December 2000: 6 month old boy with 2 week history of progressive lethargy.

This 6-month-old Caucasian boy presented with a 10-day history of lethargy, obtundation, inability to hold his head up and mild torticollis. MRI and CT scans showed a large solid and cystic mass involving the right temporal, parietal and occipital lobes, pineal, superior pons, mesencephalon and posterior right thalamus. He underwent craniotomy initially for a partial tumor resection with an intraoperative diagnosis of desmoplastic astrocytoma. With immunohistochemistry and special stains the diagnosis of desmoplastic infantile ganglioglioma (DIG) was made. A near total resection was performed a week after initial resection.The patient then was treated with chemotherapy. Two months later an MRI showed tumor growth. Following additional aggressive chemotherapy, an MRI at 5 months post-resection indicated further tumor progression. This case illustrates that some DIGs may behave more aggressively than typical WHO grade I lesions.

In utero repair of myelomeningocele: a comparison of endoscopy and hysterotomy.

OBJECTIVE: To compare endoscopic coverage of myelomeningocele with a maternal split-thickness skin graft in utero to definitive neurosurgical closure through a hysterotomy. METHODS: Four fetuses with isolated myelomeningocele underwent endoscopic coverage of the defect with a maternal split-thickness skin graft in a CO(2) environment at 22-24 weeks' gestation. Subsequently, 4 fetuses underwent standard neurosurgical closure of their myelomeningoceles at 28-29 weeks' gestation. RESULTS: The mean operating time for the endoscopic procedures was 297 +/- 69 min. Two fetal losses occurred as a result of chorioamnionitis and placental abruption, respectively. A third baby delivered at 28 weeks' gestation after prolonged disruption of the membranes. The 2 survivors required standard closure of the myelomeningocele after delivery. The mean operating time for the hysterotomy procedures was 125 +/- 8 min. No mortality occurred, and all the infants delivered between 33 and 36 weeks with well-healed myelomeningocele scars. At present, the functional levels of all infants approximate the anatomical levels of the lesions. CONCLUSION: With current technology, in utero repair of congenital myelomeningocele through a hysterotomy appears to be technically superior to procedures performed endoscopically.

Endoscopic coverage of fetal myelomeningocele in utero.

OBJECTIVE: Our goal was to evaluate the safety and efficacy of minimally invasive surgery for the coverage of myelomeningocele in utero. STUDY DESIGN: Women in the mid-second trimester of a pregnancy complicated by fetal myelomeningocele were offered an experimental procedure designed to prevent ongoing exposure of the spinal cord to the intrauterine environment. The procedure consisted of maternal laparotomy while the patient was under both general and epidural anesthesia, with exposure of the gravid uterus. Endoscopic ports were placed for camera and operating instruments. Amniotic fluid was removed and replaced with carbon dioxide. The fetus was then positioned and a maternal split-thickness skin graft was placed over the exposed spinal cord or neural elements. The skin graft and a covering of Surgicel Absorbable Hemostat were attached with fibrin glue prepared from autologous cryoprecipitate. RESULTS: Four fetuses with open myelomeningocele underwent endoscopic coverage of the spinal lesion between 22 weeks 3 days and 24 weeks 3 days of gestation. One infant, delivered by planned cesarean section at 35 weeks' gestation after demonstration of fetal lung maturity, is almost 3 years old. A second infant was delivered by cesarean section at 28 weeks after preterm labor and is now almost 6 months old. Both survivors manifest only mild motor and somatosensory deficits. One fetus who was delivered 1 week after operation after development of amnionitis died in the delivery room of extreme prematurity. The final fetus died intraoperatively from abruptio placentae. CONCLUSION: Minimally invasive fetal surgery appears to constitute a feasible approach to nonlethal fetal malformations that result in progressive and disabling organ damage.

A model for in utero endoscopic treatment of myelomeningocele.

An animal model for intrauterine surgical treatment of myelomeningocele is described using sheep. We report the technical feasibility of endoscopic intrauterine skin graft placement over surgically induced defects, including over exposed spinal cord. These grafts exclude amniotic fluid from the underlying lesion and provide a matrix for fetal skin growth below the graft. The potential for human application is discussed.

PET studies of parkinsonian patients treated with autologous adrenal implants.

Transplantation of autologous adrenal medulla tissue into the striatum has recently been proposed as a treatment for Parkinson's disease. We report the use of positron emission tomography (PET) to evaluate patients who had adrenal implants placed into the right caudate. 6-[18F] fluoro-L-dopa (6-FD) scans were performed to study the integrity and activity of the implant, and the nigrostriatal dopamine system before and six weeks after transplantation surgery. [68Ga] Gallium-ethylenediaminetetraacetate (Ga) scans were also performed to assess the blood brain barrier. The Ga scans performed on two patients showed increased permeability of the blood brain barrier at the surgical site. 6-FD PET scans in five patients did not show a consistent change in striatal uptake following adrenal medullary implantation after six weeks. Further assessment of implant viability with 6-FD PET scans after longer follow up may provide useful information if the blood-brain barrier becomes re-established with the passage of time.

