The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas.

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. Recent data suggested that the hypopituitarism and mild hyperprolactinemia in this setting are largely due to compression of pituitary stalk and portal vessels. Headaches (HAs) are frequently seen in patients with large adenomas and at times in those with microadenomas. Because the walls of the sella turcica are relatively rigid, we postulate that tumor growth within the sella increases intrasellar pressure (ISP), which in turn impairs portal blood flow, resulting in mild hyperprolactinemia and hypopituitarism. We also postulate that increased mean ISP (MISP) contributes to the development of HAs. Normal MISP is not known but is unlikely to exceed normal intracranial pressure of less than 10-15 mm Hg. We determined MISP in 49 patients who had transsphenoidal surgery for pituitary adenomas. MISP was measured using a commonly available intracranial monitoring kit where a fiberoptic transducer was inserted through a 2-mm dural incision at the time of adenomectomy. Patients with deficient FSH, LH, ACTH, or TSH secretion were considered hypopituitary. Data on serum PRL levels were included for analysis only in patients whose adenomas had negative immunostaining for the hormone. MISP measurements ranged from 7-56 mm Hg, with a mean (+/-SD) of 28.8 +/- 13.5 and a median of 26 mm Hg. The pressure measurements were higher in patients with hypopituitarism than in those with normal pituitary function (P = 4.6013 x 10(-6)). Patients presenting with HAs had higher MISP than those who did not (P = 5.44 x 10(-7)), regardless of their pituitary function or tumor sizes. PRL levels correlated positively with MISP values (r = 0.715, P < 0.0001). Tumor size did not correlate with MISP or PRL levels. The findings of increased MISP in hypopituitary patients and the documented correlation with PRL levels, suggest that ISP is a major mechanism involved in the pathogenesis of hypopituitarism and hyperprolactinemia. Similarly, the increased MISP in patients with HAs, irrespective of tumor size or pituitary function, suggest that increased ISP is a major mechanism involved in the pathogenesis of this symptom. The data support the hypothesis that in patients with pituitary adenomas increased ISP is a major mechanism contributing to the development of hyperprolactinemia, hypopituitarism, and HAs. Increased ISP in these patients leads to compression of the portal vessels and the associated interruption of the delivery of hypothalamic hormones to the anterior pituitary. This would explain the reversibility of pituitary function observed in most patients after adenomectomy. However, increased ISP may also lead to decreased blood supply, resulting in ischemic necrosis in some regions of the pituitary. The latter could limit potential recovery of pituitary function after adenomectomy.

Square-wave jerks induced by pallidotomy in parkinsonian patients.

Square-wave jerks (SWJs) are small, inappropriate saccades that intrude on steady fixation by taking the eye away from the target and then returning it after approximately 200 msec. The pathophysiology of SWJs is unknown; they have not been attributed to any specific lesion. We found that unilateral pallidotomy substantially increased the frequency of SWJs in three patients with Parkinson's disease. This effect is likely due to imbalance in the fixation system caused by asymmetric reactivation of prefrontal cortex via ascending thalamocortical projections. Alternatively, disruption of nigral projections to the superior colliculus might be responsible.

Transient neurologic deficit caused by chronic subdural hematoma.

Transient neurologic deficits are an unusual presentation of chronic subdural hematoma. Presented herein are three patients with transient aphasia and right-sided sensory-motor abnormalities caused by subdural hematoma. Review of the literature revealed 32 cases similar to ours. Presenting complaints were aphasia (77%), sensory symptoms (57%), headache (48%), hemiparesis (50%), and visual disturbance (3%). Fifteen patients underwent cerebral angiography; only three showed significant carotid atherosclerosis. Electroencephalograms were performed in seven patients; five revealed lateralized slowing, but none showed epileptiform activity. Drainage of the hematoma was uniformly curative, although six patients had transient postoperative symptoms. Patients presenting with transient deficits require imaging to rule out the presence of a chronic subdural hematoma.

Bridge grafts of fibroblast growth factor-4-secreting schwannoma cells promote functional axonal regeneration in the nigrostriatal pathway of the adult rat.

