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Biomedical subjects

I F Pollack

Publications and source records attributed to I F Pollack.

At least 91 records · Page 5Linked to original sources
PubMed1995

Surgical management of the cloverleaf skull deformity.

The cloverleaf skull deformity, or Kleeblattschädel, is a rare malformation caused by synostosis of multiple cranial sutures. This anomaly has been reported to carry a dismal prognosis both in terms of neurological outcome as well as cosmetic appearance if treatment is delayed. Due to the paucity of data concerning the results of early operative intervention, it remains uncertain whether aggressive craniofacial decompressive/reconstructive procedures are effective in ameliorating the effects of the malformation on both neurological development and cosmetic appearance. This paper reports the treatment and outcome of 7 children with the cloverleaf skull malformation treated at our institution between 1981 and 1993. All children underwent an initial decompressive craniectomy with the removal of at least 50% of the cranial vault for relief of high intracranial pressure in early infancy. Our first 4 patients underwent near total calvariectomy whereas the 3 children treated subsequently have undergone a staged approach with anterior followed by posterior craniectomies with bone morcellation and replacement. Subsequent reconstructions, intended to further improve the cosmetic appearance, were performed later in infancy or in early childhood. Follow-up ranges from 17 months to 9 years, with a mean of 61 months. Long-term results are reported with regard to neurological outcome as well as normalization of skull shape in terms of both the cephalic indices and general cosmetic appearance. Of the 4 children initially treated with total calvariectomy, only 1 child is neurologically normal and has a good cosmetic appearance. One child is severely impaired neurologically following a sagittal sinus thrombosis suffered during a secondary reconstructive procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cephalometry↗
PubMed1995

Intracranial ependymomas of childhood: long-term outcome and prognostic factors.

A detailed outcome analysis was performed on 40 children with intracranial ependymomas treated at our institution between 1975 and 1993 to identify those factors that were predictive of overall and progression-free survival. Three patients (7.5%) who were treated in the first 5 years of the study died within 3 months of surgery and were excluded from further outcome assessments. Eight (22%) of the 37 patients who survived the perioperative period had evidence of leptomeningeal dissemination at presentation, on the basis of either imaging (three children) and/or cytological (six children) results. The 5- and 10-year progression-free survival rates among these 37 patients were 45.1 and 36.1%, respectively; overall survival rates were 57.1 and 45.0%, respectively. The site of progression was local in 17 of 19 patients with progressive disease. Three factors were found to have a significant association (P < or = 0.05) with the outcome on both univariate and multivariate analyses: 1) the extent of the resection, 2) the age of the patient at diagnosis, and 3) the duration of the symptoms before diagnosis. The 5-year progression-free and overall survivals were 8.9 and 22%, respectively, among patients who had evidence of residual disease on postoperative imaging studies, compared with 68 and 80% rates among patients with no apparent residual disease (P = 0.0001 and P < 0.0001, respectively). Patients younger than 3 years fared significantly worse than older children (5-year progression-free and overall survival rates of 12 and 22%, respectively, in the younger children versus 60 and 75% in older children (P = 0.003 and P = 0.01, respectively). In addition, patients with a duration of symptoms before diagnosis of < 1 month had a worse outcome than those with a more protracted course (5-year progression-free and overall survival rates of 33 and 33%, respectively, versus rates of 53 and 64%, respectively (P = 0.02 for both). Neither the finding of evidence for dissemination at presentation nor the detection of anaplastic histological features (e.g., dense cellularity or high numbers of mitoses) were associated with a significantly worse outcome in this series. The combination of variables that had the strongest association with both favorable and unfavorable outcomes was the combination of the age of the patient and the resection extent. Only 2 of 17 patients older than 3 years with gross total resections have died, whereas 13 of 20 children who were either younger than 3 years or had radiologically incomplete resections have died (P < 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology.

