Theo D. Witkamp

Cerebral lactate and N-acetyl-aspartate/choline ratios in asphyxiated full-term neonates demonstrated in vivo using proton magnetic resonance spectroscopy.

ABSTRACT: The purpose of this study was to test the hypothesis that a high lactate signal and a low N-acetyl-aspartate/choline ratio in neonates with postasphyxial encephalopathy indicated a high chance of an adverse outcome in vivo when proton magnetic resonance spectroscopy was used. Twenty-one full-term asphyxiated neonates were examined at a mean postnatal age of 7.1 d. Five patients died, and five survivors had handicaps. Eleven of the 16 survivors (seven without handicaps and four with handicaps) had a second examination at 3 mo of age. After magnetic resonance imaging, spectra were obtained at 1.5 tesla. A 20-mm-thick slice was selected through the basal ganglia. After optimizing the B-0 field, we used a double spin-echo pulse sequence (90–180-180°) with a time to repeat of 2000 ms and a time to echo of 272 ms. Two-dimensional spectroscopic imaging was performed by 32 ± 32 phase encoding steps in two directions in a 225-mm field of view, resulting in 1-mL volumes, followed by computerized processing. Neuromotor development was examined at 6 wk, 3 mo, and every 3 mo thereafter. Lactate resonances were seen only in the five patients with grade 3 postasphyxial encephalopathy. Lactate was distributed diffusely (n = 4), or localized in areas of infarction (n = 1). N-acetyl-aspartate/choline ratios were significantly lower in the patients with an adverse outcome than in the survivors without handicaps, both neonatally (p < 0.005, Wilcoxons rank sum test) and at 3 mo (p < 0.05). In conclusion, the presence of cerebral lactate and a low N-acetyl-aspartate/choline ratio demonstrated in vivo using proton magnetic resonance spectroscopy in full-term neonates with postasphyxial encephalopathy indicate a poor outcome.

Silent Brain Infarcts in Patients With Manifest Vascular Disease

Background and Purpose— Silent infarcts are frequently found on MRIs of brains of healthy elderly persons (aged >60 years). The purpose of this study was to investigate the prevalence and determinants of silent infarcts in a population of patients with clinically manifest vascular disease. Methods— To detect silent infarcts, MR images were made in 308 participants of the Second Manifestations of ARTerial disease (SMART) study (mean age, 58 years) without prior stroke or transient ischemic attack. These are patients referred to the University Medical Center Utrecht because of atherosclerotic vascular disease. Risk factors were assessed by questionnaire and by physical, ultrasonographic, and laboratory examinations. Results— Silent infarcts were found in 51 patients (17%). Most infarcts (62%) were located in white matter, 20% in basal ganglia, 14% in brain stem and cerebellum, and 4% in cortical area. Categorical determinants for presence of silent infarct(s) that remained (borderline) significant after adjustment for age were hypertension (odds ratio [OR]=2.2; 95% CI, 1.2 to 4.2), abdominal aortic aneurysm (OR=2.4; 95% CI, 0.9 to 6.4), severe renal failure (OR=7.3; 95% CI, 2.1 to 25.2), and hyperhomocysteinemia (OR=2.6; 95% CI, 1.1 to 5.9). Conclusions— Patients with manifest vascular disease are at risk for silent infarcts at a younger age. In particular, patients with the aforementioned risk factors should be considered for treatment or (secondary) prevention.

Brain volumes and cerebrovascular lesions on MRI in patients with atherosclerotic disease. The SMART-MR study

OBJECTIVE To estimate brain volumes, white matter lesion (WML) volume and asymptomatic infarcts on MRI in a large cohort of patients with atherosclerotic disease. METHODS Within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) study, a prospective cohort study on determinants and course of brain changes on MRI, cross-sectional analyses were performed in 1044 patients (mean age 58+/-10 years, 80% male) with coronary artery disease, cerebrovascular disease, peripheral arterial disease, or abdominal aortic aneurysm. Brain segmentation was used to quantify volumes of cortical gray matter, white matter, sulcal and ventricular cerebrospinal fluid, and WML. All volumes were expressed relative to intracranial volume. Brain infarcts were rated visually and distinctions were made between cortical infarcts, large subcortical infarcts, lacunar infarcts, and infarcts in the cerebellum and brainstem. RESULTS With older age a nonlinear (quadratic) decrease in total brain volume was observed and a nonlinear increase in ventricular volume and WML. Cortical gray matter volume showed a linear decrease with age and was stronger in men than in women. WML volumes also increased more strongly in men than in women, while ventricular volume decrease showed no sex difference. Silent brain infarcts were present in 14% of men and women, and increased to 24% of subjects aged 65 years or older. CONCLUSION In a population with atherosclerotic diseases, decrease in brain volumes with increasing age is comparable with findings from the general population. However, vascular pathology on MRI, as indicated by white matter lesions and silent brain infarcts may be more common.