Adrenal medullary transplantation to the caudate nucleus in Parkinson's disease. Initial clinical results in 18 patients.

Results from a pilot study of adrenal medullary autotransplantation for Parkinson's disease are presented. Eighteen patients were studied; 12 were followed up for 1 year, and 6 were followed up for 6 months. Four of 12 patients showed distinct improvement in the signs and symptoms of their disease, as assessed using the Columbia Rating Scale, at 1 year; none showed distinct deterioration. The 6 patients who were followed up for only 6 months were an average of 20 years older and generally more severely affected. None distinctly improved. Morbidity was considered to be minor and transient among the first 12 patients, while 4 of the last 6 patients experienced alteration in mental status lasting as long as several months. This problem has led us to conclude that older patients with preexisting cognitive impairment should not be included in future studies until the benefits are more clearly established. However, we believe that the distinct and persistent improvement seen in some of the younger patients warrants the initiation of a well-designed, randomized, and controlled trial of adrenal medullary autotransplantation for the purpose of confirming these results and assessing the effect of the procedure on the natural progression of Parkinson's disease.

Alteration of kainic acid and quinolinic acid toxicity by neostriatal transplants in vitro.

Mature (greater than 21 days in vitro) organotypic corticostriatal cultures prepared from newborn rat brain were incubated in either kainic acid (KA) 10(-3) M or quinolinic acid (QUIN) 10(-3) M for up to 48 h. Other identical cultures were similarly incubated immediately after they had received one or two additional explants of neonatal striatal tissue placed beside each corticostriatal culture. The cultures incubated with either KA or QUIN in the presence of the neonatal striatal tissue showed better preservation than cultures incubated with KA or QUIN alone. Results suggest that the neonatal striatal explants or 'transplants' afford some protective effect against the toxicity or either KA or QUIN.

Comparison of CT and MRI brain tumor imaging using a canine glioma model.

A canine gliosarcoma model was used to study the effectiveness of magnetic resonance imaging (MRI) with gadolinium contrast enhancement in defining the histologic margins of brain tumors. The effectiveness of this technique was compared to conventional computed tomography (CT) using iodinated contrast enhancement. Cultured canine gliosarcoma cells were injected into the left hemisphere of adult mongrel dogs. The dogs developed brain tumors and progressive clinical signs. Serial MRI with and without gadolinium diethylene triamine penta-acetic acid was compared to serial CT with and without sodium iothalamate obtained on the same days. After the final scans, animals were sacrificed; the brains were removed and processed for routine histopathologic study. All tumors were visualized with contrast-enhanced MRI which proved most sensitive. Gadolinium di-ethylene triamine penta-acetic acid caused bright enhancement of tumors in a distribution that consistently corresponded to areas of pathologically proved tumor infiltration. Gross and microscopic autopsy findings correlated better with MRI than with CT which tended to produce poorer resolution and underrepresent the size of viable tumor. Gadolinium-enhanced MRI is more accurate than unenhanced MRI, unenhanced CT, or enhanced CT in defining the histologic margins of tumors.

Pituitary transplantation: cyclosporine enables transplantation across a minor histocompatibility barrier.

Pituitary glands from neonatal donors were transplanted to the median eminence of hypophysectomized adult rats. Rats with transplants were then treated for 2 weeks with the immunosuppressive drug cyclosporine. For 5 weeks thereafter, blood was drawn at regular intervals for determination of serum thyroxine, prolactin, and luteinizing hormone. Cyclosporine-treated recipients of grafts with minor histocompatibility differences had normal levels of thyroxine and prolactin, whereas untreated animals did not. In addition, the treated animals responded to oophorectomy with a marked elevation in serum luteinizing hormone. This evidence indicates that cyclosporine enables successful transplantation across a minor histocompatibility barrier. It also suggests that these grafts interact with the hypothalamus. Transplantation across a major histocompatibility barrier was unsuccessful even in the presence of cyclosporine.

Pituitary transplantation: Part 1. Successful reconstitution of pituitary-dependent hormone levels.

Neonatal or adult pituitary glands were transplanted to the median eminence of adult rats of the same or a histoincompatible inbred strain. The hormonal status of 39 transplanted rats and of control animals was evaluated by serial determination of serum prolactin and thyroxine. Grafts of neonatal tissue to adults of the same strain resulted in normal postoperative hormone levels. This indicates not only that pituitary grafts had survived, but also that the transplants were under hypothalamic control. Grafts of adult tissue were less successful. The prolactin value was lower, but still within the normal range, whereas the thyroxine value was lower than normal, suggesting that viable pituitary tissue had survived but was not under hypothalamic control. Transplantation across a histocompatibility barrier was uniformly unsuccessful. Postoperative prolactin levels were low and thyroxine levels were not significantly different from those in hypophysectomized controls.