MUTISM AND A variety of other neurobehavioral symptoms have been reported anecdotally after the removal of posterior fossa mass lesions. To determine the incidence and clinical spectrum of this syndrome, a detailed review was performed of patients undergoing resection of infratentorial tumors at our institution during the last 9 years; 12 of 142 patients (8.5%) manifested this syndrome, the largest series of such patients reported to date. Each child had a lesion that involved the vermis; seven had medulloblastomas, three had astrocytomas, and two had ependymomas. The incidence among children with vermian neoplasms was 13%. Ten children underwent division of the inferior vermis during tumor resection, and three had a superior vermian incision; one child underwent both superior and inferior vermian incisions. In 10 children, mutism developed in a delayed fashion postoperatively. The speech disturbance was associated with poor oral intake in 9 children, urinary retention in 5, long-tract signs in 6, and bizarre personality changes, emotional lability, and/or decreased initiation of voluntary movements in all 12. Neuropsychiatric testing, performed in seven children, confirmed impairments not only in speech but also in initiation of other motor activities. Ten children regained normal speech, bladder control, and neurological functioning, other than ataxia and mild dysarthria, within 1 to 16 weeks; two children had significant residual deficits. Characteristically, affect and oral intake returned to their preoperative baseline before the speech difficulties began to resolve. A detailed radiological review of these cases in parallel with 24 cases of vermian tumors without mutism identified only one factor that was significantly associated with the mutism syndrome, bilateral edema within the brachium pontis (P < 0.01). Neither the size of the tumor nor the length of vermian incision was associated with the development of mutism. The clinical features of this syndrome in the context of these imaging findings suggest that the mutism syndrome results from transient impairment of the afferent and/or efferent pathways of the dendate nuclei that are involved in initiating complex volitional movements. The clinical courses of our patients are presented and compared with those of similar cases in the literature in an attempt to evaluate the validity of this hypothesis.

Adolescent↗
PubMed1995

Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases.

Low-grade gliomas constitute the largest group of cerebral hemispheric tumors in the pediatric population. Although complete tumor resection is generally the goal in the management of these lesions, this can prove difficult to achieve because tumor margins may blend into the surrounding brain. This raises several important questions on the long-term behavior of the residual tumor and the role of adjuvant therapy in the management of these lesions. To examine these issues, the authors reviewed their experience in 71 children with low-grade cerebral hemispheric gliomas who were treated at their institution between 1956 and 1991 and assessed the relationship between clinical, radiographic, pathological, and treatment-related factors and outcome. Only seven patients in the series died, one from perioperative complications, five from progressive disease, and one (a child with neurofibromatosis) from a second neoplasm. For the 70 patients who survived the perioperative period, overall actuarial survivals at 5, 10, and 20 years were 95%, 93%, and 85%, respectively; progression-free status was maintained in 88%, 79%, and 76%, respectively. On univariate analysis, the factor that was most strongly associated with both overall and progression-free survival was the extent of tumor resection (p = 0.013 and p = 0.015, respectively). A relationship between extent of resection and progression-free survival was present both in patients with pilocytic astrocytomas (p = 0.041) and those with nonpilocytic tumors (p = 0.037). Histopathological diagnosis was also associated with overall survival on univariate analysis; poorer results were seen in the patients with nonpilocytic astrocytoma compared to those with other low-grade gliomas, such as pilocytic astrocytoma, mixed glioma, and oligodendroglioma (p = 0.021). The use of radiotherapy was not associated with a significant improvement in overall survival (p = 0.6). All three patients who ultimately developed histologically confirmed anaplastic changes in the vicinity of the original tumor had received prior radiotherapy, 20, 46, and 137 months, respectively, before the detection of malignant progression. In addition, children who received radiotherapy had a significantly higher incidence of late cognitive and endocrine dysfunction than the nonirradiated patients (p < 0.01 and 0.05, respectively). The authors conclude that children with low-grade gliomas of the cerebral hemispheres have an excellent overall prognosis. Complete tumor resection provides the best opportunity for long-term progression-free survival. However, even with incomplete tumor excision, long-term progression-free survival is common.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1995

Bobble-head doll syndrome and drop attacks in a child with a cystic choroid plexus papilloma of the third ventricle. Case report.

