Unilateral Endoscopic Endonasal Surgery for Resection of an Olfactory Schwannoma of the Anterior Cranial Base in a Patient with Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: Olfactory schwannomas of the anterior cranial base (ACB) are rare tumors, and their association with hereditary hemorrhagic telangiectasia (HHT) has not previously been described. The majority of ACB schwannomas arise from the sinonasal tracts and may demonstrate intracranial extension. We report a case of an olfactory schwannoma-dense adherence to the basal frontal lobe. Complete tumor resection was performed through a unilateral extended endonasal endoscopic approach with preservation of the contralateral olfactory bulb. Anterior cranial base repair was achieved with the use of a mucoperichondrial vascularized pedicled nasoseptal flap. CLINICAL PRESENTATION: A 25-year-old woman with a history of migraines presented with unilateral epistaxis and progressive worsening of her headache symptoms. The patient had a history of HHT. Nasal endoscopy showed mild telangiectasias, but no clear evidence of a mass. A computerized tomographic scan showed a large left-sided expansile lesion in the left ethmoid region with expansion and remodeling of the anterior cranial base and medial left orbit. Magnetic resonance imaging with contrast showed the mass to be avidly enhancing. Angiography was performed and demonstrated a mild vascular blush. CONCLUSIONS: We report a rare case of HTT and olfactory schwannoma completely resected with a unilateral extended endoscopic endonasal approach. Reconstruction was performed with the use of nasoseptal flap. This is the first reported single-stage fully endoscopic endonasal unilateral approach for resection of an olfactory schwannoma with preservation of the contralateral olfactory cleft. The patient's sense of smell and taste was maintained after surgery.

Unilateral Tailored Fronto-Orbital Approach for Giant Olfactory Groove Meningiomas: Technical Nuances.

OBJECTIVE: Giant olfactory groove meningiomas (maximum diameter ≥6 cm) remain a surgical challenge. Historically, extensive anterior and antero-lateral approaches have been the primary approaches for removal of such large tumors with limitations and morbidity pertaining to each approach. Herein, the authors describe a minimally invasive, unilateral, tailored fronto-orbital approach for resection of these complex lesions with an emphasis on preservation of the anterior cerebral arteries and olfactory nerves. METHODS: A 4-stage approach using neuronavigation is performed: 1) predefined corridor, 2) identification of the ipsilateral anterior cerebral artery, 3) postdefined corridor, and 4) tumor base. The details of this approach are described below in a stepwise fashion and supplemented by a sample of 3 cases utilizing this technique. RESULTS: In the 3 representative cases in which this technique was used, gross total resection was achieved without injury to any of the adjacent neurovascular structures. Significant sellar extension can be resected through a second stage endoscopic endonasal approach. CONCLUSION: Giant olfactory groove meningiomas (≥6 cm) can be safely and completely resected with this 4-stage, unilateral fronto-orbital technique. Furthermore, early identification and preservation of the adjacent critical neurovascular structures can be achieved. This technique avoids the inherent limitations and morbidity associated with the more classic pterional and bifrontal approaches respectively while minimizing normal tissue disruption.

The blood-brain barrier and nasal drug delivery to the central nervous system.

BACKGROUND: The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. METHODS: The objective of this study is to generally review these strategies of drug administration to the CNS. RESULTS: Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. CONCLUSION: Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

Preservation of olfaction in surgery of olfactory groove meningiomas.

