Excitatory-inhibitory mismatch shapes node recruitment in an epileptic network.

OBJECTIVE: Focal epilepsy is thought to be a network disease, in which epileptiform activity can spread noncontiguously through the brain via highly interconnected nodes, or hubs, within existing networks. Animal models confirming this hypothesis are scarce, and our understanding of how distant nodes are recruited is also lacking. Whether interictal spikes (IISs) also create and reverberate through a network is not well understood. METHODS: We injected bicuculline into the S1 barrel cortex and employed multisite local field potential and Thy-1 and parvalbumin (PV) cell mesoscopic calcium imaging during IISs to monitor excitatory and inhibitory cells in two monosynaptically connected nodes and one disynaptically connected node: ipsilateral secondary motor area (iM2), contralateral S1 (cS1), and contralateral secondary motor area (cM2). Node participation was analyzed with spike-triggered coactivity maps. Experiments were repeated with 4-aminopyridine as an epileptic agent. RESULTS: We found that each IIS reverberated throughout the network, differentially recruiting both excitatory and inhibitory cells in all connected nodes. The strongest response was found in iM2. Paradoxically, node cM2, which was connected disynaptically to the focus, was recruited more intensely than node cS1, which was connected monosynaptically. The explanation for this effect could be found in node-specific excitatory/inhibitory (E/I) balance, as cS1 demonstrated greater PV inhibitory cell activation compared with cM2, where Thy-1 excitatory cells were more heavily recruited. SIGNIFICANCE: Our data show that IISs spread noncontiguously by exploiting fiber pathways that connect nodes in a distributed network and that E/I balance plays a critical role in node recruitment. This multinodal IIS network model can be used to investigate cell-specific dynamics in the spatial propagation of epileptiform activity.

The lateral transorbital approach to the medial sphenoid wing, anterior clinoid, middle fossa, cavernous sinus, and Meckel's cave: target-based classification, approach-related complications, and intermediate-term ocular outcomes.

OBJECTIVE: The lateral transorbital approach (LTOA) is a relatively new minimal access skull base approach suited for addressing paramedian pathology of the anterior and middle fossa. The authors define target zones for this approach and describe a series of cases with detailed measurements of visual outcomes, including those obtained with exophthalmometry. METHODS: The authors performed a retrospective analysis of a consecutive series of LTOA patients. Seven target zones were identified: 1) the orbit, 2) the lesser sphenoid wing and anterior clinoid, 3) the middle fossa, 4) the lateral wall of the cavernous sinus and Meckel's cave, 5) the infratemporal fossa, 6) the petrous apex, and 7) the anterior fossa. The authors used volumetric analyses of preoperative and postoperative MR and CT imaging data to calculate the volume of bone and tumor removed and to provide detailed ophthalmological, neurological, and cosmetic outcomes. RESULTS: Of the 20 patients in this cohort, pathology was in zone 2 (n = 10), zone 4 (n = 6), zone 3 (n = 2), zone 1 (n = 1), and zone 5 (n = 1). Pathology was meningioma (n = 10), schwannoma (n = 2), metastasis (n = 2), epidermoid (n = 1), dermoid (n = 1), encephalocele (n = 1), adenoma (n = 1), glioblastoma (n = 1), and inflammatory lesion (n = 1). The goal was gross-total resection (GTR) in 9 patients, all of whom achieved GTR. Subtotal resection (STR) was the goal in 8 patients (5 spheno-orbital meningiomas, 1 giant cavernous sinus/Meckel's cave schwannoma, 1 cavernous sinus prolactinoma, and 1 cavernous sinus dermoid), 7 of whom achieved STR and 1 of whom achieved GTR. The goal was biopsy in 2 patient and repair of encephalocele in 1. Visual acuity was stable or improved in 18 patients and worse in 2. Transient early postoperative diplopia, ptosis, eyelid swelling, and peri-orbital numbness were common. All 9 patients with preoperative diplopia improved at their last follow-up. Seven of 8 patients with preoperative exophthalmos improved after surgery (average correction of 64%). There were no cases of clinically significant (> 2 mm) postoperative enophthalmos. The most frequent postoperative complaint was peri-orbital numbness (40%). There was 1 CSF leak. Most patients were satisfied with their ocular (84%-100% of patients provided positive satisfaction-related responses) and cosmetic (75%-100%) outcomes. CONCLUSIONS: The LTOA is a safe minimal access approach to a variety of paramedian anterior skull base pathologies in several locations. Early follow-up revealed excellent resolution of exophthalmos with little risk of clinically significant enophthalmos. Transient diplopia, ptosis, and peri-orbital numbness were common but improved. Careful case selection is critical to ensure good outcome.