The authors report an unusual case of a 2-year-old boy with a 3-month history of episodic rightward anterolateral head tilt and large-amplitude positional anteroposterior head bobbing reminiscent of bobble-head doll syndrome. This child experienced a sudden onset of drop attacks and then, within several hours, deep coma. The causative lesion was a contrast-enhancing, partially cystic third ventricular mass, which ultimately obstructed the aqueduct, producing profound obstructive hydrocephalus. An emergency ventriculostomy and endoscopic fenestration of the septum pellucidum was performed. Four days later, the tumor was completely resected by a transcallosal-transforaminal approach. The lesion was freely mobile within the third ventricle and contained a large cyst within its posterior pole; following drainage of the cyst, the lesion was easily delivered through the foramen of Monro. The histopathological diagnosis was choroid plexus papilloma. The child's neurological deficits, head tilt, and head bobbing resolved immediately after operation. To the best of the authors' knowledge, this represents the first well-documented report of bobble-head doll syndrome and drop attacks secondary to a choroid plexus papilloma. The highly mobile nature of the cystic lesion presumably led to its intermittent impaction within the foramen of Monro and/or proximal aqueduct; this produced the intermittent head tilt and bobble-head symptoms and, ultimately, resulted in acute obstruction of the aqueduct, causing the child's precipitous neurological decline.

Brain Neoplasms↗
PubMed1994

Dissemination of low grade intracranial astrocytomas in children.

The authors report three cases of histologically benign intracranial astrocytomas that developed in children and disseminated within the neuraxis. Multicentric disease was evident at the time of diagnosis in two of these patients, one of whom subsequently developed peritoneal seeding of tumor after placement of a ventriculoperitoneal shunt. To our knowledge, this latter represents the first documented case of extraneural seeding of a benign astrocytoma. All three children are currently alive and well 17-117 months after the diagnosis of tumor dissemination. We review the literature regarding this uncommon problem and discuss the pathophysiology and treatment options. Our results indicate that the presence of disseminated disease may not preclude long term survival, provided the lesions are truly benign histologically and that adjuvant therapy is instituted promptly.

Astrocytoma↗
PubMed1994

The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors.

Benign intrinsic tumors arising in the dorsal midbrain have long been recognized as a potential cause of late-onset aqueductal stenosis. Where histopathological studies of such lesions have been performed, the majority have been reported to be low-grade gliomas. Because these tumors often present with a paucity of neurological findings and a characteristic radiographic appearance and because there has been substantial uncertainty regarding their potential for long-term progression, the authors have routinely deferred biopsy and/or radiotherapy for these lesions until there has been clear-cut evidence of disease progression. Herein, the authors report their experience with 16 children manifesting this syndrome who were treated between 1979 and 1992. The patients ranged in age from 6 months to 14 years at presentation (median 9.75 years). In general, symptoms of increased intracranial pressure developed insidiously; three of the older children had exhibited profound macrocephaly since infancy, which predated the onset of other symptoms of hydrocephalus by several years. Only one of the 16 children showed evidence of brain-stem dysfunction at presentation, a partial Parinaud's syndrome that resolved following placement of a ventriculoperitoneal shunt. In 12 patients, the tumor was detected by magnetic resonance (MR) imaging at initial evaluation as a bulbous enlargement of the tectal plate. In four patients who presented before the advent of MR imaging, initial computerized tomography (CT) scans failed to delineate the tectal lesion convincingly; however, subsequent MR studies clearly demonstrated the presence of an intrinsic tectal mass. All 16 patients underwent cerebrospinal fluid diversion initially, with conservative management of the tectal lesion and close long-term follow-up monitoring. Four children ultimately demonstrated clinical signs of progressive tumor growth with the insidious onset of partial or complete Parinaud's syndrome, despite the presence of a functioning shunt. The median interval to symptom progression was 7.8 years from the time of shunt insertion and 11.5 years from the onset of initial symptoms and signs of hydrocephalus. Follow-up CT and MR studies demonstrated obvious tumor enlargement in three of the four patients who then underwent stereotactic or open biopsy. The histological diagnosis in these three was benign mixed glioma, anaplastic astrocytoma, and low-grade astrocytoma. All four patients with clinical evidence of disease progression were treated with conventional radiotherapy; the patient with an anaplastic astrocytoma also received focal stereotactic radiosurgery. These patients subsequently remained clinically stable, with three showing tumor regression and one showing stable disease on serial MR studies (median follow-up period from tumor progression, 4.25 years).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Intracranial infantile myofibromatosis.

