Allopurinol and blood pressure variability following ischemic stroke and transient ischemic attack: a secondary analysis of XILO-FIST.

Blood Pressure Variability (BPV) is associated with cardiovascular risk and serum uric acid level. We investigated whether BPV was lowered by allopurinol and whether it was related to neuroimaging markers of cerebral small vessel disease (CSVD) and cognition. We used data from a randomised, double-blind, placebo-controlled trial of two years allopurinol treatment after recent ischemic stroke or transient ischemic attack. Visit-to-visit BPV was assessed using brachial blood pressure (BP) recordings. Short-term BPV was assessed using ambulatory BP monitoring (ABPM) performed at 4 weeks and 2 years. Brain MRI was performed at baseline and 2 years. BPV measures were compared between the allopurinol and placebo groups, and with CSVD and cognition. 409 participants (205 allopurinol; 204 placebo) were included in the visit-to-visit BPV analyses. There were no significant differences found between placebo and allopurinol groups for any measure of visit-to-visit BPV. 196 participants were included in analyses of short-term BPV at week 4. Two measures were reduced by allopurinol: the standard deviation (SD) of systolic BP (by 1.30 mmHg (95% confidence interval (CI) 0.18-2.42, p = 0.023)); and the average real variability (ARV) of systolic BP (by 1.31 mmHg (95% CI 0.31-2.32, p = 0.011)). There were no differences in other measures at week 4 or in any measure at 2 years, and BPV was not associated with CSVD or cognition. Allopurinol treatment did not affect visit-to-visit BPV in people with recent ischemic stroke or TIA. Two BPV measures were reduced at week 4 by allopurinol but not at 2 years.

Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST): a multicentre, double-blinded, randomised, placebo-controlled trial.

Background: People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). Methods: In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. Findings: Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference -0.17, 95% CI -0.52 to 0.17, p = 0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. Interpretation: Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. Funding: The British Heart Foundation and the UK Stroke Association.

Neuronal antibody prevalence in children with seizures under 3 years: A prospective national cohort.

OBJECTIVE: To report the prevalence of anti-neuronal antibodies in a prospective whole-nation cohort of children presenting with seizures before their third birthday. METHODS: This was a prospective population-based national cohort study involving all children presenting with new-onset epilepsy or complex febrile seizures before their third birthday over a 3-year period. Patients with previously identified structural, metabolic, or infectious cause for seizures were excluded. Serum samples were obtained at first presentation and tested for 7 neuronal antibodies using live cell-based assays. Clinical data were collected with structured proformas at recruitment and 24 months after presentation. In addition, patients with seizures and clinically suspected autoimmune encephalitis were independently identified by a review of the case records of all children <3 years of age in Scotland who had undergone EEG. RESULTS: Two hundred ninety-eight patients were identified and recruited and underwent autoantibody testing. Antibody positivity was identified in 18 of 298 (6.0%). The antibodies identified were GABA receptor B (n = 8, 2.7%), contactin-associated protein 2 (n = 4, 1.3%), glycine receptor (n = 3, 1.0%), leucine-rich glioma inactivated 1 (n = 2, 0.7%), NMDA receptor (n = 1, 0.3%), and GABA receptor A (n = 1, 0.3%). None of these patients had a clinical picture of autoimmune encephalitis. Seizure classification and clinical phenotype did not correlate with antibody positivity. CONCLUSIONS: Autoimmune encephalitis is very rare in early childhood. However serum neuronal antibodies are identified in 6.4% of children presenting with seizures at <3 years of age. Antibody testing should not be a routine clinical test in early childhood-onset epilepsy because, in the absence of other features of autoimmune encephalitis, antibody positivity is of doubtful clinical significance. Antibody testing should be reserved for patients with additional features of encephalitis.

Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients.

