William S. Ball

NMR Relaxation Times in the Human Brain at 3.0 Tesla

Relaxation time measurements at 3.0 T are reported for both gray and white matter in normal human brain. Measurements were made using a 3.0 T Bruker Biospec magnetic resonance imaging (MRI) scanner in normal adults with no clinical evidence of neurological disease. Nineteen subjects, 8 female and 11 male, were studied for T1 and T2 measurements, and 7 males were studied for T*2. Measurements were made using a saturation recovery method for T1, a multiple spin‐echo experiment for T2, and a fast low‐angle shot (FLASH) sequence with 14 different echo times for T*2. Results of the measurements are summarized as follows. Average T1 values measured for gray matter and white matter were 1331 and 832 msec, respectively. Average T2 values measured for gray matter and white matter were 80 and 110 msec, respectively. The average T*2 values for occipital and frontal gray matter were 41.6 and 51.8 msec, respectively. Average T*2 values for occipital and frontal white matter were 48.4 and 44.7 msec, respectively. ANOVA tests of the measurements revealed that for both gray and white matter there were no significant differences in T1 from one location in the brain to another. T2 in occipital gray matter was significantly higher (0.0001 < P < .0375) than the rest of the gray matter, while T2 in frontal white matter was significantly lower (P < 0.0001). Statistical analysis of cerebral hemispheric differences in relaxation time measurements showed no significant differences in T1 values from the left hemisphere compared with the right, except in insular gray matter, where this difference was significant at P = 0.0320. No significant difference in T2 values existed between the left and right cerebral hemispheres. Significant differences were apparent between male and female relaxation time measurements in brain. J. Magn. Reson. Imaging 1999;9:531–538.

X-Linked Creatine-Transporter Gene (SLC6A8) Defect: A New Creatine-Deficiency Syndrome

We report the first X-linked creatine-deficiency syndrome caused by a defective creatine transporter. The male index patient presented with developmental delay and hypotonia. Proton magnetic-resonance spectroscopy of his brain revealed absence of the creatine signal. However, creatine in urine and plasma was increased, and guanidinoacetate levels were normal. In three female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present, to various extents. Fibroblasts from the index patient contained a hemizygous nonsense mutation in the gene SLC6A8 and were defective in creatine uptake. The three female relatives were heterozygous for this mutation in SLC6A8, which has been mapped to Xq28.

Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia

BACKGROUND Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).

Percutaneous Stone Removal in Children

Percutaneous removal of renal and ureteral calculi has become an established and successful procedure in adults. Stone disease in children often is metabolic or infectious in origin and multiple surgical procedures during a long interval may be required. Therefore, percutaneous stone removal could be particularly advantageous in these patients. We have performed percutaneous stone removal successfully in 7 children, none of whom required a second procedure or were discharged from the hospital with a nephrostomy tube.

Irreversible brain creatine deficiency with elevated serum and urine creatine: A creatine transporter defect?

Recent reports highlight the utility of in vivo magnetic resonance spectroscopy (MRS) techniques to recognize creatine deficiency syndromes affecting the central nervous system (CNS). Reported cases demonstrate partial reversibility of neurologic symptoms upon restoration of CNS creatine levels with the administration of oral creatine. We describe a patient with a brain creatine deficiency syndrome detected by proton MRS that differs from published reports. Metabolic screening revealed elevated creatine in the serum and urine, with normal levels of guanidino acetic acid. Unlike the case with other reported creatine deficiency syndromes, treatment with oral creatine monohydrate demonstrated no observable increase in brain creatine with proton MRS and no improvement in clinical symptoms. In this study, we report a novel brain creatine deficiency syndrome most likely representing a creatine transporter defect. Ann Neurol 2001;49:401–404

Traumatic intracranial aneurysms in childhood: two cases and a review of the literature

