A Predictive Model for Intraoperative Cerebrospinal Fluid Leak During Endonasal Pituitary Adenoma Resection Using a Convolutional Neural Network.

BACKGROUND: Cerebrospinal fluid (CSF) leak during endoscopic endonasal transsphenoidal surgery can lead to postoperative complications. The clinical and anatomic risk factors of intraoperative CSF leak are not well defined. We applied a two-dimensional (2D) convolutional neural network (CNN) machine learning model to identify risk factors from preoperative magnetic resonance imaging. METHODS: All adults who underwent endoscopic endonasal transsphenoidal surgery at our institution from January 2007 to March 2023 who had accessible preoperative stereotactic magnetic resonance imaging were included. A retrospective classic statistical analysis was performed to identify demographic, clinical, and anatomic risk factors of intraoperative CSF leak. Stereotactic T2-weighted brain magnetic resonance imaging scans were used to train and test a 2D CNN model. RESULTS: Of 220 included patients, 81 (36.8%) experienced intraoperative CSF leak. Among all preoperative variables, visual disturbance was the only statistically significant identified risk factor (P = 0.008). The trained 2D CNN model predicted CSF leak with 92% accuracy and area under receiver operating characteristic curve of 0.90 (sensitivity of 86% and specificity of 93%). Class activation mapping of this model revealed that anatomic regions of CSF flow were most important in predicting CSF leak. CONCLUSIONS: Further review of the class activation mapping gradients revealed regions of the diaphragma sellae, clinoid processes, temporal horns, and optic nerves to have anatomic correlation to intraoperative CSF leak risk. Additionally, visual disturbances from anatomic compression of the optic chiasm were the only identified clinical risk factor. Our 2D CNN model can help a treating team to better anticipate and prepare for intraoperative CSF leak.

Arteriovenous malformation presenting as complex regional pain syndrome: illustrative case.

BACKGROUND: Complex regional pain syndrome (CRPS) is typically described as a peripheral nerve disorder in which exaggerated allodynia and hyperalgesia follow a minor injury. Some researchers propose a central mechanism, although current evidence is lacking. OBSERVATIONS: A 14-year-old female presented with classic CRPS symptoms of left upper-extremity weakness and hyperalgesia after a bout of sharp pain in her thumb while shoveling snow. A possible seizure prompted magnetic resonance imaging, revealing a right frontal Spetzler-Martin grade II arteriovenous malformation (AVM) adjacent to the primary motor cortex. Brodmann areas 1, 3a, and 3b, which are responsible for localizing and processing burning and painful sensations, were also involved. The patient underwent transarterial Onyx embolization in two sessions and microsurgical resection, after which her CRPS symptoms completely resolved. LESSONS: To our knowledge, this is the first reported case of a cerebral AVM presenting as CRPS, which supports a central mechanism. The authors propose that rapid growth of the AVM led to a vascular steal phenomenon of surrounding parenchyma, which disrupted the patient's normal motor function and nociceptive processing. Further validation in other series is needed.

MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series.

We present three cases of O6-Methylguanine-DNA Methyl-transferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

Trigeminal neuralgia induced by brainstem infarction treated with pontine descending tractotomy: illustrative case.

BACKGROUND: While cases of trigeminal neuralgia induced by a brainstem infarct have been reported, the neurosurgical literature lacks clear treatment recommendations in this subpopulation. OBSERVATIONS: The authors present the first case report of infarct-related trigeminal neuralgia treated with pontine descending tractotomy that resulted in durable pain relief after multiple failed surgical interventions, including previous microvascular decompressions and stereotactic radiosurgery. A neuronavigated pontine descending tractotomy of the spinal trigeminal tract was performed and resulted in successful pain relief for a 50-month follow-up period. LESSONS: While many cases of ischemic brainstem lesions are caused by acute stroke, the authors assert that cerebral small vessel disease also plays a role in certain cases and that the relationship between these chronic ischemic brainstem lesions and trigeminal neuralgia is more likely to be overlooked. Furthermore, neurovascular compression may obscure the causative mechanism of infarct-related trigeminal neuralgia, leading to unsuccessful decompressive surgeries in cases in which neurovascular compression may be noncontributory to pain symptomatology. Pontine descending tractotomy may be beneficial in select patients and can be performed either alone or concurrently with microvascular decompression in cases in which the interplay between ischemic lesion and neurovascular compression in the pathophysiology of disease is not clear.

