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.

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.

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.

Networks of coactive neurons in developing layer 1.

Spontaneous neuronal activity plays an important role in the development of cortical circuitry, yet its spatio-temporal dynamics are poorly understood. Cajal-Retzius (CR) neurons in developing layer 1 are necessary for correct cortical lamination and are strategically located to coordinate early circuit activity. To characterize the spontaneous activity of CR and other layer 1 neurons during cortical development, we imaged calcium transients in populations of layer 1 neurons in hemispheres and slices from postnatal rat somato-sensory neocortex. The spontaneous activity in layer 1 had complex spatio-temporal patterns. Groups of non-CR cells showed synchronous activations and formed networks of correlated neurons superimposed in the same territory. Correlated activity among non-CR cells was mediated by a depolarizing effect of GABA and was modulated by glutamate, probably released by CR cells. Our findings demonstrate that developing layer 1 can sustain complex patterns of correlated activity and reveal a circuit mechanism that can mediate this patterned activity.

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.

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.

The effects of 0.1 and 1.0 per cent erythrocytes and hemolysis on serum chemistry values.

Changes in serum chemistry values as a result of incomplete removal of erythrocytes and in vitro hemolysis during the preparative process have been studied. Two levels of contamination, corresponding to removal of 99% and 99.9% of the erythrocytes, were used to examine the effects of both hemolyzed and intact cells. Forty chemical procedures and methods were considered. Serum LDH values were most strongly affected by hemolyzed erythrocytes. Potassium, creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, and iron showed smaller but significant effects due to the presence of 1% hemolyzed cells, with lesser effects observed at the 0.1% level. The presence of non-hemolyzed cells at either level did not significantly alter chemistry results.

A proposed blind routine quality control system for multichannel analyzers.

A blind quality control system using a special type of commercial reference serum is described. As packaged, the product contains six pools of analyzed reference sera with vials identified by coded numbers. The test constituents in the pools cover the range of multichannel analyzers in a random manner, i.e., each pool contains constituents in the low, normal and elevated ranges. As specific pools are not identified, and the analyst is unaware of the expected values for each constituent, results collected for quality control purposes are unbiased, i.e., free of conscious or unconscious editing. Data analysis in the proposed system is by least-squares technics. During an eight-week period, performance was studied using the standard error of the estimate to evaluate precision and the slope of the regression line to evaluate accuracy on the SMA and Mark X instruments. As an empirical comparison, the data are expressed as relative errors and precision and accuracy of analyzer performance evaluated as mean and standard deviation. The proposed regression analysis-based technic has the advantage of simultaneously evaluating linearity, as well as checking accuracy and precision over the total dynamic range of the instrument by use of a series of related serum pools.

Changes in serum chemical values as a result of prolonged contact with the clot.

Changes in serum biochemical values as a function of serum-clot contact time were investigated. Time extending to 48 hours were studied by drawing sets of six specimens from ten subjects. Glucose, lactic dehydrogenase, the transaminases, potassium, alkaline phosphatase, and iron showed significant changes. Other common tests, including electrophoretic separations, were not affected.

Assessment of the serum separator tube as an intermediate storage device within the laboratory.

An integral blood-drawing-serum separator tube, (SST) is evaluated for use as an in-laboratory serum storage device. Sera stored in the SST were compared with paired controls that were specimens from the same subjects stored in closed culture tubes. Eighty-six serum chemistry determinations showed no clinically significant change as a result of 48 hours of storage in the original blood-drawing tubes. Storage of serum in this manner provides the laboratory with specimens for reanalysis or additional analyses while eliminating manipulative steps, including serum removal, tube relabeling, and intertube transfers, and reducing errors due to misidentification and/or contamination.

Cerebral lateralization of neuronal activity during naming, reading and line-matching.

