[show abstract][hide abstract] ABSTRACT: The pathophysiological factors of neurogenic or sympathetically mediated essential hypertension are unknown. Neurons close to the surface of the ventrolateral medulla (specifically, in the retro-olivary sulcus [ROS]) are integrally involved in the control of blood pressure by means of efferent connections to presympathetic neurons in the spinal cord. It is hypothesized that vascular contact with the ROS is pathogenically involved in neurogenically mediated hypertension. We evaluated that theory in 20 subjects with uncomplicated stage 1 to stage 2 essential hypertension (EHTN) (18 of whom completed the study). The baseline supine plasma norepinephrine level served as an index of central sympathetic outflow. The response of blood pressure to clonidine was used as a surrogate marker for neurogenically mediated hypertension. We also examined the relationship between those markers and evidence of anatomic abnormalities in the area of the ROS that was provided by magnetic resonance imaging. A vessel contacted the left ROS in 5 of the 18 subjects. Those 5 subjects had higher plasma norepinephrine concentrations than did the 13 subjects without this vascular contact (358+/-46 versus 76+/-43 pg/mL, P<0.001). These 5 subjects also exhibited a significant depressor response to clonidine that tended to be greater than that seen in the 13 subjects without vascular contact (-20.6+/-3.2 versus -13.6+/-9 mm Hg). Both race and baseline mean blood pressure had only an independent effect on the depressor response to clonidine. The findings are consistent with the theory that vascular contact with the left ROS may contribute to neurogenically mediated "essential" hypertension in some patients.
[show abstract][hide abstract] ABSTRACT: X-linked adrenoleukodystrophy (X-ALD) is a progressive demyelinating disorder whose neurological signs and symptoms can manifest in childhood as cerebral ALD or in adulthood in the form of a progressive myelopathy (AMN). The consistent metabolic abnormality in all forms of X-ALD is an inherited defect in the peroxisomal beta-oxidation of very long chain (VLC) fatty acids (>C(22:0)) which may in turn lead to a neuroinflammatory process associated with demyelination of the cerebral white matter. The current treatment for X-ALD with Lorenzo's oil aims to lower the excessive quantities of VLC fatty acids that accumulate in the patients' plasma and tissues, but does not directly address the inflammatory process in X-ALD. We have previously demonstrated that lovastatin and other 3-HMG-CoA reductase inhibitors are capable of normalizing VLC fatty acid levels in primary skin fibroblasts derived from X-ALD patients. Lovastatin can block the induction of inducible nitric oxide synthase and proinflammatory cytokines in astrocytes, microglia, and macrophages in vitro. In a preliminary report, we demonstrated that lovastatin therapy can normalize VLC fatty acids in the plasma of patients with X-ALD. Here we report our clinical and biochemical observations on 12 patients with X-ALD who were treated with lovastatin for up to 12 months. Our results show that the high plasma levels of hexacosanoic acid (C(26:0)) showed a decline from pretreatment values within 1 to 3 months of starting therapy with 40 mg of lovastatin per day and stabilized at various levels during a period of observation up to 12 months. The percentage decline from pretreatment values varied and did not correlate with the type of ALD gene mutation (point mutation versus gene deletion). In 6 patients, in whom red cell membrane fatty acid composition was studied, a mean correction of 50% of the excess C(26:0) was observed after 6 months of therapy suggesting sustained benefit. In a few patients who discontinued lovastatin therapy plasma C(26:0) levels reverted to pretreatment values suggesting a cause and effect relationship between these events. Two patients dropped out of the study claiming no clinical benefit, 1 was withdrawn due to adverse effects, and an adult patient with cerebral involvement died during the study. A 10-year-old boy with severe cerebral involvement showed worsening of his neurological status. All patients with AMN remained neurologically stable or showed modest subjective improvement. All patients who did not have Addison's disease at the time of enrollment maintained normal adrenal function throughout the study. The implications of our findings for developing an effective therapy for X-ALD are discussed.
Molecular Genetics and Metabolism 04/2000; 69(4):312-22. · 2.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Eleven children who had post-pump choreoathetosis develop after cardiopulmonary bypass were evaluated in their perioperative course to determine factors that may correlate with their neurologic outcome. Results showed that preoperative cyanosis is associated with the development of a basal ganglia lesion. An acquired basal ganglia lesion and preoperative cyanosis are associated with persistence of post-pump choreoathetosis. The combination of cyanotic heart disease and a scan-identified basal ganglia lesion indicates a poor prognosis for the patient with persistent post-pump choreoathetosis. Also, the presence of total circulatory arrest is associated with a decrease in developmental quotient but not the persistence of post-pump choreoathetosis.
Journal of Pediatrics 02/1998; 132(1):162-4. · 4.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the presence of small cystlike structures in the cerebral hemispheric white matter on MR images of patients with tuberous sclerosis.
The MR images of 18 consecutive patients with tuberous sclerosis were reviewed retrospectively.