Infantile myofibromatosis is a proliferative disorder of infancy and early childhood characterized by nodular or diffuse growth of lesions that are comprised of a mixture of mesenchymal elements within the skin, subcutaneous tissues, skeletal muscle, bone, and/or visceral organs. Although these pseudotumors are considered to be the most common fibrous "neoplasm" of infancy, central nervous system involvement is reportedly rare. During the last 7 years, the authors have treated three children with intracranial myofibromas who presented at 6 weeks, 7 months, and 3 3/4 years of age, respectively. Each child had a large calvarial mass that produced significant brain compression despite a paucity of neurological signs. On computerized tomography, these tumors were isodense to brain tissue, enhanced strongly with intravenous contrast material, and showed smoothly marginated bone erosion without surrounding sclerosis. On magnetic resonance imaging, the tumors were hypointense on T1-weighted images, with dense enhancement following the administration of intravenous contrast medium, and hyperintense on T2-weighted images. At operation, the tumors were highly vascular and appeared to arise from within the leaves of the dura, eroding through the overlying bone, but not violating the galeal or arachnoidal layers. Two of the lesions were adherent to major dural venous sinuses. Both of these lesions were completely resected in continuity with the involved dura, and have not recurred 6 years and 1 year, respectively, postoperatively. However, in one patient in whom the involved dura was not resected at the initial procedure, the tumor recurred rapidly. A complete excision of the tumor and involved dura was then performed and the patient is now recurrence-free, 5 1/2 years after the second surgical resection. All patients tolerated resection well, but two have required cranioplasty for persistent calvarial defects. The surgical experience with these lesions is reviewed and the distinctive features of their clinical presentation, radiographic appearance, operative management, and outcome are discussed.

Brain Neoplasms↗
PubMed1993

The long-term outcome after surgical treatment of dorsally exophytic brain-stem gliomas.

Dorsally exophytic brain-stem gliomas represent a distinctive subgroup of pediatric brain-stem neoplasms that are amenable to radical excision because of their benign histology and growth characteristics. However, their attachment to the floor of the fourth ventricle invariably precludes complete tumor excision. The long-term behavior of the residual tumor remains a subject of concern. To address this issue, the authors reviewed their experience with 18 dorsally exophytic brain-stem gliomas treated between 1974 and 1990. At operation, the tumors filled the fourth ventricle, fungating out of a broad-based area of the dorsal brain stem. The exophytic tumor was resected, but no attempt was made to remove tumor from the brain stem. Histological examination showed that 16 of the tumors were grade I or II astrocytomas, one was a ganglioglioma, and one was an otherwise benign-appearing glioma with several foci of anaplasia that was classified as a grade III astrocytoma. The latter patient was one of only two in the series to receive postoperative radiation therapy; both cases so treated have no evidence of disease on follow-up imaging studies 61 and 135 months postoperatively. One other child who had stable disease postoperatively died of shunt malfunction 18 months after tumor excision. Serial radiographic studies in the other 15 patients have shown no evidence of disease in three, stable residual disease in eight, and tumor enlargement 12, 28, 40, and 84 months postoperatively in four (median follow-up period 113 months). Each of the four patients with tumor regrowth underwent repeat tumor excision. Two of these children received perioperative radiation therapy at the time of disease progression and both showed reduction in tumor volume 28 and 65 months after their second operation. In contrast, both patients who did not receive radiotherapy at the time of disease progression had further tumor enlargement 48 and 84 months after their second operation and underwent a third tumor resection; one received postoperative radiation therapy and has no evidence of disease 58 months after his third operation and the other child has stable disease 27 months postoperatively. Histological examination of tumor specimens obtained at second and third operations showed no change from the appearance of the tumor on the initial resection. The authors conclude that the majority of dorsally exophytic brain-stem gliomas can be managed successfully with subtotal excision and, if necessary, cerebrospinal fluid diversion. The small percentage of tumors in this series that showed recurrent growth remained benign histologically.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Long-term survival of mouse corpus callosum grafts in neonatal rat recipients, and the effect of host sensitization.