Short-term repeat cognitive testing and its relationship to hippocampal volumes in older adults.

BACKGROUND: Practice effects are improvements in cognitive test scores due to repeated exposure to testing materials. If practice effects provide information about Alzheimer's disease pathology, then they could be useful for clinical trials enrichment. The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to neuroimaging biomarkers. METHODS: Twenty-five, non-demented older adults (8 cognitively intact, 17 with mild cognitive impairment) received magnetic resonance imaging and two testing sessions across one week to determine practice effects on seven neuropsychological test scores. A series of correlations examined if hippocampal volume was associated with baseline, one-week, or practice effects scores on these tests. Next, a series of stepwise multiple regression models examined which of the three test scores best predicted hippocampal volumes RESULTS: In the correlation analysis, baseline scores on 5 of the 7 tests were significantly associated with hippocampal volumes, one week scores were significantly related for 7 of the 7 tests, and practice effects scores were significantly correlated for 4 of the 7 tests. In the stepwise regression models, 5 of the 7 tests indicated that one-week scores best predicted hippocampal volumes. For the other models, baseline score and practice effects score each best predicted hippocampal volume. CONCLUSIONS: These results add to the growing body of evidence suggesting that diminished practice effects on short-term repeat testing is related to neuroimaging biomarkers of Alzheimer's disease and may serve as a screening tool for clinical practice and to enrich samples for research trials.

Abnormal Functional Connectivity Between Default and Salience Networks in Pediatric Bipolar Disorder.

BACKGROUND: Pediatric bipolar disorder (PBD) (occurring prior to 18 years of age) is a developmental brain disorder that is among the most severe and disabling psychiatric conditions affecting youth. Despite increasing evidence that brain connectivity is atypical in adults with bipolar disorder, it is not clear how brain connectivity may be altered in youths with PBD. METHODS: This cross-sectional resting-state functional magnetic resonance imaging study included 80 participants recruited over 4 years: 32 youths with PBD, currently euthymic (13 males; 15.1 years old), and 48 healthy control (HC) subjects (27 males; 14.5 years old). Functional connectivity between eight major intrinsic connectivity networks, along with connectivity measurements between 333 brain regions, was compared between PBD and HC subjects. Additionally, connectivity differences were evaluated between PBD and HC samples in negatively correlated connections, as defined by 839 subjects of the Human Connectome Project dataset. RESULTS: We found increased inter- but not intranetwork functional connectivity in PBD between the default mode and salience networks (p = .0017). Throughout the brain, atypical connections showed failure to develop anticorrelation with age during adolescence in PBD but not HC samples among connections that exhibit negative correlation in adulthood. CONCLUSIONS: Youths with PBD demonstrate reduced anticorrelation between default mode and salience networks. Further evaluation of the interaction between these networks is needed in development and with other mood states such as depression and mania to clarify if this atypical connectivity is a PBD trait biomarker.

Molecular Imaging and Precision Medicine in Dementia and Movement Disorders.

Precision medicine (PM) has been defined as "prevention and treatment strategies that take individual variability into account." Molecular imaging (MI) is an ideally suited tool for PM approaches to neurodegenerative dementia and movement disorders (MD). Here we review PM approaches and discuss how they may be applied to other associated neurodegenerative dementia and MD. With ongoing major therapeutic research initiatives that include the use of molecular imaging, we look forward to established interventions targeted to specific molecular pathophysiology and expect the potential benefit of MI PM approaches in neurodegenerative dementia and MD will only increase.

In vitro imaging using laser photostimulation with flavoprotein autofluorescence.

Imaging of 300-500 µm mouse brain slices by laser photostimulation with flavoprotein autofluorescence (LFPA) allows the rapid and sensitive mapping of neuronal connectivity. It is accomplished using UV laser-based photo-uncaging of glutamate and imaging neuronal activation by capturing changes in green light (∼520 nm) emitted under blue light (∼460 nm) excitation. This fluorescence is generated by the oxidized form of flavoprotein and is a measure of metabolic activity. LPFA offers several advantages over imaging techniques that rely on dye loading. First, as flavoprotein imaging measures endogenous signals, it avoids the use of heterogeneously loaded and potentially cytotoxic dyes. Second, flavoprotein signals are large (1-20% above baseline), obviating the need for averaging. Third, the use of photostimulation ensures orthodromic neuronal activation and permits the rapid interrogation of multiple stimulation sites of the slice with a high degree of precision (∼50 µm). Here we describe a step-by-step protocol for the incorporation of LPFA into virtually any slice rig, as well as how to do the experiment.