Eight of the 18 patients were found to have cystlike structures in the cerebral white matter. The signal intensity of these lesions was isointense with cerebrospinal fluid on T1-, proton density-, and T2-weighted images. Four patients were imaged with a fluid-attenuated inversion recovery sequence, which in each case also showed fluid-type signal in these areas. Three of the patients had CT for correlation, and these scans supported the diagnosis of cystic lesions. Cysts ranged in number from one to 12 per patient and were usually smaller than 1 cm. The most common location was adjacent to the occipital horn or trigone of the lateral ventricle (six of eight patients). Less frequent sites were near the frontal horns, in the corpus callosum, and in the deep white matter near the body of the lateral ventricle. Cysts in five patients were either immediately adjacent to a cortical tuber or in the center of a white matter dysplastic lesion. A cyst in one patient had septa, and none of the cysts enhanced.
Cystlike structures in the cerebral hemispheric white matter were seen on the MR images of 44% of 18 patients with tuberous sclerosis. Whether these findings represent cystic degeneration of dysplastic tissue or are unrelated to the disease process of tuberous sclerosis is unknown. More than one pathogenesis may exist.
American Journal of Neuroradiology 09/1997; 18(7):1367-73. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: The epidermal nevus syndrome (ENS) is an unusual neurocutaneous disorder consisting of the combination of an epidermal nevus and a central nervous system (CNS), ophthalmological, and/or skeletal abnormality. The study reports four new patients with ENS. Each had a confirmatory biopsy of the epidermal nevus, abnormal neurological examination findings, and documented CNS anatomical studies by imaging or autopsy. The paper also reviews the literature in English to determine neurological abnormalities found in skin-biopsy-proven cases of ENS. Hemi-atrophy, hemimegalencephaly, migrational abnormalities and vascular anomalies were found to be the most frequent intracranial abnormalities associated with ENS. Seizures and/or disabling moderate to severe developmental delays were present in a majority of patients. Seizure onset during the neonatal period or early infancy was associated with major hemispheric malformations. Neuroectodermal-derived ocular lesions were often bilateral. No consistent relation between laterality of the nevus and laterality of CNS abnormalities was found, supporting the gene mosaicism theory of pathogenesis.
[show abstract][hide abstract] ABSTRACT: To study the association between petrous carotid canal (PCC) and internal carotid artery (ICA) stenoses in patients with malignant osteopetrosis.
Mean and minimum PCC diameters obtained from cranial computed tomographic (CT) scans in 20 patients were compared with similar measurements in 52 control subjects. ICA caliber, evaluated with magnetic resonance (MR) arteriography, was correlated with age and PCC dimensions.
There was a statistically significant difference between patient and control PCC diameters. There was a strong positive correlation between age and PCC diameter in the control subjects, but only a weakly positive correlation in the patients. One or both ICAs were stenotic on all patient MR arteriograms. MR angiographic stenosis grade correlated positively with age but not with PCC diameters.
PCC and ICA stenoses occur frequently in patients with malignant osteopetrosis. Bony overgrowth or a "persistent fetal state" may produce the PPC stenoses. The findings do not support progressive PCC narrowing in these patients.
[show abstract][hide abstract] ABSTRACT: We report the MR imaging findings in two cases of nasolabial cysts. Demonstration of their extraosseous location with cross-sectional imaging should prevent confusion with maxillary cysts and obviate unwarranted dental or maxillary surgery.
American Journal of Neuroradiology 04/1996; 17(3):585-8. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: A boy with sickle cell anemia underwent bone marrow transplantation (BMT). He was normal on neurological examination, but had radiologic evidence of an old left frontal lobe infarct, multiple cerebral vascular stenoses and moyamoya collaterals. After BMT he developed seizures with extension of the infarct and subarachnoid hemorrhage. One year later angiography revealed worsening stenosis of the M1 segments of both middle cerebral arteries. At that time an increase in von Willebrand's factor with decreased large molecular weight multimers (LvWF) was observed. We speculate that LvWF dependent, shear-induced platelet aggregation, together with endothelial damage may have contributed to the development of neurologic complications in this patient.
Bone Marrow Transplantation 04/1996; 17(3):405-7. · 3.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Progressive cerebral sinovenous occlusion in a neonate with Sturge-Weber syndrome was documented by using two-dimensional time-of-flight MR venography. There was no evidence of intraluminal thrombus on routine spin-echo images obtained either before or after the onset of seizures, despite MR venographic evidence in both studies of venous abnormalities.
American Journal of Neuroradiology 09/1995; 16(7):1539-42. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Congenital osteopetrosis is a rare osteosclerotic bone disease characterized by both a defect in osteoclastic function and reduced generation of superoxide by leukocytes. The disease is frequently fatal during the first decade of life. A six-month trial of therapy with recombinant human interferon gamma-1b in eight patients with osteopetrosis provided evidence of benefit, prompting this study of more prolonged therapy.