Previous studies have suggested that the incidence of spontaneous rejection among immunogenetically mismatched neural transplants in neonatal recipients varies significantly depending on the cellular composition of the graft material. For example, neuron-rich grafts of embryonic mouse retina generally survive for extended periods without showing signs of rejection after implantation into neonatal rats, whereas cortical xenografts, which contain abundant glial and endothelial cells as well as neurons, typically undergo rejection 4-6 weeks after implantation. To determine whether the presence of donor glia is responsible for this high incidence of spontaneous rejection, we examined the fate of a non-neuronal graft material composed predominantly of xenogeneic glial cells (post-natal day 3, PD3, CD-1 mouse corpus callosum) implanted into the mesencephalon of PD1 Sprague-Dawley rats. The distribution and survival of donor astrocytes were assessed using a monoclonal antibody specific for a mouse astrocyte surface antigen, M2. Thirteen of 16 animals sacrificed within 2 months of implantation had detectable transplants. In these animals, M2-positive cells frequently migrated well away from body of the graft, clustering in large numbers in several characteristic regions of the host brain. Unlike cortical grafts of similar age, the vast majority (93%) of callosal transplants showed no histological signs of rejection or major histocompatibility complex antigen expression in and around the transplant-derived cells. As previously noted in the neonatal retinal transplant paradigm, however, well-integrated 1-month-old corpus callosum grafts could be induced to reject by appropriate sensitization of the host immune system, implying that the host was not immunologically tolerant to the foreign neural graft. With longer survival times in unsensitized hosts, a progressively smaller percentage of animals had detectable donor astrocytes (5 of 10 animals at 3 months postimplantation and 4 of 16 animals at 4 months); in those 9 animals with surviving grafts, only small numbers of M2-positive cells were seen within the graft bed and surrounding host brain. However, only 2 of the 26 "long-term" animals showed evidence of graft rejection. These results indicate that mouse astrocytes show characteristic patterns of migration into the host brain when implanted into neonatal rats; however, these xenogeneic cells have a limited duration of survival. The infrequency with which even subtle signs of spontaneous rejection were detected in animals that had received corpus callosum xenografts suggests that an immune-mediated process is unlikely to be responsible for the time-dependent elimination of the donor astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

A partially thrombosed, fenestrated basilar artery mimicking an aneurysm of the vertebrobasilar junction: case report.

We report a patient with a subarachnoid hemorrhage in whom a partially thrombosed, fenestrated basilar artery mimicked an aneurysm of the vertebrobasilar junction on preoperative angiography. Intraoperatively, no aneurysm was detected; instead, the patient was found to have partial thrombosis of one limb of the fenestrated basilar artery. The nodular appearance of the residual lumen of the vessel corresponded exactly to the angiographic findings. To our knowledge, no similar case has been reported.

Adult↗
PubMed1992

The treatment of intracranial malignant gliomas using orally administered tamoxifen therapy: preliminary results in a series of "failed" patients.

In vitro studies have shown that the nonsteroidal antiestrogen tamoxifen can suppress deoxyribonucleic acid synthesis and cell proliferation in cultured human gliomas. This growth suppression is independent of its antiestrogenic properties. Tamoxifen may act through the inhibition of the enzyme protein kinase C, which transduces mitogenic signals from the cell surface to the nucleus. Based on these preclinical studies, we initiated a clinical trial of orally administered tamoxifen, 20 mg twice daily, to patients with recurrent, progressive malignant gliomas who were not candidates for other "failed" protocols, such as brachytherapy. No limits were placed on age, Karnofsky Performance Score (KPS), or expected survival. Thirty-two patients were entered in the study, 29 with a glioblastoma multiforme and 3 with an anaplastic astrocytoma. The mean age of the group was 48 years, and the mean KPS was 65. Median survival of the entire cohort from the onset of tamoxifen therapy was 17 weeks; the median survival of those patients with an initial KPS of 70 or more was 21 weeks. Seven patients survived for more than 6 months with no change in their baseline computed tomographic scans or KPS on tamoxifen, including 2 patients with computed tomographic evidence of regression during the course of therapy. There were no significant patient-reported side effects of the treatment. Three patients had thromboembolic complications during tamoxifen administration. We conclude that tamoxifen can be administered safely to these patients and may show some efficacy against glial neoplasms.

Administration, Oral↗
PubMed1992

Outcome following hindbrain decompression of symptomatic Chiari malformations in children previously treated with myelomeningocele closure and shunts.

