Tumors of the endolymphatic sac in von Hippel-Lindau disease.
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Adult↗
Biomedical subjects
John A Butman
Publications and source records attributed to John A Butman.
West Nile virus: pathogenesis and therapeutic options.
West Nile virus, a member of the family Flaviviridae, has spread throughout the United States. With more than 9000 cases and 200 deaths in 2003, West Nile virus has become the most common cause of viral encephalitis in several states. West Nile virus encephalitis is a zoonosis. The life cycle of the virus includes mainly birds as hosts and mosquitoes as vectors. Humans are accidental hosts, insufficient to support the life cycle of the virus because of low-grade, transient viremia. However, human-tohuman transmission through blood, organ transplantation, and lactation has been documented. The frequency of severe neurologic disease in the current epidemic suggests a more neurovirulent strain of virus than the one classically associated with West Nile fever. Several neurologic manifestations have been described, but the most characteristic presentation is encephalitis with weakness. Magnetic resonance imaging scans may be normal initially, but a characteristic pattern of involvement of deep gray matter nuclei can be recognized. Although results of polymerase chain reaction may be positive in the cerebrospinal fluid early in the course of the disease, diagnosis is based on serologic tests. Possible cross-reactivity with other members of the genus flavivirus mandates caution when serologic testing results are interpreted. Thus far, no therapeutic intervention has shown consistent clinical efficacy in West Nile virus disease. Several approaches, including interferon-alpha2b and immunoglobulin with high titer against West Nile virus, offer promise based on animal models and limited clinical experience. New drugs with in vitro activity are being investigated, and a vaccine is being developed.
Animals↗
Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors.
Adaptation to hypoxia is critical for survival and regulates multiple processes, including erythropoiesis and vasculogenesis. Chuvash polycythemia is a hypoxia-sensing disorder characterized by homozygous mutation (598C>T) of von Hippel-Lindau gene (VHL), a negative regulator of hypoxia sensing. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and originates from a single ancient event. That VHL 598C>T homozygosity causes elevated normoxic levels of the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha), serum erythropoietin and hemoglobin is known, but the disease phenotype has not been documented in a controlled manner. In this matched cohort study, VHL 598C>T homozygosity was associated with vertebral hemangiomas, varicose veins, lower blood pressures, and elevated serum vascular endothelial growth factor (VEGF) concentrations (P <.0005), as well as premature mortality related to cerebral vascular events and peripheral thrombosis. Spinocerebellar hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical VHL syndrome were not found, suggesting that overexpression of HIF-1alpha and VEGF is not sufficient for tumorigenesis. Although hemoglobin-adjusted serum erythropoietin concentrations were approximately 10-fold higher in VHL 598C>T homozygotes than in controls, erythropoietin response to hypoxia was identical. Thus, Chuvash polycythemia is a distinct VHL syndrome manifested by thrombosis, vascular abnormalities, and intact hypoxic regulation despite increased basal expression of hypoxia-regulated genes.
Adaptation, Physiological↗
Thoracic spinal nerve hemangioblastoma. Case illustration.
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Hemangioblastoma↗
Sacral hemangioblastoma in a patient with von Hippel-Lindau disease. Case report and review of the literature.
Hemangioblastomas are histologically benign neoplasms that occur sporadically or as part of von Hippel-Lindau disease. Hemangioblastomas may occur anywhere along the neuraxis, but sacral hemangioblastomas are extremely rare. To identify features that will help guide the operative and clinical management of these lesions, the authors describe the management of a large von Hippel-Lindau disease-associated sacral hemangioblastoma and review the literature. The authors present the case of a 38-year-old woman with von Hippel-Lindau disease and a 10-year history of progressive back pain, as well as left lower-extremity pain and numbness. Neurological examination revealed decreased sensation in the left S-1 and S-2 dermatomes. Magnetic resonance imaging demonstrated a large enhancing lesion in the sacral region, with associated erosion of the sacrum. The patient underwent arteriography and embolization of the tumor and then resection. The histopathological diagnosis was consistent with hemangioblastoma and showed intrafascicular tumor infiltration of the S-2 nerve root. At 1-year follow-up examination, pain had resolved and numbness improved. Sacral nerve root hemangioblastomas may be safely removed in most patients, resulting in stabilization or improvement in symptomatology. Generally, hemangioblastomas of the sacral nerve roots should be removed when they cause symptoms. Because they originate from the nerve root, the nerve root from which the hemangioblastoma originates must be sacrificed to achieve complete resection.
