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N J Patronas

Publications and source records attributed to N J Patronas.

At least 37 records · Page 2Linked to original sources
PubMed1997

Proton magnetic resonance spectroscopic imaging in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration.

We used proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the in vivo cortical and subcortical neuronal involvement in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration. This technique permitted the simultaneous measurement of compounds containing N-acetylaspartate (NA), choline (Cho), creatine-phosphocreatine (Cre) and lactate, from four 15-mm slices divided into 0.84-ml single-volume elements. The study included 12 patients with progressive supranuclear palsy, 10 with Parkinson's disease, nine with corticobasal degeneration and 11 age-matched normal control subjects. Regions of interest were selected from the brainstem, caudate, thalamus, lentiform nucleus, centrum semiovale, and from frontal, parietal, precentral, temporal and occipital cortices. Progressive supranuclear palsy patients, compared with control subjects, had significantly reduced NA/Cre in the brainstem, centrum semiovale, frontal and precentral cortex, and significantly reduced NA/Cho in the lentiform nucleus. Corticobasal degeneration patients, compared with control subjects, had significantly reduced NA/Cre in the centrum semiovale, and significantly reduced NA/Cho in the lentiform nucleus and parietal cortex. There were no significant differences between Parkinson's disease patients and control subjects, or between patients groups in any individual region of interest. In the parietal cortex of corticobasal degeneration patients, NA/Cho was significantly reduced contralateral to the most affected side. There were statistically significant group differences in the regional pattern of NA/Cre and NA/Cho reduction, comparing normal control subjects with all patient groups, Parkinson's disease with corticobasal degeneration, and Parkinson's disease with progressive supranuclear palsy. Although the occurrence of significant groups differences does not imply that it is possible to differentiate between individual patients using 1H-MRSI in progressive supranuclear palsy and corticobasal degeneration, detection of specific cortical and subcortical patterns of neuronal involvement is possible with this technique. We suggest that this regional pattern of neuronal involvement found in progressive supranuclear palsy and corticobasal degeneration may help in the diagnostic evaluation of affected individuals.

Aged↗
PubMed1996

Proton magnetic resonance spectroscopic imaging in patients with cerebellar degeneration.

Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age-matched normal control subjects. This technique permits the simultaneous measurement of N-acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and lactate signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. Because patients with cerebellar degeneration often show substantial atrophy on magnetic resonance imaging (MRI), we specifically chose to analyze the spectroscopic signals only from tissue that did not have an atrophic appearance on the MRI. The spectroscopic findings showed a significant reduction of N-acetylaspartate in all parts of the cerebellum, a significant correlation with MRI scores of cerebellar atrophy, and a significant correlation with clinical rating scores of cerebellar disturbance. Our method of analysis suggests the presence of a neurodegenerative process in cerebellar areas that do not appear to be atrophic on the MRI. Some limitations of proton magnetic resonance spectroscopic imaging in the present study were related to the partial field inhomogeneity characteristics of the posterior fossa, the anatomical location of the cerebellum, and the particularly severe cerebellar atrophy in some of the patients.

Adult↗
PubMed1996

Successful early copper therapy in Menkes disease associated with a mutant transcript containing a small In-frame deletion.

Classical Menkes disease is a fatal X-linked neurodegenerative disorder caused by defects in a gene (MNK) that encodes a copper-transporting ATPase. Treatment with parenteral copper has been proposed for patients identified before symptoms develop. We recently described suboptimal outcomes despite early copper replacement in two classical Menkes patients whose mutation predicts little if any functional copper transporter. Here, we describe successful copper replacement therapy in a patient with Menkes disease with a splice acceptor site mutation (IVS8,AS,dup5) that causes exon-skipping and generates a mutant transcript with a small in-frame deletion in a noncritical region. The patient was diagnosed by analysis of neurochemical levels in cord blood, and parenteral copper replacement was begun at 8 days of life. Throughout infancy, he showed normal head growth, brain myelination, and age-appropriate neurodevelopment, including independent walking at 14 months of age. In contrast, his affected half-brother and first cousin with the same mutation, but who were not diagnosed and treated from an early age, showed arrested head growth, cerebral atrophy, delayed myelination, and abnormal neurodevelopment. We propose that the successful neurological outcome in this patient was related to early repletion of circulating copper levels, in combination with residual copper transport by a partially functional MNK ATPase containing the small deletion. We hypothesize that raising plasma copper concentrations in patients with Menkes disease with some residual functional gene product can increase the ligand: transporter ratio and thus alter favorably the kinetics of copper transport into and within the brain.

