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Background: Cerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing ABCD1 complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy., Methods: In a phase 2-3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI). The primary efficacy end point was survival without any of six major functional disabilities at month 24. The secondary end points included overall survival at month 24 and the change from baseline to month 24 in the total neurologic function score., Results: A total of 32 patients received eli-cel; 29 patients (91%) completed the 24-month study and are being monitored in the long-term follow-up study. At month 24, none of these 29 patients had major functional disabilities; overall survival was 94%. At the most recent assessment (median follow-up, 6 years), the neurologic function score was stable as compared with the baseline score in 30 of 32 patients (94%); 26 patients (81%) had no major functional disabilities. Four patients had adverse events that were directly related to eli-cel. Myelodysplastic syndrome (MDS) with excess blasts developed in 1 patient at month 92; the patient underwent allogeneic hematopoietic stem-cell transplantation and did not have MDS at the most recent follow-up., Conclusions: At a median follow-up of 6 years after lentiviral gene therapy, most patients with early cerebral adrenoleukodystrophy and MRI abnormalities had no major functional disabilities. However, insertional oncogenesis is an ongoing risk associated with the integration of viral vectors. (Funded by Bluebird Bio; ALD-102 and LTF-304 ClinicalTrials.gov numbers NCT01896102 and NCT02698579, respectively.)., (Copyright © 2024 Massachusetts Medical Society.)

