic flow alterations and/or leptomeningeal collateral flow. One hundred seventy-seven ISs were detected by TCCS. The number and grade (<50%/50%-69%/≥70%) of ISs were MCA 70 (39/19/12), BA 24 (9/11/4), ACA 21 (14/7/0), PCA 49 (29/15/5) and VA 13 (2/6/5). IS localization was confirmed by CTA in 84 of 177 cases (48%): MCA, 41/70 (59%); BA, 16/24 (67%); ACA 2/21, (10%); PCA, 17/49 (35%); VA, 8/13 (62%). Concordance between TCCS and CTA grading was (<50%/50%-69%/≥70%) 17%/19%/77%. TCCS and CTA exhibited substantial differences in the detection and grading of IS. Higher concordance rates for severe stenosis support our proposed TCCS criteria.

Delirium is associated with frequency band specific dysconnectivity in intrinsic connectivity networks: preliminary evidence from a large retrospective pilot case-control study.

BACKGROUND: Pathophysiological concepts in delirium are not sufficient to define objective biomarkers suited to improve clinical approaches. Advances in neuroimaging have revalued electroencephalography (EEG) as a tool to assess oscillatory network activity in neuropsychiatric disease. Yet, research in the field is limited to small populations and largely confined to postoperative delirium, which impedes generalizability of findings and planning of prospective studies in other populations. This study aimed to assess effect sizes of connectivity measures in a large mixed population to demonstrate that there are measurable EEG differences between delirium and control patients. METHODS: This retrospective pilot study investigated EEG measures as biomarkers in delirium using a case-control design including patients diagnosed with delirium (DSM-5 criteria) and age-/gender-matched controls drawn from a database of 9980 patients (n = 129 and 414, respectively). Assessors were not blinded for groups. Power spectra and connectivity estimates, using the weighted phase log index, of continuous EEG data were compared between conditions. Alterations of information flow through nodes of intrinsic connectivity networks (ICN; default mode, salience, and executive control network) were evaluated in source space using betweenness centrality. This was done frequency specific and network nodes were defined by the multimodal human cerebral cortex parcellation based on human connectome project data. RESULTS: Delirium and control patients exhibited distinct EEG power, connectivity, and network characteristics (F (72,540) = 70.3, p < .001; F (493,1079) = 2.69, p < .001; and F (718,2159) = 1.14, p = .007, respectively). Connectivity analyses revealed global alpha and regional beta band disconnectivity that was accompanied by theta band hyperconnectivity in delirious patients. Source and network analyses yielded that these changes are not specific to single intrinsic connectivity networks but affect multiple nodes of networks engaged in level of consciousness, attention, working memory, executive control, and salience detection. Effect sizes were medium to strong in this mixed population of delirious patients. CONCLUSIONS: We quantified effect sizes for EEG connectivity and network analyses to be expected in delirium. This study implicates that theta band hyperconnectivity and alpha band disconnectivity may be essential mechanisms in the pathophysiology of delirium. Upcoming prospective studies will build upon these results and evaluate the clinical utility of identified EEG measures as therapeutic and prognostic biomarkers.

Diagnostic Performance and Utility of Quantitative EEG Analyses in Delirium: Confirmatory Results From a Large Retrospective Case-Control Study.

Background. The lack of objective disease markers is a major cause of misdiagnosis and nonstandardized approaches in delirium. Recent studies conducted in well-selected patients and confined study environments suggest that quantitative electroencephalography (qEEG) can provide such markers. We hypothesize that qEEG helps remedy diagnostic uncertainty not only in well-defined study cohorts but also in a heterogeneous hospital population. Methods. In this retrospective case-control study, EEG power spectra of delirious patients and age-/gender-matched controls (n = 31 and n = 345, respectively) were fitted in a linear model to test their performance as binary classifiers. We subsequently evaluated the diagnostic performance of the best classifiers in control samples with normal EEGs (n = 534) and real-world samples including pathologic findings (n = 4294). Test reliability was estimated through split-half analyses. Results. We found that the combination of spectral power at F3-P4 at 2 Hz (area under the curve [AUC] = .994) and C3-O1 at 19 Hz (AUC = .993) provided a sensitivity of 100% and a specificity of 99% to identify delirious patients among normal controls. These classifiers also yielded a false positive rate as low as 5% and increased the pretest probability of being delirious by 57% in an unselected real-world sample. Split-half reliabilities were .98 and .99, respectively. Conclusion. This retrospective study yielded preliminary evidence that qEEG provides excellent diagnostic performance to identify delirious patients even outside confined study environments. It furthermore revealed reduced beta power as a novel specific finding in delirium and that a normal EEG excludes delirium. Prospective studies including parameters of pretest probability and delirium severity are required to elaborate on these promising findings.