Axons damaged in the adult mammalian central nervous system are able to regenerate when their inhibitory glial environment is replaced with a more permissive substrate. Here, we have used long oblique "bridge" grafts of fibroblast growth factor-4-transfected RN-22 schwannoma cells to allow mechanically lesioned nigrostriatal axons to regenerate back to their original target in the adult rat brain. Regenerated axons were able to leave the bridge graft to form terminal arborizations and increase the density of tyrosine hydroxylase-immunoreactive fibres within the striatum. Bridge grafting also resulted in an increase in the number of neurons within the substantia nigra pars compacta taking up the fluorescent retrograde tracer Fluoro-Gold from the striatum. Animals which had received RN-22 bridge grafts showed lower rates of amphetamine-induced rotation 10 weeks after a mechanical lesion of the nigrostriatal tract compared to lesioned controls, the magnitude of the behavioural effect being related to the number of regenerated axons, and this comparative reduction was reversed by mechanical section of the bridge graft. It is concluded that our bridge grafting strategy allowed the partial anatomical and functional regeneration of the mechanically lesioned nigrostriatal tract, an unmyelinated central axon bundle, and that bridge grafting therefore represents a realistic approach to the repair of central nervous system lesions involving axon tract damage.

Functional and anatomical reconstruction of the 6-hydroxydopamine lesioned nigrostriatal system of the adult rat.

In an attempt to reconstruct the 6-hydroxydopamine lesioned nigrostriatal system of the adult rat we have combined homotopic grafting of embryonic ventral mesencephalon suspensions with the implantation of long oblique "bridge" grafts of fibroblast growth factor-4-transfected RN-22 schwannoma cells stretching from the site of the neuronal grafts to the striatum. At seven weeks after receiving both grafts, animals were killed and processed for immunohistochemistry against tyrosine hydroxylase. Tyrosine hydroxylase-immunoreactive axons were seen to extend from the nigral grafts, along the bridge graft to the striatum where terminal arborizations could be seen. The retrograde tracer Fluoro-gold was injected intrastriatally in some of the experimental animals and was taken up by grafted neurons confirming their projection to the striatum. In parallel to the anatomical reconstruction of the system, a decrease in amphetamine-induced rotation was demonstrated in those animals receiving both grafts which had received > 98% complete lesions. This decrease was greatest in those animals with the most tyrosine hydroxylase-immunoreactive axons in their bridge grafts. The presence of the bridge graft also led to an increase in neuronal graft survival with twice as many tyrosine hydroxylase-immunoreactive neurons being found in the grafts of those animals that had received both grafts compared to those that had received a neuronal graft but no bridge graft.

In vivo effects of kFGF on embryonic nigral grafts in a rat model of Parkinson's disease.

Central injections of FGF have been reported to promote the survival of dopamine neurones in nigral grafts. With the goal of developing an improved delivery of trophic molecules, an immortalized RN22 Schwann cell line transfected with a secretory form of FGF, kFGF, was irradiated and co-transplanted with embryonic nigral grafts in the 6-OHDA lesioned rat striatum. Amphetamine-induced turning was alleviated by nigral grafts, but was not further improved by co-grafts, whether or not transfected to secrete kFGF. Histological analysis showed similar numbers of surviving transplanted cells and a similar extent of fibre growth from the nigral grafts whether implanted alone or co-grafted with the Schwann cells. These results suggest that kFGF does not have any clear in vivo effect on embryonic nigral grafts in this model.

The neurotrophin NT4/5, but not NT3, enhances the efficacy of nigral grafts in a rat model of Parkinson's disease.

The neurotrophins NT4/5 and NT3 have previously been shown to improve the survival and fibre outgrowth of embryonic dopaminergic neurons in vitro. In the present study we attempted to augment the efficacy of embryonic nigral grafts in vivo. This was done by directly infusing the neurotrophins intraparenchymally in close proximity to transplanted nigral tissue placed in the dopamine depleted striatum of 6-hydroxydopamine lesioned rats. Our results indicated that NT4/5, but not NT3, stimulated fibre growth from embryonic nigral cells and enhanced functional efficacy of the grafts as assessed by metamphetamine-induced rotation.

Harvey Cushing and Claude Beck: a surgical legacy.

Harvey cushing's contribution to neurosurgery and other surgical specialties has been profound. The accomplishments of his many pupils have further immortalized Cushing's role as a pioneering advocate of surgical science. Claude S. Beck, the first professor of cardiovascular surgery in the United States, was one such student. Beck's career and successes are illustrative of Cushing's guidance and enduring support for his surgical heirs. Beck's first encounter with Cushing evoked a spirit of fraternity and fashioned a respect and loyalty to Cushing that lasted for the duration of Beck's career. Cushing's personality and the methods by which he perpetuated a rich surgical tradition are illuminated by details of Beck's stay at the Peter Bent Brigham Hospital as a Cabot Fellow in Cushing's laboratory, by diary accounts of his later 6-week visit in 1927, and by the numerous telling correspondences between the two men. This article traces Beck's association with Cushing and provides unique insights into Cushing, his Cleveland connections, and his neurosurgical service at the Brigham.

