Cost-Effectiveness Analysis of 68Ga-DOTATATE PET/MRI in Radiotherapy Planning in Patients with Intermediate-Risk Meningioma.

BACKGROUND AND PURPOSE: While contrast-enhanced MR imaging is the criterion standard in meningioma diagnosis and treatment response assessment, gallium 68Ga-DOTATATE PET/MR imaging has increasingly demonstrated utility in meningioma diagnosis and management. Integrating 68Ga-DOTATATE PET/MR imaging in postsurgical radiation planning reduces the planning target volume and organ-at-risk dose. However, 68Ga-DOTATATE PET/MR imaging is not widely implemented in clinical practice due to higher perceived costs. Our study analyzes the cost-effectiveness of 68Ga-DOTATATE PET/MR imaging for postresection radiation therapy planning in patients with intermediate-risk meningioma. MATERIALS AND METHODS: We developed a decision-analytical model based on both recommended guidelines on meningioma management and our institutional experience. Markov models were implemented to estimate quality-adjusted life-years (QALY). Cost-effectiveness analyses with willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY were performed from a societal perspective. Sensitivity analyses were conducted to validate the results. Model input values were based on published literature. RESULTS: The cost-effectiveness results demonstrated that 68Ga-DOTATATE PET/MR imaging yields higher QALY (5.47 versus 5.05) at a higher cost ($404,260 versus $395,535) compared with MR imaging alone. The incremental cost-effectiveness ratio analysis determined that 68Ga-DOTATATE PET/MR imaging is cost-effective at a willingness to pay of $50,000/QALY and $100,000/QALY. Furthermore, sensitivity analyses showed that 68Ga-DOTATATE PET/MR imaging is cost-effective at $50,000/QALY ($100,000/QALY) for specificity and sensitivity values above 76% (58%) and 53% (44%), respectively. CONCLUSIONS: 68Ga-DOTATATE PET/MR imaging as an adjunct imaging technique is cost-effective in postoperative treatment planning in patients with meningiomas. Most important, the model results show that the sensitivity and specificity cost-effective thresholds of 68Ga-DOTATATE PET/MR imaging could be attained in clinical practice.

Prognostic Implications of Gadolinium Enhancement of Skull Base Chordomas.

BACKGROUND AND PURPOSE: Skull base chordomas often demonstrate variable MR imaging characteristics, and there has been limited prior research investigating the potential clinical relevance of this variability. The purpose of this retrospective study was to assess the prognostic implications of signal intensity on standard imaging techniques for the biologic behavior of skull base chordomas. MATERIALS AND METHODS: Medical records were retrospectively reviewed for 22 patients with pathologically confirmed skull base chordomas. Clinical data were recorded, including the degree of surgical resection, the presence or absence of radiation therapy, and time to progression/recurrence of the tumor or time without progression/recurrence of the tumor following initial treatment. Pretreatment imaging was reviewed for the presence or absence of enhancement and the T2 signal characteristics. Tumor-to-brain stem signal intensity ratios on T2, precontrast T1, and postcontrast T1 spin-echo sequences were also calculated. Statistical analysis was then performed to assess correlations between imaging characteristics and tumor progression/recurrence. RESULTS: Progression/recurrence of skull base chordomas was seen following surgical resection in 11 of 14 (78.6%) patients with enhancing tumors and in zero of 8 patients with nonenhancing tumors. There was a statistically significant correlation between skull base chordoma enhancement and subsequent tumor progression/recurrence (P < .001), which remained significant after controlling for differences in treatment strategy (P < .001). There was also a correlation between postcontrast T1 signal intensity (as measured by postcontrast T1 tumor-to-brain stem signal intensity ratios) and recurrence/progression (P = .02). While T2 signal intensity was higher in patients without tumor progression (median tumor-to-brain stem signal intensity ratios on T2 = 2.27) than in those with progression (median tumor-to-brain stem signal intensity ratios on T2 = 1.78), this association was not significant (P = .12). CONCLUSIONS: Enhancement of skull base chordomas is a risk factor for tumor progression/recurrence following surgical resection.