Blood-brain barrier disruption marks the onset of cerebral adrenoleukodystrophy (CALD), a devastating cerebral demyelinating disease caused by loss of ABCD1 gene function. The underlying mechanism are not well understood, but evidence suggests that microvascular dysfunction is involved. We analyzed cerebral perfusion imaging in boys with CALD treated with autologous hematopoietic stem-cells transduced with the Lenti-D lentiviral vector that contains ABCD1 cDNA as part of a single group, open-label phase 2-3 safety and efficacy study (NCT01896102) and patients treated with allogeneic hematopoietic stem cell transplantation. We found widespread and sustained normalization of white matter permeability and microvascular flow. We demonstrate that ABCD1 functional bone marrow-derived cells can engraft in the cerebral vascular and perivascular space. Inverse correlation between gene dosage and lesion growth suggests that corrected cells contribute long-term to remodeling of brain microvascular function. Further studies are needed to explore the longevity of these effects., (© 2023. The Author(s).)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy can stabilize neurologic function and improve survival but has associated risks including transplant-related mortality (TRM), graft failure, and graft-versus-host disease (GVHD). An observational study of 59 patients with median age at allo-HSCT of 8 years addressed impact of donor source, donor match, conditioning regimen, and cerebral disease stage on first allo-HSCT outcomes. Efficacy analyses included 53 patients stratified by disease category: advanced disease (AD; n = 16) with Loes score >9 or neurological function score (NFS) >1 and 2 early disease (ED) cohorts (ED1 [Loes ≤4 and NFS ≤1; n = 24] and ED2 [Loes >4-9 and NFS ≤1; n = 13]). Survival free of major functional disabilities and without second allo-HSCT at 4 years was significantly higher in the ED (66%) vs AD (41%) cohort (P = .015) and comparable between ED1 and ED2 cohorts (P = .991). The stabilization of neurologic function posttransplant was greater in the ED vs AD cohort, with a median change from baseline at 24 months after allo-HSCT in NFS and Loes score, respectively, of 0 and 0.5 in ED1 (n = 13), 0.5 and 0 in ED2 (n = 6), and 2.5 and 3.0 (n = 4) in AD cohort. TRM was lower in the ED (7%) compared with the AD (22%) cohort; however, the difference was not significant (P = .094). Transplant-related safety outcomes were also affected by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts vs matched related donors (P = .039), and acute GVHD and graft failure incidences varied by conditioning regimen. This study was registered at www://clinicaltrials.gov as #NCT02204904., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Up to 40% of boys with adrenoleukodystrophy develop a severe central nervous system demyelinating form (cALD) characterized by white matter changes and gadolinium enhancement on magnetic resonance imaging (MRI). Hematopoietic cell transplant (HCT) is the only proven means to attenuate cALD progression. The elimination of active neuroinflammation is indicated radiographically by the resolution of gadolinium (Gd) enhancement and correlates to speed of donor neutrophil recovery. We analyzed 66 boys with cALD undergoing HCT for biomarkers correlating with early (30 days post-HCT) Gd signal resolution. We found that log Gd volume (cm 3 ) on pre-HCT MRI strongly positively correlated to day 30 Gd resolution (P = .0003) with smaller volume correlating to higher proportion resolved, as was the baseline gadolinium intensity score (P = .04), plasma chitotriosidase activity (P = .04), and faster absolute neutrophil count recovery (P = .03). In multivariate analysis, log Gd volume remained superior in determining which patients would have Gd signal resolution by 30 days post-HCT (P = .016). A final analysis indicated that early Gd resolution also correlated with less neurologic progression from baseline to 1 year following HCT (P = .006). MRI Gd volume may serve as a contributing biomarker to better delineate outcomes and an important metric in comparing therapies in the treatment of cALD., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Cerebral adrenoleukodystrophy is an inflammatory demyelinating condition that is the result of a mutation in the X-linked ABCD1 gene, a peroxisomal very long chain fatty acid transporter. Although mutations in this gene result in adrenal insufficiency in the majority of affected individuals, 40% of those affected develop the demyelinating cerebral form, cerebral adrenoleukodystrophy (CALD). CALD is characterized by imaging findings of demyelination and contrast enhancement on magnetic resonance imaging (MRI). Although allogeneic hematopoietic cell transplantation can arrest progression of CALD early in its course, there is no accepted therapy for patients with advanced CALD. Mesenchymal stem cells (MSCs) have been used in a variety of clinical trials to capitalize on their anti-inflammatory properties as well as promote tissue repair. We delivered MSCs via intrathecal (IT) route to two boys with rapidly advancing CALD. The first boy received three doses 1 week apart, whereas the second boy received a single dose of IT MSCs. We note delivery of IT MSCs was feasible and without complication. Follow-up MRI scans after IT MSC delivery showed progressive demyelination in the first patient and no change in demyelination or contrast enhancement in the second patient. Although the infusion of IT MSCs was safe, it did not halt CALD progression in this setting, and future studies should focus on patient selection and dose optimization., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background and Purpose: MR perfusion has shown abnormalities of affected WM in cerebral X-linked adrenoleukodystrophy, but serial data is needed to explore the import of such findings after hematopoietic stem cell transplantation. Our aim was to prospectively measure MR perfusion parameters in patients with cerebral adrenoleukodystrophy pre- and post-hematopoietic stem cell transplantation, and to correlate those measurements with clinical outcome., Materials and Methods: Ten patients with cerebral adrenoleukodystrophy prospectively underwent DSC-MR perfusion imaging at <45 days pre- (baseline), 30-60 days post-, and 1 year post-hematopoietic stem cell transplantation. MR perfusion measurements in the 10 patients and 8 controls were obtained from the parieto-occipital WM, splenium of the corpus callosum, leading enhancing edge, and normal-appearing frontal white matter. MR imaging severity scores and clinical neurologic function and neurocognitive scores were also obtained. MR perfusion values were analyzed in the patients with cerebral adrenoleukodystrophy at each time point and compared with those in controls. Correlations were calculated between the pre-hematopoietic stem cell transplantation MR perfusion values and 1-year clinical scores, with P value adjustment for multiple comparisons., Results: At baseline in patients with cerebral adrenoleukodystrophy, both relative CBV and relative CBF within the splenium of the corpus callosum and parieto-occipital WM significantly differed from those in controls (P = .005-.031) and remained so 1 year post-hematopoietic stem cell transplantation (P = .003-.005). Meanwhile, no MR perfusion parameter within the leading enhancing edge differed significantly from that in controls at baseline or at 1 year (P = .074-.999) or significantly changed by 1 year post-hematopoietic stem cell transplantation (P = .142-.887). Baseline Loes scores correlated with 1-year clinical neurologic function (r = 0.813, P < .0001), while splenium of the corpus callosum relative CBV also significantly correlated with 1-year neurologic function scale and the neurocognitive full-scale intelligence quotient and performance intelligence quotient scores (r = -0.730-0.815, P = .007-.038)., Conclusions: Leading enhancing edge measurements likely remain normal post-hematopoietic stem cell transplantation in cerebral adrenoleukodystrophy, suggesting local disease stabilization. Meanwhile, parieto-occipital WM and splenium of the corpus callosum relative CBV and relative CBF values worsened; this change signified irreversible injury. Baseline splenium of the corpus callosum relative CBV may predict clinical outcomes following hematopoietic stem cell transplantation., (© 2016 by American Journal of Neuroradiology.)

