Biomedical subjects

Jeroen van der Grond

Publications and source records attributed to Jeroen van der Grond.

At least 19 recordsLinked to original sources

PubMed2007

Increasing levels of TNFalpha are associated with increased brain perfusion.

OBJECTIVE: Recent reports of animal models have shown that growth factors have stimulating effect on brain perfusion via the development of blood vessels. However, studies on the effect of growth factors on brain perfusion in humans are lacking. The aim of our study was to prospectively investigate in humans the relation between growth factors and brain perfusion. METHODS: We analyzed circulating levels of vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating growth factor (GM-CSF), tumor necrosis factor alpha (TNFalpha) and basic fibroblast growth factor (bFGF) in 121 consecutive patients (99 men and 22 women, age 58+/-10 years) who were enrolled in a prospective cohort study of patients with symptomatic atherosclerotic disease. In all patients regional cerebral blood flow (rCBF; in mL/min/100g) measurements were performed with arterial spin labeling magnetic resonance imaging. Cerebrovascular risk factors were assessed by means of a questionnaire and physical, ultrasonographic and laboratory examination. RESULTS: Increasing levels of TNFalpha were significantly associated with a higher rCBF (beta=7.0; 95% confidence interval 0.7; 13.9), independent of the presence of cerebrovascular risk factors. No significant association was found for VEGF, GM-CSF and bFGF. CONCLUSIONS: Increasing levels of TNFalpha are associated with increased rCBF, independent of the presence of cerebrovascular risk factors.

Aged↗

PubMed2007

Sensitivity comparison of multiple vs. single inversion time pulsed arterial spin labeling fMRI.

PURPOSE: To study the sensitivity for detection of activation for multiple vs. single inversion time (TI) pulsed arterial spin labeling (PASL). MATERIALS AND METHODS: The number of activated voxels and the mean t-statistic over activated voxels was measured by means of multiple and single TI PASL sequences in five volunteers during visual stimulation by means of an alternating checkerboard. Acquisition was performed by means of the transfer insensitive labeling technique (TILT) and TURBO-TILT. RESULTS: It was found that the sensitivity for the detection of activation was lower for an individual TI out of a multiple TI sequence than for the corresponding single TI acquisition of equal duration. After averaging over all TIs between and including 600 and 1400 msec, the number of activated voxels and mean t-statistic were no longer statistically lower for the multiple TI sequence than for the single TI experiment. CONCLUSION: Multiple TI PASL can be used for functional MRI (fMRI) studies, when performing the detection of activated brain regions on data that is averaged over all TIs between 600 and 1400 msec. Subsequently the multi-TI data can be used to quantify cerebral blood flow (CBF) changes upon activation. Additionally, we have shown that single TI PASL fMRI overestimates the CBF changes upon activation due to transit time changes.

Adult↗

PubMed2006

Spect measurements of regional cerebral perfusion and carbondioxide reactivity: correlation with cerebral collaterals in internal carotid artery occlusive disease.

BACKGROUND: The aim of the present study was to assess the regional variation in cerebral perfusion, vasomotor reactivity (VMR) and the role of cerebral collaterals in patients with symptomatic internal carotid artery (ICA). METHODS: Seventeen functionally independent patients (60+/-9 years, mean+/-SD) with a unilateral symptomatic internal carotid artery occlusion and a <30% contralateral ICA stenosis were investigated. (99 m) Tc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) was performed to study cerebral blood flow in rest and during a CO(2) challenge in the cerebellum, temporal lobe, occipital lobe, basal ganglia, frontal lobe and parietal lobe. Time of flight and phase contrast MRA were used to study collateral flow via circle of Willis. RESULTS: In rest, cerebral perfusion on the side ipsilateral to the ICA occlusion was decreased compared with the contralateral side in the basal ganglia (p<0.05), frontal lobe (p<0.01) and parietal lobe (p<0.01). During a CO(2) challenge only the ipsilateral frontal lobe demonstrated a perfusion decrease compared with the contralateral frontal lobe (p<0.05). Furthermore, in patients without collateral flow via the anterior circle of Willis the perfusion of the ipsilateral frontal lobe was significantly decreased (p<0.01) during the CO(2) challenge and crossed cerebellar diaschisis with a decreased perfusion on the contralateral cerebellar hemisphere was detected (p<0.05). No cerebral blood flow (CBF) differences were found for present/absent collateral flow via the posterior communicating artery. CONCLUSION: Regional assessment of cerebral perfusion and VMR with SPECT demonstrated the heterogeneity of cerebral hemodynamics and the importance of collateral flow via the anterior circle of Willis.