Adenosine Triphosphatases↗
PubMed1996

Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging.

BACKGROUND: Multislide proton magnetic resonance spectroscopic imaging (1H-MRSI) permits the simultaneous acquisition of N-acetylaspartate (NA), choline (Cho), creatine/phosphocreatine (Cre), and lactate (Lac) signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. NA is inferred to be a neuron-specific molecule, whereas Cho mainly reflects glycerophosphocholine and phosphocholine, compounds involved in phospholipid metabolism. OBJECTIVE: To assess whether 1H-MRSI could detect a regional pattern of cortical and subcortical involvement in the brain of Alzheimer's disease (AD) patients. METHODS: 1H-MRSI was performed in 15 patients with probable AD and 15 age-matched healthy controls. Regions of interest (ROIs) were selected from frontal (FC), temporal (TC), parietal (PC), occipital, and insular cortices, subcortical white matter (WM), and thalamus. RESULTS: In AD patients, we found a significant reduction of NA/Cre in the FC, TC, and PC and a significant reduction of Cho/Cre in the WM. CONCLUSIONS: This 1H-MRSI study of AD patients shows a regional pattern of neuronal damage in the associative cortices, as revealed by significant reduction of NA/Cre in the FC, TC, and PC, and regional derangement of phospholipid metabolism, as revealed by significant reduction of Cho/Cre in the WM.

Aged↗
PubMed1996

Quantification and pharmacokinetics of blood-brain barrier disruption in humans.

Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K1 in all patients. Baseline K1 values were 2.1 +/- 1.4 and 34.1 +/- 22.1 microl/minute/ml (+/- standard deviation) for brain and tumor, respectively. The peak absolute increases in K1 following HBBBD were 20.8 +/- 11.7 and 19.7 +/- 10.7 microl/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K1 to near baseline for brain and tumor were 8.1 +/- 3.8 and 4.2 +/- 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure time at concentrations above 1 microM, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-brain barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs.

Adult↗
PubMed1995

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.

PURPOSE: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). METHODS: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L. RESULTS: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. CONCLUSIONS: A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

Adolescent↗
PubMed1995

von Hippel-Lindau disease: genetic, clinical, and imaging features.

von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes retinal hemangioblastomas, hemangioblastomas of the central nervous system, endolymphatic sac tumors, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas, among other less common manifestations. Although this entity has been recognized for almost 70 years, recent developments in the genetics and imaging of VHL disease have greatly improved understanding of the disease and its natural history. This review describes the major events that led to the discovery of the gene for VHL and will familiarize the reader with recent developments in the magnetic resonance Imaging, computed tomographic, and ultrasound findings of this entity. Despite advances in the genetic understanding of this disease, imaging techniques will continue to play a major role in the diagnosis, management, and treatment of VHL.

Adenoma, Islet Cell↗
PubMed1994

Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population.

OBJECTIVE: To determine the prevalence of focal lesions of the pituitary gland that suggest the presence of a pituitary adenoma in asymptomatic persons. DESIGN: 100 normal volunteers (70 women, 30 men; age range, 18 to 60 years old) were studied by high-resolution magnetic resonance imaging (MRI) of the pituitary gland before and after administration of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). SETTING: Occult pituitary adenomas are identified at autopsy in 3% to 27% of unselected asymptomatic patients. The frequency of incidental pituitary adenomas detected by MRI in normal persons is unknown. MEASUREMENTS: The MRI scans from volunteers were randomly mixed with scans of 57 patients with Cushing disease and interpreted independently by three blinded reviewers. RESULTS: Seven women (10%) and three men (10%) had focal areas of decreased signal intensity in the pituitary gland after administration of Gd-DTPA. The lesions ranged from 3 to 6 mm in greatest diameter and were diagnosed as pituitary adenomas by at least two of the three reviewers. When similar lesions were detected on MRI scans in patients with Cushing disease, the positive predictive value for identification of an adenoma at that site was 86%. CONCLUSIONS: About 10% of the normal adult population have pituitary abnormalities on MRI scans that are compatible with the diagnosis of asymptomatic pituitary adenomas. Most pituitary adenomas remain asymptomatic and do not require treatment.