Background and Purpose: Metachromatic leukodystrophy (MLD) is a devastating demyelinating disease for which novel therapies are being tested. We hypothesized that MR imaging of brain lesion involvement in MLD could be quantified along a scale., Materials and Methods: Thirty-four brain MR images in 28 patients with proved biochemical and genetic defects for MLD were reviewed: 10 patients with late infantile, 16 patients with juvenile, and 2 patients with adult MLD. All MR images were reviewed by experienced neuroradiologists and neurologists (2 readers in Germany, 2 readers in the United States) for global disease burden, as seen on the T2 and fluid-attenuated inversion recovery images. A visual scoring method was based on a point system (range, 0-34) derived from the location of white matter involvement and the presence of global atrophy, analogous to the scoring system developed for adrenoleukodystrophy. The readers were blinded to the neurologic findings., Results: Thirty-three of 34 MR images showed confluent T2 hyperintensities of white matter. The inter-rater reliability coefficient was 0.988. Scores between readers were within 2 points of each other. Serial MR imaging studies in 6 patients showed significant progressive disease in 3 patients (initial score average, 4; mean follow-up, 24.3) and no change or 1 point progression in 3 patients (initial score average, 12; mean follow-up, 12.66). Projection fibers and the cerebellum tended to be involved only in advanced stages of disease., Conclusions: The MLD MR severity scoring method can be used to provide a measure of brain MR imaging involvement in MLD patients.

Objectives: To identify asymptomatic boys with X-linked adrenoleukodystrophy who have a normal magnetic resonance image (MRI), and to assess the effect of 4:1 glyceryl trioleate-glyceryl trierucate (Lorenzo's oil) on disease progression., Method: Eighty-nine boys (mean +/- SD baseline age, 4.7 +/- 4.1 years; range, 0.2-15 years) were identified by a plasma very long-chain fatty acids assay used to screen at-risk boys. All were treated with Lorenzo's oil and moderate fat restriction. Plasma fatty acids and clinical status were followed for 6.9 +/- 2.7 years. Changes in plasma hexacosanoic acid levels were assessed by measuring the length-adjusted area under the curve, and a proportional hazards model was used to evaluate association with the development of abnormal MRI results and neurological abnormalities., Results: Of the 89 boys, 24% developed MRI abnormalities and 11% developed both neurological and MRI abnormalities. Abnormalities occurred only in the 64 patients who were aged 7 years or younger at the time therapy was started. There was significant association between the development of MRI abnormalities and a plasma hexacosanoic acid increase. (For a 0.1-microg/mL increase in the length-adjusted area under the curve for the hexacosanoic acid level, the hazard ratio for incident MRI abnormalities in the whole group was 1.36; P = .01; 95% confidence interval, 1.07-1.72.) Results for patients aged 7 years or younger were similar (P = .04)., Conclusions: In this single-arm study, hexacosanoic acid reduction by Lorenzo's oil was associated with reduced risk of developing MRI abnormalities. We recommend Lorenzo's oil therapy in asymptomatic boys with X-linked adrenoleukodystophy who have normal brain MRI results.

