Lee A. Zimmer

Olfactory nerve stimulation activates rat mitral cells via NMDA and non-NMDA receptors in vitro

THE neurotransmitter(s) and receptors mediating excitatory transmission at the mammalian olfactory nervemitral cell synapse were investigated using extracellular recordings in rat olfactory bulb slices. Single shocks applied to the olfactory nerve elicited both a short latency and a delayed excitatory response in mitral cells. Both responses were blocked after bath application of kynurenic acid, a broad-spectrum glutamate receptor antagonist, or DNQX, a preferential non-NMDA receptor antagonist. The specific NMDA receptor antagonist AP5 selectively attenuated the delayed, but not the initial excitation. These results suggest that glutamate is the major excitatory transmitter in the mammalian olfactory nerve, and excites mitral cells via NMDA and non-NMDA receptors.

Activation of Locus Coeruleus Enhances the Responses of Olfactory Bulb Mitral Cells to Weak Olfactory Nerve Input

The main olfactory bulb (MOB) receives a dense projection from the pontine nucleus locus coeruleus (LC), the largest collection of norepinephrine (NE)-containing cells in the brain. LC is the sole source of NE innervation of MOB. Previous studies of the actions of exogenously applied NE on mitral cells, the principal output neurons of MOB, are contradictory. The effect of synaptically released NE on mitral cell activity is not known, nor is the influence of NE on responses of mitral cells to olfactory nerve inputs. The goal of the present study was to assess the influence of LC activation on spontaneous and olfactory nerve-evoked activity of mitral cells. In methoxyflurane-anesthetized rats, intracoerulear microinfusions of acetylcholine (ACh) (200 mm; 90–120 nl) evoked a four- to fivefold increase in LC neuronal discharge, and a transient EEG desynchronization and decrease in mitral cell discharge. LC activation increased excitatory responses of mitral cells evoked by weak (i.e., perithreshold) nasal epithelium shocks (1.0 Hz) in 17/18 cells (mean increase = 67%). The discharge rate of mitral cells at the time that epithelium-evoked responses were increased did not differ significantly from pre-LC activation baseline values. Thus, changes in mitral baseline activity do not account for the increased response to epithelium stimulation. These findings suggest that increased activity in LC–NE projections to MOB may enhance detection of relatively weak odors.

SOMAN-INDUCED SEIZURES RAPIDLY ACTIVATE ASTROCYTES AND MICROGLIA IN DISCRETE BRAIN REGIONS

Neurons in the piriform cortex and the pontine nucleus locus coeruleus express elevated levels of the immediate early gene protein product, Fos, within 30–45 minutes of a seizurogenic dose of the anticholinesterase, soman (Zimmer et al., [1997] J. Comp. Neurol. 378:468–481). By 24 hours following soman injection, there is marked neuropathology in the piriform cortex. These findings suggest selective, regional vulnerability in response to the seizurogenic actions of soman. In the present study, we determined that soman‐induced seizures also cause selective, rapid activation of astrocytes and microglia in the piriform cortex and other brain regions. Animals were killed at different intervals between 1 hour and 24 hours after a convulsive dose of soman. Brain sections were processed for immunocytochemical detection of astrocytes with antibodies against glial fibrillary acidic protein, and microglia and macrophages with antibodies against the complement receptor 3 protein, OX‐42.

Current use of 18F-fluorodeoxyglucose positron emission tomography and combined positron emission tomography and computed tomography in squamous cell carcinoma of the head and neck.

The history and physical examination, computed tomography (CT) and magnetic resonance imaging are the cornerstones for identifying new and recurrent cancers of the head and neck. The advent of positron emission tomography (PET) and combined PET/CT imaging technology is a promising development. These modalities have the potential to help stage patients presenting with head and neck cancer, identify responses to nonsurgical therapy, and allow earlier detection of recurrence in the hope of improving survival. The following paper provides a brief history of PET and PET/CT imaging. The current PET and PET/CT literature for squamous cell carcinoma of the head and neck is reviewed, and specific recommendations for its use are provided.

Combined positron emission tomography/computed tomography imaging of recurrent thyroid cancer.