Adult↗
Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy.
The pathologic substrate of essential tremor (ET) remains unknown. The authors studied 10 patients with ET and 10 volunteers using a multislice MR spectroscopy imaging sequence. Left and right cerebellar hemisphere NAA/CR and NAA/Cho ratios were significantly smaller in the ET patients than healthy subjects. The authors' data suggest that the decreased NAA/Cr and NAA/Cho ratios within the cerebellum may represent an abnormality in neuronal function.
Adult↗
Surgical management of lumbosacral nerve root hemangioblastomas in von Hippel-Lindau syndrome.
OBJECT: Hemangioblastomas in the lumbosacral region are rare, and the authors of prior reports have not defined the surgical management, histopathological features, or outcome in a group of patients after resection of these tumors. To identify features that will help guide the operative and clinical management of these lesions, the authors reviewed data obtained in a series of patients with von Hippel-Lindau syndrome who underwent resection of lumbosacral nerve root hemangioblastomas. METHODS: Six consecutive patients (three men and three women; mean age at surgery 39 years [range 31-48 years]) who underwent operations for resection of lumbosacral nerve root hemangioblastomas were included in this study. The mean follow-up period was 23 months (range 6-45 months). Data derived from examination, hospital charts, operative findings, histopathological analysis, and magnetic resonance imaging were used to analyze surgical management and clinical outcome. The resected tumors were located in the lumbar (five cases) or sacral (one case) regions; the mean tumor size was 2728 mm3 (range 80-15,022 mm3). Consistent with central nervous system (CNS) regional variation of space available to accommodate the neural compressive effect of the hemangioblastoma size, the mean tumor volume (2728 mm3) of these symptomatic lesions was much larger than that of symptomatic hemangioblastomas resected in the other regions of the CNS. Histopathological examination showed infiltration of the associated nerve root by the hemangioblastoma in each case. In five of the six patients complete resection was achieved, and in one patient intradural exploration of two hemangioblastomas was performed, but resection was not achieved because of motor root involvement. In all cases involving complete resections the patients experienced symptomatic improvement. CONCLUSIONS: Lumbosacral nerve root hemangioblastomas can be safely removed in most patients with von Hippel-Lindau syndrome. Generally, hemangioblastomas of the lumbosacral nerve roots should be resected when they become symptomatic. Because these neoplasms appear to originate from the nerve root, it is necessary to sacrifice the nerve root from which the hemangioblastoma originates to achieve complete resection.
Adult↗
Normal vision despite narrowing of the optic canal in fibrous dysplasia.
BACKGROUND: Fibrous dysplasia of bone frequently involves the anterior base of the cranium and results in encasement of the optic-nerve canals. It has been assumed that such encasement leads to constriction and eventual blindness. There is controversy about whether patients should be regularly monitored or whether they should undergo prophylactic decompression of the optic nerve. This question is of particular concern in patients with normal vision, since the risks associated with surgical decompression include blindness. METHODS: We studied 38 patients with fibrous dysplasia of the lesser wing of the sphenoid bone. The patients underwent a detailed neuro-ophthalmologic examination and computed tomography of the face and skull, reformatted to measure the extent of involvement of the optic canal and the area of the canals. The results were compared with those of 38 age- and sex-matched controls. RESULTS: Of the 38 patients, 15 were male and 23 female, and their mean age was 26 years. Twelve had polyostotic fibrous dysplasia, and 26 had the McCune-Albright syndrome. Sixty-seven optic canals were affected by fibrous dysplasia; in 49 of them (73 percent) there was complete encasement. The mean (+/-SD) areas of the right and left canals were 9.6+/-3.8 mm2 and 9.9+/-3.6 mm2, respectively, in the patients, as compared with 12.0+/-2.9 mm2 and 11.9+/-2.7 mm2 in the controls (P=0.009 for the comparison of the right areas and P=0.03 for the comparison of the left areas by the paired t-test). In all but two of the patients, the results of neuro-ophthalmologic examination were normal. In the two patients with monocular visual impairment, the areas of the optic canals were similar on the normal and abnormal sides. CONCLUSIONS: Encasement of the optic canal in fibrous dysplasia causes narrowing of the canal, but that in itself does not result in visual loss. Therefore, prophylactic decompression of the optic nerve does not appear to be indicated on the basis of the presence of fibrous dysplasia on diagnostic images alone, since it does not correlate with visual loss.