INTRODUCTION: Olfaction is commonly considered as secondary among the sensory functions, perhaps reflecting a lack of interest in sparing olfaction after surgery for the olfactory groove meningiomas (OGM). However, considering the repercussions of olfaction for the quality of life, the assessment of post-operative olfaction should be necessary. We retrospectively reviewed the olfactory outcome in patients with OGM and investigated the factors associated with sparing the post-operative olfaction. METHODS: Between 1993 and 2012, 40 patients with OGM underwent surgical resection and estimated the olfactory function using the Korean version of "Sniffin'Sticks" test (KVSS). Variable factors, such as tumor size, degree of preoperative edema, tumor consistency, preoperative olfactory function, surgical approaches, patient's age, and gender were analyzed with attention to the post-operative olfactory function. RESULTS: Anatomical and functional preservation of olfactory structures were achieved in 26 patients (65%) and 22 patients (55%), respectively. Among the variable factors, size of tumor was significant related to the preservation of post-operative olfaction. (78.6% in size<4 cm and 42.3% in size>4 cm, p=0.035). Sparing the olfaction was significantly better in patients without preoperative olfactory dysfunction (84.6%) compared with ones with preoperative olfactory dysfunction (40.7%, p=0.016). The frontolateral approach achieved much more excellent post-operative olfactory function (71.4%) than the bifrontal approach (36.8%, p=0.032). CONCLUSIONS: If the tumor was smaller than 4 cm and the patients did not present olfactory dysfunction preoperatively, the possibility of sparing the post-operative olfaction was high. Among the variable surgical approaches, frontolateral route may be preferable sparing the post-operative olfaction.

Giant olfactory groove meningiomas: extent of frontal lobes damage and long-term outcome after the pterional approach.

OBJECTIVE: The treatment of giant olfactory groove meningiomas (OGMs; maximum diameter ≥ 6 cm) poses special problems and represents a surgical challenge. We discuss the long-term results in a series of 18 patients with giant OGMs and report our experience on a global strategy encompassing the pterional approach to manage the lesion and an extended transbasal approach to treat recurrences. METHODS: Between February 1991 and December 2007, 18 patients with giant OGMs were surgically managed via a pterional craniotomy. Postoperative follow-up imaging was obtained at one, six, and 12 months and then yearly. In preoperative images, data from tumor volume were assessed. The volume of the residual right frontal porencephalic cave (ipsilateral to the operative side) was compared with the volume of the porencephalic cave measured in the left frontal lobe (internal control) in each case. Comparison between porencephalic cave and the original tumor volume for each side was also performed. RESULTS: At the first operation in 17 of 18 patients (94.4%), the tumor resection was accomplished by a complete macroscopic lesion removal and coagulation of its dural attachment (Simpson grade II). In one patient, a Simpson grade V resection was obtained. The mean follow-up was 93.5 months, ranging from 12 to 214 months. Recurrences were observed in three patients (16.7%) at 103, 102, and 128 months, respectively, from the time of the first operation. These patients were operated on via an extended subfrontal transbasal approach accomplishing a complete (Simpson grade I) resection. No death occurred. The visual deficit improved in seven of 13 patients (53.8%), remained stable in five (38.5%), and worsened in one patient (7.7%). Overall, 17 of 18 patients (94.4%) had a good outcome and returned to their previous occupations. All the tumors presented with a symmetrical growth pattern. The mean meningioma volume was 23.51 ± 1.62 cm(3) for the right portion of the tumor and 23.04 ± 1.35 cm(3) for the left portion. The mean residual porencephalic volume was significantly smaller in the left frontal lobe (mean value 5.7 mL) than in the right frontal lobe (mean value 16.6 mL; P < 0.05). The mean residual porencephalic volume was significantly smaller than the tumor volume both in the left (P < 0.01) and in the right side (P < 0.05). CONCLUSION: The pterional-transsylvian approach provides two major advantages: first, it minimizes morbidity and mortality through an early neurovascular control and by limiting parenchymal damage as demonstrated by a quantitative analysis; second it is associated with low recurrence rate at a long-term follow-up.

Olfactory bulbectomy, but not odor conditioned aversion, induces the differentiation of immature neurons in the adult rat piriform cortex.