BACKGROUND: The immediate and longer-term effects of hemodialysis on cerebral circulation, cerebral structure, and cognitive function are poorly understood. METHODS: In a prospective observational cohort study of 97 adults (median age 59 years) receiving chronic hemodialysis, we used transcranial Doppler ultrasound to measure cerebral arterial mean flow velocity (MFV) throughout dialysis. Using a well validated neuropsychological protocol, we assessed cognitive function during and off dialysis and after 12 months of treatment. We also used brain magnetic resonance imaging (MRI) to assess atrophy, white matter hyperintensities (WMHs), and diffusion parameters, and tested correlations between MFV, cognitive scores, and changes on MRI. RESULTS: MFV declined significantly during dialysis, correlating with ultrafiltrate volumes. Percentage of decline in MFV correlated with intradialytic decline in cognitive function, including global function, executive function, and verbal fluency. At follow-up, 73 patients were available for repeat testing, 34 of whom underwent repeat MRI. In a subgroup of patients followed for 12 months of continued dialysis, percentage of decline in MFV correlated significantly with lower global and executive function and with progression of WMH burden (a marker of small vessel disease). Twelve of 15 patients who received renal transplants during follow-up had both early and follow-up off-dialysis assessments. After transplant, patients' memory (on a delayed recall test) improved significantly; increased fractional anisotropy of white matter (a measure of cerebral diffusion) in these patients correlated with improving executive function. CONCLUSIONS: Patients undergoing hemodialysis experience transient decline in cerebral blood flow, correlating with intradialytic cognitive dysfunction. Progressive cerebrovascular disease occurred in those continuing dialysis, but not in transplanted patients. Cognitive function and cerebral diffusion improved after transplant.

Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features.

PCGF2 encodes the polycomb group ring finger 2 protein, a transcriptional repressor involved in cell proliferation, differentiation, and embryogenesis. PCGF2 is a component of the polycomb repressive complex 1 (PRC1), a multiprotein complex which controls gene silencing through histone modification and chromatin remodelling. We report the phenotypic characterization of 13 patients (11 unrelated individuals and a pair of monozygotic twins) with missense mutations in PCGF2. All the mutations affected the same highly conserved proline in PCGF2 and were de novo, excepting maternal mosaicism in one. The patients demonstrated a recognizable facial gestalt, intellectual disability, feeding problems, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Computer structural modeling suggests the substitutions alter an N-terminal loop of PCGF2 critical for histone biding. Mutant PCGF2 may have dominant-negative effects, sequestering PRC1 components into complexes that lack the ability to interact efficiently with histones. These findings demonstrate the important role of PCGF2 in human development and confirm that heterozygous substitutions of the Pro65 residue of PCGF2 cause a recognizable syndrome characterized by distinctive craniofacial, neurological, cardiovascular, and skeletal features.

Xanthine oxidase inhibition for the improvement of long-term outcomes following ischaemic stroke and transient ischaemic attack (XILO-FIST) - Protocol for a randomised double blind placebo-controlled clinical trial.

BACKGROUND: Allopurinol, a xanthine oxidase inhibitor, reduced progression of carotid-intima media thickness and lowered blood pressure in a small clinical trial in people with ischaemic stroke. Xanthine oxidase inhibition for improvement of long-term outcomes following ischaemic stroke and transient ischaemic attack (XILO-FIST) aims to assess the effect of allopurinol treatment on white matter hyperintensity progression and blood pressure after stroke. This paper describes the XILO-FIST protocol. METHODS: XILO-FIST is a multicentre randomised double-blind, placebo-controlled, parallel group clinical trial funded by the British Heart Foundation and the Stroke Association. The trial has been adopted by the Scottish Stroke Research Network and the UK Clinical Research Network. The trial is registered in clinicaltrials.gov (registration number NCT02122718). XILO-FIST will randomise 464 participants, aged greater than 50 years, with ischaemic stroke within the past month, on a 1:1 basis, to two years treatment with allopurinol 300 mg twice daily or placebo. Participants will undergo brain magnetic resonance imaging, cognitive assessment, ambulatory blood pressure monitoring and blood sampling at baseline and after two years treatment. The primary outcome will be white matter hyperintensity progression, measured using the Rotterdam progression scale. Secondary outcomes will include change in white matter hyperintensity volume, mean day-time systolic blood pressure and measures of cognitive function. Up to 100 will undergo additional cardiac magnetic resonance imaging in a sub-study of left ventricular mass. DISCUSSION: If white matter hyperintensity progression is reduced, allopurinol could be an effective preventative treatment for patients with ischaemic stroke and clinical endpoint studies would be needed. If allopurinol reduces blood pressure after stroke, then it could be used to help patients reach blood pressure targets.