Adolescent↗
A new method for the study of velopharyngeal function using gated magnetic resonance imaging.
The purpose of this project was to assess the feasibility of imaging the velopharynx of adult volunteers during repetitive speech, using gated magnetic resonance imaging (MRI). Although a number of investigators have used conventional MRI in the study of the human vocal tract, the mismatch between the lengthy time necessary to acquire sufficiently detailed images and the rapidity of movement of the vocal tract during speech has forced investigators to acquire images either while the subject is at rest or during sustained utterances. The technique used here acquired a portion of each image during repetitive utterances, building the full image over multiple utterance cycles. The velopharyngeal portal was imaged on a 1.5-Tesla GE Signa LX 8.2 platform with gated fast spoiled gradient echo protocol. An external 1-Hertz trigger was fed to the cardiac gate. Subjects synchronized utterance of consonant-vowel syllables to a flashing light synchronized with the external trigger. Each acquisition of 30 phases per second at a single-slice location took 22 to 29 seconds. Four consonant-vowel syllables (/pa/, /ma/, /sa/, and /ka/) were evaluated. Subjects vocalized throughout the acquisition, beginning 5 to 6 seconds beforehand to establish a regular rhythm. Imaging of the velopharyngeal portal was performed for sagittal, velopharyngeal axial (aligned perpendicular to the "knee" of the velum), axial, and coronal planes. Volumes were obtained by sequential acquisition of six to 10 slices (each with 30 phases) in the axial or sagittal planes during repetition of the /pa/ syllable. Spatiotemporal volumes of the single-slice data were sectioned to provide time-motion images (analogous to M-mode echocardiograms). Three-dimensional dynamic volume renderings of palate motion were displayed interactively (Vortex; CieMed, Singapore). A method suitable for the collection and visualization of four-dimensional information regarding monosyllabic speech using gated MRI was developed. These techniques were applied to a population of adult volunteer subjects with no history of speech problems and two patients with a history of cleft lip and palate. The techniques allowed good real-time visualization of velopharyngeal anatomy during its entire range of motion and was also able to image pathology-specific anatomic differences in the subjects with cleft lip and cleft palate. These methods may be applicable to a wide spectrum of problems in speech physiology research and for clinical decision-making regarding surgery for speech and outcomes analysis.
Adult↗
Cerebrovascular disease in HIV-infected pediatric patients: neuroimaging findings.
OBJECTIVE: The goal of our study was to report on the prevalence and the neuroradiologic manifestations of cerebrovascular complications in children infected with HIV. We also elucidate the types of vascular involvement, identify their anatomic distribution, and discuss possible causes. MATERIALS AND METHODS: We conducted a retrospective study of 567 patients (age range, 1 month-29 years; median age, 5.47 years) who acquired HIV as children. Of these, 426 patients (75%) were evaluated with neuroimaging studies. We reviewed these studies to identify the cerebrovascular abnormalities and classify them by type, anatomic location, and shape. RESULTS: Eleven children (2.6%) were found to have cerebrovascular lesions. Only one had focal neurologic symptoms at the time of diagnosis. Twenty-six aneurysms were found in seven patients, and 27 infarctions were found in eight patients. In four of the patients with infarctions, fusiform aneurysms of the cerebral arteries were also identified. Most patients had advanced HIV disease. Nine of the 11 patients were infected by a vertical transmission route or during blood transfusion early in the neonatal period. In this group of patients, the diagnosis of cerebrovascular disease was made earlier (mean age at diagnosis, 8.2 years) than in the two patients who were infected later in life (mean age at diagnosis, 14.9 years). CONCLUSION: HIV-infected children have an increased incidence of cerebrovascular disease that is associated with severe immune suppression and with vertically acquired HIV infection or exposure to the virus in the neonatal period. Despite extensive lesions, most children in our study were asymptomatic. Screening with MR imaging should be considered for high-risk children and is advisable when evidence of neurologic symptoms or neurocognitive dysfunction is noted.
AIDS Arteritis, Central Nervous System↗
Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion.