Changes in human right or left temporal cortical neuronal activity during language and visuospatial tasks were investigated during craniotomy under local anesthesia for medically intractable epilepsy in patients known to be left dominant for language based on preoperative intracarotid amobarbital perfusion testing. Extracellular recordings were obtained from 57 neuronal populations (26 from the left hemisphere) in the superior and middle temporal gyri of 34 patients. Frequency of activity was compared during over and silent object naming, word reading and line-matching. Although all recordings were from the cortex not essential for language, statistically significant changes in activity during these tasks were identified in 49% of the populations. Most populations showed significant changes to only one of the tasks, indicating discrete neural networks for reading and naming. Nearby neuronal populations recorded by the same microelectrode usually had different behavioral correlates. There were no significant differences in the proportion of neurons changing activity with language or spatial measures between right (non-dominant) or left (dominant) temporal lobes. Left superior and middle temporal gyrus populations, however, demonstrated significant early reductions in activity during overt or silent naming, while right middle temporal gyrus recordings showed significant early increased activity only during overt naming. Although reading measures elicited more activity from the non-dominant temporal lobe, early reductions in activity were recorded exclusively from the dominant side. Visuospatial tasks evoked changes in neuronal frequency predominantly in the middle temporal gyrus, and during one of these tasks, significant later increases in activity were present bilaterally. Our results indicate that the functional lateralization of cognitive behaviors may depend less on the anatomic location of the associated neuronal activity than on the neurophysiologic characteristics of that activity.

Perimesencephalic nonaneurysmal subarachnoid hemorrhage: review of the literature.

OBJECTIVE: A critical review of the literature on the incidence, presentation, diagnosis, and prognosis of perimesencephalic nonaneurysmal subarachnoid hemorrhage. METHODS: Review of the relevant literature. CONCLUSION: The importance of early computed tomography (< 3 d), anatomy of the perimesencephalic and neighboring cisterns, and adequate four-vessel angiography are discussed. Treatment strategies, including the avoidance of repeated angiographic studies and surgical exploration, are presented.

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.

Unusual intramedullary vascular lesion: report of two cases.

OBJECTIVE AND IMPORTANCE: Spinal arteriovenous malformations have been divided by location into dural (Type I), intramedullary glomus (Type II), juvenile (Type III), and perimedullary direct arteriovenous fistulae (Type IV). We report two cases of an unusual intramedullary proliferation of hyalinized capillaries that do not fit into any of these categories. CLINICAL PRESENTATION: A 27-year-old woman and a 62-year-old man presented with subacute progressive caudal myelopathy. Magnetic resonance imaging revealed focal spinal cord enlargement, high signal on T2-weighted images, and patchy enhancement with gadolinium consistent with tumor. No serpentine flow voids were visualized on the surface of the spinal cord. Spinal angiography revealed nothing abnormal. No abnormal vasculature was grossly visible on open biopsy. Histological examination of the tissue specimens revealed a proliferation of capillary-sized vessels with varying degrees of vascular wall changes ranging from endothelial hyperplasia to concentric hyalinization, suggesting ongoing evolution of the lesion. Surrounding neural tissue demonstrated ischemic changes characterized by myelin and axonal loss and astrocytosis but no necrosis. INTERVENTION: Patients were treated with chronic anticoagulation, which seemed to slow, but not halt, symptomatic disease progression. CONCLUSION: Although the pathological substrate seems to be an acquired intramedullary vascular lesion characterized primarily by capillary proliferation, the cause of this lesion is unknown. This disease differs from Foix-Alajouanine syndrome and subacute necrotizing myelopathy by an absence of abnormal surface vessels and a lack of intramedullary necrosis. The histological findings are reminiscent of the process that occurs in the kidney and various end organs from long-standing mild to moderate elevations in blood pressure or chronic diabetes. Tissue ischemia may result from luminal obstruction by severe hyalinization and thrombosis. Because the natural history of this disease is unknown, it is unclear whether anticoagulation slowed disease progression.

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.

Functional magnetic resonance imaging localization of ictal onset to a dysplastic cleft with simultaneous sensorimotor mapping: intraoperative electrophysiological confirmation and postoperative follow-up: technical note.