Cerebral X-linked adrenoleukodystrophy (X-ALD) is a disorder of very-long-chain fatty acid metabolism, adrenal insufficiency, and cerebral demyelination. Death occurs within 2 to 5 years of clinical onset without hematopoietic cell transplantation (HCT). One hundred twenty-six boys with X-ALD received HCT from 1982 to 1999. Survival, engraftment, and acute graft-versus-host disease were studied. Degree of disability associated with neurologic and neuropsychological function and cerebral demyelination were evaluated before and after HCT. Complete data were available and analyzed for 94 boys with cerebral X-ALD. The estimated 5- and 8-year survival was 56%. The leading cause of death was disease progression. Donor-derived engraftment occurred in 86% of patients. Demyelination involved parietal-occipital lobes in 90%, leading to visual and auditory processing deficits in many boys. Overall 5-year survival of 92% in patients with 0 or 1 neurologic deficits and magnetic resonance imaging (MRI) severity score less than 9 before HCT was superior to survival for all others (45%; P <.01). Baseline neurologic and neuropsychological function, degree of disability, and neuroradiologic status predicted outcomes following HCT. In this first comprehensive report of the international HCT experience for X-ALD, we conclude that boys with early-stage disease benefit from HCT, whereas boys with advanced disease may be candidates for experimental therapies.

Our objective was to study the phenotype evolution of X-linked adrenoleukodystrophy (X-ALD) and the relation between axonal degeneration and cerebral demyelination. Although different X-ALD phenotypes are recognized, little is known about their evolution. Neuropathological and electrophysiological studies have shown that X-ALD is a disease with mixed features of axonal degeneration, leading to myeloneuropathy, and a severe inflammatory reaction in the cerebral white matter, resulting in demyelination. Retrospectively, 129 men with X-ALD were studied who were 1) at least 20 years presently or at the time of death, and 2) regularly monitored. Phenotype assignments were made at diagnosis and at present, or at death, using medical history and findings of neurological examination. Handicap was studied with the modified Rankin scale, and cerebral abnormalities with the X-ALD MRI severity (Loes) score. The mean follow-up interval was 10.1 +/- 5.0 years. Among 32 patients neurologically asymptomatic at diagnosis, 16 (50%) developed neurological deficits. Among 68 adrenomyeloneuropathy (AMN) patients initially without clinical brain involvement, 13 (19%) additionally developed cerebral demyelination. In a subset of 60 AMN patients, a moderate handicap evolved over a period of 16.2 +/- 8.9 years. Among 13 AMN patients with additional definite or probable cerebral involvement at diagnosis, eight died and one remained in a vegetative state. Most of the 16 patients with the cerebral phenotypes deteriorated. There is a high risk for adult neurologically asymptomatic patients to develop neurological deficits and for AMN patients to develop cerebral demyelination. Axonal degeneration and cerebral demyelination emerge in X-ALD independently of each other. This may have implications for the phenotype classification, the search for modifying factors, and the development and evaluation of new therapies.

The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy (AMN) in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. This study reports on 372 patients ranging in age from less than 3 years to adulthood, who have been followed at the Kennedy Krieger Institute. With the aim of determining whether a method could be developed to predict clinical course by analysis of data available at time of first contact, the patients were subdivided into 18 subgroups on the basis of age and the extent of brain magnetic resonance (MRI) abnormality utilizing the MRI scoring system devised by Loes et al. Scores to grade degree of neurologic and neuropsychologic impairment were also developed. There was strong correlation between MRI and the neurology and neuropsychology scores at baseline. Information based exclusively on age and MRI score at time of first contact was highly predictive of future clinical course and should aid the evaluation of the effects of bone marrow transplantation and the selection of patients for this procedure, as well as the evaluation of other therapies that may be developed in the future.