Adenoma↗
PubMed1994

Pathophysiology of syringomyelia associated with Chiari I malformation of the cerebellar tonsils. Implications for diagnosis and treatment.

The mechanisms previously proposed for the progression of syringomyelia associated with Chiari I malformation of the cerebellar tonsils are controversial, leave many clinical observations unexplained, and underlie the prevalence of different operations currently used as initial treatment. To explore the mechanism of syringomyelia progression in this setting, the authors used anatomical and dynamic (phase-contrast and phase-contrast cine) magnetic resonance (MR) imaging, and intraoperative ultrasonography to examine the anatomy and dynamics of movement of the cerebellar tonsils, the wall of the spinal cord surrounding the syrinx, and the movement of cerebrospinal fluid (CSF) and syrinx fluid at rest, during the respiratory and cardiac cycles, and during Valsalva maneuver in seven affected patients. In all patients the cerebellar tonsils occluded the subarachnoid space at the level of the foramen magnum. Syringomyelia extended from the cervical to the lower thoracic segment of the spinal cord. No patient had evidence of a patent communication between the fourth ventricle and the syrinx on anatomical MR images, dynamic MR images, or intraoperative ultrasound studies. Dynamic MR images of three patients revealed abrupt downward movement of the spinal CSF and the syrinx fluid during systole and upward movement during diastole, but limited movement of CSF across the foramen magnum during the cardiac cycle. Intraoperative ultrasound studies demonstrated abrupt downward movement of the cerebellar tonsils during systole that was synchronous with sudden constriction of the spinal cord and syrinx. Decompression of the foramen magnum was achieved via suboccipital craniectomy, laminectomy of C-1 and C-2, and dural grafting, leaving the arachnoid intact. Immediately after surgery, the pulsatile downward thrust of the tonsils and constriction of the spinal cord and syrinx disappeared. Syringomyelia resolved within 1 to 6 months after surgery in all patients. Observations by the authors suggest the following previously unrecognized mechanism for progression of syringomyelia associated with occlusion of the subarachnoid space at the foramen magnum. The brain expands as it fills with blood during systole, imparting a systolic pressure wave to the intracranial CSF that is accommodated in normal subjects by sudden movement of CSF from the basal cisterns to the upper portion of the spinal canal. With obstruction to rapid movement of CSF at the foramen magnum, the cerebellar tonsils, which plug the subarachnoid space posteriorly, move downward with each systolic pulse, acting as a piston on the partially isolated spinal CSF and producing a systolic pressure wave in the spinal CSF that acts on the surface of the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Long-term effects of radiation therapy for a catecholamine-producing glomus jugulare tumor. Case report.

A 42-year-old woman presented with otorrhea 22 years after extracranial resection of a norepinephrine-secreting glomus jugulare tumor with intravascular embolization and radiation therapy to the intracranial portion of the tumor. Tumor growth was arrested and was associated with a decrease in blood and urine norepinephrine levels. Extensive evaluation of the otorrhea, including computerized tomography-cisternography, gadolinium-enhanced magnetic resonance imaging, and arteriography showed marked diffuse necrosis of the temporal bone and skull base with limited tumor vascularity. Cerebrospinal fluid (CSF) collected from the right ear showed norepinephrine levels of 2975 pg/ml; plasma norepinephrine levels were normal. The precise site of CSF leakage could not be delineated. Exploration of the posterior fossa revealed a large dural defect at the anteromedial aspect of the petrous bone through which CSF flowed over the surface of the residual extradural glomus tumor. The defect was successfully sealed with a fascial patch. Postoperatively, CSF norepinephrine levels were normal and no further leakage was observed.

