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N T Zervas

Publications and source records attributed to N T Zervas.

At least 19 recordsLinked to original sources
PubMed2006

From spreading depression to the trigeminovascular system.

Migraine headaches have a complex pathophysiology; both vascular and neuronal mechanisms have been proposed. One possible scenario begins with brain-initiated events evolving to cortical spreading depression (CSD), which in turn activates the trigeminal nerve to cause headaches. Experimental evidence supports a relationship between CSD as a cause of migraine aura as well as CSD as a cause of trigeminal activation. Susceptibility to CSD and to migraine appears to be genetically determined. In some migraine subtypes, genes controlling translocation of calcium, sodium and potassium have been implicated, perhaps altering the susceptibility to CSD. This chapter briefly reviews current knowledge pertaining to migraine pathophysiology with emphasis on current notions linking disturbances in ion flux to the genesis of headache.

Cerebrovascular Circulation↗
PubMed1999

Long-term mortality after transsphenoidal surgery for Cushing disease.

BACKGROUND: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported. OBJECTIVE: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques. DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996. INTERVENTION: Transsphenoidal adenomectomy and as-needed adjunctive therapy. MEASUREMENT: Record review with follow-up interview. RESULTS: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2). CONCLUSION: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.

Adenoma↗
PubMed1999

Gangliocytoma masquerading as a prolactinoma. Case report.

The authors describe the case of a 36-year-old man who presented with bitemporal hemianopsia and a serum prolactin concentration of 1440 ng/ml. Magnetic resonance imaging of the pituitary revealed a presumed macroadenoma with suprasellar and temporal lobe extension. Although the patient's prolactin level was lowered to 55 ng/ml by bromocriptine therapy, no tumor shrinkage occurred. Fourteen months later, progression of visual field defects necessitated transsphenoidal resection, which was incomplete. Immunocytochemical analysis of the biopsy tissue was positive for prolactin and, in view of the clinical picture, more detailed analysis was not performed. External-beam radiotherapy was given 2 years later because of enlargement of residual tumor. Subsequently, despite a fall in the serum prolactin concentration to less than 20 ng/ml in response to the course of bromocriptine, the mass displayed further extension into the temporal lobe. Nine years after the patient's initial presentation, he underwent transfrontal craniotomy for sudden deterioration in visual acuity caused by hemorrhage into the mass. No adenohypophyseal tissue was identified in the resected tissue. The mass was composed of dysplastic neurons that were strongly immunoreactive for synaptophysin and neurofilament (indicating neural differentiation) and prolactin. Review of the original biopsy specimen indicated that the prolactin-positive cells had striking neuronal morphological characteristics. The final diagnosis in this case is prolactin-secreting gangliocytoma. Although exceedingly rare, this disease must be added to the differential diagnosis in cases of "prolactinoma" when bromocriptine therapy is followed by a marked decline in serum prolactin that is not accompanied by significant tumor shrinkage. Furthermore, in such instances, consideration should be given to "obtaining a biopsy sample prior to electing for radiotherapy.

Adult↗
PubMed1999

Renal cell carcinoma: a rare source of cauda equina metastasis. Case report.

The authors present the case of a patient in whom intradural metastasis from renal cell carcinoma spread to the cauda equina. To the authors' knowledge, this is only the second report of its kind. This male patient had undergone nephrectomy for the treatment of renal cell carcinoma for 5 years and was diagnosed as having metastatic lung disease 1 year prior to admission. The patient presented with lower back pain that radiated to both legs, but he exhibited no sensorimotor deficits. The majority of cauda equina tumors are primary tumors, and metastases are very rare. The literature is reviewed with reference to current molecular genetic paradigms of metastatic renal cell carcinoma.

Aged↗
PubMed1998

Co-expression of Fas and Fas ligand in malignant glial tumors and cell lines.

Fas ligand (FasL) is involved in tumor evasion from the immune system. We analyzed 22 human gliomas for expression of FasL and its receptor, Fas. Positive FasL and Fas immunoreactivity was detected in 13 out of 22 tumors by Western blotting and in 15 out of 22 tumors by immunohistochemistry. Immunohistochemistry also showed that Fas and FasL expression was confined to tumor cells. Co-expression of these molecules was confirmed by Western blotting and immunohistochemistry in 4 of 7 glioma cell lines. Co-expression of FasL and Fas within tumor cells suggests that their contribution in vivo to the process of immune system evasion and tumor cell apoptosis is complex and probably involves additional factors.

Astrocytoma↗
PubMed1998

A mobile computed tomographic scanner with intraoperative and intensive care unit applications.