Background and Purpose: Early assignment of disease progression among patients with X-linked adrenoleukodystrophy (ALD) is critical for the appropriate selection of effective therapy. We evaluated the association between contrast enhancement on T1-weighted spin-echo MR images and disease progression., Methods: Clinical charts of patients with X-linked ALD were reviewed for age, availability of MR images of the brain, severity of neurologic impairment, and duration and number of follow-up evaluations. Forty-three male patients with X-linked ALD had undergone multiple MR imaging examinations of the brain that consisted of at least sagittal and axial T1-weighted spin-echo, axial double-echo spin-echo, and contrast-enhanced axial T1-weighted spin-echo imaging. The MR images were reviewed for the presence of contrast enhancement. In addition, global disease burden, as shown by the double-echo spin-echo images, was assessed using a visual scoring method (Loes score)., Results: Enhancement was seen on the initial T1-weighted spin-echo MR images of 21 (49%) patients; 18 (86%) of the 21 patients had disease progression revealed by the follow-up evaluations based on MR imaging (Loes) and neurologic scores. No enhancement was seen on the initial T1-weighted spin-echo MR images of 22 (51%) patients; for 18 (82%) of the 22 patients, no evidence of disease progression was revealed by the follow-up evaluations., Conclusion: There is a very strong association between the presence of contrast enhancement on T1-weighted MR images and X-linked ALD progression based on clinical evaluation and MR imaging.

Background and Purpose: Our purpose was to determine the characteristic MR features of early-onset (before age 2 years) versus late-onset (after age 2 years) globoid cell leukodystrophy (GLD)., Methods: Thirty-four brain MR images in 22 patients with GLD were reviewed. A severity score (0 to 32), based on a point system derived from the location and extent of disease and the presence of focal and/or global atrophy, was calculated for each examination., Results: Of the 22 patients, three were asymptomatic and 19 were symptomatic. Ten patients had early-onset disease, whereas nine had late-onset disease. MR images of all patients showed abnormalities. In the early-onset group (n = 10; mean maximum MR score, 8.1; range, 3-18), 90% had pyramidal tract involvement, 80% had cerebellar white matter involvement, 70% had deep gray matter involvement, 60% had posterior corpus callosal involvement, 50% had parietooccipital white matter involvement, and 40% had cerebral atrophy. Serial MR imaging in four of these patients revealed progressive disease. In the late-onset group (n = 9; mean maximum MR score, 5.6; range, 4-10), 100% had pyramidal tract involvement, 100% had parietooccipital white matter involvement, 89% had posterior corpus callosal involvement, and none had cerebellar white matter involvement, deep gray matter involvement, or cerebral atrophy. Serial MR imaging in one patient with late-onset GLD did not reveal any change. A spectrum of findings was observed in the three patients who were asymptomatic., Conclusion: Cerebellar white matter and deep gray matter involvement are present only in early-onset GLD. Pyramidal tract involvement is a characteristic finding in both early- and late-onset GLD. This scoring method for brain MR observations will assist in the objective assessment of the impact of hematopoietic stem cell transplantation in patients with GLD.

Background: Globoid-cell leukodystrophy is caused by a deficiency of galactocerebrosidase, which results in progressive central nervous system deterioration. We investigated whether allogeneic hematopoietic stem-cell transplantation can provide a source of leukocyte galactocerebrosidase and thereby prevent the decline of central nervous system function in patients with the disease., Methods: Five children with globoid-cell leukodystrophy (one with the infantile type and four with late-onset disease) were treated with allogeneic hematopoietic stem-cell transplantation. Measurement of leukocyte galactocerebrosidase levels, neurologic examinations, neuropsychological tests, magnetic resonance imaging of the central nervous system, cerebrospinal fluid protein assays, and neurophysiologic measurements were performed before and after transplantation, with follow-up ranging from one to nine years., Results: Engraftment of donor-derived hematopoietic cells occurred in all patients and was followed by restoration of normal leukocyte galactocerebrosidase levels. In the four patients with late-onset disease, the central nervous system deterioration was reversed, and in the patient with the infantile form of the disease, signs and symptoms have not appeared. Magnetic resonance imaging showed a decrease in signal intensity in the three patients with late-onset disease who were assessed both before and after transplantation. Abnormalities in cerebrospinal fluid total protein levels were corrected in three patients with late-onset disease and substantially reduced in the patient with the infantile form., Conclusions: Central nervous system manifestations of globoid-cell leukodystrophy can be reversed by allogeneic hematopoietic stem-cell transplantation.