Between 1975 and 1989, 25 children treated with myelomeningocele closure and shunting for hydrocephalus at the Children's Hospital of Pittsburgh developed progressive lower brain-stem dysfunction from their Chiari malformation. Retrospective univariate and multivariate analyses of these cases were undertaken to assess the relationship between preoperative clinical factors and postoperative outcome. Since earlier reports have suggested that neonates with symptomatic Chiari malformations show a less favorable response than older children to craniocervical decompression, particular attention was directed at examining the effect of age on preoperative symptoms and postoperative outcome. Patients were subdivided by age into two groups, namely: 13 patients who became symptomatic before 2 months of age (neonatal group) and 12 older infants and children who developed initial symptoms between 6 months and 10 years of age. Once symptoms developed, patients in both groups deteriorated progressively until brain-stem decompression was performed. The mode of presentation and the rate and extent of neurological deterioration differed substantially in the two groups. Whereas the neonates typically showed rapid neurological deterioration and often manifested profound brain-stem dysfunction within a period of several days, the older patients experienced a more insidious symptom progression and rarely demonstrated the severe degree of impairment seen in the neonates. All patients underwent suboccipital craniectomy, cervical laminectomy, and dural decompression. A shunt from the fourth ventricle and/or syrinx to the subarachnoid space was placed in those with significant syringomyelia. Following surgery, 17 patients had complete or nearly complete resolution of all signs of brain-stem compression, three had mild to moderate residual deficits, and five showed no improvement. Outcome correlated closely with the preoperative neurological status. In particular, the presence of bilateral vocal cord paralysis was associated with a poor response to surgery (p < 0.001 on both univariate and multivariate analyses). Of the six patients (all neonates) who progressed to complete bilateral vocal cord paralysis before surgery, only one improved. In contrast, all patients with less profound but nonetheless severe deficits recovered function postoperatively. Although the neonates as a group had a poorer outcome than did the older patients (p = 0.02 on univariate analysis), this in large part reflected their more severe preoperative impairments; neonates who still had some preservation of vocal cord function before surgery subsequently did as well as the older patients. Accordingly, age did not prove to be an independent prognostic factor on multivariate analysis. Taken together, these results indicate that, in most patients with symptomatic Chiari II malformations (including neonates), neurological deficits are potentially reversible if hindbrain decompression is performed expeditiously.

Age Factors↗
PubMed1992

Cricopharyngeal dysfunction associated with Chiari malformations.

UNLABELLED: Dysphagia due to upper esophageal sphincter (UES) dysfunction can be a manifestation of Chiari malformation. We evaluated five young children with dysphagia and a Chiari malformation before and after craniocervical decompression. Preoperatively, esophageal manometry with a multilumen perfused catheter revealed failure of complete relaxation of the UES in three patients, pharyngo-UES incoordination in one patient, and both abnormalities in the last patient. Preoperative barium esophagograms were obtained in four of the patients and were normal in two. One patient had nasal regurgitation of barium and delayed passage of barium through the UES. One patient had a posterior pharyngeal impression (bar) at the level of the UES and delayed transit of barium. All patients had clinical and manometric resolution of UES dysfunction following surgical decompression of the Chiari malformation. All swallows were coordinated, and UES relaxations were complete. However, the posterior pharyngeal bar persisted on postoperative esophagogram in the only patient who had had the abnormality preoperatively, although it no longer interfered with passage of barium. Another patient had a narrowed UES with decreased relaxation. Swallowing was radiographically normal in three patients postoperatively. CONCLUSION: Surgical decompression of Chiari malformation may lead to complete clinical and manometric resolution of dysphagia due to upper esophageal sphincter dysfunction. Esophageal manometry is more likely than barium swallow to demonstrate the abnormality, and correlates better with symptomatic improvement postoperatively.

Arnold-Chiari Malformation↗
PubMed1992

Neurogenic dysphagia resulting from Chiari malformations.

Between 1980 and 1989, 15 of 46 patients (11 children, 4 adults) who underwent suboccipital craniectomy and cervical laminectomy for symptomatic Chiari malformations presented with manifestations of neurogenic dysphagia. Each of these patients had normal swallowing function before the development of dysphagic symptoms. Dysphagia was progressive in all 15 and, in most cases, preceded the onset of other severe brain stem signs. The rate of symptom progression varied depending on the age of the patient. Whereas the six infants (all Chiari II) deteriorated rapidly after the onset of initial symptoms, the five older children (two Chiari I, three Chiari II) and four adults (all Chiari I) showed a more gradual deterioration. In 11 patients with severe dysphagia, barium video esophagograms, pharyngoesophageal motility studies, continuous esophageal pH monitoring, and appropriate scintigraphic studies were useful in defining the scope of the swallowing impairment and determining whether perioperative nasogastric or gastrostomy feedings, gastric fundoplication, and/or tracheostomy were needed to maintain adequate nutrition and avoid aspiration. These patients all had widespread dysfunction of the swallowing mechanism, with a combination of diffuse pharyngoesophageal dysmotility, cricopharyngeal achalasia, nasal regurgitation, tracheal aspiration, and gastroesophageal reflux. The pathophysiology of these swallowing impairments and their relation to the hindbrain malformation is discussed. Postoperative outcome with regard to swallowing function correlated with the severity of preoperative symptoms. The four patients with mild dysphagia showed rapid improvement in swallowing function after surgery. Seven patients with more severe impairment but without other signs of severe brain stem compromise, such as central apnea or complete bilateral vocal cord paralysis, also improved, albeit more slowly. In contrast, the outcome in the four patients who developed other signs of severe brain stem dysfunction before surgery was poor. Early recognition of neurogenic dysphagia and expeditious intervention are therefore crucial in ensuring a favorable neurological outcome.