Total cerebral blood flow, white matter lesions and brain atrophy: the SMART-MR study

We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58±10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0±10.2 mL/min per 100 mL, mean BPF was 79.2±2.9%, and mean VF was 2.03±0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.

Intracranial Aneurysms Treated with Coil Placement: Test Characteristics of Follow-up MR Angiography—Multicenter Study

PURPOSE To determine the test characteristics of magnetic resonance (MR) angiography in the assessment of occlusion of aneurysms treated with coil placement. MATERIALS AND METHODS This was an ethics committee-approved multicenter study. written informed consent was obtained in 311 patients with 343 aneurysms, who had been treated with coil placement and were scheduled for routine follow-up with intraarterial digital subtraction angiography (DSA). Thirty-five patients participated two or three times. Either 3.0- or 1.5-T time-of-flight (TOF) and contrast material-enhanced MR angiography were performed in addition to intraarterial DSA. Aneurysm occlusion was evaluated by independent readers at DSA and MR angiography. The test characteristics of MR angiography were assessed by using DSA as the standard. The area under the receiver operating characteristic curve (AUC) was calculated for 3.0- versus 1.5-T MR angiography and for TOF versus contrast-enhanced MR angiography, and factors associated with discrepancies between MR angiography and DSA were assessed with logistic regression. RESULTS Aneurysm assessments (n = 381) at DSA and MR angiography were compared. Incomplete occlusion was seen at DSA in 88 aneurysms (23%). Negative predictive value of MR angiography was 94% (95% confidence interval [CI]: 91%, 97%), positive predictive value was 69% (95% CI: 60%, 78%), sensitivity was 82% (95% CI: 72%, 89%), and specificity was 89% (95% CI: 85%, 93%). AUCs were similar for 3.0- (0.90 [95% CI: 0.86, 0.94]) and 1.5-T MR (0.87 [95% CI: 0.78, 0.95]) and for TOF MR (0.86 [95% CI: 0.81, 0.91]) versus contrast-enhanced MR (0.85 [95% CI: 0.80, 0.91]). A small residual lumen (odds ratio, 2.1 [95% CI: 1.1, 4.3]) and suboptimal projection at DSA (odds ratio, 5.5 [95% CI: 1.5, 21.0]) were independently associated with discordance between intraarterial DSA and MR angiography. CONCLUSION Documentation of good diagnostic performance of TOF MR angiography at both 1.5 and 3.0 T in the current study represents an important step toward replacing intraarterial DSA with MR angiography in the follow-up of patients with aneurysms treated with coils.

Radiation-induced brachial plexopathy : MR imaging

Abstract Objective. To describe the MR imaging appearance of radiation-induced brachial plexopathy. Design. MR imaging was performed in two patients with the clinical diagnosis of radiation-induced brachial plexopathy and in one with surgically proven radiation fibrosis of the brachial plexus. Patients. Three patients who had had radiation therapy to the axilla and supraclavicular region (two with breast carcinoma and one with Hodgkin’s lymphoma) presented with symptoms in the arm and hand. To exclude metastases or tumor recurrence MR imaging was performed. Results and conclusion. In one patient, fibrosis showing low signal intensity was found, while in two patients high signal intensity fibrosis surrounding the brachial plexus was found on the T2-weighted images. In one case gadolinium enhancement of the fibrosis was seen 21 years after radiation therapy. It is concluded that radiation-induced brachial plexopathy can have different MR imaging appearances. We found that radiation fibrosis can have both low or high signal intensities on T2-weighted images, and that fibrosis can enhance even 21 years after radiation therapy.