INTRODUCTION: A mobile computed tomographic scanner has been developed in which the scan plane is selected by means of gantry translation, rather than by translation of the patient table. This permits computed tomographic scanning in situ of any patient who is positioned on a radiolucent surface that fits within the inner diameter of the gantry. We report the design of and initial experience with this scanner as used with adapters for intraoperative and bedside computed tomography (CT). METHODS: The scanner is equipped with wheels, draws power from wall outlets (120 V, 20 A) in combination with batteries, and has a translating gantry. Preclinical studies of image quality were performed with phantoms. An operating table adapter was built for use with a radiolucent cranial fixation device. A bedside adapter was built that holds the head and shoulders of a patient in the intensive care unit. RESULTS: The preclinical phantom studies showed satisfactory image spatial resolution (0.8 mm) and low-contrast resolution signal-to-noise relative standard deviation (0.37%). Experience to date with 12 patients has confirmed the feasibility of intraoperative CT on demand. Experience to date with 26 patients has confirmed the feasibility of routine bedside CT in the intensive care unit. CONCLUSION: With these adaptations, mobile CT may increase the efficiency of intraoperative scanning by making it available to multiple operating rooms without committing it to any room for an entire operation and may increase the efficiency and safety of CT of critically ill patients who currently need to leave the intensive care unit to travel to a fixed CT installation and back.

Child↗
PubMed1998

Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly.

To analyze the long term outcome after multimodality therapy for acromegaly, a retrospective review was performed on 162 patients who underwent transsphenoidal surgery at Massachusetts General Hospital between 1978 and 1996. The surgical cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was 57% overall. The surgical cure rate was significantly dependent on tumor size, but was not dependent on age or sex. An improvement in the surgical cure rate was noted over the course of the review, from 45% before 1987 to 73% since 1991. Long term follow-up was obtained in 99% of U.S. residents (149 of 151), with a mean follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical remission as determined by normalization of serum insulin-like growth factor I levels or by GH suppression after oral glucose tolerance testing at last contact or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery in those patients who initially met the criteria for surgical cure. The 10-yr survival rate was 88%, and there were 12 deaths at postoperative intervals of 2-12 yr, with the most common cause of death being cardiovascular disease. A Cox proportional hazards model showed that patient-years with persistent disease carried a 3.5-fold [95% confidence interval (CI), 1.0-12; P = 0.02] relative mortality risk compared to those patient-years in remission. A Poisson person-years regression analysis showed no significant difference in survival between those 86 patients cured at operation and an age- and sex-matched sample from the U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3-2.2; P = 0.35]. A similar analysis on the entire group of 149 patients showed no significant difference in survival from that in a control sample (SMR, 1.16; 95% CI, 0.66-2.0; P = 0.3). Mortality risk for patient-years with persistent active disease after unsuccessful treatment vs. that in the U.S. population sample remained increased (SMR, 1.8; 95% CI, 0.9-3.6; P = .05). This analysis suggests that the decreased survival previously reported to be associated with acromegaly can be normalized by successful surgical and adjunctive therapy.

Acromegaly↗
PubMed1998

Biochemical assessment of Cushing's disease in patients with corticotroph macroadenomas.

