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Biomedical subjects

D S Heffez

Publications and source records attributed to D S Heffez.

16 recordsLinked to original sources

The effect of incomplete patient follow-up on the reported results of AVM radiosurgery.

BACKGROUND: The reported efficacy of AVM radiosurgery--80-85% 2-year obliteration rate--is based exclusively on the results of follow-up arteriography in a small percentage of treated patients; it is therefore inaccurate. We examined the effect of incomplete follow-up on the results of AVM radiosurgery. METHODS: We reviewed the results of AVM radiosurgery in 82 patients after a minimum of 24 months of follow-up. Patients were not preselected to undergo arteriography on the basis of any other imaging study. Data were analyzed using the Kaplan-Meier method and stratified by size of AVM. Results were compared with those obtained from the same data using the reporting techniques described in the literature. RESULTS: When data analysis was limited to patients who had follow-up arteriography, the 2-, 3-, and 4-year obliteration rates were 37%, 73%, and 84% after a minimum 24-month follow-up. Using Kaplan-Meier analysis the 2-, 3-, and 4-year obliteration rates were 32%, 55%, and 55% (95% CI = +/-18%), respectively. The 2-year obliteration rate was 43% for AVMs <30 mm in diameter and 16% for AVMs >30 mm in diameter, respectively. CONCLUSION: If data analysis is limited to the patients who undergo follow-up arteriography, the obliteration rate of AVM radiosurgery is overestimated. The actual 2-year obliteration rate if all data is considered is in the range of 40% rather than the commonly reported 80%. Therefore, treated patients are exposed to the risk of intracerebral hemorrhage for a longer period than previously appreciated. Compulsive long-term follow-up is required to document the true AVM obliteration rate after treatment by radiosurgery.

Algorithms

Stereotactic transsylvian, transinsular approach for deep-seated lesions.

BACKGROUND: Lesions located deep within the frontal and parietal lobes adjacent to the internal capsule are often considered surgically inaccessible. We have used intraoperative stereotactic lesion localization in conjunction with microsurgical dissection of the lateral sylvian fissure to accurately and atraumatically approach such lesions through the insular cortex. METHODS: When possible, the sylvian fissure is widely opened using standard microsurgical technique. However, exploration through a precisely placed exposure no more than 1.0 cm in length is still feasible. Repeated intraoperative lesion localization employing ultrasound, frame-based or frameless stereotaxis was used to guide dissection deep to the Insular cortex. RESULTS: Using this approach we have resected five cavernous angiomas, three plexiform AVMs and 2 low-grade gliomas. There was a single case of transient dysphasia in seven dominant hemisphere explorations and a single case of transient somatosensory impairment. Otherwise, there were no new transient or permanent postoperative neurologic deficits. In two cases, hemiparesis present prior to surgery improved following resection of a cavernous angioma. CONCLUSIONS: The transsylvian, transinsular approach can be employed to safely expose lesions deep within the cerebral hemisphere. Anatomic considerations, surgical technical refinements, and clinical results are the subject of this report.

Adolescent

Operative confirmation of three-dimensional computed tomographic and magnetic resonance imaging of cerebrovascular pathology.

The conventional neuroradiological evaluation of aneurysms and arteriovenous malformations employs computed tomography (CT), magnetic resonance imaging (MRI), and detailed cerebral angiography. These techniques may be inadequate to define fully the cerebrovascular anatomy in patients with giant aneurysms or with arteriovenous malformations (AVMs) located near so-called eloquent brain structures. Therefore, we examined the usefulness of three-dimensional (3-D) MRI and CT images of the brain and cerebral vessels for predicting operative anatomical findings in selected cases of complex cerebrovascular pathology. In six of nine (67%) patients with giant aneurysms undergoing direct surgical treatment, the 3-D images were confirmed to be accurate, and they furnished information that is not available by conventional imaging. In three of these nine (33%) patients, failure of the 3-D images to predict operative findings accurately could be directly related to inappropriate imaging technique or to anatomical findings below the limit of resolution for CT or MRI. In 13 of 19 (68%) patients with an AVM, the 3-D images were considered helpful for treatment selection or planning, primarily because they enhanced the understanding of the relationship of the AVM nidus to brain structures of known functional significance. The results of our initial experience with 3-D imaging of cerebrovascular pathology are described in this report.

Adolescent

Intrauterine repair of experimental surgically created dysraphism.

The paralysis seen in children with myelomeningocele has been attributed to congenital myelodysplasia. Clinical and pathological data, however, suggest that the paralysis may be due in part to a spinal cord injury caused by exposure of the neural tube to the intrauterine environment. This possibility has been supported by experimental data obtained using a fetal rat model of surgically created dysraphism. In this paper, we report the results of intrauterine treatment of experimental dysraphism in the fetal rat and the fetal pig. These studies confirm our earlier findings and suggest that both physical trauma and toxic injury may contribute to the spinal cord injury.

Animals

Pituitary gigantism caused by growth hormone excess from infancy.