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke.

BACKGROUND AND PURPOSE: Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. METHODS: Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl-Meyer Assessment-Upper Extremity). RESULTS: Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, -0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). CONCLUSIONS: This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161.

Advances in neuroimaging.

Over the last 20 years there have been great advances in the field of neuroimaging. However, information is still lacking for patients with a disorder of sex development (DSD) due to the rarity of these conditions. In this chapter the authors will review newly emerging techniques with a focus on the connectivity of the brain, describe sexually dimorphic brain structures and functions, and summarise what is known about the neuroanatomy and neurochemistry of individuals with a DSD. Sexual dimorphism exists in all aspects of neuroanatomy, neurochemistry and neurofunction, but the major challenge is to evaluate the relationship between these differences and relate them to the genetic and hormonal environment of the individual. Further imaging studies of normal gender differences are needed before the implications of neuroimaging findings for individuals with a DSD can be determined. Future directions for study include the association between gender-specific brain connectivity patterns and gender-related differences of various brain diseases.

Hypocupremia associated cytopenia and myelopathy: a national retrospective review.

Copper is an essential trace element that is involved in a number of important enzymatic processes throughout the body. Recent single case reports and small studies have shown that deficiency of copper can cause reversible haematological changes and irreversible neurological injury. We chose to undertake a national study, looking at all cases of copper deficiency in Scotland over a 5-yr period using information from a national reference laboratory. From 16 identified patients, we determined that 86% had both haematological and neurological features of copper deficiency, while 18% had haematological features only at presentation. Twelve of the sixteen patients had high serum zinc concentrations (>18 µm/L) nine patients were using zinc-containing dental fixatives at time of diagnosis. 94% of patients had haematological features as an initial manifestation of copper deficiency, which included anaemia, thrombocytopenia and neutropenia. Patients who underwent later bone marrow testing had appearances in keeping with refractory cytopenia with multilineage dysplasia, refractory anaemia with excess of blasts, unclassified marrow dysplasia or probable myelodysplasia (MDS). 75% of patients had neurological symptoms or signs, including progressive walking difficulties and paraesthesia, or gait difficulties without sensory signs. Clinical examination was in keeping with spastic paraparesis (either with or without sensory neuropathy). Magnetic resonance imaging (MRI) showed multifocal T2 hyper intense foci in the subcortical white matter, and atrophy of the cerebrum and cerebellum was also seen on computerised tomography (CT). MRI of the spinal cord showed signal change in the dorsal columns in either the cervical or thoracic cord. 93% of cytopenias responded to copper replacement and addressing the original cause of the copper deficiency, but only 25% of patients had improvement in their neurological function, while 33% deteriorated and 42% remained unchanged. Our study demonstrates that copper deficiency is an under-recognised cause of several types of cytopenia, which are reversible but can progress to significant neurological injury if left untreated. We illustrate the importance of identifying these patients early to prevent irreversible neurological injury.

Initial experience of 3 Tesla versus conventional field strength magnetic resonance imaging of small functioning pituitary tumours.