Endoscopic management of a rare case of nasal glioma in Meckel's cave in an adult: case report.

BACKGROUND: Nasal glioma or glial heterotopia is a rare embryologic anomaly that heralds its presence shortly after birth or in childhood. Nasal glioma in an adult is very rare, often asymptomatic and the occurrence of nasal glioma in Meckel's cave in an adult has not been previously reported. CASE REPORT: The authors encountered a case of an incidentally diagnosed Meckel's cave nasal glioma in a 40-year-old male which was successfully excised by an endonasal endoscopic transmaxillary transpterygoid approach. CONCLUSION: The occurrence of a nasal glioma in Meckel's cave an adult is very rare. Considering the deep skull base location, endonasal endoscopic surgery provides a minimal access technique to reach this location with excellent results.

Combined supraciliary and endoscopic endonasal approach for resection of frontal sinus mucoceles: technical note.

OBJECTIVE: Mucoceles are progressive, slow-growing lesions of the paranasal sinuses that, left untreated, can erode into surrounding structures. Complete obliteration and exenteration of the frontal sinus via a bicoronal skin incision and frontal craniotomy is the standard neurosurgical approach to treat these lesions. TECHNIQUE: We describe two patients who underwent a combined supraciliary "keyhole" craniotomy and endonasal endoscopic resection of mucoceles with frontal sinus obliteration. The technique takes advantage of a smaller incision, while preserving adequate visualization and the ability for surgical instrumentation. Through the craniotomy, the frontal sinus mucosa is fully exenterated, the posterior table of the sinus is removed to establish communication with the intracranial space, and the nasal frontal ducts are packed with autologous tissue. The endoscopic endonasal route allows a minimally invasive access to the frontal nasal duct to ensure its blockage from the intracranial compartment. Additionally, the endoscope can be used from above through the supraciliary approach to allow for contralateral frontal sinus exposure and mucosal exenteration. CONCLUSION: The combined supraciliary-endoscopic endonasal approach provides a minimally invasive access for the treatment of sinonasal disease with frontal sinus mucoceles that invade the intracranial cavity.

Three-dimensional neurostereoendoscopy: subjective and objective comparison to 2D.

Neuroendoscopic procedures, particularly transnasal skull-base procedures, are currently performed with 2D endoscopes that lack stereoscopic vision and depth of field. In principal, 3D vision should be preferable to the operating surgeon, but the previously existing systems have not been adopted. We evaluated a novel 3D endoscope to compare with 2D endoscopy. 33 neurosurgeons and skull-base otolaryngologists were recruited, and randomized to complete two runs of a task-based simulator paradigm using 2D and/or 3D visualization. After the two trials, each subject completed a questionnaire assessing professional demographics and preferences for visualization. The task paradigm had objective endpoints that measured speed, efficiency, and error rates. 75% of respondents preferred 3D endoscopy, and 87.5% determined that 3D visualization either somewhat or greatly helped with the assigned tasks. In the second run, subjects using 3D demonstrated a significantly higher efficiency than subjects using 2D (p=0.04). Subjects' speed and efficiency improved significantly when moving from 2D to 3D, and speed and efficiency improved significantly from Run 1 to Run 2 for 3D visualization. Subjective and objective outcomes support the utility of 3D visualization for neuroendoscopic techniques. Visualization that provides real-time, high-resolution binocular depth perception has a role in endoscopic skull base surgery and other neuroendoscopic procedures.

Combined simultaneous endoscopic transsphenoidal and endoscopic transventricular resection of a giant pituitary macroadenoma.