Emergency Room Use of "Fast-Track" Ultrasound in Acute Stroke: An Observational Study.

Early information on vascular status in acute stroke is essential. We analyzed whether duplex ultrasound (DUS) using a fast-track protocol provides this information without relevant delay. One hundred forty-six patients were prospectively enrolled. DUS was performed by sonographers with two levels of experience. The carotid and vertebral arteries, as well as all basal cerebral arteries, were bilaterally analyzed. Criteria for vessel analysis were (i) normal or stenosis <50%, (ii) stenosis ≥50% and (iii) occlusion. The mean duration of the ultrasound investigation was 6:07 ± 2:06 min with a significant difference between more and less experienced investigators (p < 0.0001). Insonation times decreased during the study in both groups. The sensitivity, specificity, positive predictive value and negative predictive value of ultrasound findings in comparison with computed tomography angiography were 73%, 99%, 84% and 98%, respectively. Our data suggest that "fast track" DUS is feasible and reliable. The time required for DUS assessment depends on the sonographer´s experience.

Brain parenchyma sonography and 123I-FP-CIT SPECT in Parkinson's disease and essential tremor.

We aimed to investigate the accuracy of transcranial brain parenchyma sonography (TCS) for differentiation between idiopathic Parkinson's disease (PD) and essential tremor (ET) in comparison to (123)I-FP-CIT SPECT (FP-CIT SPECT). Seventy-four patients, in whom PD or ET was suspected on the basis of clinical criteria, were analyzed. The echogenicity of the substantia nigra (SN) and the striatal binding of dopamine transporters (DAT) were evaluated by TCS and FP-CIT SPECT, respectively. Three patients were excluded due to an insufficient transtemporal bone window using TCS. Forty-six and 25 patients were clinically classified as PD and ET. SPECT revealed a reduced DAT binding in 42 of all 71 included patients. Thirty-six of the 42 patients with abnormal FP-CIT SPECT findings had a pathological SN hyperechogenicity, whereas TCS findings in the remaining 6 patients were normal. In 27 of 29 patients with normal SPECT findings the SN echogenicity was regular. Referring to FP-CIT SPECT, the sensitivity and specificity of TCS for detection of PD were 86 and 93%; the positive and negative predictive values were 95 and 82%, respectively. Sensitivity and specificity in detection of clinically diagnosed PD patients were 78 and 92% for TCS and 91 and 100% for FP-CIT SPECT, respectively. In patients with pathological FP-CIT SPECT and pathological TCS, the extent of SN hyperechogenicity did not correlate with the degree of reduction in dopamine transporter binding on the side opposite of the more affected limb. TCS allows a reliable differentiation of PD and ET. The TCS SN hyperechogenicity does not correlate with the extent of dopaminergic neuron degeneration.

Diagnostic transcranial ultrasound perfusion-imaging at 2.5 MHz does not affect the blood-brain barrier.

