Academic Appointments

Administrative Appointments

  • Acting Chairman, Department of Neeurosurgery (1989 - 1992)

Professional Education

  • MD, Stanford University, Medicine (1964)
  • BA, Dartmouth College, English Literature (1959)

Current Research and Scholarly Interests

I have developed a model of aging in the Brown Norway/Fisher rat and a separate model of chronic hydrocephalus in a kaolin-induced hydrocephalus rat model. We are studying the accumulation of amyloid by immunostaining and ELISA in relation to age and hydrocephalus-induced decrease in CSF formation and turnover, measured by ventricular cisternal perfusion, and the change in expression of the blood-brain barrier receptors for A-beta transport, LRP-1 and RAGE, measured by immunostaining, PCR and western blot.

Thus far we have found that A-beta accumulation increases with age and this increase is related to a decrese in microvessel expression of LRP-1, the endothelial receptor that transports A-beta from the brain to the plasma pool, an increase in microvesselRAGE, the endothelial receptor that transfers A-beta from the plasma to the brain interstitium. CSF production and turnover falls and further A-beta accumulation occurs. Changes similar to advanced aging occur with the rat kaolin-hydrocephalus model, but at an earlier age, and amyloid accumulates prematurely, as is seen in patients with NPH.

All Publications

  • Brain amyloid accumulates in aged rats with kaolin-induced hydrocephalus NEUROREPORT Klinge, P. M., Samii, A., Niescken, S., Brinker, T., Silverberg, G. D. 2006; 17 (6): 657-660


    Amyloid beta-peptide (Abeta) accumulation in aged Sprague-Dawley rats (12 months) with kaolin-induced hydrocephalus was investigated by Abeta(1-40) and Abeta(1-42) immunohistochemistry at 2, 6 and 10 weeks after induction. The low-density lipoprotein receptor-related protein-1 transporting Abeta across the blood-brain barrier was assayed. Age-matched controls showed some positive Abeta staining, mainly in the choroid plexus. At 2 weeks after induction, Abeta staining of the arachnoid and subependymal layer was observed. At 6 weeks, larger Abeta accumulations were prominent at the endothelial and perivascular sites. Intraparenchymal Abeta positively stained accumulations occurred at 10 weeks. Microvessel lipoprotein receptor-related protein-1 staining was progressively reduced from 2 to 10 weeks. The pattern of Abeta deposition and lipoprotein receptor-related protein-1 loss suggests reduced Abeta clearance in chronic hydrocephalus.

    View details for Web of Science ID 000237529300020

    View details for PubMedID 16603930

  • Novel ventriculo-peritoneal shunt in Alzheimer's disease cerebrospinal fluid biomarkers. Expert review of neurotherapeutics Silverberg, G. D., Mayo, M., Saul, T., Carvalho, J., McGuire, D. 2004; 4 (1): 97-107


    Alzheimer's disease is an age-related dementia and its incidence is rising in developed countries as the population ages. Amyloid plaques and tau-rich neurofibrillary tangles are pathologic hallmarks of the disease. Treatment is symptomatic, consisting of compounds that block enzymatic acetylcholine degradation (acetylcholinesterase inhibitors). Cognitive benefits of the four approved antidementia drugs are typically modest and limited in duration. While Alzheimer's disease is undoubtedly multifactorial in cause, advancing age is the most important risk factor. Any robust theory of pathogenesis must account for the profound influence of age on the emergence of Alzheimer's disease. There is evidence that senescent changes in cerebrospinal fluid production, circulation, turnover and clearance of amyloid beta-peptides may be a key factor in the onset and progression of Alzheimer's disease. The effect of increasing cerebrospinal fluid circulation and turnover in Alzheimer's disease patients by implanting a novel, low-flow drainage system (COGNIshunt) has been studied and promising trends in cognitive stabilization and improvement in cerebrospinal fluid biomarkers have been found.