Purpose: To determine the potential of proton MR spectroscopy to monitor patients with childhood-onset cerebral adrenoleukodystrophy (COCALD)., Methods: Single-voxel MR spectroscopy was performed in 16 children with COCALD (24 examinations) who had had no treatment and in 7 children (13 examinations) who had had bone marrow transplantation., Results: In the untreated children with clinically active COCALD, the metabolite ratios N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Ch) were decreased while Ch/Cr was increased. This trend agrees well with those reported by other researchers, although different experimental sequences and parameters were used in our study. Comparison of these ratios with those from a control group yielded significant differences in the occipital region. In the children who were clinically stable after bone marrow transplantation, the mean levels of the three ratios were between those of the control subjects and the patients with untreated COCALD: the differences in these ratios approached significance. In patients who had been monitored periodically, MR spectroscopy metabolite ratios correlated well with the dementia rating score, reflecting clinical status., Conclusion: There is good correlation between MR spectroscopy metabolite ratios and a patient's clinical status. MR spectroscopy appears to be a useful, noninvasive tool to monitor patients with adrenoleukodystrophy, and it increases the overall sensitivity of MR techniques in clinical applications.

Trauma to the cerebrovascular system can result in vascular injuries, such as dissection, pseudoaneurysm, thrombosis, rupture, and arteriovenous fistula. Although the diagnosis of vascular injury is usually considered in all cases of penetrating trauma, it may be overlooked in patients with nonpenetrating trauma. The possibility of vascular injury should be considered in all patients with head and neck trauma, especially those patients with acute or delayed neurologic dysfunction. Although intra-arterial angiography remains the gold standard diagnostic tool, the combination of MR imaging and MR angiography may permit noninvasive diagnosis of vascular injury. Moreover, MR readily provides detection of intracranial sequelae, such as cerebral infarction and intracranial hemorrhage.

Purpose: To report the serial brain MR observations in patients with childhood-onset cerebral adrenoleukodystrophy 1 to 2 years after bone marrow transplantation., Methods: Eight boys with childhood-onset cerebral adrenoleukodystrophy have undergone successful transplantation at our institution. Seven patients (mean age, 8 years 10 months; range, 5 years 3 months to 11 years 9 months) had serial MR studies before and after transplantation. An MR severity score (0 to 34) based on disease location and the presence or absence of focal atrophy was calculated for each patient scan., Results: Posttransplantation serial MR showed improvement in two patients, stabilization in three patients, and worsening of MR signal changes in two patients. The patient with the most striking progression had systemic graft-versus-host disease. Although the adrenoleukodystrophy MR severity score did not change in three patients after transplantation, two of these patients did show improved margination of disease., Conclusion: Bone marrow transplantation can affect brain MR observations in childhood-onset cerebral adrenoleukodystrophy. Although brain MR findings do not typically resolve, they do seem to stabilize, which is an improvement over the natural MR history of the disease.

Purpose: To develop a scoring method for brain observations in patients with X-linked adrenoleukodystrophy., Methods: One hundred seventy-five brain MR scans in 83 male subjects less than 20 years of age with proved biochemical defects were reviewed. A severity score (0 to 34), based on a point system derived from location and extent of disease and the presence of focal and/or global atrophy, was calculated for each exam., Results: Fifty-five of the 83 patients showed MR findings consistent with adrenoleukodystrophy. Two major patterns were observed. A posterior pattern (mean score, 9; range, 0.5 to 25) was present in 80% of patients, and an anterior pattern (mean score, 10; range, 2 to 18) was present in 15% of patients. Serial MR imaging, positive for adrenoleukodystrophy in 34 patients (mean follow-up, 23 months; range, 2 months to 6 years 11 months), showed progressive disease in 52%, progressive disease with subsequent stabilization in 18%, stable disease in 24%, and minimal improvement in 6%., Conclusion: The adrenoleukodystrophy MR severity scoring method is a measure that can be used with standard MR images. When used in conjunction with clinical parameters, this scoring method may help define better the natural history of adrenoleukodystrophy and monitor response to developing therapies.