The purpose was to assess whether standard ultrasound (US) perfusion-imaging by means of contrast-enhanced transcranial color-coded sonography (TCCS) affects the blood-brain barrier (BBB) in patients with small-vessel disease (SVD). One week after a screening MRI to exclude a preexisting BBB disruption, unilateral TCCS phase inversion harmonic imaging (PIHI) was performed in an axial diencephalic plane after intravenous bolus application of 2.5 mL SonoVue (IGEA, Bracco, Italy). Magnetic resonance imaging (MRI) was performed immediately after US. In five patients, PIHI was performed applying a mean mechanical index (MI) of 0.7 +/- 0.1 for a time period of 2.5 min. MRI was started 12 +/- 2 min after US contrast injection. Comparisons of initial and post-US MRI by four blinded readers did not show any signs of BBB disruption. It is concluded that standard contrast-enhanced US perfusion imaging in patients with SVD did not lead to MRI-detectable BBB changes. This gives further evidence for safety of diagnostic US. Future investigations with larger sample sizes and higher-field MRI might give further insights into potential bioeffects of diagnostic, as well as therapeutic, contrast-enhanced transcranial US.

Internal jugular vein valve incompetence in COPD and primary pulmonary hypertension.

PURPOSE: Under physiologic conditions, intact internal jugular vein valves (IJVVs) efficiently prevent retrograde venous flow during intrathoracic pressure increase. Chronically elevated central venous pressure found in patients with chronic obstructive pulmonary disease (COPD) and primary pulmonary hypertension (PPH) might lead to IJVV incompetence (IJVVI). The aim of this study was to analyze the prevalence of IJVVI in patients with COPD and PPH using duplex sonography (DUS). METHOD: We included 30 COPD patients, 5 PPH patients, and 100 healthy controls in the study. IJVVI was diagnosed if retrograde jugular blood flow was seen on DUS during a Valsalva maneuver. Retrograde venous flow intensity was evaluated and graded according to extent and duration of reflux. RESULTS: IJVVI was found in 18 (60%) COPD patients and in all 5 (100%) PPH patients, which was significantly different from the controls (27%; p < 0.005). The intensity of venous retrograde flow correlated with the pulmonary artery pressure. CONCLUSION: Compared with healthy controls, COPDand PPH patients demonstrated a significantlygreater prevalence of IJVVI, which seems to be caused by the elevated central venous pressure. These patients may be at higher risk to develop central nervous system diseases related to cerebral outflow obstruction.

Assessment of intracranial venous blood flow after subarachnoid hemorrhage: a new approach to diagnose vasospasm with transcranial color-coded duplex sonography.

OBJECTIVETranscranial color-coded duplex sonography (TCCS) is a reliable tool that is used to assess vasospasm in the M1 segment of the middle cerebral artery (MCA) after subarachnoid hemorrhage (SAH). A distinct increase in blood flow velocity (BFV) is the principal criterion for vasospasm. The MCA/internal carotid artery (ICA) index (Lindegaard Index) is also widely used to distinguish between vasospasm and cerebral hyperperfusion. However, extracranial ultrasonography assessment of the neck vessels might be difficult in an intensive care unit. Therefore, the authors evaluated whether the relationship of intracranial arterial to venous BFV might indicate vasospasm with similar or even better accuracy.METHODSPatients who presented between 2008 and 2015 with aneurysmal SAH were prospectively enrolled in the study. Digital subtraction angiography (DSA) and TCCS were performed within 24 hours of each other to assess vasospasm 8-10 days after SAH. The following different TCCS parameters were analyzed to assess vasospasm in the MCA and were compared with the gold-standard DSA parameters: 1) mean time-averaged maximum BFV (Vmean) of the MCA, 2) peak systolic velocity (PSV) of the MCA, 3) the Lindegaard Index using Vmean as well as PSV, and 4) a new arteriovenous index (AVI) between the MCA and the basal vein of Rosenthal using Vmean and PSV. The best cutoff values for these parameters to distinguish vasospasm from normal perfusion or hyperperfusion were calculated using receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, and negative predictive value as well as the overall accuracy for each cutoff value were analyzed.RESULTSA total of 102 patients (mean age 52 ± 12 years) were evaluated. Bilateral MCA assessment by TCCS was successful in all patients. In 6 cases (3%), the BFV of the basal vein of Rosenthal could not be analyzed. The AVI could not be calculated in 50 of 204 cases (25%) because the insonation quality was very low in one of the ICAs. An AVI > 10 for Vmean and an AVI > 12 for systolic velocity provided the highest accuracies of 87% and 86%, respectively. Regarding the Lindegaard Index, the accuracy was highest using a threshold of > 3 for the mean BFV (84%) as well as systolic BFV (80%). BFVs in the MCA of ≥ 120 cm/sec (Vmean) and ≥ 200 cm/sec (PSV) predicted vasospasm with accuracies of 84% and 83%, respectively. A combined analysis of the MCA BFV and the AVI led to a slight increase in specificity (Vmean, 94%; PSV, 93%) and positive predictive value (Vmean, 88%; PSV 86%) without further improvement in accuracy (Vmean, 88%; PSV, 84%).CONCLUSIONSThe intracranial AVI is a reliable parameter that can be used to assess vasospasm after SAH. Its reliability for differentiating vasospasm and hyperperfusion is slightly higher than that for the established Lindegaard Index, and this method has the additional advantage of a remarkably lower failure rate.