    View details for PubMedID 15853620

  • Effects of tumor suppressor gene (p53) on brain tumor angiogenesis and expression of angiogenic modulators ANTICANCER RESEARCH Tse, V., Yung, Y., Santarelli, J. G., Juan, D., Hsiao, M., Haas, M., Harsh, G., Silverberg, G. 2004; 24 (1): 1-10


    p53 retarded tumor growth by several known mechanisms, including suppression of cell proliferation and inhibition of tumor angiogenesis. Vascular endothelial growth factors (VEGF) and angiopoietins (Ang-1, Ang-2) are major angiogeneic modulators. The current study examined the effect of p53 on the expression of these factors in conjunction with tumor growth and vascular formation.Growth characteristics of rat glioma cells (RT-2) infected with retrovirus (MSCV) encoding a full-length human wild-type p53 gene were examined by clonogenic assay. Expression of the transgene in vitro was verified by RT-PCR and immunoprecipitation. Tumor morphology, vascular architecture and the expression of VEGF, Ang-1, Ang-2 and Tie-2 were examined by immunohistochemistry and semi-quantitative RT-PCR.p53-infected cells showed retardation in growth and colony formation. In vivo, expression of the transgene resulted in prolonged survival and reduction of tumor volume (62%) and reduced the expression of VEGF (57.8%) and Tie-2 (15.4%) but not Ang-1 and Ang-2. The tumor exhibited increased necrosis (38%), hemorrhage and abnormal vascular architecture.p53 causes tumor regression by suppressing tumor proliferation and indirectly induces involution of tumor vessels by fostering unopposed activity of Ang-2 in an environment of diminishing VEGF.

    View details for PubMedID 15015569

  • The temporal-spatial expression of VEGF, angiopoietins-1 and 2, and Tie-2 during tumor angionenesis and their functional correlation with tumor neovascular architecture NEUROLOGICAL RESEARCH Tse, V., Xu, L., Yung, Y. C., Santarelli, J. G., Juan, D., Fabel, K., Silverberg, G., Harsh, G. 2003; 25 (7): 729-738


    Angiopoietins play a pivotal role in tumor angiogenesis by modulating vascular endothelial proliferation and survival. The expression of angiopoietins 1 and 2 (Ang-1 and Ang-2) and vascular endothelial growth factor (VEGF) has been documented in human malignant glioma. The expression of Ang-1, Ang-2, VEGF, and Tie-2, a member of the receptor tyrosine kinases and the natural receptor for both Ang-1 and Ang-2, follows a distinct transcriptional profile in vivo. Ang-2 and VEGF were expressed early in tumor formation and their levels increased throughout tumor growth. Their expression coincided with the expansion of the tumor mass and the formation of the vascular tree. There was no significant change in the expression of Tie-2 and Ang-1. The expression of Ang-1 and Tie-2 was more noticeable at the periphery of the tumor. The expression of Ang-2 was more robust at the periphery and within the tumor mass, and VEGF was more concentrated within the center of the tumor. This distinct expression profile may explain the morphology of the newly formed vessels at various times and regions of the tumor. The lack of concomitant expression of Ang-1 may underscore the unopposed endovascular induction by Ang-2 and VEGF resulting in the chaotic appearance and fragility of tumor vessels.

    View details for Web of Science ID 000186229300010

    View details for PubMedID 14579791

  • Alzheimer's disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis LANCET NEUROLOGY Silverberg, G. D., Mayo, M., Saul, T., Rubenstein, E., McGuire, D. 2003; 2 (8): 506-511


    There is evidence that production and turnover of CSF help to clear toxic molecules such as amyloid-beta peptide (Abeta) from the interstitial-fluid space of the brain to the bloodstream. Two changes in CSF circulatory physiology have been noted as part of ageing: first, a trend towards lower CSF production, hence a decrease in CSF turnover; and second, greater resistance to CSF outflow. Our hypothesis is that, all else being equal, the initially dominant physiological change determines whether CSF circulatory failure manifests as Alzheimer's disease (AD) or as normal-pressure hydrocephalus (NPH). If CSF production failure predominates, AD develops. However, if resistance to CSF outflow predominates, NPH results. Once either disease process takes hold, the risk of the other disorder may rise. In AD, increased deposition of Abeta in the meninges leads to greater resistance to CSF outflow. In NPH, raised CSF pressure causes lower CSF production and less clearance of Abeta. The disorders may ultimately converge in vulnerable individuals, resulting in a hybrid as has been observed in several clinical series. We postulate a new nosological entity of CSF circulatory failure, with features of AD and NPH. NPH-AD may cover an important subset of patients who carry the diagnosis of either AD or NPH.