The piriform cortex layer II of young-adult rats presents a population of prenatally generated cells, which express immature neuronal markers, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX), and display structural characteristics of immature neurons. The number of PSA-NCAM/DCX expressing cells in this region decreases markedly as age progresses, suggesting that these cells differentiate or die. Since the piriform cortex receives a major input from the olfactory bulb and participates in olfactory information processing, it is possible that the immature neurons in layer II are affected by manipulations of the olfactory bulb or olfactory learning. It is not known whether these cells can be induced to differentiate and, if so, what would be their fate. In order to address these questions, we have performed unilateral olfactory bulbectomy (OBX) and an olfactory learning paradigm (taste-potentiated odor aversion, TPOA), in young-adult rats and have studied the expression of different mature and immature neuronal markers, as well as the presence of cell death. We have found that 14 h after OBX there was a dramatic decrease in the number of both PSA-NCAM and DCX expressing cells in piriform cortex layer II, whereas that of cells expressing NeuN, a mature neuronal marker, increased. By contrast, the number of cells expressing glutamate decarboxylase, isoform 67 (GAD67), a marker for interneurons, decreased slightly. Additionally, we have not found evidence of numbers of dying cells high enough to justify the disappearance of immature neurons. Analysis of animals subjected to TPOA revealed that this paradigm does not affect PSA-NCAM expressing cells. Our results strongly suggest that OBX can induce the maturation of immature neurons in the piriform cortex layer II and that these cells do not become interneurons. By contrast, these cells do not seem to play a crucial role in olfactory memory.

Re-evaluation of spontaneous regeneration of the lateral olfactory tract.

Spontaneous regeneration of the lateral olfactory tract (LOT) was re-evaluated in newborn rats using a fluorescent retrograde neuronal tracer as objective indicators of complete LOT transection. Complete LOT transection was evidenced by the loss of the white myelinated band characteristic for adult LOT and the total lack of retrograde neuronal labeling of mitral cells by Fast Blue that was injected during LOT transection. In completely LOT-transected young adult rats, mitral cells were retrogradely labeled consistently only by Fluoro-Gold that was injected into the olfactory cortex at the adult stage. Moreover, an anterograde neuronal tracer, biotinylated dextran amine (BDA), was demonstrated to pass from the neonatally LOT-transected bulb, through the transected retrobulbar site, towards the olfactory cortex, far caudally at a level near the optic chiasm. The regenerated structures lacked immunoreactivity for myelin basic protein and electron-dense myelinated axon bundles, and were also characterized by the thinness of the BDA+ terminal zone within the olfactory cortex and the lack of its caudal extension. Young adult rats subjected to unilateral bulbectomy contralateral to the neonatally LOT-transected side showed perfect ability to discriminate cycloheximide solution by olfaction. From these findings, we conclude that the spontaneously regenerated olfactory system is functional despite structural incompleteness.

Spontaneous recovery of the injured higher olfactory center in the terrestrial slug limax.

BACKGROUND: Of all organs and tissues in adult mammals, the brain shows the most limited regeneration and recovery after injury. This is one reason why treating neurological damage such as ischemic injury after stroke presents such a challenge. Here we report a novel mode of regeneration which the slug's cognitive center, the procerebrum, shows after surgical lesioning in the adult. It is well known that the land slug Limax possesses the capacity to demonstrate conditioned food aversion. This learning ability critically depends on the procerebrum, which is the higher olfactory center in the brain of the terrestrial mollusk. PRINCIPAL FINDINGS: In the present study, after a 1-month recovery period post-surgical lesioning of the procerebrum we investigated whether the brain of the slug shows recovery from damage. We found that learning ability, local field potential oscillation, and the number of cells in the procerebrum (PC) all recovered spontaneously within 1 month of bilateral lesioning of the PC. Moreover, neurogenesis was enhanced in the lesioned PC. However, memory acquired before the surgery could not be retrieved 1 month after surgery although the procerebrum had recovered from injury by this time, consistent with the notion that the procerebrum is the storage site of odor-aversion memory, or deeply involved in the memory recall process. SIGNIFICANCE: Our findings are the first to demonstrate that a brain region responsible for the associative memory of an adult organism can spontaneously reconstitute itself, and can recover its function following injury.