Mesoscopic mapping of hemodynamic responses and neuronal activity during pharmacologically induced interictal spikes in awake and anesthetized mice.

Imaging hemodynamic responses to interictal spikes holds promise for presurgical epilepsy evaluations. Understanding the hemodynamic response function is crucial for accurate interpretation. Prior interictal neurovascular coupling data primarily come from anesthetized animals, impacting reliability. We simultaneously monitored calcium fluctuations in excitatory neurons, hemodynamics, and local field potentials (LFP) during bicuculline-induced interictal events in both isoflurane-anesthetized and awake mice. Isoflurane significantly affected LFP amplitude but had little impact on the amplitude and area of the calcium signal. Anesthesia also dramatically blunted the amplitude and latency of the hemodynamic response, although not its area of spread. Cerebral blood volume change provided the best spatial estimation of excitatory neuronal activity in both states. Targeted silencing of the thalamus in awake mice failed to recapitulate the impact of anesthesia on hemodynamic responses suggesting that isoflurane's interruption of the thalamocortical loop did not contribute either to the dissociation between the LFP and the calcium signal nor to the alterations in interictal neurovascular coupling. The blood volume increase associated with interictal spikes represents a promising mapping signal in both the awake and anesthetized states.

Olfactory groove meningiomas: supraorbital keyhole versus orbitofrontal, frontotemporal, or bifrontal approaches.

OBJECTIVE: Olfactory groove meningiomas (OGMs) often require surgical removal. The introduction of recent keyhole approaches raises the question of whether these tumors may be better treated through a smaller cranial opening. One such approach, the supraorbital keyhole craniotomy, has never been compared with more traditional open transcranial approaches with regard to outcome. In this study, the authors compared clinical, radiographic, and functional quality of life (QOL) outcomes between the keyhole supraorbital approach (SOA) and traditional transcranial approach (TTA) for OGMs. They sought to examine the potential advantages and disadvantages of open/TTA versus keyhole SOA for the resection of OGMs in a relatively case-matched series of patients. METHODS: A retrospective, single-institution review of 57 patients undergoing a keyhole SOA or larger traditional transcranial (frontotemporal, pterional, or bifrontal) craniotomy for newly diagnosed OGMs between 2005 and 2023 was performed. Extent of resection, olfaction, length of stay (LOS), radiographic volumetric assessment of postoperative vasogenic and cytotoxic edema, and QOL (using the Anterior Skull Base Questionnaire) were assessed. RESULTS: Thirty-two SOA and 25 TTA patients were included. The mean EOR was not significantly different by approach (TTA: 99.1% vs SOA: 98.4%, p = 0.91). Olfaction was preserved or improved at similar rates (TTA: 47% vs SOA: 43%, p = 0.99). The mean LOS was significantly shorter for SOA patients (4.1 ± 2.8 days) than for TTA patients (9.4 ± 11.2 days) (p = 0.002). The authors found an association between an increase in postoperative FLAIR cerebral edema and TTA (p = 0.031). QOL as assessed by the ASQB at last follow-up did not differ significantly between groups (p = 0.74). CONCLUSIONS: The keyhole SOA was associated with a statistically significant decrease in LOS and less postoperative edema relative to traditional open approaches.