    View details for Web of Science ID 000184314700020

    View details for PubMedID 12878439

  • Downregulation of cerebrospinal fluid production in patients with chronic hydrocephalus JOURNAL OF NEUROSURGERY Silverberg, G. D., Huhn, S., Jaffe, R. A., Chang, S. D., Saul, T., Heit, G., Von Essen, A., Rubenstein, E. 2002; 97 (6): 1271-1275


    The goal of this study was to determine the effect of hydrocephalus on cerebrospinal fluid (CSF) production rates in patients with acute and chronic hydrocephalus.The authors studied CSF production both in patients presenting with acute and chronic hydrocephalus, and patients with Parkinson disease (PD) of a similar mean age, whose CSF production was known to be normal. A modification of the Masserman method was used to measure CSF production through a ventricular catheter. The CSF production rates (means +/- standard deviations) in the three groups were then compared. The patients with PD had a mean CSF production rate of 0.42 +/- 0.13 ml/minute; this value lies within the normal range measured using this technique. Patients with acute hydrocephalus had a similar CSF production rate of 0.4 +/- 0.13 ml/minute, whereas patients with chronic hydrocephalus had a significantly decreased mean CSF production rate of 0.25 +/- 0.08 ml/minute.The authors postulate that chronic increased intracranial pressure causes downregulation of CSF production.

    View details for Web of Science ID 000179901000004

    View details for PubMedID 12507122

  • Assessment of low-flow CSF drainage as a treatment for AD - Results of a randomized pilot study NEUROLOGY Silverberg, G. D., Levinthal, E., SULLIVAN, E. V., Bloch, D. A., Chang, S. D., Leverenz, J., Flitman, S., Winn, R., Marciano, F., Saul, T., Huhn, S., Mayo, M., McGuire, D. 2002; 59 (8): 1139-1145


    This prospective, randomized, controlled study was designed to investigate the safety, feasibility, and preliminary efficacy of long-term CSF drainage via a low-flow ventriculoperitoneal shunt in subjects suffering from AD.Twenty-nine subjects selected for probable AD (National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Dementias Association criteria) were screened to exclude normal pressure hydrocephalus or other etiologies of dementia and randomized to treatment (shunt) or no treatment groups. The study endpoint was the comparison of group performance on psychometric testing at quarterly intervals for 1 year. Shunted subjects had CSF withdrawn for MAP-tau and Abeta((1-42)) assays at the same time intervals.There was no mortality from the surgical procedure, and no patient sustained a subdural hematoma. Five notable postoperative adverse events, which resolved without permanent neurologic deficit, were reported in the shunt group. Group mean Mattis Dementia Rating Scale total scores showed little change over the year in the shunt-treatment group, in contrast to a decline in the control group (p = 0.06). Mini-Mental State Examination mean scores supported a trend in favor of shunt treatment (p = 0.1). There was a concomitant decrease in ventricular CSF concentrations of AD biomarkers MAP-tau and Abeta((1-42)).The surgical procedure and the device are reasonably safe. Adverse events were consistent with shunt procedures for hydrocephalus in this older population. The endpoint data show a trend in favor of the treated group. A larger, randomized, double-blinded, controlled, clinical trial is underway.

    View details for Web of Science ID 000178726700007

    View details for PubMedID 12391340

  • The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer's type NEUROLOGY Silverberg, G. D., Heit, G., Huhn, S., Jaffe, R. A., Chang, S. D., Bronte-Stewart, H., Rubenstein, E., Possin, K., Saul, T. A. 2001; 57 (10): 1763-1766


    To evaluate the production rate of CSF in patients with differing disease states.The authors measured the production rate of CSF in three groups of patients: five patients with PD below age 60 (aged 51 +/- 4 years, mean +/- SD), nine with PD over age 60 (aged 69 +/- 6 years, mean +/- SD), and seven with dementia of the Alzheimer's type (AD) (aged 72 +/- 9 years, mean +/- SD). This method, based on the Masserman technique, employs ventricular rather than a lumbar access to the CSF space. Furthermore, the volume of CSF removed during the procedure is only 3 mL rather than 10 mL.These measurements indicate that the mean rate of CSF production in patients with PD under age 60 was 0.47 +/- 0.13 mL/minute, in patients with PD aged 60 or older the mean rate was 0.40 +/- 0.12 mL/minute, and in patients with AD the mean rate was 0.20 +/- 0.06 mL/minute.These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.