Olfactory ensheathing cell tumor with neurofibroma-like features: a case report and review of the literature.

A 32-year-old man had seizure attack since April 2008 and radiographic examination revealed a heterogeneous enhancing mass at the left subfrontal region. He underwent craniotomy for tumor removal on October 1, 2008. The tumor, which was grayish white with glistening appearance and rubbery consistency, was traced to the proximal part of left olfactory tract. Histopathological examination revealed a hypocellular tumor with dense hyalinization in most areas. The tumor cells had ovoid to elongate and often comma-shaped nucleus. Myxoid change of the stroma was apparent in places. Most of the tumor cells were immuno-reactive for S-100 protein. Staining for Leu 7 (CD57 or HNK-1) was negative. Bodian method illustrated many axons within the tumor. Ultrastructural study of the tumor cells showed features compatible with those of olfactory ensheathing cell. The tumor was designated as olfactory ensheathing cell tumor with neurofibroma-like features. There have been 14 nerve sheath tumors arising from the olfactory nerve reported in the literature; all of them had the morphology of schwannoma. Our case, which had the morphology simulating neurofibroma was the first of its kind to be recorded.

Olfactory groove meningiomas: approaches and complications.

Olfactory groove meningiomas (OGM) account for 4.5% of all intracranial meningiomas. We report 21 patients with OGMs. Tumors were operated on using three surgical approaches: bifrontal (7 patients), fronto-pterional (11 patients) and fronto-orbital (3 patients). Total tumor removal (Simpson Grade 1) was achieved in 13 patients and Simpson II in 8 patients. Perioperative mortality was 4.76%. The average size of the OGM was 4.3+/-1.1cm. The overall recurrence rate was 19%. We preferred to use the pterional approach, which provides quick access to the tumor with less brain exposure. It also allows complete drainage of cisternal cerebrospinal fluid, providing a good level of brain relaxation during surgery. However, for long, thin tumors, hemostasis can be difficult using this approach.

Solitary olfactory groove schwannoma.

Intracranial schwannomas that do not involve major cranial nerves in the posterior fossa are uncommon, especially if they are not associated with neurofibromatosis type II (NF-2). Subfrontal olfactory groove schwannomas are extremely rare. We report a cystic schwannoma arising from the olfactory groove in a 38-year-old Caucasian male who presented with headache, vomiting and visual impairment. We briefly review the pertinent literature, stress the distinctive clinical and neuroradiological findings and discuss the surgical planning and theories about the pathogenesis of schwannomas in this unusual location.

Wiring stability of the adult Drosophila olfactory circuit after lesion.

Neuronal wiring plasticity in response to experience or injury has been reported in many parts of the adult nervous system. For instance, visual or somatosensory cortical maps can reorganize significantly in response to peripheral lesions, yet a certain degree of stability is essential for neuronal circuits to perform their dedicated functions. Previous studies on lesion-induced neuronal reorganization have primarily focused on systems that use continuous neural maps. Here, we assess wiring plasticity in a discrete neural map represented by the adult Drosophila olfactory circuit. Using conditional expression of toxins, we genetically ablated specific classes of neurons and examined the consequences on their synaptic partners or neighboring classes in the adult antennal lobe. We find no alteration of connection specificity between olfactory receptor neurons (ORNs) and their postsynaptic targets, the projection neurons (PNs). Ablating an ORN class maintains PN dendrites within their glomerular borders, and ORN axons normally innervating an adjacent target do not expand. Likewise, ablating PN classes does not alter their partner ORN axon connectivity. Interestingly, an increase in the contralateral ORN axon terminal density occurs in response to the removal of competing ipsilateral ORNs. Therefore, plasticity in this circuit can occur but is confined within a glomerulus, thereby retaining the wiring specificity of ORNs and PNs. We conclude that, although adult olfactory neurons can undergo plastic changes in response to the loss of competition, the olfactory circuit overall is extremely stable in preserving segregated information channels in this discrete map.

Sensory mediation of female-male mounting in the rat: I. Role of olfactory cues.