Intrasellar and sellar-suprasellar adenomas are generally removed through a transsphenoidal approach. Giant adenomas with significant suprasellar extension often require a craniotomy or combined "above and below" approach. The use of endoscopes has increased the visualization capacity of the transsphenoidal route and made these surgeries less invasive. In this report, we describe a novel combination of the endoscopic transsphenoidal approach with the endoscopic transventricular approach to remove a giant pituitary macroadenoma extending into the third and lateral ventricles. The tumor was initially removed via an endoscopic transnasal transsphenoidal, transtuberculum, transplanum approach. A second endoscope was then advanced into the lateral ventricle through a pre-coronal burr hole to assist in mobilizing the tumor and assure a complete resection. Multilayer closure and a ventriculo-peritoneal shunt were performed to insure a watertight seal of the skull base. Giant pituitary adenomas have traditionally been removed with staged or combined transsphenoidal and transcranial approaches. We describe the successful implementation of a minimal access endoscopic combined extended transsphenoidal and transventricular approach that avoids craniotomy and brain retraction.

Reassessment: neuroimaging in the emergency patient presenting with seizure (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To reassess the value of neuroimaging of the emergency patient presenting with seizure as a screening procedure for providing information that will change acute management, and to reassess clinical and historical features associated with an abnormal neuroimaging study in these patients. METHODS: A broad-based panel with topic expertise evaluated the available evidence based on a structured literature review using a Medline search from 1966 until November 2004. RESULTS: The 15 articles meeting criteria were Class II or III evidence since interpretation was not masked to the patient's clinical presentation; most were series including 22 to 875 patients. There is evidence that for adults with first seizure, cranial CT will change acute management in 9 to 17% of patients. CT in the emergency department for children presenting with first seizure will change acute management in approximately 3 to 8%. There is no clear difference between rates of abnormal emergent CT for patients with chronic seizures vs first. Children <6 months presenting with seizures have clinically relevant abnormalities on CT scans 50% of the time. Persons with AIDS and first seizure have high rates of abnormalities, and CNS toxoplasmosis is frequently found. Abnormal neurologic examination, predisposing history, or focal seizure onset are probably predictive of an abnormal CT study in this context. CONCLUSIONS: Immediate noncontrast CT is possibly useful for emergency patients presenting with seizure to guide appropriate acute management especially where there is an abnormal neurologic examination, predisposing history, or focal seizure onset.

Strategies for reoperation after comprehensive epilepsy surgery.

OBJECT: Prior reports of seizure control following reoperation for failed epilepsy surgery have shown good results. These studies included patients who presented during the era preceding magnetic resonance (MR) imaging, and the patients were often not monitored intracranially or underwent subtotal hippocampal resections. In this study, the authors hypothesized that reoperation for recurrent seizures following a more comprehensive initial workup and surgery would not yield such good results. METHODS: The authors examined a consecutive series of patients who underwent two operations at Yale-New Haven Hospital for medically intractable epilepsy and in whom there was a minimum of 1-year follow up after the second surgery. All patients were evaluated and treated according to a standard protocol, including preoperative MR imaging, a low threshold for invasive monitoring, and a radical amygdalohippocampectomy when indicated. Twenty-seven patients were identified (five with mesial temporal sclerosis, 20 with neocortical disease, and two with multifocal sites of seizure onset) of whom six (22%) underwent intentionally palliative second surgery (corpus callostomy or placement of a vagus nerve stimulator [VNS]). Of the remaining 21 patients, only four (19%) became seizure free after a second resective operation. The most common causes of treatment failure were dual pathology, recurrent tumor, limited resection to preserve function, widespread developmental abnormalities, and electrographic sampling error. Successful outcomes resulted from removal of recurrent tumors, completion of a functional hemispherectomy, or repeated invasive monitoring to correct a sampling error. Five (83%) of the six intentionally palliative second operations resulted in more than a 50% decrease in seizure frequency. CONCLUSIONS: If an aggressive preoperative evaluation and surgical resection are performed, reoperation for recurrent seizures has a much lower likelihood of cure than previously reported. Intentionally palliative surgery such as placement of a VNS unit may be considered for patients in whom the initial operation fails to decrease seizure frequency.

In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex.