Aged↗

PubMed2006

Hemodynamic effect of carotid stenting and carotid endarterectomy.

BACKGROUND: Carotid angioplasty with stent placement (CAS) may offer an alternative treatment to carotid endarterectomy (CEA). However, in contrast to CEA, which has been shown to normalize impaired cerebral hemodynamics, the effects of CAS remain unclear. To investigate alterations in cerebral hemodynamics, we prospectively studied patients undergoing CAS and compared them with a group of similar patients undergoing CEA. METHODS: Twenty-three patients undergoing CAS for recently symptomatic internal carotid artery (ICA) stenosis were prospectively studied. Volume flow in the ICAs and basilar artery (BA) were measured with magnetic resonance volume flow quantification before CAS and 1 month after. The results were compared with those in 13 similar patients undergoing CEA and 40 control subjects without ICA stenosis. RESULTS: After CAS, volume flow in the ipsilateral ICA increased from 114 +/- 17 to 231 +/- 17 mL/min (P < .001), and total volume flow (ICAs plus BA) increased from 495 +/- 24 to 552 +/- 28 mL/min (P < .05). No significant changes were seen in the contralateral ICA and BA after CAS. Total volume flow and flow in the stenosed ICA normalized after CAS compared with control subjects. Volume flow values similarly improved after CEA. CONCLUSIONS: CAS results in a normalization of impaired cerebral hemodynamics, as assessed by magnetic resonance volume flow measurements. The degree of improvement is similar to that seen after CEA.

Aged↗

PubMed2006

Magnetic resonance evaluation of the cerebral circulation in obstructive arterial disease.

BACKGROUND: The aim of the current overview is to highlight the possibilities of magnetic resonance imaging (MRI) in the assessment of patients with obstructive arterial disease. The anatomic and hemodynamic aspects of the extra- and intracranial cerebral circulation were analyzed and show the importance of combining both aspects in studying cerebral hemodynamic changes. RESULTS: Three levels of cerebral circulation are distinguished: blood flow to the brain (level 1); the distribution of blood flow in the brain (level 2), and finally perfusion of the brain (level 3). To investigate the anatomy of the arteries in the neck and the circle of Willis, contrast-enhanced, time-of-flight and phase contrast MR angiography (MRA) are available. To evaluate the hemodynamics at the 1st and 2nd level of the cerebral circulation two-dimensional phase contrast (volume flow and flow direction) MRA can be used. In addition, the distribution of blood via the circle of Willis can be visualized with dynamic MRA. At the 3rd level, measurements of regional brain perfusion can be obtained by injecting gadolinium, dynamic susceptibility contrast MRI, or noninvasively with arterial spin labeling (ASL) MRI. In addition, selective ASL MRI is able to evaluate the perfused territories of individual brain-feeding arteries. CONCLUSION: The currently available MR techniques allow evaluation of the cerebral circulation from the aortic arch upwards towards the microvasculature and brain tissue perfusion in a comprehensive 20-min protocol. The combined use of the described MR methods in patients with steno-occlusive disease will further clarify the pathophysiological relations between the vasculature, perfusion and brain function.

Arterial Occlusive Diseases↗

PubMed2006

MRI, volumetry, 1H spectroscopy, and cerebropetal blood flowmetry in childhood idiopathic anatomic megalencephaly.

