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A J Barkovich

Publications and source records attributed to A J Barkovich.

At least 19 recordsLinked to original sources
PubMed2006

A magnetic resonance approach to metabolic disorders in childhood.

INTRODUCTION: Inborn errors of metabolism are a difficult group of disorders to diagnose. Clinical signs and symptoms overlap among the different diseases, biochemical tests are often nonspecific or unrevealing, and genetic analyses are time consuming, expensive, and often not commercially available. Imaging can aid in diagnosing some disorders, but the imaging findings of many disorders seem to overlap, particularly as more and more disorders are identified and described. DEVELOPMENT: Several groups have proposed an imaging approach based upon pattern recognition on magnetic resonance imaging, supplemented by metabolic data from proton magnetic resonance spectroscopy and microstructural data, as assessed by diffusion weighted imaging. CONCLUSION: When properly used, this pattern recognition approach in conjunction with the other imaging tools can be very useful for separating the complex group of metabolic disorders into more manageable groups. Indeed, sometimes this approach allows a specific diagnosis to be made.

Brain Diseases, Metabolic↗
PubMed2006

Diffusion MRI abnormalities after prolonged febrile seizures with encephalopathy.

BACKGROUND: Patients with encephalopathy heralded by a prolonged seizure as the initial symptom often have abnormal subcortical white matter on diffusion-weighted MRI (DWI). OBJECTIVE: To determine if these patients share other common features. METHODS: Patients with encephalopathy heralded by a prolonged seizure and followed by the identification of abnormal subcortical white matter on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Seventeen patients were identified, ages 10 months to 4 years. All had a prolonged febrile seizure (longer than 1 hour in 12 patients) as their initial symptom. Subsequent seizures, most often in clusters of complex partial seizures, were seen 4 to 6 days after the initial seizure in 16 patients. Outcome ranged from almost normal to severe mental retardation. MRI performed within 2 days of presentation showed no abnormality. Subcortical white matter lesions were observed on DWI between 3 and 9 days in all 17 patients. T2-weighted images showed linear high intensity of subcortical U fibers in 13 patients. The lesions were predominantly frontal or frontoparietal in location with sparing of the perirolandic region. The diffusion abnormality disappeared between days 9 and 25, and cerebral atrophy was detected later than 2 weeks. Three patients having only frontal lesions had relatively good clinical outcome. CONCLUSIONS: Although the pathophysiologic mechanism remains unknown, these patients seem to have a distinctive encephalopathy syndrome. MRI is helpful in establishing the diagnosis of this encephalopathy.

Atrophy↗
PubMed2006

A familial syndrome of unilateral polymicrogyria affecting the right hemisphere.

A number of familial syndromes of bilateral polymicrogyria (PMG) have been described, but reported unilateral PMG cases have generally been sporadic. The authors identified four families in which unilateral right-sided PMG on MRI was present in more than one individual, with pathologic confirmation in one. Core clinical features included contralateral hemiparesis, developmental delay, and focal seizures. The authors' findings suggest that unilateral PMG exists in a familial syndrome of probable germline genetic origin.

Adolescent↗
PubMed2006

MR imaging of the neonatal brain.

The advent of modern neuroimaging tools and methods has revolutionized the evaluation of the brain in neonates. The development of magnetic resonance (MR)-compatible monitoring tools and incubators has alleviated concerns regarding transportation of these unstable infants. The development of dedicated neonatal imaging coils has increased signal-to-noise ratios dramatically in images of the neonatal brain; this has made high-quality anatomic imaging, diffusion tensor imaging, and proton MR spectroscopy feasible in a normal imaging time. In centers that are equipped properly for neonatal MR imaging, MR is now unquestionably the study of choice for neonates who have encephalopathy or suspected brain injury. This article discusses the application of modern MR techniques to some of the causes of encephalopathy in neonates.

Basal Ganglia Diseases↗
PubMed2006

MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy.