Previous research has shown that olfactory cues mediate the mounting of female rats by male or other female rats. The present study examined whether olfactory cues might mediate the mounting of castrated, sexually inactive male rats by sexually receptive female rats (female-male mounting, or FMM). The effects of olfactory impairment, created by either olfactory bulbectomy (OBx) or olfactory occlusion (OOc), on FMM were investigated. Ovariectomized, hormone-primed female rats were given either OBx (OBx+) or sham (OBx-) surgeries. OBx+ females did not engage in any FMM after surgery, whereas sham-operated females continued to mount at baseline levels. This effect was replicated using OOc, a reversible form of olfactory impairment that involves the cannulation of the nasal cavity with a flexible tube. Females were either given the OOc surgery (OOc+), the OOc surgery with the tube removed immediately after placement (OOc-), or sham surgery in which the animal was only anesthetisized. OOc+ females, like OBx+ females, did not display FMM, whereas both control groups continued to mount at baseline levels. The effect of prior experience with FMM was also examined. Females were given either 0 or 5 encounters with castrated males prior to OBx+, OOc+, or OOc- surgeries. OBx+ and OOc+ females did not mount, regardless of prior mounting experience. These data indicate that the olfactory sense is a prime mediator of FMM, and that prior mounting experience does not offset the disruption of FMM caused by the elimination of olfactory cues.

Microsurgical anatomic features of the olfactory nerve: relevance to olfaction preservation in the pterional approach.

OBJECTIVE: The pterional approach represents the standard approach for most lesions of the anterior and middle cranial fossa. It requires some degree of frontal lobe retraction, which may result in temporary or permanent damage of olfaction because of nerve avulsion or mechanical compression. The purpose of this study, based on microanatomic dissection of human cadaveric specimens, was to review the microsurgical anatomic features of the nerve and suggest operative nuances that may contribute to reducing the rate of postoperative olfactory dysfunction. METHODS: Twenty olfactory nerves and tracts were examined in 10 human cadaveric heads obtained from three fresh and seven formalin-fixed adult cadavers. A standard pterional craniotomy was performed. The olfactory nerve was dissected from its arachnoidal envelopes and then mobilized for an average length of 30 mm (range, 25-35 mm). RESULTS: The possible retraction of the frontal lobe was 10 to 15 mm. More retraction invariably resulted in nerve disruption. CONCLUSION: The standard sylvian and basal cistern opening may be insufficient to guarantee preservation of olfactory function. Early identification and arachnoidal dissection of the nerve may reduce the rate of olfaction compromise. The opening of the subarachnoidal space should be performed in a proximal-to-distal manner to allow early visualization of the olfactory bulb and its dissection. The arachnoidal dissection should be performed with sharp instruments, avoiding any traction on the posterior portion of the olfactory tract. Any direct retractor compression should also be avoided to spare the microvasculature lying on the dorsal surface of the nerve.

The olfactory bulbectomised rat as a model of depression.

Bilateral olfactory bulbectomy results in changes in behavior, and in the endocrine, immune and neurotransmitter systems, that simulates many of those seen in patients with major depression. The olfactory system in the rat forms a part of the limbic region in which the amygdala and hippocampus contribute to the emotional and memory components of behavior. However, the loss of olfaction alone, which results from bulbectomy, is not the major factor that contributes to the behavioral abnormalities as peripherally induced anosmia does not cause the same behavioral changes. Thus it would appear that bulbectomy causes a major dysfunction of the cortical-hippocampal-amygdala circuit that underlies the behavioral and other changes. These neuroanatomical areas also seem to be dysfunctional in the patient with major depression. Chronic, but not acute, administration of antidepressants largely corrects most the behavioral, endocrine, immune and neurotransmitter changes that occur following bulbectomy. Thus the olfactory bulbectomized rat is not only a model for detecting antidepressant activity but also one for exploring the inter-relationships between these systems that are also dysfunctional in patients with major depression.