The population of neurons participating in an epileptiform event varies from moment to moment. Most techniques currently used to localize epileptiform events in vivo have spatial and/or temporal sampling limitations. Here we show in an animal model that optical imaging based on intrinsic signals is an excellent method for in vivo mapping of clinically relevant epileptiform events, such as interictal spikes, ictal onsets, ictal spread and secondary homotopic foci. In addition, a decrease in the optical signal correlates spatially with a decrease in neuronal activity recorded from cortex surrounding an epileptic focus. Optical mapping of epilepsy might be a useful adjunct in the surgical treatment of neocortical epilepsy, which critically depends on the precise localization of intrinsically epileptogenic neurons.

Extended frontal approach with bilateral orbitofrontoethmoidal osteotomies for removal of a giant extracranial schwannoma in the nasopharynx, sphenoid sinus, and parapharyngeal space.

BACKGROUND: Although parapharyngeal schwannomas are not uncommon, schwannomas of the nasopharynx and paranasal sinuses are rare lesions. In the absence of intracranial extension, they are usually removed with transantral, lateral rhinotomy or more complex transfacial approaches. CASE DESCRIPTION: We report a 24-year-old patient with a giant benign schwannoma involving the superior parapharyngeal space, pterygopalatine fossa, nasopharynx, and sphenoid sinus with erosion into the clivus that was removed with an extended frontal approach including bilateral orbitofrontoethmoidal osteotomies. CONCLUSION: The advantages of the extended subfrontal over more standard transfacial approaches for lesions in this location include the early dissection of critical neural structures, preserving cosmetics and facilitating management of an inadvertent cerebrospinal fluid leak.

Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.

OBJECTIVE: Intracranial plasmacytomas are rare lesions that can arise from the calvarium, dura, or cranial base and exhibit a benign course unless associated with myeloma. Attention has recently been focused on the role of the cell adhesion molecules CD56 and CD31 in the pathogenesis of myeloma. No such information is available for intracranial plasmacytomas and myeloma-associated lesions. METHODS: We investigated the relationship between CD56 and CD31 expression, intracranial location, and progression to myeloma for a series of nine intracranial plasmacytomas (three dural, one calvarial, and five cranial base lesions). These parameters were also correlated with proliferation indices, as assessed by MIB-1 immunostaining of the histological sections. A single pathologist (AO) performed immunohistochemical analyses and reviewed all slides. RESULTS: Intracranial plasmacytomas presented more commonly in female patients (89%). The three dural lesions were CD56- and CD31-negative and exhibited MIB-1 staining of less than 10%; no patient developed myeloma or recurrence. Of the five cranial base lesions, three were CD56-positive, none was CD31-positive, and two exhibited MIB-1 labeling of more than 45%, with plasmablastic morphological features. Compared with other intracranial plasmacytomas, five of five patients with cranial base lesions developed bone marrow biopsy-proven myeloma (P < 0.05) within 8 months. The calvarial lesion was CD56- and CD31-positive, and the patient developed myeloma soon after diagnosis. Both of the two highly proliferative plasmablastic lesions recurred, one after gross total resection without radiotherapy and the other after a biopsy and 2000-cGy radiotherapy. CONCLUSION: Among intracranial plasmacytomas, cranial base location was the strongest predictor of the development of multiple myeloma. Expression of the cell adhesion molecules CD31 and CD56 was not predictive of outcome. Extramedullary dural-based lesions were CD56-negative and were not associated with myeloma. A high proliferation index and plasmablastic morphological features were predictive of a short time to recurrence and aggressive behavior. We recommend 4050- to 5040-cGy fractionated radiotherapy for all intracranial plasma cell neoplasms and gross total resection for non-cranial base lesions.

Do reactive post-resection "injury" spikes exist?