    View details for Web of Science ID 000172334700006

    View details for PubMedID 11723260

  • Sonic hedgehog promotes proliferation and tyrosine hydroxylase induction of postnatal sympathetic cells in vitro NEUROREPORT Williams, Z., Tse, V., Hou, L., Xu, L., Silverberg, G. D. 2000; 11 (15): 3315-3319


    The role of Sonic hedgehog (shh) in neural crest development was initially suggested by its involvement in patterning of the neural tube. While largely implicated in cell fate determination during development, its recently discovered role in the development of neurons postnatally prompted the possibility that neural crest derivatives of the sympathoadrenal lineage may respond to Shh postnatally. In the present study, we show that Shh promotes proliferation of postnatal sympathetic cells in culture. While it has been previously found to induce tyrosine hydroxylase (TH) production in the developing midbrain, we also demonstrated that Shh is capable of promoting TH induction of mature sympathetic neurons in vitro. This duality in Shh can be inhibited by activation of protein kinase A. These findings suggest that cell response to Shh is conserved in sympathetic ganglia derived from the neural crest, and further supports the notion that Shh can function postnatally in a dose-dependent manner to mediate neuronal cell fate.

    View details for Web of Science ID 000090010200006

    View details for PubMedID 11059894

  • Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF NEUROLOGY Kahle, P. J., Jakowec, M., Teipel, S. J., Hampel, H., Petzinger, G. M., Di Monte, D. A., Silverberg, G. D., Moller, H. J., Yesavage, J. A., Tinklenberg, J. R., Shooter, E. M., Murphy, G. M. 2000; 54 (7): 1498-1504


    Comparative study of CSF levels of tau and AD7C-neuronal thread protein (NTP) in patients with AD and control subjects.AD is characterized by neurofibrillary tangles composed of the abnormally hyperphosphorylated microtubule-associated protein tau. AD7C-NTP is a proposed AD marker expressed at early stages of neurofibrillary degeneration.Enzyme-linked immunosorbent assays specific for tau and AD7C-NTP. CSF samples were obtained from 35 demented patients (25 with antemortem clinical diagnosis of probable AD, 5 with neuropathologic diagnosis of definite AD, 5 with Lewy body pathology), 29 nondemented patients with PD, and 16 elderly healthy control subjects. Receiver operating characteristics (ROC) and multivariate discriminant analysis for AD versus controls. Correlational analysis of CSF tau and AD7C-NTP and of each marker with Mini-Mental State Examination (MMSE) scores was performed.Levels of both tau and AD7C-NTP were significantly elevated in the AD patients compared with control subjects. ROC analysis showed that CSF tau distinguished between patients with AD and nondemented control subjects with 63% sensitivity and 89% specificity, AD7C-NTP with 70% sensitivity and 87% specificity. Combined evaluation of both markers with discriminant analysis raised the specificity to 93% at a 63% sensitivity level. Both markers positively correlated with each other within the AD group, but not among control subjects. CSF levels of AD7C-NTP, but not of tau, showed a small but significant inverse correlation (r = -0.43) with MMSE scores of AD patients.CSF levels of tau and AD7C-NTP may be useful biomarkers for AD.

