Martin Schöning

Estimation of cerebral blood flow through color duplex sonography of the carotid and vertebral arteries in healthy adults.

Background and Purpose To noninvasively estimate cerebral blood flow volume, a prospective study of color duplex sonography of the common, external, and internal carotid arteries and vertebral arteries of healthy adults was done. Cerebral blood flow was calculated with the sum of flow volumes in the internal carotid and vertebral arteries of both sides. Methods Using a 7.0-MHz linear transducer of a computed sonography system, cervical arteries of 48 volunteers (23 women, 25 men; mean age, 35 ±12 years) were examined. We measured angle-corrected time-averaged velocities and the diameter of the vessels and calculated the flow volumes of all arteries. In addition, peak systolic, maximum end-diastolic, and time-averaged maximum velocities and the resistance, pulsatility, and spectral broadening indexes were determined. Furthermore, we analyzed the side-to-side difference, age dependence, and long-term reproducibility of these parameters. Results The mean±SD values of flow volumes in the common, internal, and external carotid and vertebral arteries were 470+120, 265±62,160±66, and 85±33 mL/min on either side, respectively. Total cerebral blood flow was 701 ±104 mL/min (corresponding to 54±8 mL/100 g per minute), with no variation in age or sex. Long-term reproducibility of cerebral blood flow and flow volumes in all vessels was significant (P < .01). Conclusions We conclude that color duplex sonography of cervical arteries is potentially a practical method for estimating total cerebral blood flow. This noninvasive technique may be ideally suited for bedside and follow-up examinations of the critically ill patient. In future studies it should be compared with established radionuclide techniques.

Vessel Wall Contrast Enhancement: A Diagnostic Sign of Cerebral Vasculitis

Purpose: Inflammatory stenoses of cerebral arteries cause stroke in patients with florid vasculitis. However, diagnosis is often difficult even with digital subtraction angiography (DSA) and biopsy. The purpose of this study was to establish the value of contrast-enhanced MRI, proven to be sensitive to extradural arteritis, for the identification of intracranial vessel wall inflammation. Patients and Methods: Twenty-seven patients with a diagnosis of cerebral vasculitis affecting large brain vessels were retrieved from the files: 8 children (2–10 years, 7 female, 1 male) and 19 adults (16–76 years, 10 female, 9 male). Diagnosis was based on histological or serological proof of vasculitis or on clinical and imaging criteria. All MRI examinations included diffusion-weighted imaging, time-of-flight magnetic resonance angiography (TOF-MRA) and contrast-enhanced scans. MRI scans were assessed for the presence of ischemic brain lesions, arterial stenoses, vessel wall thickening and contrast uptake. Results: Ischemic changes of the brain tissue were seen in 24/27 patients and restricted diffusion suggestive of recent ischemia in 17/27; 25/27 patients had uni- or multifocal stenoses of intracranial arteries on TOF-MRA and 5/6 had stenoses on DSA. Vessel wall thickening was identified in 25/27, wall enhancement in 23/27 patients. Conclusion: Wall thickening and intramural contrast uptake are frequent findings in patients with active cerebral vasculitis affecting large brain arteries. Further prospective studies are required to determine the specificity of this finding.

Evaluation of the vertebrobasilar-posterior system by transcranial color duplex sonography in adults.

Background and Purpose: The transcranial color duplex sonography technique was applied to the vertebrobasilar-posterior system to provide normal data for clinical application. Methods: The intracranial posterior circulation was studied in 49 healthy volunteers (mean±SD age, 35±12 years) by a transcranial and suboccipital approach with a 2.0-MHz sector transducer of a computed sonography system. Results: The posterior cerebral artery and the vertebrobasilar system were depicted clearly in the color Doppler mode. Pulsed Doppler signals could be recorded in the posterior cerebral (100%), basilar (92%), and vertebral arteries (89%). The following normal values were provided for all vessels: systolic peak, end-diastolic maximum, time-averaged, and time-averaged maximum velocities; resistance and pulsatility indexes; and a spectral broadening index. Mean±SD values were 45.9±9.6, 45.5±10.8, and 39.2±10.6 cm/sec for time-averaged maximum velocity, and 28.3±6.5, 30.6±7.2, and 24.7±8.4 cm/sec for timeaveraged velocity in the posterior cerebral, basilar, and vertebral arteries, respectively. In a reproducibility study, duplex measurements of the posterior cerebral arteries were repeated in 27 subjects. The correlation between the two examiners was high (r=0.56, p<0.0001 for time-averaged maximum velocity). Conclusions: Color duplex sonography of the vertebrobasilar-posterior system is a new, noninvasive, bedside investigative technique. It permits visualization of artery flow in real time, relating these to adjacent brain and cranial structures, as well as angle-corrected duplex measurement of “true” flow velocities at defined sites of the vessels. Thus, it will open new diagnostic possibilities in disorders of the posterior circulation.