B-mode ultrasound assessment of pupillary function: Feasibility, reliability and normal values.

PURPOSE: To evaluate B-mode ultrasound as a novel method for the examination of pupillary function and to provide normal values for the pupillary reflex as assessed by B-mode ultrasound. METHODS: 100 subjects (49 female, 51 male, mean [range] age 51 [18-80 years]) with no history of ophthalmologic disease, no clinically detectable pupillary defects, and corrected visual acuity ≥ 0.8 were included in this prospective observational study. B-mode ultrasound was performed with the subjects eyes closed using an Esaote-Mylab25 system according to current guidelines for orbital insonation. A standardized light stimulus was applied. RESULTS: The mean ± standard deviation left and right pupillary diameters (PD) at rest were 4.7 ± 0.8 and 4.5 ± 0.8 mm. Following an ipsilateral light stimulus (Lstim), left and right constricted PD were 2.8 ± 0.6 and 2.7 ± 0.6 mm. Following a contralateral Lstim, left and right constricted PD were 2.7 ± 0.6 and 2.6 ± 0.5 mm. Left and right pupillary constriction time (PCT) following ipsilateral Lstim were 970 ± 261.6 and 967 ± 220 ms. Left and right PCT following a contralateral Lstim were 993.8 ± 192.6 and 963 ± 189.4 ms. Patient age was inversely correlated with PD at rest and with PD after ipsilateral and contralateral Lstim (all p<0.001), but not with PCT. CONCLUSIONS: B-mode ultrasound is a simple, rapid and objective method for the quantitative assessment of pupillary function, which may prove useful in a variety of settings where eyelid retraction is impeded or an infrared pupillometry device is unavailable.

Transcranial and extracranial ultrasound assessment of cerebral hemodynamics in vascular and Alzheimer's dementia.

BACKGROUND: Increasing life expectancy of the population leads to a higher incidence of dementia. Exact differentiation between the most common types, vascular dementia (VD) and Alzheimer's dementia (AD), is crucial to the development and application of new treatment strategies. Both conditions are thought to differ greatly by their extent of microvascular affection. Transcranial and extracranial ultrasound permits analysis of cerebral hemodynamics and should help to differentiate between VD and AD. We compare multimodal ultrasound data between VD, AD and controls, and give an overview of the literature on this topic. METHODS: Twenty VD and 20 AD patients were studied and compared with 12 age-matched controls. Transcranial color-coded ultrasound was performed to assess blood flow velocity (V(mean)) and pulsatility indices (PI) of the middle cerebral artery (MCA). Extracranial duplex and Doppler ultrasound techniques were used to assess the blood volume flow (BVF) in the anterior circulation (both internal carotid arteries [ICA]) and posterior circulation (both vertebral arteries [VA]), the global cerebral blood flow (CBF = BVF(ICA) + BVF(VA)), the global cerebral circulation time (CCT = time delay of echo-contrast bolus arrival between ICA and internal jugular vein) and global cerebral blood volume (CBV = CCT x CBF). RESULTS: MCA V(mean) in VD (36 +/- 8 cm/s) and AD (43 +/- 13 cm/s) were significantly lower than in controls (59 +/- 13 cm/s) but did not differ significantly between VD and AD groups. PI (1.1 +/- 0.2; 1 +/- 0.2; 0.9 +/- 0.2) only differed significantly between VD group and controls. CBF and CCT in VD (570 +/- 61 ml/min; 8.8 +/- 2.6 s) and AD (578 +/- 77 ml/min; 8.2 +/- 1.4 s) were similar but differed significantly from controls (733 +/- 54 ml/min; 6.4 +/- 0.8 s). BVF in the anterior and posterior circulation of VD group (412 +/- 62 and 158 +/- 38 ml/min) and AD group (428 +/- 62 and 150 +/- 41 ml/min) were significantly lower than in controls (537 +/- 48 and 199 +/- 26 ml/min) but did not differ significantly between the patient groups. DISCUSSION: Transcranial and extracranial ultrasound does not help to distinguish between VD and AD. However, our results add insight into the pathophysiology of dementia, arguing in favor of a common 'vascular' pathway in both conditions.