    View details for Web of Science ID 000086460900021

    View details for PubMedID 10751266

  • Differential contributions of cognitive and motor component processes to physical and instrumental activities of daily living in Parkinson's disease ARCHIVES OF CLINICAL NEUROPSYCHOLOGY Cahn, D. A., SULLIVAN, E. V., Shear, P. K., Pfefferbaum, A., Heit, G., Silverberg, G. 1998; 13 (7): 575-583


    Patients with Parkinson's disease (PD) become dependent upon caregivers because motor and cognitive disabilities interfere with their ability to carry out activities of daily living (ADLs). However, PD patients display diverse motor and cognitive symptoms, and it is not yet known which are most responsible for ADL dysfunction. The purpose of this study was to identify the contributions that specific cognitive and motor functions make to ADLs. Executive functioning, in particular sequencing, was a significant independent predictor of instrumental ADLs whereas simple motor functioning was not. By contrast, simple motor functioning, but not executive functioning, was a significant independent predictor of physical ADLs. Dementia severity, as measured by the Dementia Rating Scale, was significantly correlated with instrumental but not physical ADLs. The identification of selective relationships between motor and cognitive functioning and ADLs may ultimately provide a model for evaluating the benefits and limitations of different treatments for PD.

    View details for Web of Science ID 000075851200001

    View details for PubMedID 14590618

  • Trigeminal neuralgia resulting from infarction of the root entry zone of the trigeminal nerve: Case report NEUROSURGERY Golby, A. J., Norbash, A., Silverberg, G. D. 1998; 43 (3): 620-622


    OBJECTIVE AND CLINICAL IMPORTANCE: We present a case of trigeminal neuralgia resulting from infarction of the root entry zone of the trigeminal nerve. This is the first reported case of an unusual cause of trigeminal neuralgia.A 71-year-old man presented with severe lancinating pain in the left V1 and V2 distributions. Magnetic resonance imaging of the brain demonstrated a small wedge-shaped infarct at the root entry zone of the left trigeminal nerve in the pons.Medical management with carbamazepine was initially successful, but the patient later developed refractory pain and was unable to tolerate side effects of the medication. The patient underwent subsequent percutaneous glycerol rhizotomy, which resulted in complete resolution of his pain.Infarction of the root entry zone may produce typical symptoms of trigeminal neuralgia similar to a multiple sclerosis plaque at the root entry zone. Treatment of trigeminal neuralgia must consider the underlying cause. Glycerol rhizotomy may provide relief of pain for patients in whom there is no evidence of vascular compression.

    View details for Web of Science ID 000075614700117

    View details for PubMedID 9733319

  • Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma NEUROLOGICAL RESEARCH Chang, S. D., Vanefsky, M. A., Havton, L. A., Silverberg, G. D. 1998; 20 (6): 529-532


    We report a case of multiple parietal cavernous malformations in a thirteen year old female who received cranial irradiation following incomplete resection of a choroid plexus papilloma. The cavernous malformations, which developed within the prior parietal radiation ports, were diagnosed nine years after the patients' radiation treatment when the patient presented with increasing frequency of seizures. Family history was negative for familial cavernous malformations. Due to the worsening frequency of seizures, the patient underwent resection of these two cavernous malformations with diagnosis confirmed by pathology. Post-operative, there was a significant reduction in seizure frequency. The origin and pathophysiology of cavernous malformations remains controversial. Cranial radiation treatment for tumors, particularly in children, may possibly lead to the development of these lesions, as occurred in this case. This is, to our knowledge, the first case of multiple cavernous malformations occurring within a previous radiation field following radiotherapy for a neoplasm.

    View details for Web of Science ID 000075190700009

    View details for PubMedID 9713844

  • Neuropsychological and motor functioning after unilateral anatomically guided posterior ventral pallidotomy - Preoperative performance and three-month follow-up NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY Cahn, D. A., SULLIVAN, E. V., Shear, P. K., Heit, G., Lim, K. O., Marsh, L., Lane, B., Wasserstein, P., Silverberg, G. D. 1998; 11 (3): 136-145


    This study presents baseline and 3-month follow-up motor and neuropsychological data for 22 patients with Parkinson's disease (PD) who underwent anatomically guided unilateral posterior ventral pallidotomy (PVP). Postsurgical improvements were seen in psychomotor speed, fine motor accuracy, and dyskinesia, whereas grip strength decreased on the side contralateral to the surgery. No change was detected in overall level of cognitive functioning, nor were changes demonstrated in memory, language, or working memory when the entire sample of patients was evaluated. When the group was divided on the basis of side of surgery, patients with left-sided pallidotomies showed a decline in verbal fluency. Patients and caregivers reported improvement in psychosocial functioning. These initial findings of improved motor performance and largely unaffected cognitive functions are consistent with results obtained with functional PVP and provide support for the use of anatomically guided posterior ventral pallidotomy in the treatment of motor symptoms of PD.