Traumatic intracranial aneurysms in childhood are rare. To date, 67 well-documented cases in children have been reported. We present 2 additional cases and review the literature. Traumatic aneurysms can best be categorized based on mechanism of injury and location. Aneurysms secondary to penetrating trauma occur most commonly in teenage boys suffering gunshot wounds. Aneurysms secondary to nonpenetrating trauma occur at the skull base or in the periphery, with motor vehicle accidents and falls as the most common modes of injury. Skull base traumatic aneurysms most commonly involve the petrous, cavernous, or supraclinoid carotid artery and also show a predominance in teenage boys. Peripheral traumatic aneurysms can further be divided into distal anterior cerebral artery aneurysms secondary to trauma against the falcine edge and distal cortical artery aneurysms associated with an overlying skull fracture. Peripheral traumatic aneurysms tend to occur in younger patients with a less marked male predominance. Two-thirds of the patients suffered symptomatic aneurysmal hemorrhage, with an associated mortality rate of 31%. The clinical presentation, diagnosis, and treatment of traumatic intracranial aneurysms are discussed.

Nanotube electrodes and biosensors

This article reviews the state of the art in carbon nanotube electrode and biosensor research. Carbon nanotubes have unique mechanical, electrical, and geometrical properties that are ideal for developing different types of nanoscale electrodes and biosensors. Carbon nanotube synthesis and subsequent functionalization strategies to immobilize special biomolecules are discussed first. Then different types of carbon nanotube biosensors and electroanalytical methods are reviewed particularly considering their capabilities for low detection limits, point-of-care applications, and label-free use. Detection strategies for proteins and nucleic acids, as well as mammalian and bacterial cells are also outlined. We conclude with some speculations and predictions on future exciting and challenging directions for nanotube biosensor research and applications.

Cerebral infarctions due to CNS infection with Enterobacter sakazakii.

Recent reports have implicatedEnterobacter sakazakii, a gramnegative enteric bacillus, in neonatal sepsis and meningitis [1–4]. Cases of severe central nervous system involvement, including ventriculitis, brain abscess, infarction, and cyst formation, have been described [1]. We present serial head CT findings in a case of neonatalE. sakazakii meningitis complicated by a ring enhancing cerebral infarction which mimicked abscess formation. In meningitis secondary to this agent, a recognized pattern of cerebral hypodensity with or without cystic degeneration late in the course of the infection is likely to represent cerebral infarction rather than an abscess especially if there is a lack of culture evidence of a bacterial infection.

The clinical syndrome of creatine transporter deficiency

To describe the clinical, spectroscopic and neuropsychological features of the first family diagnosed with a defect in the creatine transporter.Proton Magnetic Resonance Spectroscopy (MRS) indicated an absence of creatine and phosphocreatine in the brain of a male patient characterized by developmental delay, mild epilepsy and severe expressive language impairment. Subsequent genetic testing revealed a defect in the X-linked creatine transporter (SLC6A8/CT1), with a hemizygous mutation in the patient and a heterozygous mutation for the female carriers.Magnetic resonance imaging and spectroscopy examinations were performed on a 1.5T clinical MR Scanner. Neuropsychological examinations were performed on the index patient and maternal relatives.Preliminary spectroscopy results indicate the disorder prevents transport of creatine and phosphocreatine in the brain of the affected male. However, the skeletal muscle demonstrates the presence of creatine and phosphocreatine which correlates clinically with normal structure and function. Female carriers demonstrated impairments in confrontational naming and verbal memory assessments.This new neurological syndrome is associated with developmental delay, mild epilepsy, severe language impairment. MR Spectroscopy is a non-invasive method for obtaining a preliminary diagnosis of this disorder. Muscle creatine uptake may be normal in this disorder.

Review of the embryologic development of the pituitary gland and report of a case of hypophyseal duplication detected by MRI

We describe the clinical manifestations, associated abnormalities, MRI appearances and pathologic significance of a case of hypophyseal duplication. A 16-year-old girl presented with delayed sexual development and history of midline craniofacial anomalies. MRI revealed paired infundibula extending inferiorly to two small pituitary glands, a midline hypothalamic mass, and a midline cleft in the basisphenoid. Twelve cases of pituitary duplication have previously been described. The suggested pathogenesis is duplication of the prechordal plate and anterior end of the notochord during early embryologic development.