Adult↗
PubMed1992

Terminal transverse limb defects associated with familial cavernous angiomatosis.

Terminal transverse limb defects rarely are reported as familial. Multiple pathogenetic mechanisms, including vascular disruption, have been proposed to account for these defects. We report on a family followed over the past 6 years known to have familial cavernous angiomatosis in which 2 relatives have similar terminal transverse defects at the mid-forearm. Multiple relatives have had episodic bleeding from intracranial cavernous angiomas, a distinct finding in this disorder. Other findings in this family include retinal cavernous angiomas (2 patients), a high incidence of skin angiomas (12 patients), cavernous angiomas of the soft tissue (2 patients), and a hepatic angioma (one patient). One of the 2 individuals with the limb defect was evaluated extensively. Magnetic resonance imaging of the forearm with the terminal transverse defect using gadolinium-DTPA enhancement showed abrupt termination of all structures distal to the normal radial and ulnar heads. We propose that familial cavernous angiomatosis may be a new cause of vascular disruption resulting in terminal transverse limb defects.

Adolescent↗
PubMed1991

Magnetic resonance imaging of canine salivary glands after ductal ligation and stimulation by pilocarpine.

We performed magnetic resonance imaging in six dogs after submandibular ductal ligation on one side, followed by secretory stimulation with intraperitoneal injection of pilocarpine (5 mg/kg). On the images obtained after ductal ligation but before stimulation, there was no significant change in signal intensity on either side. After injection of pilocarpine the signal intensity of the ligated gland increased significantly (p less than 0.01) in T2-weighted images and nonsignificantly in inversion recovery images, and remained constant in T1-weighted images. Significant (p less than 0.01) volume increases of the glands after ligation and stimulation were measured for the T1, T2, and inversion recovery protocols. These findings likely reflect the retention of saliva caused by pilocarpine stimulation and the absence of drainage through the obstructed duct. The results indicate that the T2-weighted images obtained after pilocarpine stimulation may be useful for studying patients with disturbance of major salivary gland function and may provide an objective basis for the noninvasive diagnosis of unilateral stenosis.

Animals↗
PubMed1991

Pulse cyclophosphamide for severe neuropsychiatric lupus.

We studied the effect of parenteral pulse cyclophosphamide therapy in nine patients with active systemic lupus erythematosus and severe central nervous system involvement. Seven patients had focal neurological deficits and/or seizures associated with abnormalities on cerebrospinal fluid analysis and/or magnetic resonance imaging. Two patients had organic brain syndrome with psychosis and normal cerebrospinal fluid and/or magnetic resonance imaging analysis. Six patients were unresponsive to treatment with high dose corticosteroid. Cyclophosphamide, 0.75-1.0 g/m2 body surface area, was administered intravenously every month for at least 2 months. Eight patients had a complete recovery or recovered with minor residuals. Cyclophosphamide was well tolerated with few side effects. We conclude that parenteral pulse cyclophosphamide is an effective adjunctive therapy for the management of patients with active systemic lupus erythematosus and central nervous system symptoms.

Adolescent↗
PubMed1991

Positron emission tomography of pituitary macroadenomas: hormone production and effects of therapies.