BACKGROUND: Although the imaging, spectroscopic, and diffusion characteristics of brains of infants with neonatal encephalopathy have been described, the time course during which these changes evolve is not clear. The results of sequential MR imaging studies--including anatomic MR imaging, proton MR spectroscopy, and diffusion tensor imaging (DTI)--of 10 patients enrolled prospectively in a study of neonatal encephalopathy are reported to help to clarify the time course of changes in different brain regions during the first 2 weeks of life. METHODS: Ten neonates were prospectively enrolled in a study of the evolution of MR findings in neonatal encephalopathy and were studied 2 (8 patients) or 3 (2 patients) times within the first 2 weeks of life. The MR examination included spin-echo T1 and T2-weighted images, DTI, and long echo time (288 milliseconds) proton MR spectroscopy. Diffusion parameters (diffusivity [D(av)], fractional anisotropy [FA], and individual eigenvalues) were calculated for 10 1-cm2 regions of interest in each hemisphere that were placed based on anatomic landmarks. D(av) and FA were then measured manually in the same areas on a workstation. Metabolite ratios (NAA/Ch, Cr/Ch, Cr/NAA, Lac/Ch, and Lac/NAA) were calculated in 7 regions of interest. Imaging appearance, diffusion parameters, and metabolite ratios were then evaluated longitudinally (comparing with other studies on the same patient at different times) and cross-sectionally (comparing all studies performed on the same postnatal day). RESULTS: In most of the patients a characteristic evolution of DTI and MR spectroscopy parameters was seen during the first 2 weeks after birth. Although the anatomic images were normal or nearly normal on the first 2 days after birth in most patients, abnormalities were detected on DTI (both visually and by quantitative interrogation of D(av) maps) and proton MR spectroscopy (abnormal metabolite ratios). These parameters tended to worsen until about day 5 and then normalize, though in several patients abnormal metabolite ratios persisted. Of interest, as areas of abnormal diffusivity pseudonormalized within one region of the brain they would develop in other areas. Therefore, the pattern of injury looked very different when imaging was performed at different times during this evolution. CONCLUSION: Patterns of injury detected by standard anatomic imaging sequences, DTI sequences, and proton MR spectroscopy varied considerably during the first 2 weeks after injury. The appearance of new areas of reduced diffusion simultaneous with the pseudonormalization of areas that had reduced diffusion at earlier times can result in an entirely different pattern of injury on diffusivity maps acquired at different time points. Awareness of these evolving patterns is essential if studies are performed and interpreted during this critical period of time.

Brain Diseases↗
PubMed2006

Widening spectrum of a reversible splenial lesion with transiently reduced diffusion.

Four patients with encephalitis/encephalopathy and parenchymal lesions accompanying reversible splenial lesions were retrospectively evaluated. In 3 patients, reversible lesions with transiently reduced diffusion were seen in the splenium and symmetrically in the peripheral frontoparietal white matter, clinical signs and symptoms were mild, and recovery was complete. These and previous observations suggest a less severe course and outcome for patients with reversible lesions isolated to the splenium or to the splenium and peripheral frontoparietal white matter.

Brain Diseases↗
PubMed2006

Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis, part 1.

Fetal MR imaging is an increasingly available technique used to evaluate the fetal brain and spine. This is made possible by recent advances in technology, such as rapid pulse sequences, parallel imaging and advances in coil design. This provides a unique opportunity to evaluate processes that cannot be approached by any other current imaging technique and affords a unique opportunity for studying in vivo brain development and early diagnosis of congenital abnormalities inadequately visualized or undetectable by prenatal sonography. This 2-part review summarizes some of the latest developments in MR imaging of the fetal brain and spine and its application to prenatal diagnosis. This first part discusses the utility, safety, and technical aspects of fetal MR imaging, the appearance of normal fetal brain development, and the role of fetal MR imaging in the evaluation of fetal ventriculomegaly. The second part focuses on additional clinical applications of fetal MR imaging, including suspected abnormalities of the corpus callosum, malformations of cortical development, and spine abnormalities.