BACKGROUND: Higher field strength magnetic resonance imaging (MRI) is becoming increasingly available and offers improved image quality; however, the clinical usefulness of this technique for the demonstration of surgically treatable functional pituitary adenomas has not been clearly established. OBJECTIVE: To determine whether 3 Tesla (3T) MRI improves the detection of ACTH- and GH-secreting microadenomas over conventional imaging at field strengths of up to 1·5 Tesla (1·5T). DESIGN: Data sets from postgadolinium T1-weighted MRI at 1·5T and 3T were blinded, randomly ordered and assessed for the presence of pituitary tumour by two radiologists. Where possible, lesion signal difference to noise ratio (SDNR) was calculated for quantitative comparison. Imaging diagnoses were correlated with subsequent surgical and histological findings. PATIENTS: Twenty-four patients (10 men, 14 women) with biochemical evidence of Cushing's disease (19) or acromegaly (5) were identified over a 5-year period. RESULTS: 1·5T MRI gave a clear diagnosis of 12 pituitary tumours, all confirmed at 3T. Four additional definite lesions and one suspicious case were correctly identified at 3T. Histological correlation in 21 cases showed sensitivity improving from 54% with 1·5T to 85% with 3T. Radiologists' subjective image preference favoured 3T in 92%. Quantitative difference between tumour and parenchymal signal was significantly greater at 3T (mean SDNR -7·9 [3T] and -2·8 [1·5T], paired t-test P < 0·05). CONCLUSIONS: 3T MRI appears to offer increased conspicuity and detection of GH- and ACTH-secreting pituitary microadenomas. It is potentially clinically useful when 1·5T imaging is negative or equivocal.

Impact of GP direct-access computerised tomography for the investigation of chronic daily headache.

BACKGROUND: Chronic daily headache is a major healthcare problem, with significant resource implications for specialist services. Since 1999, GPs in Greater Glasgow have had direct access to computerised tomography (CT) for investigation of chronic daily headache. AIM: The purpose of this study is to assess the significance of pathology, impact of the service, and GP satisfaction. METHOD: The direct-access CT findings in patients between 1999 and 2007 were reviewed. Radiological reports were reviewed for abnormal findings by a radiologist. A neurologist reviewed those cases with abnormalities to assess their potential causation in presenting symptoms. A questionnaire was sent to the referring GP for every patient referred for direct-access CT. Data from the Information Services Division of NHS National Services Scotland was used to estimate potential cost benefits. RESULTS: A total of 4404 CT scans were performed. Abnormal findings were reported in 461 (10.5%), and the reported abnormalities were considered a potential causative factor for the presenting symptoms in 60 patients (1.4%). Other abnormalities mostly resulted from established cerebrovascular disease and atrophy; 986 GP questionnaires were analysed. The major body of GP opinion (n = 460, 47%) indicated that direct-access CT was their preferred choice for referral of chronic daily headache. If direct-access CT was not available, neurology (n = 448, 45%) and general medicine (n = 379, 38%) would be the commonest referral choices. This study also reveals that 86% did not require further specialist referral. Projecting the GP questionnaire data to the study group gave an approximate cost saving of at least £86 681.81. CONCLUSION: Direct-access CT is now the preferred choice of management for patients with chronic daily headache in primary care. Patients and GPs are reassured by a normal scan in the majority of cases. There may be cost savings, although confirmation of cost-effectiveness would require further study.

Perioperative ischemic complications of the brain after carotid endarterectomy.