A "PICA communicating artery" aneurysm: case report.

We present an unusual case of an aneurysm of the distal posterior inferior cerebellar artery (PICA). The aneurysm was associated with a unilateral PICA that supplied both cerebellar hemispheres and arose from an anastomotic vessel to the contralateral circulation, a branch of the contralateral PICA. Such an aneurysm has not been reported previously. The associated of vascular anomalies with aneurysms of the PICA is discussed.

Small bowel obstruction secondary to incomplete removal of a ventriculoperitoneal shunt: case report.

Small bowel obstruction and partial enteral loss secondary to entrapment by an incompletely removed ventriculoperitoneal shunt is a previously unreported hazard.

Spinal epidural abscess: a ten-year perspective.

A retrospective study of spinal epidural abscess spanning 10 years and encompassing 40 patients was done. Epidemiology, clinical features, laboratory findings, radiographic imaging, therapy, and outcome were examined and compared with previous series. An increasing incidence of the disease (up to 1.96 patients per 10,000 admissions per year) and an older, more debilitated population (67% having factors predisposing them to infection) were discovered. Over half of the population was studied with magnetic resonance imaging, which was found to be equally as sensitive (91%) as myelography with computed tomography (92%). Magnetic resonance imaging offers the advantages of being noninvasive and able to delineate other entities, which makes it the imaging modality of choice. Preoperative paralysis and neurological deterioration from normal were identified as poor prognostic features. Of 7 patients with preoperative paralysis, 5 died, and the rest failed to recover neurological function. Eleven patients with initially normal neurological exams deteriorated in the hospital before surgical intervention. Eight of these patients were being treated with appropriate antibiotics; 2 became paralyzed despite more than 3 weeks of antibiotic therapy. Only 3 of these 11 patients recovered fully. Immediate surgical decompression combined with antibiotics remains the treatment of choice.

Intracranial suppuration: a modern decade of postoperative subdural empyema and epidural abscess.

A retrospective study of subdural empyema and epidural abscess spanning 11 years and encompassing 41 patients was performed, demonstrating that the clinical characteristics of intracranial suppuration have changed over time. Sinusitis and otitis media, previously the predominant etiologies, were predisposing factors in only 29% of patients. A prior craniotomy had been performed in 66% of cases and was the most common risk factor for abscess development. The postoperative patients were subjected to detailed analysis. Patients who had undergone a prior craniotomy were notable for the following features: older age, lack of fever, evidence of wound infection, frequent false-negative computed tomographic scans, and a high percentage of Gram negative aerobic organisms or skin flora as pathogens. The population at highest risk for abscess development ranged from 50 to 60 years old, older than in previous series. Older age and an advanced degree of encephalopathy were indicative of a poor prognosis. Patients with subdural empyema had a worse prognosis as well. Hyponatremia was a frequent complicating factor. A much greater percentage of Gram-negative aerobic bacteria were isolated than in previous studies. Computed tomographic scans, half of which were performed with intravenous contrast material, were nondiagnostic in 30% of patients. The mortality rate was 18.5%, and delay in treatment correlated with increased risk of poor outcome. All patients were treated with a craniotomy. Repeated operations were required in three patients and were associated with the development of intraparenchymal abscess.

Case Western Reserve University and University Hospitals of Cleveland: a neurosurgical chronicle.

There is a strong tradition of neurosurgery in Cleveland. This article traces the origin of Case Western Reserve University School of Medicine and University Hospitals of Cleveland and examines the evolution of neurological surgery at these institutions. It looks at the strong Cushing influence on the process, by both Harvey Cushing and his family. The contributions of such luminaries as George Crile, Elliott Cutler, Claude Beck, and Frank Nulsen are described.

Primary intrinsic brainstem oligodendroglioma in an adult. Case report and review of the literature.

Primary intrinsic oligodendrogliomas of the brainstem are exceedingly unusual. The authors report the case of an intraaxial brainstem oligodendroglioma in an adult. In an extensive review of oligodendrogliomas, only six (0.4%) of 1593 cases recorded could be identified as intrinsic brainstem tumors. Five of these cases were found in children. This report documents a 25-year-old woman with a pontomedullary oligodendroglioma. An analysis of the world literature on this tumor type finds that posterior fossa oligodendrogliomas present at an earlier age and appear to be more aggressive biologically than their supratentorial counterparts. The overall prognosis for patients harboring an intrinsic brainstem oligodendroglioma remains unclear, with significant variability between patients.