PURPOSE: New post-resection spikes on electrocorticography (ECoG) after lesionectomy in patients with seizures may represent residual epileptogenic tissue or presumed reactive injury spikes. We investigated the existence of post-resection injury spikes by eliminating the possibility of residual epileptogenic tissue. METHODS: Preresection and post-resection ECoG was performed on seven patients with an intra-axial neocortical tumor (glioblastoma multiforme or metastasis) and no history of seizures. All tumors were gross-totally resected. RESULTS: The mean age of the patients was 59 years. The tumor location was frontal in four patients, parietal in two, and temporal in one. Two patients had preresection spikes with an average rate of 68 spikes/min that disappeared after surgery. Two different patients had new post-resection spikes, with an average firing rate of 4 spikes/min, despite normal preresection ECoG. In one of these patients, the new spikes were superimposed over a burst suppression pattern. Neither patient developed seizures after surgery. CONCLUSIONS: Surgical irritation of the neocortex is sufficient to produce reactive post-resection epileptogenic discharges surrounding an intra-axial neocortical tumor even in the absence of preoperative seizures and spikes. Injury spikes fire at a slow rate and are not predictive of clinical seizures.

Intramedullary ependymomas: clinical presentation, surgical treatment strategies and prognosis.

Intramedullary ependymomas are rare tumors but comprise the majority of intramedullary glial neoplasms in the adult. These tumors are benign, slow-growing lesions which are optimally treated with gross-total surgical resection without adjuvant therapy. This objective can be attained safely in a majority, of patients. Post-operative functional outcome is related to pre-operative functional status. Hence, early diagnosis, prior to symptomatic progression, is critical to the successful treatment of these tumors. Adjuvant therapy is indicated for the rare malignant or disseminated tumor or following sub-total resection.

Non-neoplastic intramedullary pathology. Diagnostic dilemma: to Bx or not to Bx.

There are several non-neoplastic lesions which may mimic intramedullary spinal cord neoplasm in their radiographic and clinical presentation. These can be classified as either infectious (TB, fungal, bacterial, parasitic, syphilis, CMV, HSV) and non-infectious (sarcoid, MS, myelitis, ADEM, SLE) inflammatory lesions, idiopathic necrotizing myelopathy, unusual vascular lesions (amyloid, infarct, isolated intramedullary vascular lesions) and radiation myelopathy. Although biopsy may be indicated in many cases, the mistaken diagnosis of intramedullary neoplasm can often be eliminated pre-operatively.

Asymmetry of neuronal activity during extracellular microelectrode recording from left and right human temporal lobe neocortex during rhyming and line-matching.

Recordings of neuronal activity in humans have identified few correlates of the known hemispheric asymmetries of functional lateralization. Here, we examine single-unit activity recorded from both hemispheres during two delayed match-to-sample tasks that show strong hemispheric lateralization based on lesion effects; a line-matching (LM) task related to the right hemisphere, and a rhyming (RHY) task related to the left. Nineteen neuronal populations were recorded with extracellular microelectrodes from the left temporal neocortex of 11 awake patients, and 18 from the right in 9 patients during anterior temporal lobectomy for complex partial seizures under local anesthesia. All subjects were left hemisphere dominant for language. Twelve (32%) populations exhibited statistically significant changes in activity at p <.05. Although changes in firing frequency were recorded from both hemispheres during both tasks, the RHY task elicited changes in activity several hundred milliseconds earlier on the left side than on the right. The LM task, on the other hand, induced changes earlier on the right side than on the left. Both hemispheres contained units active during verbal responses regardless of which behavior elicited the response. Our results indicate that cerebral dominance is reflected in earlier neuronal activity in the anterior temporal lobe during tasks lateralized to that hemisphere.

Quadrigeminal variant of perimesencephalic nonaneurysmal subarachnoid hemorrhage.

OBJECTIVE: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSH) is a benign entity with a low risk of rebleeding. The most widely accepted definition emphasizes the presence of blood ventral to the midbrain or pons on early computed tomography. We sought to determine the frequency of PNSH with blood centered in the quadrigeminal cistern. METHODS: We reviewed a prospectively collected database of all patients admitted to our institution over a 2.5-year period with subarachnoid hemorrhage (SAH) and identified PNSH patients from early computed tomographic scans and negative four-vessel angiograms. RESULTS: Of 220 SAH patients, we identified 9 with PNSH. Two (22%) of these patients had SAH centered in the quadrigeminal cistern without pretruncal blood, negative repeat angiograms, and an uncomplicated clinical course. CONCLUSION: Quadrigeminal SAH is a variant of PNSH that is not well described in the literature. It may comprise up to one-fifth of PNSH cases and carries a similar benign prognosis.