PURPOSE: To evaluate cerebral abnormalities in childhood idiopathic anatomic megalencephaly (MC) by means of different magnetic resonance (MR) modalities. MATERIALS AND METHODS: MRI, volumetry, spectroscopy, and cerebropetal blood flowmetry were performed in six children with idiopathic anatomic MC, and seven volunteers. RESULTS: MRI revealed an increased ventricular system in five of six patients. A thalamic hamartoma was found in one patient and a Chiari I malformation was found in two. Volumetric analysis showed a disproportional increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF) volume. Supratentorial volume was disproportionally increased compared to cerebellar volume. Intracranial volume correlated significantly with skull circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak ratios in WM were significantly higher in patients than in controls. Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients. Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was increased in MC, possibly related to increased brain volume. CONCLUSION: This study reveals associated developmental anomalies for idiopathic anatomic MC. A relative ventriculomegaly was found, which should not be misinterpreted as true hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances. Total intracranial volume is correlated to skull circumference and cerebropetal blood flow.

Aspartic Acid↗

PubMed2006

Magnetic resonance angiography of the human middle meningeal artery: implications for migraine.

PURPOSE: To describe a novel noninvasive method for studying middle meningeal artery (MMA) diameter changes in vivo in humans. Dilatation of the MMA has been implicated in the pathophysiology of migraine headache, but no direct evidence has been obtained in humans. MATERIALS AND METHODS: The diameter of the MMA (the extracranial part) was measured in 19 healthy volunteers before and after administration of a vasodilator (nitroglycerin (NTG), 1.2 mg sublingually) known to provoke headache. We used magnetic resonance angiography (MRA) in combination with a 47-mm microscopy coil and a semiautomatic contour detection program. RESULTS: The diameter of the MMA was 1.5+/-0.26 mm (mean+/-SD) before and 1.79+/-0.30 mm after NTG administration. This increase was 20.1% (95% CI=12.9-27.3; P<0.001). The mean increase in subjects who developed headache (N=11) was 0.34+/-0.19 mm as compared to 0.22 mm+/-0.20 mm in the eight subjects who did not (95% CI for difference=-0.07 to 0.31; P=0.188). CONCLUSION: MRA in combination with a 47-mm microscopy coil is a novel, noninvasive method to measure changes in the diameter of human meningeal vessels, with potential applications for migraine and other fields of neurovascular research.

Adolescent↗

PubMed2006

Effect of satiety on brain activation during chocolate tasting in men and women.

BACKGROUND: The brain plays a crucial role in the decision to eat, integrating multiple hormonal and neural signals. A key factor controlling food intake is selective satiety, ie, the phenomenon that the motivation to eat more of a food decreases more than does the motivation to eat foods not eaten. OBJECTIVE: We investigated the effect of satiation with chocolate on the brain activation associated with chocolate taste in men and women. DESIGN: Twelve men and 12 women participated. Subjects fasted overnight and were scanned by use of functional magnetic resonance imaging while tasting chocolate milk, before and after eating chocolate until they were satiated. RESULTS: In men, chocolate satiation was associated with increased taste activation in the ventral striatum, insula, and orbitofrontal and medial orbitofrontal cortex and with decreased taste activation in somatosensory areas. Women showed increased taste activation in the precentral gyrus, superior temporal gyrus, and putamen and decreased taste activation in the hypothalamus and amygdala. Sex differences in the effect of chocolate satiation were found in the hypothalamus, ventral striatum, and medial prefrontal cortex (all P < 0.005). CONCLUSIONS: Our results indicate that men and women differ in their response to satiation and suggest that the regulation of food intake by the brain may vary between the sexes. Therefore, sex differences are a covariate of interest in studies of the brain's responses to food.

Adult↗

PubMed2006

Selective involvement of the amygdala in systemic lupus erythematosus.