OBJECTIVE: The study goal was to evaluate the use of combined positron emission tomography/computed tomography (PET/CT) imaging for localization of recurrent disease in thyroid cancer patients. STUDY DESIGN AND SETTING: Eight patients with suspected recurrence of thyroid cancer on the basis of elevated serum thyroglobulin or calcitonin levels underwent combined PET/CT imaging on a prototype device. All 8 patients had previously undergone total thyroidectomy and 131I ablation for thyroid carcinoma. Patients with papillary carcinoma had negative 131I scans. RESULTS: Eight patients underwent combined PET/CT scanning. Four (50%) of 8 patients underwent PET/CT indicating recurrence in the head and neck. A total of 11 lesions in these 4 patients were suspicious for recurrence on combined PET/CT imaging. Three patients with 8 lesions suspicious for recurrence on PET/CT underwent surgical removal of disease. All 3 patients had pathologic confirmation of recurrence, with 6 (75.0%) of 8 lesions being positive. CONCLUSION: Combined PET/CT imaging is a valuable tool for the diagnosis and anatomic localization of recurrent thyroid cancer.

Endoscopic approach to the infratemporal fossa: anatomic study.

OBJECTIVEClassic surgical exposures of the infratemporal fossa region, including the adjacent intracranial space, temporal bone, and sinonasal region, require the extensive exposure associated with the transcranial, transfacial, and transmandibular approaches with their inherent neurological and cosmetic morbidities. In this study, we evaluated the feasibility and exposure afforded by combining 2 endoscopic transmaxillary approaches, endonasal and Caldwell-Luc supplement, to the infratemporal fossa. METHODSEndoscopic transmaxillary dissection was performed in 4 formalin-fixed cadaver heads (8 sides). We quantified the extent of exposure achieved within the pterygopalatine and infratemporal fossae after our initial dissection, which was endonasal with a medial antrostomy, and after addition of a Caldwell-Luc incision with an anterior antrostomy. Complementing this anatomic study, we report on a patient in whom this endoscopic transmaxillary approach combining the endonasal and Caldwell-Luc approaches was used for resection of a trigeminal schwannoma in the infratemporal fossa. RESULTSThe combination of these 2 endoscopic transmaxillary approaches enabled visualization of the entire region of the pterygopalatine fossa and anteromedial aspect of the infratemporal fossa. Additional posterolateral exposure of the infratemporal fossa requires significant traumatic traction on the nose. Addition of the Caldwell-Luc transmaxillary approach exposed the remainder of the infratemporal fossa, including the mandibular nerve and branches, middle meningeal artery, and even the distal cervical portion of the internal carotid artery. CONCLUSIONEndoscopic exposure of the infratemporal fossa is feasible. Using the combination of the endonasal and Caldwell-Luc approaches for direct transmaxillary access significantly extended exposure, allowing safe and effective resection of infratemporal fossa lesions.

Maximizing the extent of tumor resection during transsphenoidal surgery for pituitary macroadenomas: can endoscopy replace intraoperative magnetic resonance imaging?

OBJECT Endoscopic approaches to pituitary tumors have become an effective alternative to traditional microscopic transsphenoidal approaches. Despite a proven potential to decrease unexpected residual tumor, intraoperative MR (iMR) imaging is infrequently used even in the few operating environments in which such technology is available. Its use is prohibitive because of its cost, increased complexity, and longer operative times. The authors assessed the potential of intrasellar endoscopy to replace the need for iMR imaging without sacrificing the maximum extent of resection. METHODS In this retrospective study, 27 consecutive patients underwent fully endoscopic resection of pituitary macroadenomas. Intrasellar endoscopy was used to determine the presence of residual tumor within the sella turcica and tumor cavity. Intraoperative MR imaging was used to identify rates of unexpected residual tumor and the need for further tumor resection. RESULTS Intraoperative estimates of the extent of tumor resection were correct in 23 patients (85%). Of 4 patients with unacceptable tumor residuals, 3 underwent further tumor resection. After iMR imaging, the rate of successful completion of the planned extent of resection increased to 26 patients (96%). Rates of both endocrinopathy reversal and postoperative complications were consistent with previously published results for microscopic and endoscopic resection techniques. CONCLUSIONS The findings in this study provided quantitative evidence that intrasellar endoscopy has significant promise for maximizing the extent of tumor resection and is a useful adjunct to surgical approaches to pituitary tumors, particularly when iMR imaging is unavailable. A larger prospective study on the extent of resection following endoscopic transsphenoidal surgery would strengthen these findings.