Brain↗
PubMed2005

Genomic microarray analysis identifies candidate loci in patients with corpus callosum anomalies.

Absence of the corpus callosum is often associated with cognitive deficits, autism, and epilepsy. Using a genomic microarray, the authors analyzed DNA from 25 patients with radiographically confirmed callosal anomalies and identified three patients with de novo copy number changes in chromosome regions 2q37, 6qter, and 8p. Chromosomal deletions and duplications may be a relatively common cause of cerebral malformations.

Agenesis of Corpus Callosum↗
PubMed2005

A developmental and genetic classification for malformations of cortical development.

Increasing recognition of malformations of cortical development and continuing improvements in imaging techniques, molecular biologic techniques, and knowledge of mechanisms of brain development have resulted in continual improvement of the understanding of these disorders. The authors propose a revised classification based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories are based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In those cases in which the precise developmental and genetic features are uncertain, classification is based on known relationships among the genetics, pathologic features, and neuroimaging features. The major change since the prior classification has been a shift to using genotype, rather than phenotype, as the basis for classifying disorders wherever the genotype-phenotype relationship is adequately understood. Other substantial changes include more detailed classification of congenital microcephalies, particularly those in which the genes have been mapped or identified, and revised classification of congenital muscular dystrophies and polymicrogyrias. Information on genetic testing is also included. This classification allows a better conceptual understanding of the disorders, and the use of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications.

Cerebral Cortex↗
PubMed2005

New and reliable MRI diagnosis for progressive supranuclear palsy.

OBJECTIVE: To evaluate the area of the midbrain and pons on mid-sagittal MRI in patients with progressive supranuclear palsy (PSP), Parkinson disease (PD), and multiple-system atrophy of the Parkinson type (MSA-P), compare these appearances and values with those of normal control subjects, and establish diagnostic MRI criteria for the diagnosis of PSP. METHODS: The authors prospectively studied MRI of 21 patients with PSP, 23 patients with PD, 25 patients with MSA-P, and 31 age-matched normal control subjects. The areas of the midbrain tegmentum and the pons were measured on mid-sagittal MRI using the display tools of a workstation. The ratio of the area of the midbrain to the area of the pons was also evaluated in all subjects. RESULTS: The average midbrain area of the patients with PSP (56.0 mm2) was significantly smaller than that of the patients with PD (103.0 mm2) and MSA-P (97.2 mm2) and that of the age-matched control group (117.7 mm2). The values of the area of the midbrain showed no overlap between patients with PSP and patients with PD or normal control subjects. However, patients with MSA-P showed some overlap of the values of individual areas with values from patients with PSP. The ratio of the area of the midbrain to the area of pons in the patients with PSP (0.124) was significantly smaller than that in those with PD (0.208) and MSA-P (0.266) and in normal control subjects (0.237). Use of the ratio allowed differentiation between the PSP group and the MSA-P group. CONCLUSION: The area of the midbrain on mid-sagittal MRI can differentiate PSP from PD, MSA-P, and normal aging.

Aged↗
PubMed2005

Maternal and infant characteristics associated with perinatal arterial stroke in the infant.