Molecular structure and functional testing of human L1CAM: an interspecies comparison.

The rodent, avian, and insect L1-like cell adhesion molecules are members of the immunoglobulin superfamily that have been implicated in axon growth. We have isolated an L1-like molecule from human brain and found that it also supports neurite growth in vitro. We have also cloned and sequenced the entire coding region of human L1CAM and found that it shows a very high degree of homology to mouse L1cam, with 92% identity at the amino acid level. This similarity suggests that L1CAM is an important molecule in normal human nervous system development and nerve regeneration. Overall, there is substantially less homology to chick Ng-CAM; they are 40% identical at the amino acid level but many regions are highly conserved. Comparison of the sequences from human, mouse, chick, and Drosophila indicates that the L1 immunoglobulin domain 2 and fibronectin type III domain 2 are strongly conserved and thus are likely functionally important.

Adhesion molecules and inherited diseases of the human nervous system.

Mutations in the human genes for the adhesion molecules Po, L1, and merosin cause severe abnormalities in nervous system development. Po and merosin are required for normal myelination in the nervous system, and L1 is essential for development of major axon pathways such as the corticospinal tract and corpus callosum. While mutations that lead to a loss of the adhesive function of these molecules produce severe phenotypes, mutations that disrupt intracellular signals or intracellular interactions are also deleterious. Geneticists have found that more than one clinical syndrome can be caused by mutations in each of these adhesion molecules, confirming that these proteins are multifunctional. This review focuses on identifying common mechanisms by which mutations in adhesion molecules alter neural development.

Role of L1 in neural development: what the knockouts tell us.

Mutations in the cell adhesion molecule L1 cause severe developmental anomalies in the human nervous system. Recent descriptions of L1 gene knock-out mice from three research groups demonstrate that these mice are strikingly similar to humans with mutations in the L1 gene. In both humans and mice there are defects in the development of the corticospinal tract and cerebellar vermis, hydrocephalus, and impaired learning. The production of a viable animal model for X-linked hydrocephalus suggests that unanswerable questions posed by the human disease will finally be approachable using modern experimental methods.

Central nervous system complications of cystosarcoma phyllodes.

BACKGROUND: Cystosarcoma phyllodes (CP) is an uncommon fibroepithelial breast neoplasm that rarely involves the central nervous system (CNS). METHODS: The authors encountered two patients with CNS metastases and reviewed the literature to identify reports of CP affecting the nervous system. Patients must have been reported in sufficient detail to characterize clinical course, extent of tumor burden, and histologic type of the primary tumor and metastasis to be included in the study. RESULTS: Eleven cases were identified from the literature, but only six were presented in sufficient detail for analysis. Including the current patients, the mean age of patients with CP metastases was 52 years. The time between initial diagnosis and CNS involvement was 5 years. Parenchymal brain metastases respond poorly to treatment, with a mean survival of 29 days, whereas survival is significantly longer with CNS involvement secondary to epidural extension of tumor from adjacent bony structures. Local recurrence or widespread metastases nearly always were present at the time of CNS involvement. CONCLUSIONS: Brain metastases from CP are refractory to therapy and carry a dismal prognosis. Patients with CP and brain metastases should undergo brain biopsy to exclude metastases from associated epithelial breast tumors, which have significantly better prognoses. Patients with compressive lesions arising from bone have a better prognosis and may benefit from aggressive management.

Neurite growth on different substrates: permissive versus instructive influences and the role of adhesive strength.

Growing axons use environmental cues to guide them to their targets. One class of cues is thought to be adhesion molecules on cells and in the extracellular matrix that axons interact with as they grow to their targets. In choosing between two possible pathways, the relative adhesiveness of the two substrates could be an important factor in controlling neurite growth. We conducted experiments in vitro to study how naturally occurring adhesion molecules influence neurite growth. Neurite growth rates, the degree of neurite fasciculation, the choices neurites make between two substrates, and the relative adhesiveness of different substrates were examined. We found that the relative adhesiveness of a substrate was a poor predictor of either axon growth rate or the degree of fasciculation. Furthermore, neurites showed little selectivity between three different naturally occurring substrates, L1, N-cadherin, and laminin. These results suggest that some adhesion molecules may serve as permissive substrates in that they can define axonal pathways but they do not provide information about which path to take at a choice point or about which direction to go along the path. Finally, these results suggest that substrates in vivo may not exert their effects on axon guidance principally via relative adhesiveness.