BACKGROUND: Antibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE). The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE. METHODS AND FINDINGS: We analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE), 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI). In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC) was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 x 10(-6) mm2/s; p = 0.006 and 949 x 10(-6) mm2/s; p = 0.019, respectively) was lower than in healthy control participants (1152 x 10(-6) mm2/s). Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 x 10(-6) mm2/s) was lower (p = 0.029) than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 x 10(-6) mm2/s) and also lower (p = 0.001) than in healthy control participants. CONCLUSIONS: This is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies.

Adult↗

PubMed2006

Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes.

The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic control subjects and assessed the relationship between cognition and MRI findings and blood pressure and metabolic control. The study included 113 patients and 51 control subjects. Brain MRI scans were rated for white matter lesions (WMLs), cortical and subcortical atrophy, and infarcts. Neuropsychological test scores were divided into five cognitive domains and expressed as standardized Z values. Type 2 diabetes was associated with deep WMLs (P = 0.02), cortical (P < 0.001) and subcortical (P < 0.05) atrophy, (silent) infarcts (P = 0.06), and impaired cognitive performance (attention and executive function, information-processing speed, and memory, all P < 0.05). Adjustment for hypertension did not affect the results. Within the type 2 diabetic group, cognitive function was inversely related with WMLs, atrophy, and the presence of infarcts (adjusted for age, sex, and estimated IQ), and there was a modest association with HbA1c and diabetes duration. This association was strongest for age, even more so than in control subjects. We conclude that cognitive impairments in patients with type 2 diabetes are not only associated with subcortical ischemic changes in the brain, but also with increased brain atrophy.

Aged↗

PubMed2005

Association between supine cerebral perfusion and symptomatic orthostatic hypotension.

The goal of this study was to investigate whether the supine resting perfusion of brain tissue in symptomatic patients suffering from orthostatic hypotension (OH) is changed compared to control subjects and whether an association exists between the resting perfusion and the severity of OH. Ten symptomatic OH patients and 8 control subjects were included in this study. One patient was retrospectively excluded because he suffered from multiple system atrophy. Systolic and diastolic blood pressure changes were measured during a tilting bed procedure. Cerebral blood flow, cerebral blood volume and mean transit time were determined by bolus-tracking perfusion MRI and correlated with blood pressure changes. Cerebral blood volume was significantly increased in OH patients compared with control subjects for white matter (P = 0.019) and the mean transit time was significantly increased for gray (P = 0.010) and white matter (P = 0.015). The cerebral blood flow of the gray (r = 0.74, P = 0.022) and white matter (r = 0.75, P = 0.020) was significantly, positively correlated with systolic blood pressure changes. The mean transit time in white matter was significantly, negatively correlated with systolic blood pressure changes (r = -0.68, P = 0.045). This study suggests that in symptomatic patients with OH the cerebral perfusion of the brain in the resting, supine position correlates with the severity of OH as measured by postural changes in blood pressure.

Aged↗

PubMed2005

Probabilistic segmentation of brain tissue in MR imaging.

A new method has been developed for probabilistic segmentation of five different types of brain structures: white matter, gray matter, cerebro-spinal fluid without ventricles, ventricles and white matter lesion in cranial MR imaging. The algorithm is based on information from T1-weighted (T1-w), inversion recovery (IR), proton density-weighted (PD), T2-weighted (T2-w) and fluid attenuation inversion recovery (FLAIR) scans. It uses the K-Nearest Neighbor classification technique that builds a feature space from spatial information and voxel intensities. The technique generates for each tissue type an image representing the probability per voxel being part of it. By application of thresholds on these probability maps, binary segmentations can be obtained. A similarity index (SI) and a probabilistic SI (PSI) were calculated for quantitative evaluation of the results. The influence of each image type on the performance was investigated by alternately leaving out one of the five scan types. This procedure showed that the incorporation of the T1-w, PD or T2-w did not significantly improve the segmentation results. Further investigation indicated that the combination of IR and FLAIR was optimal for segmentation of the five brain tissue types. Evaluation with respect to the gold standard showed that the SI-values for all tissues exceeded 0.8 and all PSI-values exceeded 0.7, implying an excellent agreement.