BACKGROUND: The potential morbidity of cerebral ischemia after carotid endarterectomy (CEA) has been recognized, but its reported incidence varies widely. OBJECTIVE: To prospectively evaluate the development of cerebral ischemic complications in patients treated by CEA at a high-volume cerebrovascular center. METHODS: Fifty patients with moderate or severe carotid stenosis awaiting CEA were studied with perioperative diffusion-weighted imaging of the brain and standardized neurological evaluations. Microsurgical CEA was performed by 1 of 2 vascular neurosurgeons. Radiological studies were evaluated by faculty neuroradiologists who were blinded to the details of the clinical situation. RESULTS: Preoperative diffusion-weighted imaging studies were performed within 24 hours of surgery. A second study was obtained within 24 (92% of patients), 48 (4% of patients), or 72 (4% of patients) hours after surgery. Intraluminal shunting was used in 1 patient (2%), and patch angioplasty was used in 2 patients (4%). No patient had diffusion-weighted imaging evidence of procedure-related cerebral ischemia. Nonischemic complications consisted of postoperative confusion in an 87-year-old man with a urinary tract infection and a marginal mandibular nerve paresis in another patient. Radiological studies were normal in both patients. CONCLUSION: CEA is a relatively safe procedure that may be performed with an acceptable risk of cerebral ischemia in select patients. The low rate of ischemic complications associated with CEA sets a standard to which other carotid revascularization techniques should be held. The current results are presented with a discussion of the senior author's preferred surgical technique and a brief review of the literature.

Brain imaging in the unsedated pediatric patient: comparison of periodically rotated overlapping parallel lines with enhanced reconstruction and single-shot fast spin-echo sequences.

BACKGROUND AND PURPOSE: Periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER or PROP) is an effective means of compensating for head motion during MR imaging in adults. The aim of this study was to assess the value of this novel technique in unsedated children. METHODS: PROP T2-weighted fast spin-echo (FSE) imaging (TR/TE/NEX, 4000/83/2; 50 seconds) and T2-weighted single-shot FSE (SS-FSE) imaging (19,929/92/0.5; imaging time, 25 seconds) were performed in 35 unsedated children (mean age, 4.7 years +/- 4.2) who were undergoing brain MR imaging. Two observers assessed unlabelled images for motion artifact, other artifacts, visibility of pathology, and the preferred image overall. Sequences were compared by using the chi(2) test and concordant data from both observers. RESULTS: Both PROP and the SS-FSE imaging offered equal degrees of motion correction. Metallic artifacts were worse on PROP imaging, likely because of a higher receiver bandwidth (P <.001, chi(2) test). Pathology was present in 28 subjects and equally well seen on PROP and SS-FSE images. Overall, PROP was preferred, largely because of its improvements in image contrast (P <.001, chi(2) test). CONCLUSION: SS-FSE imaging and PROP provide equal motion correction, although PROP enables better assessment of the brain parenchyma.

Effects of zero-filled interpolation on cervical magnetic resonance angiographic measurement.

BACKGROUND AND PURPOSE: The aim of this study was to assess the effect of zero-filled interpolation (ZIP) on measurements of the cervical arteries because its benefits on the accuracy and precision of measurements in medium-sized arteries remains unknown. METHODS: Three observers measured 36 computer-simulated vessels (2-6.8 mm) and 130 normal cervical vessels (assessed with two-dimensional time-of-flight MR angiography) from 512-, 256-, and 256-ZIP matrix source images. The accuracy and precision of measurement was assessed for each matrix by using the Student t test and F test of variance, respectively. The effect of vessel size and matrix placement on measurement error was determined by means of linear regression and the Student t test, respectively. RESULTS: No significant difference was observed between simulated measurements obtained on the 512 matrix and their true value. The 256 matrix caused overestimation of vessel diameter compared with 512 matrix (mean bias, 0.3 mm for computer-simulated vessels and 0.1 mm for normal vessels). This effect was reduced with ZIP, by a mean of 0.1 mm for both groups (P <.03). Precision was not affected by the matrix size or ZIP, and vessel size and matrix placement did not alter the measurement error. CONCLUSION: Vessel diameter is overestimated on 256-matrix MR angiographic source images. ZIP reduces this overestimation; however, the effect is small and unlikely to be clinically important.

Improved image quality and detection of acute cerebral infarction with PROPELLER diffusion-weighted MR imaging.