The childhood-onset cerebral form of adrenoleukodystrophy has a devastating neurologic prognosis. Unfortunately, there is no early method of distinguishing it from the more benign forms of adrenoleukodystrophy, such as adrenomyeloneuropathy. To evaluate the manner in which this disease entity may be reflected in the cerebrospinal fluid, we studied a consecutive series of 19 patients, all with biochemically proved adrenoleukodystrophy. total protein, immunoglobulin production, cytokine levels, and cerebrospinal fluid pressure were measured. In this single sample of cerebrospinal fluid, a significant correlation existed between clinical stage of the illness and cerebrospinal fluid myelin basic protein. No correlation existed with total protein, cytokines, or measures of immunoglobulin production.

The authors describe a steady-state free precession technique for imaging the inner ear. Although the signal-to-noise ratio is not as great as with other three-dimensional MR techniques, the inherent high contrast of inner ear structures makes this a valuable technique for patients with sensorineural hearing loss and for those who refuse paramagnetic contrast material.

Glioma represents the most common primary intra-axial brain tumor. Currently, magnetic resonance (MR) imaging is the study of choice for the radiographic evaluation of patients with primary central nervous system glioma prior to and following therapeutic intervention. Computed tomography and MR imaging are frequently used for stereotactic biopsy and mapping. MR spectroscopy and/or thallium-201 single photon emission computed tomography may prove helpful in differentiating recurrent malignancy from radiation-induced necrosis.

Eighty patients with a total of 82 ischemic lesions were examined with contrast-enhanced MR imaging 1 hr to 1 month after onset of symptoms. The studies were reviewed retrospectively to determine the presence of arterial enhancement and the patterns of parenchymal enhancement. Arterial enhancement was often detected on the initial MR examination (45%), was frequently demonstrated in cortical infarction (86%), in some cases preceded the development of signal changes on T2-weighted images, and resolved by 11 days. The presence of arterial enhancement appeared to be a better indicator of clinical severity than was the presence of proximal vessel occlusion on MR or angiographic studies. Two patterns of parenchymal enhancement were seen: progressive enhancement and early and/or intense enhancement. In patients with the progressive pattern, parenchymal enhancement on postcontrast T1-weighted images was rarely seen before 7 days, while signal abnormalities on T2-weighted images were intense during the first few days. The early and/or intense enhancement pattern was usually present within the first 3 days, approximated or exceeded the area and intensity of signal changes on T2-weighted images, and was usually associated with minimal or reversible neurologic sequelae (except when located in or near a watershed zone), suggesting a lesser degree of ischemic insult than was associated with the progressive pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

MR changes of cerebral ischemia have been shown to occur as early as 1-2 hr after vessel occlusion in experimental models of stroke. However, the MR findings in the early stages of ischemic stroke in the clinical population have not been well established. We studied 41 lesions in 39 patients in whom MR was performed within the first 24 hr after onset of ischemic symptoms. Twenty-five lesions were studied with gadopentetate dimeglumine. Vascular flow-related abnormalities, including absence of normal flow void and presence of arterial enhancement, were the earliest MR findings, detected within minutes of onset. Morphologic changes (brain swelling) on T1-weighted images without signal changes on T2-weighted images could be detected within the first few hours. Signal changes were not usually found before 8 hr on T2-weighted images or before 16 hr on T1-weighted images. In contrast to the absence of parenchymal enhancement typically found in cortical infarctions in the first 24 hr, a few lesions (including transient occlusions, partial occlusions, and isolated watershed infarctions) exhibited early, exaggerated parenchymal enhancement. We conclude that signal changes may not be reliable in detecting ischemic stroke within the first 8 hr after onset. Vascular abnormalities, when present, are the most reliable and earliest findings. Other MR findings of early ischemic stroke, including morphologic changes and early, exaggerated parenchymal enhancement, may also precede signal changes. Paramagnetic contrast administration often provides valuable information in the detection and evaluation of acute ischemia.