A 2 1/4-year-old boy with pituitary gigantism had a large pituitary macroadenoma. Gross tumor removal has prevented further visual losses, but he has had persistent hypersecretion of growth hormone and prolactin. Treatment with somatostatin analog has decreased both hormone secretion and growth velocity.

Adenoma

Sustained release of papaverine for the treatment of cerebral vasospasm: in vitro evaluation of release kinetics and biological activity.

Cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage. To date, pharmacological treatment has been plagued in part by an inability to attain sufficiently high concentrations of vasodilator drug in the cerebrospinal fluid without precipitating systemic side effects such as hypotension. To circumvent this limitation of current pharmacological therapy, the authors have developed a sustained-release preparation of papaverine that can be implanted intracranially at the time of surgery for aneurysm clipping. In vitro evaluation of drug-release kinetics has demonstrated that reliable, sustained release of effective amounts of papaverine is possible. An in vitro bioassay using isolated preparations of canine basilar artery has confirmed the biological activity of this preparation. These in vitro studies are described.

Animals

Cerebrovascular CO2 reactivity during delayed vasospasm in a canine model of subarachnoid hemorrhage.

While the in vitro reactivity of cerebral conducting vessels following subarachnoid hemorrhage has been extensively studied, in vivo cerebrovascular CO2 reactivity has not been systematically investigated. We tested the hypothesis that, in the canine model of subarachnoid hemorrhage, the rise in cerebral blood flow normally seen with hypercapnia is blunted during delayed vasospasm. Four groups of animals were studied: one received two 4-ml subarachnoid injections of nonheparinized arterial blood into the cisterna magna (n = 8), one received three subarachnoid injections of 5 ml blood (n = 5), one received two subarachnoid injections of 4 ml saline (n = 5), and a control group (n = 5) had no subarachnoid injections or angiography. Basilar artery diameter was measured from baseline and follow-up angiography. We determined CO2 reactivity by randomly varying the concentration of inspired CO2 and measuring regional cerebral blood flow with radiolabeled microspheres. Basilar artery diameter was not affected by saline injection and was reduced by 26 +/- 2.9% in the two-hemorrhage group and 55 +/- 1.9% in the three-hemorrhage group. Baseline cerebral blood flow and CO2 reactivity were similar in all four groups. We conclude that, in this model of delayed vasospasm, regional cerebral vascular CO2 reactivity is intact and extrapolation of in vitro data regarding basilar artery diameter and reactivity to cerebral blood flow must be done cautiously.

Animals

Surgical resection of intrinsic brain stem lesions: an overview.

A major limitation to the effective treatment of intrinsic mass lesions of the brain stem has been the inability to clearly define the pathological anatomy radiographically. The improved soft tissue resolution offered by magnetic resonance imaging, as compared with axial computed tomography, now makes it possible not only to accurately distinguish anatomical relationships, but also to predict the pathological nature of the lesion. Accordingly, we have been encouraged to pursue a more aggressive approach to intrinsic lesions of the brain stem that appear well circumscribed on magnetic resonance imaging scan. The object of this paper is to report the successful treatment of four intrinsic lesions of the brain stem and to present an overview of the relevant published experience.

Adult

Inflammatory intracranial mass lesion: an unusual complication resulting from the use of Gelfoam.

There are few reported complications associated with the use of Gelfoam. We report the case of a 29-year-old woman who developed signs and symptoms of meningeal inflammation and an expanding intracranial mass related to the intracranial use of Gelfoam. Findings were confirmed by surgical exploration. Signs and symptoms resolved promptly after therapy with intravenous dexamethasone, but complete resolution of radiological findings required 5 months. As the use of Gelfoam is essential to neurosurgical practice, it is important to be aware of significant complications related to its use.

Adult

The paralysis associated with myelomeningocele: clinical and experimental data implicating a preventable spinal cord injury.

Paralysis seen in children with myelomeningocele has been attributed to congenital myelodysplasia. We suspected that paralysis may be due in part to a spinal cord injury caused by exposure of the neural tube to the amniotic fluid. This hypothesis was tested using a fetal rat model of surgically created dysraphism. Each pup from the experimental group of rats in which the spinal cord was intentionally exposed to the amniotic fluid was born with severe deformity and weakness of the hind limbs and tail. Control fetal rats, subjected to the same procedure without directly exposing the spinal cord to the intrauterine environment, were normal at birth. Histological studies of the exposed spinal cord revealed extensive erosion and necrosis, findings similar to those described in children with myelomeningocele. We therefore propose a "two-hit" hypothesis to explain the paralysis seen in children with myelomeningocele: congenital myelodysplasia complicated by an intrauterine spinal cord injury. Intrauterine protection of the exposed spinal cord might prevent some or all of the paralysis. The possible implications of these findings for the future treatment of myelomeningocele are discussed.

Amniotic Fluid

Effect of nimodipine on cerebral metabolism during ischemia and recirculation in the mongolian gerbil.