The majority of cases of Cushing's disease are due to an underlying pituitary corticotroph microadenoma (< or = 10 mm). Corticotroph macroadenomas (> 10 mm) are a less common cause of Cushing's disease, and little is known about specific clinical and biochemical findings in such patients. To define further the clinical characteristics of patients with corticotroph macroadenomas, we performed a retrospective review of Cushing's disease due to macroadenomas seen at Massachusetts General Hospital between 1979 and 1995. Of 531 patients identified with a diagnostic code of Cushing's syndrome, 20 were determined to have Cushing's disease due to a macroadenoma based on radiographic evidence of pituitary adenoma greater than 10 mm and pathological confirmation of a pituitary adenoma. A comparison review of charts of 24 patients with Cushing's disease due to corticotroph microadenomas identified on the basis of radiographic evidence of a normal pituitary gland or a pituitary adenoma 10 mm or less in diameter was also performed. The mean ages of the patients (+/- SD) with macroadenomas and microadenomas were similar (39 +/- 12 and 38 +/- 14 yr, respectively). The baseline median 24-h urine free cortisol (UFC) excretion was 1341 nmol/day (range, 304-69,033 nmol/day) and 877 nmol/day (range, 293-2,558 nmol/day) for macroadenoma and microadenoma patients, respectively (P = 0.058). After the 48-h high dose dexamethasone suppression test, UFC decreased by 77 +/- 19% (mean +/- SD) and 91 +/- 7% in macroadenoma and microadenoma subjects, respectively (P = 0.04). Fifty-six percent of macroadenoma patients and 92% of microadenoma patients had greater than 80% suppression of UFC after high dose dexamethasone administration (P = 0.03). The baseline median 24-h urinary 17-hydroxysteroid (17-OHCS) excretion was 52 mumol/day (range, 25-786 mumol/day) and 44 mumol/day (range, 17-86 mumol/day) for macroadenoma and microadenoma subjects, respectively (P = 0.09). After the standard high dose dexamethasone suppression test, 17-OHCS excretion decreased by 46 +/- 33% and 72 +/- 22% for macroadenoma and microadenoma subjects, respectively (P = 0.02). Fifty-three percent of patients with macroadenomas and 86% of patients with microadenomas had greater than 50% suppression of 17-OHCS after high dose dexamethasone administration (P = 0.02). Baseline plasma ACTH values were above the normal range in 83.3% of macroadenoma patients and in 45% of microadenoma subjects (P = 0.05). Tumors were immunostained with the MIB-1 antibody for Ki-67 to investigate proliferation in the adenomas. There was a trend for a higher Ki-67 labeling index in corticotroph macroadenomas, and seven (44%) macroadenomas vs. three (18%) microadenomas had labeling indexes greater than 3%, but this was not statistically significant. In summary, corticotroph macroadenomas are often associated with less glucocorticoid suppressibility than the more frequently occurring microadenomas. Therefore, the lack of suppression of UFC or 17-OHCS after the administration of high dose dexamethasone in a patient with Cushing's disease does not necessarily imply the presence of ACTH-independent Cushing's syndrome and is more commonly seen in patients with corticotroph macroadenomas than in those with microadenomas. Increased plasma ACTH concentrations are typical of patients with corticotroph macroadenomas and may be a more sensitive indicator of neoplastic corticotrophs than the UFC or 17-OHCS response to standard high dose dexamethasone testing.

17-Hydroxycorticosteroids↗
PubMed1998

Spinal dural enhancement on magnetic resonance imaging associated with spontaneous intracranial hypotension. Report of three cases and review of the literature.

This report offers a description of typical changes seen on gadolinium-enhanced magnetic resonance (MR) imaging of the entire spine that indicate spontaneous intracranial hypotension (SIH). To the authors' knowledge, this is the first report of its kind. They describe three cases of SIH that were accompanied by dural enhancement throughout the neuraxis on imaging, with the evolution of associated subdural and epidural fluid collections in the spine. Recognition of this disorder is important to be able to distinguish it from an infectious or neoplastic process in which surgical intervention might be warranted. Evaluation using gadolinium-enhanced cranial and spinal MR imaging in patients with postural headaches and an (111)In-labeled cerebrospinal fluid leak study are discussed. Treatment with an epidural blood patch is shown to be particularly effective, with resolution of the radiological and clinical findings.

Adult↗
PubMed1997

The safety and efficacy of cyclosporine A in the prevention of vasospasm in patients with Fisher grade 3 subarachnoid hemorrhages: a pilot study.

OBJECTIVE: To evaluate the safety and any potential effect of cyclosporine A (CycA) in preventing cerebral vasospasm. METHODS: Nine patients with Fisher Grade 3 subarachnoid hemorrhages were studied. After a loading dose of 7.5 mg/kg of CycA was administered every 12 hours for two doses, enteral treatment with CycA was started within 72 hours of the onset of the subarachnoid hemorrhage. Whole blood CycA levels were titrated to maintain levels of 50 to 400 ng/kg. Transcranial doppler ultrasonography was performed daily. Middle cerebral artery velocities were used to assess the degree of vasospasm. Angiography was performed to confirm the vasospasm in symptomatic patients, or it was performed if transcranial doppler ultrasonograms were unobtainable. Patients were treated with a standard pharmacological regimen of nimodipine. Induced hypertension, hemodilution, and hypervolemia were instituted at the discretion of the neurosurgical team. Intra-arterial papaverine was infused into the vasospastic vessels of three recalcitrant patients. Outcome was assessed at 6 months with the Glasgow Outcome Scale. RESULTS: All the patients displayed evidence of vessel narrowing, which was disclosed by transcranial doppler ultrasonography or angiography. Five patients developed ischemic deficits, two were treated with intra-arterial papaverine, and three died of complications secondary to vasospasm. No significant hepatic, renal, or infectious complication developed as a result of the administration of CycA. CONCLUSIONS: CycA proved safe to use but failed to prevent the development of cerebral vasospasm or delayed ischemic deficits in patients considered at high risk.

Adolescent↗
PubMed1997

Initial characterization of the dosimetry and radiology of a device for administering interstitial stereotactic radiosurgery.