Adult↗
PubMed1991

Response of low-passage human malignant gliomas in vitro to stimulation and selective inhibition of growth factor-mediated pathways.

The proliferation of many nonglial tumors in vitro depends on the presence of nanomolar concentrations of one or more growth factors. To define the growth factor requirements of malignant glial tumors, the authors examined the response properties of four low-passage human malignant glioma lines to the following mitogens: epidermal growth factor (EGF), acidic and basic fibroblast growth factors (FGF's), insulin-like growth factor I (IGF-I), nerve growth factor (NGF), platelet-derived growth factor (PDGF), 12-O-tetradecanoyl-13-phorbol acetate (TPA), and serum. Each of the tumors showed increased deoxyribonucleic acid (DNA) synthesis (assessed by acid-precipitable [3H]-thymidine incorporation) in response to PDGF with a maximum effect at 50 ng/ml. Three tumors responded to EGF, three to IGF-I, two to acidic FGF, two to basic FGF, and two to TPA with maximum effects at 10, 50, 1, 1, and 10 ng/ml, respectively. None of the tumors responded to NGF. In the responsive tumors, optimum concentrations of EGF, IGF, TPA, acidic FGF, and basic FGF induced, at most, a two- to fourfold increase in [3H]-thymidine incorporation, which was only 30% to 50% of the response seen in 10% serum. In contrast, PDGF increased DNA synthesis eight- to 10-fold, equaling the effect of 10% serum. Measurements of cell proliferation also demonstrated a significant response to PDGF in each of the tumors. Appropriate concentrations of an anti-PDGF neutralizing antibody inhibited baseline DNA synthesis and proliferation in the absence of added growth factors, suggesting the possible role of PDGF in autocrine stimulation of these cells. However, this antibody produced only slight inhibition of serum-induced mitogenesis. Trapidil, an agent reported to inhibit the effects of PDGF, and polymyxin B, an inhibitor of protein kinase C, strongly inhibited baseline as well as PDGF- and serum-induced mitogenesis. It is concluded that, in the malignant gliomas studied, PDGF may be acting as a dominant mitogen to enhance DNA synthesis, and may function in autocrine stimulation. However, other factors contained in serum can also contribute to cell division.

Antibodies↗
PubMed1990

Effect of tamoxifen on DNA synthesis and proliferation of human malignant glioma lines in vitro.

Previous studies in our laboratory have shown that proliferation of human malignant gliomas in vitro depends in part upon the activation of protein kinase C (PKC) and, conversely, can be blocked by inhibitors of PKC. Here, we examined the effect of tamoxifen, a known PKC inhibitor, on DNA synthesis and proliferation of an established human glioma line (U138) and two low passage cultures of explanted human glioblastomas. Tamoxifen produced a profound, dose-dependent inhibition of both [3H] thymidine incorporation and cell proliferation, with a 50% effective dose of 20 ng/ml under serum-free conditions and 50 to 200 ng/ml in the presence of 10% serum. These tumors were estrogen receptor negative and showed no mitogenic response to estradiol. Furthermore, concentrations of estradiol as high as 10 micrograms/ml had no effect on the tamoxifen-induced inhibition. This suggests that the mechanism of growth inhibition by tamoxifen in these gliomas did not involve an estrogen receptor-mediated process but may instead result from its inhibition of PKC. In view of the profound effect of tamoxifen on cultured gliomas at concentrations that can safely be achieved therapeutically, further in vitro and in vivo studies of this agent are warranted.

Cell Division↗