    View details for Web of Science ID 000078976500004

    View details for PubMedID 9742512

  • Functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces radiosensitivity BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Hsiao, M., Tse, V., Carmel, J., Costanzi, E., Strauss, B., Haas, M., Silverberg, G. D. 1997; 233 (2): 329-335


    This study reports the successful growth suppression of a rat glioblastoma model (RT-2) both in vitro and in vivo by the insertion of p21(WAF1/CIP1), a negative cell cycle regulatory gene, into the tumor cells. Greater than 95% of the tumor cells expressed p21 protein after being infected with pCL based p21 retrovirus at 4x M.O.I. (multiplicity of infection). The p21-infected cells showed a 91% reduction in colony forming efficiency and a 66% reduction in growth rate. More prominent p21 staining was found in cells exhibiting histologic evidence of senescence. Intracranial implantation of the infected cells showed complete disappearance of the p21-infected cells at day 10 and long-term survival of the animals compared to controls. Injection of pCLp21 virus into tumor established in situ showed tumor necrosis and gene expression. In a clonogenic radiation survival assay, a 93% reduction of surviving colonies of p21-infected cells was seen in comparison to vector-infected control cells and to p53-infected cells after exposure to 8 Gy (800 rads).

    View details for Web of Science ID A1997WW74800008

    View details for PubMedID 9144534

  • Intracavitary liposome-mediated p53 gene transfer into glioblastoma with endogenous wild-type p53 in vivo results in tumor suppression and long-term survival BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Hsiao, M., Tse, V., Carmel, J., TSAI, Y., Felgner, P. L., Haas, M., Silverberg, G. D. 1997; 233 (2): 359-364


    A cavitary glioblastoma model was created by injection of RT-2 cells, which express endogenous wild type p53, into the peritoneal cavity of nude mice. This model developed multiple layers of tumor cells invading the peritoneal surface and was used to mimic the postoperative surgical cavity remaining after glioblastoma (GBM) excision in patients. Rhodamine labeled DMRIE/DOPE + DNA complexes were found to penetrate at least 20 tumor cell layers. Injection of p53 gene/liposome complexes into the intraperitoneal cavity after the tumor was established resulted in massive tumor necrosis. Prominent staining of human p53 protein using the DO-1 antibody was found in tumor cells near the necrotic lesions. Tumor explants expressed human p53 protein and showed a 54% growth reduction in an in vitro growth assay. Further, DMRIE/DOPE mediated p53 gene transfection significantly increased the mean survival time of tumor bearing mice compared to vector control. These results demonstrate the efficiency of using exogenous wild type p53 to suppress glioblastoma cell with endogenous wild type p53 in vivo through liposome mediated transfection method.

    View details for Web of Science ID A1997WW74800013

    View details for PubMedID 9144539

  • Cerebellar hemorrhage complicating temporal lobectomy - Report of four cases JOURNAL OF NEUROSURGERY Toczek, M. T., Morrell, M. J., Silverberg, G. A., Lowe, G. M. 1996; 85 (4): 718-722


    Four cases of cerebellar hemorrhage complicating temporal lobectomy are presented. A case of postoperative hemorrhage located remote from the operative site as a complication of intracranial surgery is rare, especially when it involves the cerebellum after supratentorial craniotomy. In a review of the literature, the authors identified only 12 such cases, none of which was described in the setting of a temporal lobectomy. The possible etiologies for cerebellar hemorrhage in the four cases presented are examined, including the role of epidural suction drains and the position of the head during surgery. The mechanism of cerebellar hemorrhage in this series of patients is probably multifactorial. Special attention throughout the perioperative course must be given to hemodynamic, anatomical, and physiological factors that together can affect the patient negatively.