Development of Cerebral Blood Flow Volume in Preterm Neonates during the First Two Weeks of Life

To investigate the postnatal development of cerebral perfusion in preterm neonates with normal brains over the first 2 wk of life, a prospective longitudinal study was designed. Quantitative measurement of cerebral blood flow (CBF) volume was performed using ultrasound flowmetry of the extracranial, brain-feeding arteries in 32 preterm infants of 28–35 wk gestational age. Measurements were done in the internal carotid and vertebral arteries of both sides on d 1, 2, 3, 7, and 14 after birth. A 10.0-MHz linear transducer of a computed sonography system (Acuson 128/XP10) was used. Intravascular flow volumes were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. Mean CBF volume increased markedly over the first 2 wk. One-third of this rise already occurred from the first to the second postnatal day, thereafter there was a continuous increase from d 2 to d 14 of life. Whereas the absolute level of CBF volume was primarily determined by postmenstrual age, the pattern of postnatal changes in CBF volume was found to be independent of gestational age. Arterial carbon dioxide tension, mean arterial blood pressure, and hematocrit had no influence on the development of CBF volume. The pronounced increase of CBF volume from d 1 to d 2 is likely to represent a normal adaptive response of the cerebral circulation to postnatal life. The data presented here may serve as the basis for further studies to investigate whether deviations from this adaptive response are associated with an increased risk of brain injury.

PROTON SPECTROSCOPY IN FIVE PATIENTS WITH LEIGH'S DISEASE AND MITOCHONDRIAL ENZYME DEFICIENCY

Five children with Leighs disease and progressive neurological symptoms were compared with 14 control children. In all patients, MRI showed bilateral lesions of the putamin and caudate heads. Serum lactate was normal for four of the children, and CSF lactate slightly elevated for three. Volume‐selective proton MR spectroscopy (`H‐MRS) of the basal ganglia in the Leigh patients revealed clevated lacrate, giving further evidence for a defect of energy merabolisrn In the brain. ‘H‐MRS is an important tool for non‐invasive brain tissue analysis in Leighs disease, particularly in the absence of peripheral lactate elevation.

A Longitudinal Study of Cerebral Blood Flow Over the First 30 Months

To investigate prospectively the development of cerebral perfusion during infancy, serial quantitative measurements of cerebral blood flow (CBF) volume were performed in two healthy children from birth up to the age of 30 mo. A total of 28 CBF volume measurements were done in either of the children. Absolute flows were measured in the internal carotid and vertebral arteries on both sides. Blood flow was calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. Starting from 67 and 80 mL/min, respectively, at birth an almost 10-fold increase of CBF volume was observed in both children during the examination period. Half of this rise occurred during the first 6 mo, probably reflecting the steep metabolic incline during this period of synaptogenesis. The continuous increase in CBF volume after the sixth month of life mainly corresponds to brain growth. Estimated CBF (based on estimated brain weights) increased from 21 and 23 mL 100 g−1 min−1, respectively, after birth to 46 and 53 mL 100 g−1 min−1, respectively, during the first 6 mo of life in both children, remaining stable thereafter. This study is the first to provide longitudinal data of CBF during the first 30 mo after birth.

Volume measurement of cerebral blood flow: assessment of cerebral circulatory arrest.

Background. Cerebral blood flow (CBF) volume can be measured at bedside by color duplex flowmetry of the extracranial cerebral arteries. In neurointensive care patients, we prospectively tested the hypothesis that a CBF volume <100 ml/min indicates imminent cerebral circulatory arrest. Methods. CBF volume was determined as sum of flow volumes in the internal carotid and vertebral arteries of both sides. In 192 neurointensive care patients, 829 measurements were taken. When CBF volume fell short of 100 ml/min, common carotid and external carotid artery flow volumes were also measured, and transcranial color-coded duplex sonography (TCCD) of basal cerebral arteries was performed. Results were compared with actual clinical conditions, outcome, and previously published reference data. Results. All 41 patients with CBF volume <100 ml/min (range, 0–89 ml/min) were officially declared brain dead 2–126 hours after the measurement (median, 23 hours). TCCD revealed signs of cerebral circulatory arrest in all patients with a patent acoustic bone window. External carotid artery flow volumes were normal. The lowest CBF volume rate recorded in a surviving patient was 208 ml/min. Conclusions. Early confirmation of cerebral circulatory arrest is of decisive importance if the patient is a potential organ donor. CBF volume measurement allows confirming the arrest of cerebral circulation even in patients without a patent acoustic bone window for TCCD. Because the critical lower threshold for survival appears to lie at 200 ml/min, bedside monitoring of CBF volume in neurointensive care patients may indicate a therapeutic window before irreversible circulatory arrest occurs.