We studied 14 patients with severe osteopetrosis treated with subcutaneous injections of recombinant human interferon gamma-1b (1.5 micrograms per kilogram of body weight per dose) three times per week for at least 6 months; 11 patients were treated for 18 months. We assessed the effect of therapy by evaluating the patients' clinical status, measuring blood counts and biochemical markers of bone turnover, and performing bone marrow imaging and bone biopsies.
After 6 months of therapy, all 14 patients had decreases in trabecular-bone area (determined by histomorphometric analysis of bone-biopsy specimens) and increases in bone marrow space (determined by marrow imaging), and the improvement was sustained in the 11 patients treated for 18 months. The mean (+SD) hemoglobin concentration increased from 7.5 +/- 2.9 to 10.5 +/- 0.3 g per deciliter (P = 0.05), and superoxide generation by granulocyte-macrophage colonies increased (P < 0.001) after 18 months of therapy. In six patients for whom pretreatment data were available, there was a 96 percent decrease in the frequency of infections requiring antibiotic therapy during interferon treatment. There were no side effects necessitating the discontinuation of therapy.
Long-term therapy with interferon gamma in patients with osteopetrosis increases bone resorption and hematopoiesis and improves leukocyte function.
New England Journal of Medicine 07/1995; 332(24):1594-9. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: This article reviews the gamut of cystic lesions, unrelated to neoplastic disease, that are found in the brain, subarachnoid space, and ventricles. The utility of MRI in diagnosing these entities is shown.
Seminars in Ultrasound CT and MRI 07/1995; 16(3):186-211. · 1.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: The clinical, MR imaging, surgical, and histologic findings in two cases of cystic aberrant cervical thymus were reviewed. Aberrant cervical thymic tissue was sharply circumscribed and extended deep to the posterior pharyngeal wall at the level of the piriform sinus in both cases. Both lesions had cyst contents that were of increased signal intensity on T1-weighted images. Solid components displayed MR signal characteristics identical to normal thymus.
American Journal of Neuroradiology 06/1995; 16(5):1124-7. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: The normal and variant anatomy of the cerebral veins and dural venous sinuses is poorly understood by many radiologists. Beginning with a discussion of cerebral venous anatomy, this review illustrates clinically pertinent anatomy of the cerebral sinovenous system. Various methods of imaging cerebral veins and dural venous sinuses are described. Techniques and pitfalls of MR venography are emphasized.
Seminars in Ultrasound CT and MRI 01/1995; 15(6):499-519. · 1.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: The imaging features of a variety of dural venous sinus (DVS) abnormalities are reviewed. Congenital and heritable diseases affecting the DVS, tumor-related sinus compression, and traumatic injuries of the DVS are discussed. The causes, clinical manifestations, and imaging findings in cerebral sinovenous thrombosis are described, and pertinent imaging techniques and pitfalls are illustrated. Etiologic theories about the formation of dural arteriovenous malformations are discussed and their imaging features are demonstrated.
Seminars in Ultrasound CT and MRI 01/1995; 15(6):520-39. · 1.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: The authors present the initial and follow-up MR findings in a patient with subacute combined degeneration of the spinal cord, a complication of vitamin B12 deficiency, and a rare cause of demyelination of the dorsal and lateral columns of the spinal cord. Initial study showed high intensity in the dorsal columns of the cervical and thoracic spinal cord on T2-weighted image. Five months after treatment, the abnormal signal intensity was noted to have decreased.
American Journal of Neuroradiology 14(5):1224-7. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to describe the cranial MR imaging manifestations of osteopetrosis. These features have not previously been reported in the literature.
Cranial MR studies, obtained with a uniform imaging protocol, were reviewed in 47 patients with osteopetrosis. Thirty-four patients had autosomal recessive (malignant) osteopetrosis (AROP), seven had intermediate osteopetrosis (IOP), and six had either type I or type II autosomal dominant osteopetrosis (ADOP I or II). The prevalence of abnormalities was tabulated and compared with the specific osteopetrosis variants.
All patients with osteopetrosis had thickening and sclerosis of the calvaria. Ventriculomegaly, tonsillar herniation, proptosis, and dural venous sinus stenosis were observed in the majority of patients with AROP and ADOP I. Optic nerve sheath dilatation occurred in many of the patients with AROP and in all patients with ADOP I. Acquired cephaloceles were also observed only in these two groups. Optic nerve atrophy and optic canal stenosis were observed in a majority of patients with AROP, IOP, and ADOP II. Middle ear fluid was prevalent in AROP and IOP, present in over half the patients in each group. Features seen most prevalently, or exclusively, in AROP included stenosis of the internal carotid and vertebral arteries and extramedullary hematopoiesis.
The cranial MR imaging features of osteopetrosis are both shared and unique among the various subtypes of the disease. The specific cranial and intracranial manifestations reflect the predominant calvarial or skull base patterns of bone thickening. The unique features seen in patients with AROP probably reflect the early age of onset and the greater severity of this form of the disease.
American Journal of Neuroradiology 21(6):1110-5. · 3.17 Impact Factor