    View details for Web of Science ID A1996VJ24700033

    View details for PubMedID 8814184

  • PLEOMORPHIC GRANULAR-CELL ASTROCYTOMA OF THE PINEAL-GLAND CANCER Snipes, G. J., Horoupian, D. S., Shuer, L. M., Silverberg, G. D. 1992; 70 (8): 2159-2165


    Primary neoplasms of the pineal gland are uncommon. Two patients with unusual primary pineal tumors that had similar distinctive histologic features are reported.The surgically resected neoplastic pineal tissue from these patients were examined by light microscopy, immunohistochemistry, and electron microscopy and correlated with the patients' clinical course.These pineal tumors consisted of a mixture of spindle-shaped cells with fibrillated cell processes and many large lipidized and/or granular pleomorphic cells, some of which were multinucleated. These two tumors superficially resembled pleomorphic xanthoastrocytoma and granular cell tumors of the central nervous system. The pleomorphic tumor cells expressed glial fibrillary acidic protein and some also produced retinal S-antigen, a marker for retinal photoreceptor cells. Long-term follow-up (8 years) on one of these patients suggested a relatively "benign" clinical course.It is possible that this newly described tumor may be a distinct subset of pineal gland neoplasias with a favorable biologic behavior despite the histologic features that would suggest otherwise.

    View details for Web of Science ID A1992JT85900024

    View details for PubMedID 1394046

  • Stereotactic, angiography-guided clipping of a distal, mycotic intracranial aneurysm using the Cosman-Roberts-Wells system: technical note. Neurosurgery Steinberg, G. K., GUPPY, K. H., Adler, J. R., Silverberg, G. D. 1992; 30 (3): 408-411


    We describe the use of stereotactic, angiographic guidance for localization and clipping of a small, distal intracranial bacterial aneurysm. The technique uses the commercially available Suetens-Gybels-Vandermeulen angiographic localizer with the widely used Cosman-Roberts-Wells stereotactic system. This method is simple and easy to use and significantly decreased the operative time. It may be quite useful for surgically treating mycotic and other peripheral aneurysms.

    View details for PubMedID 1620306



    89 patients with angiographically documented arteriovenous malformations were treated with helium ion Bragg peak radiation. The rate of complete angiographic obliteration 2 years after radiation was 94% in those lesions smaller than 4 cm3 (2.0 cm in diameter), 75% for those 4-25 cm3 and 39% for those larger than 25 cm3 (3.7 cm in diameter); at 3 years after radiation, the corresponding obliteration rates were 100, 95 and 70%. Major clinical complications occurred in 10 patients (8 permanent, 2 transient) between 3 and 21 months after treatment; all were in the initial stage of the protocol (higher radiation doses). 10 patients bled from residual malformation between 4 and 34 months after treatment. Seizures were improved in 63% and headaches in 68% of patients. Excellent or good clinical outcome was achieved in 94% of patients. Compared to the natural history and risks of surgery for these difficult malformations, we consider these results encouraging. Heavy-charged-particle radiation is a valuable therapy for surgically inaccessible symptomatic cerebral arteriovenous malformations. The current procedure has two disadvantages: the prolonged latent period before complete obliteration and the small risk of serious neurological complications.

    View details for Web of Science ID A1991HG99200005

    View details for PubMedID 1808653



    Angiographically occult vascular malformations of the optic nerve and chiasm are extremely rare. Before the advent of magnetic resonance imaging (MRI), it was difficult to diagnose these lesions preoperatively. We report MRI scan findings of optic chiasm cavernous angiomas in two patients with chiasmal syndrome. MRI was useful in localizing the vascular malformation and delineating its characteristics, especially chronic hemorrhage. One patient underwent biopsy of the lesion. The other patient underwent complete microsurgical resection of the malformation with the carbon dioxide laser with preservation of vision. Occult vascular malformations of the optic nerve and chiasm may be a more common cause of visual deterioration than previously recognized. The MRI scan is the imaging modality of choice for diagnosing and following these lesions. In certain patients, these vascular malformations may be amenable to complete surgical removal with stabilization or improvement of visual function.