The effect of nimodipine on cerebral metabolism during ischemia and reflow was studied in female mongolian gerbils. Animals were divided into three experimental groups. Group 1 received 1 mg/kg nimodipine i.p. 1 h prior to ischemia. Group 2 received an injection of the vehicle, 5% polyethylene glycol 400. Group 3 received an equal volume of normal saline. Cerebral ischemia was induced by bilateral common carotid artery occlusion for 1, 2, or 5 min. Recirculation was established for 0, 1, or 5 min. Sham-operated animals served as nonischemic controls. Gerbils were killed by microwave irradiation. Regional levels of ATP, phosphocreatine, glucose, glycogen, cyclic AMP, and cyclic GMP were measured in brain extracts using standard assay techniques. Levels of metabolites in sham-operated animals did not differ among Groups 1, 2, and 3. At 1 min of ischemia, cortical and striatal ATP levels were highest in Group 1 (p less than 0.05 and p less than 0.01, respectively). After 5 min of recirculation, cortical and striatal glucose levels were highest in Group 1 (p less than 0.005). Regional levels of the metabolites measured at other times did not differ significantly among the three groups. Pretreatment with nimodipine thus retards the fall in ATP and facilitates the recovery of glucose in mongolian gerbils subjected to common carotid artery occlusion. A regional variability of this effect was observed.

Adenosine Triphosphate

Nimodipine levels in gerbil brain following parenteral drug administration.

Nimodipine binding to the particulate fraction of gerbil brain homogenate was characterized using tritiated (3H)-nimodipine as the radioactive ligand. Binding was monophasic and saturable, with the apparent affinity constant (KD) = 0.4 nM and the maximum number of binding sites (Bmax) = 12 nmol/kg wet wt. A competitive binding assay was validated for the measurement of nimodipine using gerbil brain as the source of receptors for the drug. Binding characteristics were sufficiently similar in specimens from different animals to allow the use of homogenates from individual animals as the source of both membrane-binding sites and competing ligand. Nimodipine could be detected in the brains of animals sacrificed soon after drug injection, and reached a peak level within 15 minutes. Brain drug level at a given time was a linear function of dose administered. One hour after a 1-mg/kg dose, the level of drug measured in brain was approximately 100 nmol/kg wet wt, more that 200 times the KD. Sufficient drug to mediate a maximal pharmacological effect accumulated in brain even after a dose of only 0.25 mg/kg. Thus, in this species, effective tissue nimodipine levels may be achieved at doses which minimize the risk of systemic hypotension.

Animals

Spinal epidural extramedullary hematopoiesis with cord compression in a patient with refractory sideroblastic anemia. Case report.

Spinal cord compression by epidural extramedullary hematopoiesis (EMH) is a rare phenomenon. A case of acute compressive myelopathy is reported in a 72-year-old man with EMH secondary to sideroblastic anemia. Technetium colloid scanning was used to document extensive ectopic marrow formation. The patient improved following surgery and radiotherapy. A review of the literature revealed 23 other cases of symptomatic spinal epidural EMH. The underlying hematological disorder varied but was always of long duration. Eighty-eight percent of the patients were males. Symptoms lasted longer than 1 week in 90% of cases, and 91% demonstrated incomplete neurological deficits. Plain x-ray films were rarely helpful in establishing the diagnosis. Technetium sulfur colloid bone marrow scanning has been used successfully to detect EMH and has led to preoperative diagnosis in one case. Decompressive laminectomy with or without postoperative irradiation is the suggested therapy, although there is evidence that radiotherapy alone may be adequate in some cases. Good recovery is the rule despite long-standing neurological deficits.

Aged

Acquired spinal cord injury in human fetuses with myelomeningocele.

Experimental studies have shown that there is a potential to attempt in utero repair of myelomeningocele in human fetuses. To provide a better understanding of the pathology of these lesions we prospectively studied eight stillborn human fetuses with myelomeningocele autopsied at The Johns Hopkins Hospital. The intact vertebral column with surrounding structures was removed, processed as a single block, and prepared as serial histologic sections. Study of the slides showed in all cases that in the center of the myelomeningocele the vertebral arch was open, the arrangement of meninges was such that the dura mater was open and in continuity with the deep layers of the dermis, and the pia mater was open and in continuity with a layer consisting of the superficial dermis and the epidermis. These meningeal relationships created an abnormally configured arachnoid space containing cerebrospinal fluid ventral to the spinal cord, which rested on the open pia mater and was exposed on the dorsal aspect of the sac. At the level of the myelomeningocele the naked cord had undergone varying degrees of injury up to complete loss of neural tissue. Where ventral remnants of the cord remained it was evident that a large degree of normal development of the cord had occurred. In most instances it appeared that the injury or destruction of the dorsal spinal cord was recent and consistent with occurrence during delivery. The results of this study support the concept that in utero surgery could preserve and protect the exposed spinal cord in a myelomeningocele of a human fetus and thus could reduce the severity of the neurologic deficit at birth.

Abortion, Spontaneous