Molecular analysis of neocortical layer structure in the ferret.

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals, however, is unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for 15 layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: 1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; 2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layers 5 and 6 into 5a, 5b, 6a, and 6b are also conserved between rodents and carnivores; 3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; 4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals.

The organization of spatial frequency maps measured by cortical flavoprotein autofluorescence.

To determine the organization of spatial frequency (SF) preference within cat Area 17, we imaged responses to stimuli with different SFs using optical intrinsic signals (ISI) and flavoprotein autofluorescence (AFI). Previous studies have suggested that neurons cluster based on SF preference, but a recent report argued that SF maps measured with ISI were artifacts of the vascular bed. Because AFI derives from a non-hemodynamic signal, it is less contaminated by vasculature. The two independent imaging methods produced similar SF preference maps in the same animals, suggesting that the patchy organization of SF preference is a genuine feature of Area 17.

Glomerular activation patterns and the perception of odor mixtures.

Odor mixtures can produce several qualitatively different percepts; it is not known at which stage of processing these are determined. We asked if activity within the first stage of olfactory processing, the glomerular layer of the olfactory bulb, predicts odor mixture perception. We characterized how mice respond to components after training to five different mixture ratios of pentanal and hexanal, and found two types of responses: elemental perception and overshadowing. We then used intrinsic signal imaging to observe glomerular activity in response to the same mixtures and their components. As has been previously described, glomerular activity patterns produced by mixtures resemble the linear combination of responses to components. Mice trained to identify mixtures with more hexanal than pentanal recognized hexanal but not pentanal when the odorants were presented alone (overshadowing). Consistent with these behavioral responses, the imaged activity pattern in response to mixtures was similar to that produced to hexanal alone. Moreover, there was no significant effect of glomerular inhibition in the imaged response. In contrast, the glomerular activity patterns did not predict elemental perception: when trained to identify mixtures with more pentanal than hexanal, mice recognized both components equally well, even with highly overlapping activation patterns. This suggests that spatial activity patterns within the olfactory bulb are not always sufficient to specify component recognition in mixtures.

The representation of complex images in spatial frequency domains of primary visual cortex.

The organization of cat primary visual cortex has been well mapped using simple stimuli such as sinusoidal gratings, revealing superimposed maps of orientation and spatial frequency preferences. However, it is not yet understood how complex images are represented across these maps. In this study, we ask whether a linear filter model can explain how cortical spatial frequency domains are activated by complex images. The model assumes that the response to a stimulus at any point on the cortical surface can be predicted by its individual orientation, spatial frequency, and temporal frequency tuning curves. To test this model, we imaged the pattern of activity within cat area 17 in response to stimuli composed of multiple spatial frequencies. Consistent with the predictions of the model, the stimuli activated low and high spatial frequency domains differently: at low stimulus drift speeds, both domains were strongly activated, but activity fell off in high spatial frequency domains as drift speed increased. To determine whether the filter model quantitatively predicted the activity patterns, we measured the spatiotemporal tuning properties of the functional domains in vivo and calculated expected response amplitudes from the model. The model accurately predicted cortical response patterns for two types of complex stimuli drifting at a variety of speeds. These results suggest that the distributed activity of primary visual cortex can be predicted from cortical maps like those of orientation and SF preference generated using simple, sinusoidal stimuli, and that dynamic visual acuity is degraded at or before the level of area 17.

Functional imaging of primary visual cortex using flavoprotein autofluorescence.

Neuronal autofluorescence, which results from the oxidation of flavoproteins in the electron transport chain, has recently been used to map cortical responses to sensory stimuli. This approach could represent a substantial improvement over other optical imaging methods because it is a direct (i.e., nonhemodynamic) measure of neuronal metabolism. However, its application to functional imaging has been limited because strong responses have been reported only in rodents. In this study, we demonstrate that autofluorescence imaging (AFI) can be used to map the functional organization of primary visual cortex in both mouse and cat. In cat area 17, orientation preference maps generated by AFI had the classic pinwheel structure and matched those generated by intrinsic signal imaging in the same imaged field. The spatiotemporal profile of the autofluorescence signal had several advantages over intrinsic signal imaging, including spatially restricted fluorescence throughout its response duration, reduced susceptibility to vascular artifacts, an improved spatial response profile, and a faster time course. These results indicate that AFI is a robust and useful measure of large-scale cortical activity patterns in visual mammals.