CONTEXT: Perinatal arterial ischemic stroke (PAS) is a common cause of hemiplegic cerebral palsy. Risk factors for this condition have not been clearly defined. OBJECTIVE: To determine maternal and infant characteristics associated with PAS. DESIGN, SETTING, AND PATIENTS: Case-control study nested within the cohort of all 199,176 infants born from 1997 through 2002 in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were confirmed by review of brain imaging and medical records (n = 40). Three controls per case were randomly selected from the study population. MAIN OUTCOME MEASURE: Association of maternal and infant complications with risk of PAS. RESULTS: The population prevalence of PAS was 20 per 100,000 live births. The majority (85%) of infants with PAS were delivered at term. The following prepartum and intrapartum factors were more common among case than control infants: primiparity (73% vs 44%, P = .002), fetal heart rate abnormality (46% vs 14%, P<.001), emergency cesarean delivery (35% vs 13%, P = .002), chorioamnionitis (27% vs 11%, P = .03), prolonged rupture of membranes (26% vs 7%, P = .002), prolonged second stage of labor (25% vs 4%, P<.001), vacuum extraction (24% vs 11%, P = .04), cord abnormality (22% vs 6%, P = .01), preeclampsia (19% vs 5%, P = .01), and oligohydramnios (14% vs 3%, P = .01). Risk factors independently associated with PAS on multivariate analysis were history of infertility (odds ratio [OR], 7.5; 95% confidence interval [CI], 1.3-45.0), preeclampsia (OR, 5.3; 95% CI, 1.3-22.0), prolonged rupture of membranes (OR, 3.8; 95% CI, 1.1-12.8), and chorioamnionitis (OR, 3.4; 95% CI, 1.1-10.5). The rate of PAS increased dramatically when multiple risk factors were present. CONCLUSIONS: Perinatal arterial ischemic stroke in infants is associated with several independent maternal risk factors. How these complications, along with their potential effects on the placenta and fetus, may play a role in causing perinatal stroke deserves further study.

Brain↗
PubMed2005

Predictors of outcome in perinatal arterial stroke: a population-based study.

Some infants with perinatal arterial ischemic stroke (PAS) experience development of cerebral palsy (CP), epilepsy, and cognitive impairment, whereas others have a normal outcome. Previous prognostic studies rarely have included all diagnosed cases of PAS within a population. Among 199,176 infants born within Kaiser Permanente from 1997 to 2002, we electronically identified head imaging reports and physician diagnoses suggesting stroke. The diagnosis of PAS was confirmed by review of brain imaging and medical records. Presentation of PAS was considered delayed if symptoms were only noted after 28 days. Outcomes were determined by chart review. Of 40 infants with PAS, 36 were observed over 12 months. Abnormal outcomes included CP (58%), epilepsy (39%), language delay (25%), and behavioral abnormalities (22%). A delayed presentation was associated with increased risk for CP (relative risk [RR], 2.2; 95% confidence interval [CI], 1.2-4.2). Radiological predictors of CP included large stroke size (RR, 2.0; 95% CI, 1.2-3.2) and injury to Broca's area (RR, 2.5; 95% CI, 1.3-5.0), internal capsule (RR, 2.2; 95% CI, 1.1-4.4), Wernicke's area (RR, 2.0; 95% CI, 1.1-3.8), or basal ganglia (RR, 1.9; 95% CI, 1.1-3.3). Among infants with PAS, specific radiological findings and a lack of symptoms in the newborn period are associated with increased risk for CP.

Arterial Occlusive Diseases↗
PubMed2005

Magnetic resonance techniques in the assessment of myelin and myelination.

Leukodystrophy is a common central nervous system manifestation of inborn errors of metabolism. Until magnetic resonance imaging (MRI) emerged as a clinical tool, the diagnosis of leukodystrophy was difficult and imprecise; MRI has allowed new understandings and classifications of leukodystrophies that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. However, optimal use of MRI in this setting requires a fundamental understanding of myelin structure, myelin development, and the changes seen on MRI with myelination and demyelination. The purpose of this review is to provide the reader with the necessary tools for the use of MRI to diagnose and follow patients with leukodystrophies.