PURPOSE: To compare periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) multishot fast spin-echo diffusion-weighted magnetic resonance (MR) imaging with single-shot echo-planar diffusion-weighted MR imaging for image quality and visualization of acute cerebral infarction. MATERIALS AND METHODS: Seventy subjects (35 men, 35 women; mean age, 55 years +/- 24 [SD]) who were suspected of having acute cerebral infarction (symptom duration, 2.8 days +/- 2.7) underwent PROPELLER and echo-planar MR imaging (b = 1,000 sec/mm(2)). Two neuroradiologists compared unlabeled images for presence of artifacts, visualization of infarction, and their preference of images. Interobserver agreement and image comparison were assessed by using the kappa statistic and the chi(2) test, respectively. RESULTS: PROPELLER MR imaging reduced susceptibility artifacts (n = 70 subjects), which limited visualization of temporal (echo-planar, n = 64; PROPELLER, n = 0; P <.01, chi(2) test), frontal (echo-planar, n = 58; PROPELLER, n = 1; P <.01), and parietal lobes (echo-planar, n = 5; PROPELLER, n = 0; P <.05) and cerebellum (echo-planar, n = 36; PROPELLER, n = 0; P <.01) and brainstem (echo-planar, n = 23; PROPELLER, n = 0; P <.01). Acute infarction (n = 31 subjects) was better demonstrated at PROPELLER MR imaging (PROPELLER better, n = 18; echo-planar better, n = 1; PROPELLER and echo-planar equal, n = 12; P <.01, chi(2) test). PROPELLER MR imaging was preferred in all (n = 70) but one case in which the lesion lay within the intersection gap (PROPELLER preferred, n = 69; echo-planar preferred, n = 1; P <.01, chi(2) test). CONCLUSION: With a short increase in imaging time, PROPELLER MR imaging offers better image quality and detection of acute cerebral infarction than does echo-planar MR imaging.

Multishot diffusion-weighted FSE using PROPELLER MRI.

A method for obtaining diffusion-weighted images that are free from the artifacts associated with echo-planar acquisitions, such as signal pile-up and geometric warping, is introduced. It uses an ungated, multishot fast spin-echo (FSE) acquisition that is self-navigated. The phase of the refocusing pulses is alternated to minimize non-Carr-Purcell-Meiboom-Gill (CPMG) artifacts. Several reconstruction methods are combined to make this method robust against motion artifacts. Examples are shown of clinical diffusion-weighted imaging and high-resolution diffusion tensor imaging.

Changes in brain water diffusion during the 1st year of life.

PURPOSE: To evaluate the normal water diffusion changes that occur during the 1st year of life. MATERIALS AND METHODS: Diffusion-weighted imaging was performed in 40 subjects (age range, birth to 1 year) in whom both magnetic resonance imaging and neurologic assessment results were normal at the time of imaging and, where available, at follow-up. Apparent diffusion coefficient (ADC) was calculated in four areas of white matter (anterior and posterior subcortical and internal capsule) and four of gray matter (cortex, thalamus, head of the caudate nucleus, and lentiform nucleus). Linear regression was used to examine the effect of age on ADC, and analysis of variance was used to compare ADC within different brain regions. RESULTS: ADC decreased with age in all regions (P <.01). Data best fit with a logarithmic decline (r(2) = 0.20-0.63). ADC was significantly higher in white (113 x 10(-5) mm(2)/sec) than in gray matter (102 x 10(-5) mm(2)/sec; P <.001). Significant differences were seen among three white matter regions (subcortical, 188 x 10(-5) mm(2)/sec at birth; anterior limb of internal capsule, 130 x 10(-5) mm(2)/sec; posterior limb of internal capsule, 109 x 10(-5) mm(2)/sec) and three gray matter regions (cortex, 134 x 10(-5) mm(2)/sec at birth; head of caudate nucleus, 134 x 10(-5) mm(2)/sec at birth; and thalamus and lentiform nucleus, 120 x 10(-5) mm(2)/sec; P <.01). CONCLUSION: Results suggest that in neonates and infants, water diffusion is highly dependent on both subject age and brain location.