White Matter Lesions and Lacunar Infarcts Are Independently and Differently Associated with Brain Atrophy: The SMART-MR Study

Objective: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 ± 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid and WML. Total brain volume, ventricular volume and cortical gray matter volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), ventricular fraction (VF) and cortical gray matter fraction (GMF). Location and number of infarcts were rated visually. Results: Mean ± SD BPF was 79.3 ± 2.8%, mean ± SD VF was 2.01 ± 0.95%, and mean ± SD GMF was 36.6 ± 3.3%. Linear regression analyses, adjusted for age, sex, vascular risk factors, intima media thickness and LI showed that in patients with moderate to severe WML (upper quartile) BPF was lower (–0.51%; 95% CI –0.93 to –0.08%), VF was higher (0.48%; 95% CI 0.31–0.65%) and GMF was lower (–1.48%; 95% CI –2.07 to –0.88%) than in patients with few WML (lower quartile). Presence of LI was associated with lower BPF (–0.52%; 95% CI –0.96 to –0.07%) and higher VF (0.25%; 95% CI 0.07–0.42%), but not with GMF, independent of WML and other potential confounders. Conclusion: WML are associated with total, subcortical and cortical brain atrophy, whereas LI are associated with total and subcortical atrophy, but not with cortical atrophy, suggesting an independent role for WML and LI in the pathogenesis of brain atrophy.

Radiological findings in autistic and developmentally delayed children

PURPOSE The aim of this study was to evaluate the prevalence of brain abnormalities in a group of young children with developmental disorders, specifically including children that came to the attention of a child psychiatrist before the age of 3 years. METHODS Forty-five children participated in an MR study (mean age 43 months, SD=12, four females). The study design was approved by the local Medical Ethical Review Board. All parents gave written informed consent. Scans were independently assessed by two board-certified radiologists for malformations of gray and white matter. RESULTS Cohens kappa for the consensus between the two raters was 0.79. In 22 children (49%) abnormalities were reported. Four patients (8.5%) had an arachnoid cyst. One female was diagnosed with a Chiari I malformation. Three children show enlarged Virchow-Robin spaces, an increased occurrence when compared to the normal population. CONCLUSIONS A high rate of intracranial abnormalities was found in this study. Radiological findings do not contribute to the diagnosis of developmental disorders. However, young children with developmental disorders may not be able to express discomfort associated with brain abnormalities, such as a Chiari I malformation. Given the high prevalence of abnormalities in this sample neuroimaging may be a useful tool in clinically assessing children with developmental disorders.

Pelvic floor muscle lesions at endoanal MR imaging in female patients with faecal incontinence

To evaluate the frequency and spectrum of lesions of different pelvic floor muscles at endoanal MRI in women with severe faecal incontinence and to study their relation with incontinence severity and manometric findings. In 105 women MRI examinations were evaluated for internal anal sphincter (IAS), external anal sphincter (EAS), puborectal muscle (PM) and levator ani (LA) lesions. The relative contribution of lesions to differences in incontinence severity and manometric findings was studied. IAS (n = 59) and EAS (n = 61) defects were more common than PM (n = 23) and LA (n = 26) defects. PM and LA defects presented mainly with IAS and/or EAS defects (isolated n = 2 and n = 3). EAS atrophy (n = 73) was more common than IAS (n = 19), PM (n = 16) and LA (n = 9) atrophy and presented mainly isolated. PM and LA atrophy presented primarily with EAS atrophy (isolated n = 3 and n = 1). Patients with IAS and EAS lesions had a lower resting and squeeze pressure, respectively; no other associations were found. PM and LA lesions are relatively common in patients with severe faecal incontinence, but the majority of lesions are found in women who also have IAS and/or EAS lesions. Only an association between anal sphincter lesions and manometry was observed.

Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: prospective, multicentre cohort study

Study question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year’s follow-up. Study answer and limitations A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced permanent sequelae. Not all patients with negative CT angiography and MRI/MRA results underwent DSA. Although the previous probability of finding a macrovascular cause was lower in patients who did not undergo DSA, some small arteriovenous malformations or dural arteriovenous fistulas may have been missed. What this study adds CT angiography is an appropriate initial investigation to detect macrovascular causes of non-traumatic intracerebral haemorrhage, but accuracy is modest. Additional MRI/MRA may find cavernomas or alternative diagnoses, but DSA is needed to diagnose macrovascular causes undetected by CT angiography or MRI/MRA. Funding, competing interests, data sharing Dutch Heart Foundation and The Netherlands Organisation for Health Research and Development, ZonMw. The authors have no competing interests. Direct requests for additional data to the corresponding author.