Diffusion Magnetic Resonance Imaging↗
PubMed2004

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

OBJECTIVE: To clarify whether patients with clinical diagnoses of encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum (SCC) share common clinical features. METHODS: Possible encephalitis/encephalopathy patients with a reversible isolated SCC lesion on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Fifteen encephalitis/encephalopathy patients with a reversible isolated SCC lesion were identified among 22 patients referred for this study. All 15 patients had relatively mild clinical courses. Twelve of the 15 patients had disorders of consciousness. Eight patients had seizures, and three of them received antiepileptic drugs. All 15 patients clinically recovered completely within 1 month (8 patients within a week) after the onset of neurologic symptoms. The SCC lesion was ovoid in six patients; it extended irregularly from the center to the lateral portion of SCC in the other eight patients. Homogeneously reduced diffusion was seen in all seven patients who underwent diffusion-weighted imaging. There was no enhancement in the five patients so examined. The SCC lesion had completely disappeared in all patients at follow-up MRI exams between 3 days and 2 months after the initial MRI (within 1 week in eight patients). CONCLUSION: The clinical features among the affected patients were nearly identical, consisting of relatively mild CNS manifestations and complete recovery within 1 month.

Adolescent↗
PubMed2004

Perinatal stroke in term infants with neonatal encephalopathy.

In a prospective cohort of 124 encephalopathic term infants, six infants had an acute focal stroke. All six encephalopathic patients with strokes presented with seizures. Neurodevelopmental outcome at 30 months was abnormal in all six patients and significantly worse when compared with the entire cohort overall. These findings suggest that in newborns with encephalopathy, acute focal strokes are an uncommon but serious occurrence with substantial risk for abnormal neurodevelopmental outcome.

Adult↗
PubMed2004

Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical malformation.

BACKGROUND: Syndromes of bilateral symmetric polymicrogyria include an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), in which the malformation is most severe rostrally. The authors describe a new syndrome they have termed "bilateral generalized polymicrogyria" (BGP), in which the malformation occurs in a generalized distribution but is often most severe in the perisylvian regions. METHODS: Patients with bilateral polymicrogyria were identified from multiple medical centers worldwide. The diagnosis of BGP was based on findings from conventional spin echo MRI and, in one case, postmortem neuropathologic findings. Genetic analysis was performed for those patients from consanguineous pedigrees and those with multiple affected siblings to rule out linkage to the BFPP locus on chromosome 16q. RESULTS: Twelve patients were identified with BGP. Clinical features included cognitive and motor delay as well as seizures. Some specific features characteristic of other known bilateral polymicrogyria syndromes, such as pseudobulbar palsy and dysconjugate gaze, were not commonly seen in these patients. Radiologically, polymicrogyria appeared widespread but was often most severe in the perisylvian regions. Pathologic examination in one case revealed a diffusely thin and excessively folded cerebral cortex lacking normal six-layered architecture. Seven patients subjected to genetic analysis did not demonstrate linkage to the BFPP locus. CONCLUSIONS: BGP is a distinct syndrome of cortical malformation. Several features allow BGP to be distinguished from other disorders on the growing list of bilateral symmetric polymicrogyria syndromes.

Abnormalities, Multiple↗
PubMed2004

Head imaging abnormalities in dihydropyrimidine dehydrogenase deficiency.

Dihydropyrimidine dehydrogenase (DPD) deficiency is a rare autosomal recessive disorder of pyrimidine metabolism. Patients may present with a wide range of neurological symptoms during the first years of life. Head imaging abnormalities have been reported only rarely and include diffuse cerebral atrophy and white-matter hyperintensity. The pathogenesis of the white-matter abnormalities is unknown, although environmental factors and altered energy metabolism may be involved. To further understanding of the spectrum of brain abnormalities associated with DPD deficiency, we report a 17-month-old girl, born to a consanguineous Pakistani couple, who had a history of encephalopathy, prolonged hypoventilation, developmental delay and failure to thrive. Head MRI showed prominent sulci and abnormal T2 prolongation in the cerebral white matter and brainstem. Thus, DPD deficiency may feature prominent brain abnormalities involving the cerebral white matter and brainstem. Anoxic stress may have contributed to the clinical presentation and brain findings in this case. In order to define more clearly the contribution of DPD deficiency to the pathogenesis of these MRI abnormalities, we recommend performing detailed analysis of urine pyrimidine metabolites in patients who have such findings.

Brain↗