OBJECT: Intrinsic disease processes of the brainstem (gliomas, neurodegenerative disease, and others) have remained difficult or impossible to treat effectively because of limited drug penetration across the blood-brainstem barrier with conventional delivery methods. The authors used convection-enhanced delivery (CED) of a macromolecular tracer visible on magnetic resonance (MR) imaging to examine the utility of CED for safe perfusion of the brainstem. METHODS: Three primates (Macaca mulatta) underwent CED of various volumes of infusion ([Vis]; 85, 110, and 120 microl) of Gd-bound albumin (72 kD) in the pontine region of the brainstem during serial MR imaging. Infusate volume of distribution (Vd), homogeneity, and anatomical distribution were visualized and quantified using MR imaging. Neurological function was observed and recorded up to 35 days postinfusion. Histological analysis was performed in all animals. Large regions of the pons and midbrain were successfully and safely perfused with the macromolecular protein. The Vd was linearly proportional to the Vi (R2 = 0.94), with a Vd/Vi ratio of 8.7 +/- 1.2 (mean +/- standard deviation). Furthermore, the concentration across the perfused region was homogeneous. The Vd increased slightly at 24 hours after completion of the infusion, and remained larger until the intensity of infusion faded (by Day 7). No animal exhibited a neurological deficit after infusion. Histological analysis revealed normal tissue architecture and minimal gliosis that was limited to the region immediately surrounding the cannula track. CONCLUSIONS: First, CED can be used to perfuse the brainstem safely and effectively with macromolecules. Second, a large-molecular-weight imaging tracer can be used successfully to deliver, monitor in vivo, and control the distribution of small- and large-molecular-weight putative therapeutic agents for treatment of intrinsic brainstem processes.
Albumins↗
Quantification of brain lesions using interactive automated software.
We developed an interactive program, Analysis of Brain Lesions (ABLe) so that researchers studying the effects of brain lesions on cognition could have a user-friendly tool that could quantitatively characterize such lesions. The program was prepared in Tcl/Tk and will run on any UNIX or PC LINUX platform with the MEDx medical imaging software package. The ABLe is almost completely automated and determines the brain lesion size as well as which cytoarchitectonic brain regions (Brodmann areas) are contained within the boundaries of the lesion. Lesion data from multiple subjects can be grouped together and the degree of lesion overlap displayed. All images are analyzed and displayed within standard Talairach coordinate space, and the precision of the match between the ABLe Brodmann area graphics and the subject/patient brain is easily confirmed. The program is the first easy-to-use software that contains these specific features and is available for interested researchers with a background in lesion analysis.
Adult↗
Increased signal intensity in the pulvinar on T1-weighted images: a pathognomonic MR imaging sign of Fabry disease.
BACKGROUND AND PURPOSE: Fabry disease is a multisystem X-linked disorder characterized clinically by angiokeratoma, corneal and lenticular abnormalities, acroparesthesia, and renal and cardiac dysfunction and stroke. We sought to describe novel neuroimaging characteristics of Fabry disease. METHODS: Neuroradiologic records of 104 hemizygous patients with Fabry disease evaluated between 1994 and 2002 were reviewed. In total, 94 MR studies consisting of T1- and T2-weighted images were examined for the presence of hyperintensity on the T1-weighted images. Additional CT, gradient-echo (T2*-weighted), and fat-suppression MR studies were reviewed to characterize further the T1 abnormality in selected patients. In some patients, cerebral blood flow (CBF) was quantified by using arterial spin tagging (AST). RESULTS: Overall, 22 patients ( approximately 23%) demonstrated pulvinar hyperintensity on T1-weighted images; the frequency increased with age to over 30% by age 50 years. Susceptibility-weighted T2* studies demonstrated a low-signal-intensity abnormality in the pulvinar in the more severe cases, whereas CT demonstrated the pulvinar to be mineralized. CT attenuation corresponded with an increasing signal intensity on T1-weighted images. Posterior circulation CBF was found to be elevated on individual AST studies, especially in the thalamus. CONCLUSION: Hyperintensity in the pulvinar on T1-weighted images is a common finding in Fabry disease, likely reflecting the presence of calcification. Although other minreralizing abnormalities may result in calcification of deep gray nuclei, exclusive involvement of the pulvinar may be distinctively characteristic to Fabry disease. Increased CBF in the posterior circulation, particularly the thalamus, suggests that the dystrophic calcification is secondary to cerebral hyperperfusion and selective vulnerability of the pulvinar and adjacent thalamic nuclei. The finding of isolated pulvinar hyperintensity on T1-weighted images should suggest Fabry disease, particularly when seen in conjunction with other nonspecific neuroradiologic manifestations of the disease.
Adolescent↗