OBJECTIVE: We report the design and initial characterization of the dosimetry and radiobiology of a novel device for interstitial stereotactic radiosurgery. INSTRUMENTATION: The device is lightweight, handheld, and battery-powered, and it emits x-ray radiation from the tip of a probe 3 mm in diameter by 10 cm in length. METHODS: The dosimetry was characterized by two independent methods: thermoluminescent dosimeters and radiochromic film. The radiobiology was characterized by in vivo irradiation of rat liver, dog liver, and dog brain. The animals were killed at varying intervals of time, and histological examinations were performed. Heat transfer from the probe to dog brain was studied in vivo by placing thermocouple sensors around the probe tip before irradiating. RESULTS: Both dosimetric methods showed a steep dose-distance fall-off relationship (proportional to the reciprocal of the cube of the distance from the probe tip). Rats and dogs that were killed weeks to months after liver irradiation tended to have sharply demarcated lesions. Liver enzyme levels, measured serially in the dogs, did not give evidence of chronic inflammation. Histological examination of the brains of dogs that were killed acutely after irradiation did not show evidence of inflammation, edema, or hemorrhage. The tissue temperature elevation 1 cm from the tip never exceeded 0.5 degree C, thereby excluding hyperthermia as a significant contributor to the formation of lesions. CONCLUSIONS: Because this device requires relatively few supporting resources, has sharp dosimetric properties, and seems to be safe, it may be useful as a clinical tool for interstitial stereotactic radiosurgery.

Animals↗
PubMed1997

Interstitial irradiation of brain tumors, using a miniature radiosurgery device: initial experience.

OBJECTIVE: This report describes the clinical evaluation of a novel stereotactic radiosurgical device for interstitial irradiation of malignant brain tumors. METHODS: Fourteen patients with cerebral lesions less than 3.5 cm in greatest diameter were treated with a single fraction of stereotactic interstitial irradiation (average, 12.5 Gy). Clinical evaluation, Karnofsky Performance Scale ratings, and neuroimaging studies were obtained at 6-week intervals postoperatively to assess treatment response. Reduction or stabilization of tumor size on follow-up imaging was accepted as local control, whereas tumor enlargement indicated local failure. INSTRUMENTATION: This battery-powered miniature x-ray generator device produces low-energy x-ray photons that are attenuated rapidly within tissue. A dose decline rate proportional to 1/r3 yields extremely sharp dose fall-off curves with minimal exposure to surrounding tissue. Dose rates of 200 cGy per minute are possible, allowing for the administration of 12.5 Gy to a lesion 3 cm in diameter in less than 1 hour. RESULTS: Local control (stabilization or reduction in lesion size) was obtained in 10 of the 13 patients with tumors with follow-up of 1.5 to 36 months (mean, 12 mo). Of three patients with radiographic progression, recurrence was symptomatic in only one. All patients tolerated the procedure well, and most patients were discharged home the day after treatment. No new neurological deficits were noted after biopsy and irradiation. CONCLUSIONS: Preliminary experience with this novel radiosurgical device has demonstrated its feasibility and safety. Clinical efficacy of this technique is now under investigation in an international multicenter study.

Adult↗
PubMed1997

Augmentation of both hemolysate-induced contraction and activation of protein kinase C by submaximum activation in canine cerebral arteries in vitro.

Although phorbol esters, synthetic activators of protein kinase C (PKC), can stimulate large increases in the binding of cytosolic PKC to form membrane-bound PKC (PKCm, an indicator of PKC activation), the authors report that even small increases in PKCm induced by phorbol esters (8-12% of total PKC content) can be associated with significant PKC-mediated contractions in vitro (50-85% of maximum) in normal canine cerebral arteries. Increases in PKCm of similarly small magnitude were found in vitro when control artery segments were exposed to hemolysate, but only if the arterial smooth-muscle cells were first slightly depolarized by increased extracellular potassium to values of membrane potential similar to those observed in canine cerebral arteries during chronic cerebral vasospasm. These increases in PKCm (6-8% of total PKC content) coincided with a greatly augmented contractile response to hemolysate. These results show that the previous observation of only a small increase in PKCm (approximately 7% of total PKC content) after experimental subarachnoid hemorrhage in the canine model does not preclude a potentially important role for PKC-mediated contraction in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1996

Experimental microneurosurgery of the trigeminal nerve: surgical technique for ganglionectomy and rhizotomy in the cat.

The techniques of two experimental surgical operations on the trigeminal nerve are described, namely, excision of the trigeminal ganglion (ganglionectomy) and division of the trigeminal root (rhizotomy), in the cat. These techniques have been developed with the specific aims of achieving the trigeminal lesion and also preserving a satisfactory postoperative quality of life for the animal in order to make it possible to study the long-term effects of trigeminal dennervation. To the best of our knowledge, a detailed description of such a surgical methodology is lacking; reporting of these procedures may facilitate future research on the trigeminal nerve.

Animals↗