INTRODUCTION: Although technically challenging to obtain, ictal functional magnetic resonance imaging has been used to localize ictal onset zones in a small number of patients. We used this technique to demonstrate the inherent epileptogenicity of dysplastic cortex. METHODS: We present a 16-year-old female patient with intractable left-sided sensorimotor seizures and a congenital dysplastic cleft lying along the right rolandic fissure. Preoperative functional magnetic resonance imaging (blood oxygen level-dependent sequence, 1.5 T) localized the motor and sensory cortices to the anterior border of the cleft. During a speech activation run, the patient experienced a 20-second seizure. Initial activation was seen within the dysplastic cortex along the deep posterior margin of the cleft. Intraoperative median nerve stimulation produced a distinct N20/P20 wave inversion over the dysplastic cleft. Stimulation mapping performed with the patient awake confirmed the location of the sensorimotor cortex on the anterior border of the cleft, and preresection electrocorticography identified abundant interictal spikes along the posterior border after opening the cleft. RESULTS: After surgical resection of the dysplastic cortex, the patient exhibited transient minimal weakness and mild neglect, which resolved within 1 week. Two years after surgery, she was neurologically intact and seizure-free. CONCLUSION: This study used functional magnetic resonance imaging to demonstrate the inherent epileptogenicity of dysplastic cortex and to simultaneously map ictal and functional cortex. The N20 wave inversion can be a useful intraoperative tool for identifying the central sulcus (or its equivalent), even in the presence of abnormal cortical architecture.

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.

The predictive value of intraoperative electrocorticography in resections for limbic epilepsy associated with mesial temporal sclerosis.

OBJECTIVE: Prior studies on the predictive value of intraoperative electrocorticography (ECoG) have been performed on heterogeneous groups of patients with both temporal and extratemporal interictal spikes, lesional and nonlesional pathological findings, and variably extensive resections by different surgeons. METHODS: We performed both pre- and postresection intraoperative ECoG on 29 consecutive patients with medial temporal lobe epilepsy (17 left-sided) who underwent standard nontailored resections by one surgeon (RRG). All patients had only temporal interictal spikes (six bitemporal) and mesial temporal sclerosis diagnosed by preoperative magnetic resonance imaging and confirmed by pathological examination of resected tissue. RESULTS: After a mean follow-up of 24.8 months, there were 15 (52%) patients who were seizure-free, 6 (21%) who were seizure-free except for auras, and 8 (28%) who had any seizure after the 1st postoperative month. Fourteen patients (48%) had active interictal discharges outside the area of planned resection revealed by preresection ECoG. Neither the presence of these spikes nor their mean frequency correlated with seizure outcome. Eleven patients (38%) had residual spike discharges after resection, and 18 patients (62%) had new spikes revealed by the postresection ECoG. Neither of these findings nor the mean spike frequency of residual or new spikes related to seizure outcome. Persistent spikes increased in frequency after resection in all outcome groups. CONCLUSIONS: Electrocorticographic monitoring of interictal epileptiform activity intraoperatively is not useful in the surgical treatment of patients undergoing standard resection for medial temporal lobe epilepsy with magnetic resonance imaging evidence of mesial temporal sclerosis.

Supratentorial ependymomas in adult patients.

OBJECTIVE: Ependymomas arise from different areas in the neuraxis and have variable outcomes that depend on tumor location and patient age at the time of presentation. The predictive value of histology for these tumors is unresolved. We report a series of adult patients with supratentorial ependymomas to characterize the roles of surgery, histology, ploidy, and proliferation index in tumor control. METHODS: Fourteen of the 23 supratentorial ependymomas were in the region of the third ventricle and the remainder were located in the hemispheres. Resections were gross total in 12 patients, subtotal in 8, and biopsy in 3. A single pathologist reviewed all slides and quantitated the deoxyribonucleic acid. The mean follow-up duration was 95 months (+/-75 mo). RESULTS: All of the malignant ependymomas were hemispheric (n = 4). Mortality occurred only in patients with third ventricular tumors; two patients died as a result of surgical complications and three as a result of tumor progression. Kaplan-Meier estimates of 5- and 10-year survival rates were 100% for hemispheric and 72.5% for third ventricular tumors (62.5% including the two perioperative deaths). The median time to recurrence was 53 months, with a 10-year progression-free survival rate of 27%. Univariate analysis revealed that recurrence was associated with malignant histology, including mitoses, cellularity, and aneuploidy. For nonmalignant ependymomas, recurrence was associated with subtotal resection and metastases. S-phase fraction did not correlate with recurrence. Only malignant histology correlated with recurrence on multivariate analysis. CONCLUSION: Although the numbers are too small to draw any definite conclusions, treatment of ependymomas that arise in the supratentorial compartment in adult patients results in excellent outcomes despite frequent recurrences. Association with the third ventricle and metastases seem to have a negative impact on survival, whereas malignant histology, subtotal resection, and metastases may be predictors of recurrence.