Aged↗

PubMed2005

Early diffusion-weighted MRI and 1H-Magnetic Resonance Spectroscopy in asphyxiated full-term neonates.

AIM: To assess the predictive value of early MRI and proton MR spectroscopy ((1)H-MRS), 11 full-term neonates with severe perinatal asphyxia were studied within 48 h after birth. METHODS: T(1)- and T(2)-weighted MRI, diffusion-weighted MRI (DW-MRI), apparent diffusion coefficient of water (ADC) of the basal ganglia and parietal white matter, as well as (1)H-MRS of the basal ganglia were performed in a 1.5-Tesla magnetic field. Neurodevelopment was assessed in the survivors for at least 24 months. RESULTS: Nine of the 11 neonates had a poor outcome (7 died, 2 developed cerebral palsy). All examinations were normal in the 2 neonates with a good outcome. T(1)- and T(2)-weighted MRI were abnormal in 7, DWI was abnormal in 7, ADC was abnormal in 5, and elevated lactate/N-acetylaspartate ratios using (1)H-MRS were seen in 7 of the 9 neonates with a poor outcome. None of these 9 had completely normal MRI or (1)H-MRS findings. CONCLUSIONS: Using a combination of T(1)- and T(2)-weighted MRI, DW-MRI, ADC measurements and (1)H-MRS within 48 h after severe perinatal asphyxia, no abnormalities were seen with any of these techniques in both neonates with a good outcome.

Asphyxia Neonatorum↗

PubMed2005

In vivo flow territory mapping of major brain feeding arteries.

The ability to visualize the perfusion territories of major feeding arteries to the brain is important for many clinical applications. Since the work of Duret in 1874 on vascularization of the brain, many textbooks and atlases have shown schematic drawings of the supply areas of the major cerebral arteries. Recent postmortem studies demonstrated that the variability of the cerebral vascular territories is significantly greater than previously assumed. The aim of the present study was to investigate in vivo, the variability of flow territories of major brain feeding arteries. Flow territory mapping of the anterior (internal carotid arteries) and posterior (basilar artery) circulation was performed in 115 (58 +/- 9 years of age) subjects with selective arterial spin labeling MRI. Flow territory maps for the entire population indicated significant variation in flow territories. However, when the subjects are further categorized into groups with a complete circle of Willis, with a missing A1 segment and with a unilateral or bilateral fetal-type posterior cerebral artery, the results showed considerably lower variation within groups. It is therefore concluded that, the variation observed from the entire population is mainly caused by anatomical variants of the circle of Willis. To relate focal brain lesions to underlying flow territories in individual cases, knowledge of the anatomy of the circle of Willis is essential.

Aged↗

PubMed2005

Non-invasive visualization of collateral blood flow patterns of the circle of Willis by dynamic MR angiography.

The circle of Willis plays an important role in the distribution of blood flow in the brain. To obtain dynamic information of the blood flow through the circle of Willis, a dynamic MRA technique based on arterial spin labeling (ASL) is introduced as a non-invasive technique. When the ASL labeling slab is restricted to a single artery, it is possible to visualize selectively the flow distribution of that specific artery. However, because of the decay of the label and the presence of noise it is difficult to extract functional information from these images. In the present study we propose three visualization and post-processing methods for the interpretation of these images. Firstly, the passage of labeled blood was corrected for decay of the label and hereafter shown as a movie. Secondly, by calculating the time of arrival at every location in the arteries of the circle of Willis, a 2D image was reconstructed summarizing the information of the movie. Finally, quantitative flow values were obtained by relating the arterial input function to the passage of labeled blood through a region of interest encompassing the vessel under investigation. Experiments in a circle of Willis phantom showed a high linear relation between measured flow and true flow, although the measured values were 10-15% lower than the true flow values. Measurements in healthy volunteers showed the potential to quantify the flow in all major arteries of the circle of Willis.

Circle of Willis↗

PubMed2005

Distribution of cerebral blood flow in the circle of Willis.