Positron emission tomography with [18F]fluorodeoxyglucose (FDG) was carried out in 24 patients with pituitary macroadenomas (32 studies) to assess the glucose utilization of these tumors in vivo. The adenoma metabolic index, which is the ratio of FDG uptake of tumor to a whole brain slice, was calculated. Comparisons were made between tumor uptake of FDG and hormone secretion and response to therapies. In each positron emission tomography study, the macroadenoma could be easily identified visually as an area of increased FDG uptake near the region of the sella. FDG uptakes were highest for nonfunctional adenomas, and the prolactin, growth hormone, and thyroid-stimulating hormone-producing groups displayed similar levels of glucose metabolism. The adenoma metabolic index for all tumors averaged 1.3, ranging from 0.3 for a thyroid-stimulating hormone adenoma to 3.5 for a nonfunctional tumor. Tumors did not exhibit metabolic rates that could characterize the type of hormone produced. Recurrent macroadenomas displayed metabolism similar to tumors not operated on, whereas irradiated adenomas showed lower glucose uptake than nonirradiated tumors. Drug therapy with bromocriptine or the long-acting somatostatin analogue octreotide also decreased the glucose utilization of the tumor. There was no correlation between the amount of hormone produced and the adenoma metabolic index when a group of tumors was analyzed. Patients scanned more than once, however, demonstrated changes in hormone levels that changed or did not change in parallel with tumor metabolism. Thus, positron emission tomography offers the potential capability for predicting and defining the growth of pituitary adenomas. This may be of particular value when plasma hormone assays and conventional imaging techniques prove inadequate for monitoring patient response to therapy.

Adenoma↗
PubMed1991

Central nervous system involvement in Von Hippel-Lindau disease.

Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency and distribution of CNS lesions. The associated clinical features were also reviewed. Thirty-six (72%) of the 50 had 1 or more CNS tumors. The most frequently affected sites in the CNS excluding the retina were the cerebellum (52%), spinal cord (44%), and brainstem (18%). New regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study. Forty-one percent of all VHL patients with CNS tumors were neurologically asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem tumors (44%) were often without clinical signs or symptoms. Multiple lesions were common. The mean age of all VHL patients (34.5 years) was similar to the mean age of all CNS VHL patients (34.4 years), suggesting a lack of age association. CNS lesions commonly occurred in the 2nd decade of life. All patients at risk for VHL should be evaluated using gadolinium-enhanced MRI after 10 years of age, although ophthalmic examination should be initiated within the 1st 2 years of life. Enhanced MRI is particularly useful in the detection of CNS tumors in patients with the VHL gene.

Adolescent↗
PubMed1990

Disk fragment migration.

This report analyzes the most frequently observed migration paths of disk fragments in 47 patients who had extruded or sequestered disks. Observations are based principally on magnetic resonance (MR) images. When disk fragments moved in a superior (42%) or inferior (40%) direction from the donor disk, the displaced disk components were most frequently (94%) dislodged into the right or left half of the anterior epidural space (AES) and rarely straddled the midline. To explain this phenomenon, the authors investigated the anatomy of the AES by dissecting four cadaver specimens and reviewing 300 MR images of the spine. They conclude that the migrating path of a disk fragment is determined by the anatomy of the AES, a fairly well-defined space delimited posteriorly by the posterior longitudinal ligament and by membranes laterally attached to it. It consists of two compartments separated by a sagitally aligned septum. During migration, sequestered disk fragments usually stay in these compartments.

Cervical Vertebrae↗
PubMed1990

The diagnosis of acromegaly: value of inferior petrosal sinus sampling.

The early diagnosis of acromegaly may be difficult when serum levels of growth hormone are minimally elevated and imaging of the pituitary gland fails to show an adenoma. However, transsphenoidal surgery has the greatest chance of cure at this stage. We therefore investigated the value of sampling petrosal sinuses for measurement of growth hormone in this group of patients. Simultaneous bilateral sampling of the inferior petrosal sinuses to measure serum concentrations of growth hormone was performed in five patients suspected of having acromegaly but with nondiagnostic CT scans (n = 5) and MR images (n = 3) of the pituitary gland. Levels of growth hormone from the petrosal sinuses were five to 36 times greater than levels in the peripheral veins in all five patients, and three of four showed a marked response to growth hormone-releasing hormone. During transsphenoidal surgery, growth hormone-producing microadenomas were resected completely in four patients. In the fifth patient, a left-sided microadenoma had invaded the cavernous sinus and could not be resected completely. Lateralization of the adenomas within the pituitary gland on the basis of differences in levels of growth hormone between the two petrosal sinuses was not completely reliable. Elevated levels of growth hormone in selective samples from the inferior petrosal sinuses can help support an early diagnosis of acromegaly when peripheral growth hormone levels and imaging are not diagnostic.

Acromegaly↗