    View details for Web of Science ID A1990DV49200023

    View details for PubMedID 2234344



    Heavy-charged-particle radiation has several advantages over protons and photons for the treatment of intracranial lesions; it has an improved physical distribution of the dose deep in tissue, a small angle of lateral scattering, and a sharp distal falloff of the dose.We present detailed clinical and radiologic follow-up in 86 patients with symptomatic but surgically inaccessible cerebral arteriovenous malformations that were treated with stereotactic helium-ion Bragg-peak radiation. The doses ranged from 8.8 to 34.6 Gy delivered to volumes of tissue of 0.3 to 70 cm3.Two years after radiation treatment, the rate of complete obliteration of the lesions, as detected angiographically, was 94 percent for lesions smaller than 4 cm3, 75 percent for those of 4 to 25 cm3, and 39 percent for those larger than 25 cm3. After three years, the rates of obliteration were 100, 95, and 70 percent, respectively. Major neurologic complications occurred in 10 patients (12 percent), of whom 8 had permanent deficits. All these complications occurred in the initial stage of the protocol, before the maximal dose of radiation was reduced to 19.2 Gy. In addition, hemorrhage occurred in 10 patients from residual malformations between 4 and 34 months after treatment. Seizures and headaches were less severe in 63 percent of the 35 and 68 percent of the 40 patients, respectively, who had them initially.Given the natural history of these inaccessible lesions and the high risks of surgery, we conclude that heavy-charged-particle radiation is an effective therapy for symptomatic, surgically inaccessible intracranial arteriovenous malformations. The current procedure has two disadvantages: a prolonged latency period before complete obliteration of the vascular lesion and a small risk of serious neurologic complications.

    View details for Web of Science ID A1990DM62600005

    View details for PubMedID 2359429



    A mixed gangliocytoma-adenoma occurring in the pituitary fossa of a patient who presented with acromegaly, galactorrhea, and headaches is described. Immunohistochemical studies demonstrated the gangliocytic portion of the tumor to be composed nearly entirely of ganglion cells enmeshed in their neuritic processes and disclosed focal presence of growth hormone and prolactin-secreting cells in the adenoma. Ultrastructurally, some of the larger ganglion cells contained (and were often filled with) zebra-like bodies, while the adenoma was shown to be sparsely granulated with numerous fibrous bodies. These findings support the term of mixed gangliocytoma-adenoma for these rare intrasellar tumors and provide additional support for their nature as independent neuroendocrine units.

    View details for Web of Science ID A1989CF19100011

    View details for PubMedID 2591950



    Positive end-expiratory pressure (PEEP) has been used to prevent and treat venous air embolism in patients in the seated position undergoing neurosurgical operations. However, the safety of PEEP has recently been questioned, because of concern that PEEP might increase right atrial pressure (RAP) more than left atrial pressure, thereby predisposing patients with a probe-patent foramen ovale to paradoxical air embolism. In a prior study in dogs, the authors found that to up 10 cm H2O PEEP did not affect the interatrial pressure difference. In the present study, the authors examined the effects of 0, 5, and 10 cm H2O PEEP in 12 anesthetized neurosurgical patients positioned both supine and seated prior to operation. Measurements were made of systemic arterial pressure, RAP, mean pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), and cardiac output. PAWP was higher (average 2 mmHg) than RAP in all patients. PEEP increased RAP and PAWP in patients, both seated and supine (mean 3 mmHg at 10 cm H2O), but did not affect the PAWP-RAP difference. In an additional eight patients in the seated position, the authors examined the effects of 0, 10, and 20 cm H2O PEEP during operation. PEEP again increased PAWP and RAP, but did not significantly affect the PAWP-RAP difference. The PAWP-RAP difference became negative (-1 mmHg) in one patient with 20 cm H2O PEEP. The authors conclude that levels of PEEP up to 10 cm H2O do not alter the interatrial pressure difference in seated neurosurgical patients, and, therefore, would not predispose these patients to paradoxical air embolism.

    View details for Web of Science ID A1988N243200014

    View details for PubMedID 3285733



    A tumor arising in the pituitary fossa and having some of the histological and ultrastructural features of a recently described tumor, purportedly originating from the folliculo-stellate cells of the anterior pituitary, is presented. The results of our ultrastructural and immunohistochemical studies, however, favored a meningeal origin and suggested that the neoplasm was most likely a secretory meningioma.

    View details for Web of Science ID A1988R321800016

    View details for PubMedID 2465659