Serial ultrasound assessment of the basal vein of Rosenthal in HSV encephalitis.

Herpes simplex virus encephalitis (HSVE) typically affects the baso-temporal brain. The venous blood drainage of this region mainly occurs via the basal vein of Rosenthal (BVR), which can easily be monitored by transcranial color-coded duplex sonography (TCCS), and might be a useful parameter for the activity of the disease. Serial blood flow velocity (BFV) measurements of the BVR and the basal cerebral arteries were performed in five acute HSVE patients by means of transcranial color-coded duplex sonography (TCCS). Remarkable increased BFV of the BVR at the affected side was found in all patients, showing a maximum within the first 8 d of infection followed by a tendency toward normalisation during the next weeks. In comparison, changes of BFV in the basal cerebral arteries were much more heterogeneous. Our findings suggest that TCCS measurements of the BVR might be used as an additional diagnostic bed-side tool to evaluate patients with HSVE during the acute stage.

Transcranial duplex ultrasound of the ophthalmic artery.

The purpose of this study was to identify the ophthalmic artery (OA) by means of transcranial color-coded sonography using a new approach via the transtemporal bone window and to compare blood flow measurements with values obtained from the transorbital approach. A total of 105 subjects were included. Two individuals had an insufficient unilateral bone window, according to our inclusion criteria. Of the remaining 208 OAs, 206 (99%) could successfully be insonated via the transorbital approach and 190 (91%) via the transtemporal approach. Transorbital systolic and diastolic flow velocity (FVs) ranged between 15 and 67 cm/s (mean +/- SD: 35 +/- 10) and 4 to 36 cm/s (14 +/- 5), pulsatility index ranged between 0.4 to 2.8 (1.2 +/- 0.4). Transtemporal systolic and diastolic FVs ranged between 15 and 58 cm/s (33 +/- 9) and 4 to 25 cm/s (11 +/- 4). Transorbital and transtemporal FVs correlated significantly (p = 0.01). Our study demonstrates that transtemporal insonation of the proximal intracranial OA is feasible. Whenever OA assessment for analysis of collateral function is required, this simple approach, avoiding direct eye bulb insonation, should be considered.

Multiple brain abscesses following surgical treatment of a perianal abscess.

We report a case of multiple brain abscesses (BAs) in a 67-year-old man with symptoms of progredient disorientation and amnestic aphasia. Onset of symptoms occurred one week after surgical treatment of a perianal abscess. No other source of infection was identified and the abscesses were limited to the brain. The immune status was normal but a patent foramen ovale (pFO) was found. The patient was treated with high-dose antibiotics, leading to a complete radiological disappearance of the BAs. Hematogenous spread of infectious emboli from a perianal focus exclusively to the brain is very rare. In our patient, the mechanisms of infectious spread into the brain might have occurred via a cardiac right-to-left shunt or alternatively via the non-valvular vertebral venous system. In this manuscript, both pathways are critically reviewed.