The hypothalamus, the ventral-most portion of the diencephalon, surrounds the anterior inferior portion of the third ventricle (Fig. 1). It functions primarily as an integrative mechanism for various autonomic and neuroendocrine activities including temperature regulation, water balance, behavior, and appetite. This pictorial essay illustrates the value of MR in depicting the normal anatomy and abnormalities of the hypothalamic region.

Fifty-three magnetic resonance imaging (MRI) and 25 computed tomography (CT) studies of 53 head and neck masses in pediatric patients were reviewed retrospectively. All lesions had pathologic proof except for 2 metastatic and 2 recurrent lesions, which only had prior pathologic confirmation at their primary sites. These included 12 malignant tumors, 23 benign tumors, 6 inflammatory masses, and 12 congenital lesions. The MRI performance ranged predominantly from good to excellent in detection of the lesion and the extent of involvement and in contrast to the surrounding tissue; when CT comparison was available, MRI proved to be equal to or better than it in detection of these factors and in preoperative diagnosis. Our results suggest that MRI should be the method of choice for the initial evaluation of the pediatric head and neck region, especially in those patients requiring multiple examinations. However, CT and MRI should be used conjunctively in complicated cases, especially those possibly involving lesions with calcifications or bony involvement.

We report four cases of biopsy proved cerebral amyloid angiopathy demonstrated by MR imaging. White matter signal hyperintensities on T2-weighted spin-echo pulse sequences were present in three patients. We believe the white matter lesions associated with cerebral amyloid angiopathy are not specific to this disorder but rather reflect hypoperfusion of distal white matter resulting from vascular disease.

Cerebral angiography in patients with nontraumatic lobar intracerebral hemorrhage may or may not uncover the underlying cause of the disorder. The CT and cerebral angiographic studies of 67 consecutive patients with nontraumatic lobar intracerebral hemorrhage were reviewed to assess the relationship between CT pattern and location of hemorrhage and the frequency of diagnostic angiographic findings. Origins of these hematomas were also determined and correlated with radiographic findings. CT revealed 26 temporal, 18 frontal, 17 parietal, three occipital, and three multiple lobar hematomas. Thirty-three patients had "pure" lobar hematomas, 12 had coexistent intraventricular hemorrhage, 12 had associated subarachnoid hemorrhage, and 10 had both intraventricular and subarachnoid hemorrhage accompanying their lobar hematomas. Angiographic findings were diagnostic in 29 cases (43%). In the presence of accompanying subarachnoid hemorrhage, angiographic findings were diagnostic in 17 (77%) of 22 patients; in its absence, angiography was diagnostic in 12 (27%) of the remaining 45 patients. Diagnostic angiograms were also more frequent in the presence of a frontal or temporal lobar hematoma than with a parietal or occipital lobar hematoma. While CT patterns do influence the frequency of diagnostic angiographic findings, cerebral angiography is recommended in all patients with otherwise unexplained nontraumatic lobar intracerebral hemorrhage.

A three-year old male presented with severe hydronephrosis secondary to posterior urethral valves; a pelvic supernumerary kidney was discovered postoperatively. Radionuclide imaging assisted in the management of this patient by providing estimates of relative renal function. A report of the case and a complete summary of the literature concerning this unusual duplication anomaly follows.

An 18-month-old male sustained an intra-oral injury after falling on a pen. The internal carotid artery was occluded without evident neurologic deficit. The pen tip was surgically removed from the cerebellum.