Anatomical localization and time course of Fos expression following soman-induced seizures

Soman (pinacolymethylphosphonofluoridate), a highly potent, irreversible inhibitor of cholinesterase, causes intense convulsions, neuropathology and, ultimately, death. There is evidence that certain brain structures are selectively vulnerable to the pathological consequences of soman‐induced seizures. A working hypothesis is that central nervous system (CNS) structures with the earliest and most severe signs of neuropathology may be key sites for the initiation of the seizures. Fos, the immediate‐early gene product, increases rapidly in several animal seizure models. Thus, we reasoned that the earliest brain regions to express Fos might be involved in the initiation and maintenance of soman‐induced convulsions. To assess this, rats were injected with a single, convulsive dose of soman (77.7 μg/kg, i.m.). The animals were euthanized and processed for immunocytochemical analysis at several time points. Robust Fos expression was seen in layer II of the piriform cortex and the noradrenergic nucleus locus coeruleus within 30–45 minutes. One hour following soman injection, staining was more intense in the piriform cortex layer II and in the locus coeruleus. In addition, Fos was evident in the piriform cortex layer III, the entorhinal cortex, the endopiriform nucleus, the olfactory tubercle, the anterior olfactory nucleus and the main olfactory bulb. By 2 hours, Fos staining was present throughout the cerebral cortex, thalamus, caudate‐putamen and the hippocampus. At 8 hours and beyond, Fos expression returned to control levels throughout the CNS except for the piriform cortex and the locus coeruleus which still had robust labeling. By 24 hours, neuropathology was evident throughout the rostral‐caudal extent of layer II of the piriform cortex. The rapid induction of Fos in the piriform cortex and the locus coeruleus, taken together with previous anatomical, eletrophysiological and neurochemical studies, suggests that prolonged, excessive exposure to synaptically released acetylcholine and norepinephrine triggers the production of soman‐induced seizures initially in the piriform cortex and subsequently in other cortical and subcortical structures. J. Comp. Neurol. 378:468–481, 1997.

Sources of registration error with image guidance systems during endoscopic anterior cranial base surgery.

OBJECTIVES: The goal of this study was to evaluate the accuracy of the registration process and to identify potential sources of error during anterior cranial base surgery. STUDY DESIGN AND SETTING: The registration accuracy of image guidance and the location of excluded fiducials were recorded prospectively from 50 endoscopic, anterior cranial base procedures in an academic university setting. RESULTS: The mean error of initial registration was 2.8 mm (range, 1.4 to 7.1 mm). Following the exclusion of fiducials the mean error of registration was 1.6 mm (range, 0.6 to 3.7 mm). There was a significant improvement in the mean error rate from initial to final registration following the exclusion of fiducials (P < 0.0001). Posterior fiducials were excluded most often and anterior fiducials were excluded the least. Registration accuracy was similar for CT and MRI (P = 0.64). CONCLUSIONS: The accuracy of the Stryker Image Guidance System is enhanced by the exclusion of individual fiducials with high registration errors. SIGNIFICANCE: The exclusion of fiducials with high registration errors increases the accuracy of image guidance in anterior cranial base surgery.

Olfactory changes after endoscopic pituitary tumor resection.

OBJECTIVES: Given that the transnasal endoscopic approach to the sella involves resection of anatomical structures known to contain olfactory neuroepithelium, the effect of this approach on olfaction was evaluated. STUDY DESIGN: Case series with planned data collection. SETTING: Single tertiary care institution. SUBJECTS AND METHODS: Adults diagnosed with a pituitary mass and scheduled to undergo transnasal endoscopic resection underwent preoperative olfactory evaluation using the University of Pennsylvania Smell Identification Test (UPSIT). Repeat testing was performed at one and three months postoperatively. Paired Student t tests were used to compare preoperative and postoperative scores. RESULTS: A total of 57 consecutive patients were enrolled. Fifty patients (24 males, 26 females) completed olfactory evaluation at one month. Forty-five (23 males, 22 females) completed a three-month evaluation. The average UPSIT score (out of 40) was 31.8 preoperatively, 30.5 at one month, and 32.6 at three months. A significant difference was found between preoperative and one-month scores (P = 0.01) but not three-month scores (P = 0.08). CONCLUSION: A transient difference was found between preoperative and one month UPSIT scores. At three months, no clinically significant difference was found on repeat olfactory testing. Although the transnasal endoscopic approach to the sella removes structures known to contribute to olfactory function, it has no clinically significant effect on olfaction.