PURPOSE: To prospectively determine the effect of anatomic variations in the circle of Willis on volume flow in the internal carotid arteries (ICAs) and basilar artery (BA). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Phase-contrast magnetic resonance (MR) angiography was used to measure the volume flow in the BA and ICAs in 208 patients (182 men, 26 women; mean age, 60 years) with symptomatic atherosclerosis or risk factors for atherosclerosis. Patients with steno-occlusive disease were excluded, and flow values were normalized for age. Three-dimensional time-of-flight MR angiograms were used to assess the anatomy of the circle of Willis. Differences in volume flow between a complete circle of Willis, a circle with a missing A1 segment, and a circle with a fetal-type posterior cerebral artery were analyzed (analysis of variance and Scheffe post hoc tests). RESULTS: The ICA volume flow in subjects with a complete configuration of the circle of Willis was 245 mL/min +/- 65 (standard deviation). Flow in the contralateral ICA was significantly increased (P < .01) in subjects with a missing A1 segment (303 mL/min +/- 56) compared with control subjects and compared with flow on the ipsilateral side (214 mL/min +/- 94; P < .01). In subjects with a unilateral or bilateral fetal-type posterior cerebral artery, the ICA volume flow was increased (P < .01) and the BA volume flow was decreased (P < .01) in comparison with the flow in subjects with no fetal-type circle of Willis. CONCLUSION: Large asymmetries in volume flow between the right and left ICAs or decreased volume flow in the BA is not necessarily caused by vascular disease but may be caused by variations in the anatomy of the circle of Willis.

Adult↗

PubMed2005

Functional MRI of human hypothalamic responses following glucose ingestion.

The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI) studies have indicated that glucose consumption has some effect on the neuronal activity levels in the hypothalamus, this matter has not been investigated extensively yet. For instance, dose-dependency of the hypothalamic responses to glucose ingestion has not been addressed. We measured the effects of two different glucose loads on neuronal activity levels in the human hypothalamus using fMRI. After an overnight fast, the hypothalamus of 15 normal weight men was scanned continuously for 37 min. After 7 min, subjects ingested either water or a glucose solution containing 25 or 75 g of glucose. We observed a prolonged decrease of the fMRI signal in the hypothalamus, which started shortly after subjects began drinking the glucose solution and lasted for at least 30 min. Moreover, the observed response was dose-dependent: a larger glucose load resulted in a larger signal decrease. This effect was most pronounced in the upper anterior hypothalamus. In the upper posterior hypothalamus, the signal decrease was similar for both glucose loads. No effect was found in the lower hypothalamus. We suggest a possible relation between the observed hypothalamic response and changes in the blood insulin concentration.

Adult↗

PubMed2005

Childhood-onset growth hormone deficiency, cognitive function and brain N-acetylaspartate.

Cognitive deficits have been reported in adults with childhood-onset growth hormone (GH) deficiency. We evaluated cognitive deficits simultaneously with parameters for neuronal integrity using (1)H magnetic resonance spectroscopy (MRS) in a cross-sectional design. We studied 11 adults (mean age 24.5 years) with childhood-onset GH deficiency, which persisted after reaching final height. All subjects were evaluated after interruption of GH supplementation for at least 3 months. We performed neuropsychological assessment (NPA) using tests evaluating memory, mental processing speed, reading ability and executive functioning. MRS was used to assess brain N-acetylaspartate (NAA)/choline ratios. Data were compared with an age-, sex- and education-matched control group (n=9, mean age 27.3 years). NPA demonstrated attenuated performance of the patients in the delayed verbal memory recall score (P<0.05) and the trail making A test (P<0.05), a measure of planning of behavior, processing speed and attention. Other neuropsychological tests were not affected. NAA/choline ratios were significantly reduced (P<0.01) in GH deficient subjects. Specific cognitive defects indicating affected memory and attention were found in patients with childhood-onset GH deficiency. These defects occur simultaneously with reduced neuronal integrity.

Adolescent↗