12q24.33 deletion: Report of a patient with intellectual disability and review of the literature

Deletions of chromosome band 12q24.33 are rare. We report on a 17‐year‐old male patient with intellectual disability but no major malformations or dysmorphic features in whom a de novo interstitial 660 kb deletion in 12q24.33 was detected by SNP array analysis. This deletion was secondary to a translocation t(12;14)(q24.3;q13)dn that also led to a small deletion in 14q21.1 and a small duplication in 2p23.1. The deletion overlaps with two previously published larger deletions in patients who suffered from intellectual disability, obesity, and polycystic kidney disease, indicating that haploinsufficiency of one or several of the genes in the deleted interval of the patient reported here causes intellectual deficits, but not obesity or renal problems. The 14 RefSeq genes that are harbored by this deletion include P2RX2, which had previously been proposed as a candidate gene for intellectual disability. Thus, the patient reported here broadens our knowledge of the phenotypic consequences of deletions in 12q24.33 and facilitates genotype–phenotype correlations for chromosome aberrations of this region.

Zerebrale Infarkte bei Neugeborenen: Wertigkeit der MRT

ZusammenfassungHintergrund:Zerebrale Ischämien bei Neugeborenen sind selten. Wegen der Unreife des Gehirns sind Krampfanfälle fast immer das klinische Leitsymptom. Der hohe Wassergehalt des neonatalen Gehirns und die fehlende Myelinisierung erschweren die Diagnose mit bildgebenden Verfahren, die zur Indikationsstellung einer antikoagulatorischen Therapie jedoch erforderlich ist. Zweck dieser Studie war die Evaluation verschiedener Magnetresonanztomographie-(MRT-)Sequenzen zur Erkennung zerebraler Ischämien während der ersten 14 Lebenstage unter besonderer Berücksichtigung der diffusionsgewichteten Bildgebung.Patienten und Methoden:Sechs Patienten mit zerebralen Krampfanfällen wurden in den ersten 2 Lebenstagen nach einem festgelegten MRT-Protokoll untersucht, das neben konventionellen Sequenzen jeweils auch diffusions- und flussgewichtete Aufnahmen enthielt. Verlaufsuntersuchungen wurden bei vier Patienten nach 5 Tagen (n = 1), 7 Tagen (n = 2) und 14 Tagen (n = 1) durchgeführt.Ergebnisse:Insgesamt wurden bei den sechs Patienten 19 Infarkte festgestellt. Die Infarkte waren in der Initialphase als starke Diffusionsstörung erkennbar. Die Erkennbarkeit in den T2-gewichteten Sequenzen war bei drei Patienten initial so gering, dass die Diagnose durch die diffusionsgewichteten Sequenzen erst möglich wurde. Bei den anderen Patienten waren in der Diffusionsbildgebung deutlich mehr Läsionen (19) erkennbar als in den konventionellen Sequenzen (6). Im zeitlichen Verlauf waren die Infarkte in der Diffusionsbildgebung nach 5 Tagen bereits deutlich schlechter sichtbar und nach 1 Woche nicht mehr abgrenzbar. Eine verstärkte Diffusivität in den Infarktarealen bestand bereits 2 Wochen nach der Ischämie. Die Ischämien waren zu diesem Zeitpunkt in den T2-Sequenzen gut erkennbar.Schlussfolgerungen:Diffusionsgewichtete Sequenzen sind bei Neugeborenen am besten geeignet, zerebrale Ischämien in der Initialphase nachzuweisen. Weil ihre Sensitivität aber schon in der ersten Woche nachlässt, muss sich die Diagnose nach dem 5. Tag auf T2-gewichtete Sequenzen stützen.AbstractBackground:Ischemic stroke in neonates is a rare event presenting clinically with seizures. Due to the immature neonatal brain, diagnosis with most imaging modalities is difficult, but necessary to initiate an anticoagulatory treatment. The purpose of this study was to evaluate the sensitivity of MRI sequences within the first 14 days after birth for a reliable diagnosis of cerebral ischemia.Patients and Methods:Six patients with neonatal stroke presenting as seizures were examined using a standard MRI protocol including DWI and MRA within 3 days after birth. Follow-up examinations were performed in four patients after 5 days (n = 1), 7 days (n = 2) and after 2 weeks (n = 1) for treatment control.Results:19 infarctions were detected in the six patients with 15 lesions located in the MCA territory and four in the PCA territory. All lesions were visible using DWI, six on T2-weighted images. Whereas in two patients small lesions contralateral to a large stroke were missed on T2, the diagnosis would have been missed altogether in one baby. On follow-up examinations, the visibility of the infarctions had declined using DWI after 5 days and the lesions were invisible after 1 week. 14 days after the stroke, an increased diffusion was detected in the infarcted brain tissue. All lesions were visible on T2-weighted images.Conclusions:Infarcted brain tissue can be detected in neonates using DWI with high sensivity within the first 2 days after stroke and before other sequences are diagnostic. However, the diffusion restriction does not persist beyond 1 week. After 5 days, diagnosis has to rest on T2-weighted images.