Estrogen and progesterone receptor-negative T11 vertebral hemangioma presenting as a postpartum compression fracture: case report and management.

OBJECTIVE AND IMPORTANCE: Pregnancy-related vertebral hemangioma compressive myelopathy is a rare occurrence that tends to arise in the upper thoracic and lower cervical spine, peaks during the third trimester, and remits after parturition. Whether corticosteroid receptors play a role in the pathogenesis of these lesions is unknown. Most of these lesions have been managed with posterior decompression. CLINICAL PRESENTATION: A 29-year-old woman presented with acute-onset lower-extremity weakness and sensory loss immediately after parturition. INTERVENTION: We used a retropleural approach for anterior decompression and fusion, followed by radiation therapy. Immunohistochemical analysis of estrogen and progesterone receptor expression was performed. CONCLUSION: We report an unusual case of lower thoracic postpartum vertebral hemangioma compressive myelopathy caused by a parturition-related compression fracture. Results of tests for corticosteroid receptors were negative, which implicated a hemodynamic rather than hormonal cause for disease progression.

Involvement of cajal-retzius neurons in spontaneous correlated activity of embryonic and postnatal layer 1 from wild-type and reeler mice.

Cajal-Retzius (CR) cells are a transient population of neurons in developing cortical layer 1 that secrete reelin, a protein necessary for cortical lamination. Combining calcium imaging of cortical hemispheres and cross-correlation analysis, we previously found spontaneous correlated activity among non-CR neurons in postnatal rat layer 1. This correlated activity was blocked by GABAergic and glutamatergic antagonists, and we postulated that it was controlled by CR cells. We now investigate the correlated activity of embryonic and postnatal layer 1 in wild-type and reeler mice, mutant in the production of reelin. We find that mouse layer 1 also sustains patterned spontaneous activity and that CR cells participate in correlated networks. These networks are present in embryonic marginal zone and are blocked by GABAergic and glutamatergic antagonists. Surprisingly, network activity in reeler mice displays similar characteristics and pharmacological profile as in wild-type mice, although small differences are detected. Our results demonstrate that the embryonic marginal zone has correlated spontaneous activity that could serve as the scaffold for the development of intracortical connections. Our data also suggest that reelin does not have a major impact in the development of specific synaptic circuits in layer 1.

Function-specific high-probability "nodes" identified in posterior language cortex.

PURPOSE: Posterior, "Wenicke's," language areas have a high degree of between-subject variability, as shown by electrical-stimulation mapping. We investigated the possibility of an organized structure in the distribution of posterior language areas. METHODS: Extraoperative subdural grid stimulation was performed on 67 left hemisphere-dominant patients before resective epilepsy surgery during counting, naming, and reading. Intersubject-averaged language maps were generated in which stimulation disrupted only one language function and not the others, or combinations of language functions. RESULTS: Language sites, although highly variable between subjects, were not organized randomly and appeared to be arranged into several focal, non-contiguous, higher probability "nodes" devoted to different aspects of language processing. Speech-arrest sites were concentrated in classic Wernicke's area. Areas where stimulation induced only reading errors were found in the posterior middle temporal gyrus and the inferior parietal lobule. These regions may correspond with an orthographic input lexicon. Areas eliciting only naming errors were found in the posterior inferior temporal gyrus extending into the mid-middle temporal gyrus and may represent a visual-representation input lexicon. Sites where stimulation elicited errors in both naming and reading were more variable in location than sites devoted to only one function, extended farther anteriorly along the temporal neocortex, and may correspond with a semantic lexicon. CONCLUSIONS: The existence of high-probability nodes in posterior language cortex supports a modality-specific modular architecture and the possibility of a conserved, universal structure.