Regulator of G-protein signaling 4 (RGS4) is a potent modulator of G-protein-coupled receptor signal transduction that is expressed throughout the pain matrix. Here, we use genetic mouse models to demonstrate a role of RGS4 in the maintenance of chronic pain states in male and female mice. Using paradigms of peripheral inflammation and nerve injury, we show that the prevention of RGS4 action leads to recovery from mechanical and cold allodynia and increases the motivation for wheel running. Similarly, RGS4KO eliminates the duration of nocifensive behavior in the second phase of the formalin assay. Using the Complete Freud's Adjuvant (CFA) model of hindpaw inflammation we also demonstrate that downregulation of RGS4 in the adult ventral posterolateral thalamic nuclei promotes recovery from mechanical and cold allodynia. RNA sequencing analysis of thalamus (THL) from RGS4WT and RGS4KO mice points to many signal transduction modulators and transcription factors that are uniquely regulated in CFA-treated RGS4WT cohorts. Ingenuity pathway analysis suggests that several components of glutamatergic signaling are differentially affected by CFA treatment between RGS4WT and RGS4KO groups. Notably, Western blot analysis shows increased expression of metabotropic glutamate receptor 2 in THL synaptosomes of RGS4KO mice at time points at which they recover from mechanical allodynia. Overall, our study provides information on a novel intracellular pathway that contributes to the maintenance of chronic pain states and points to RGS4 as a potential therapeutic target.

Retrochiasmatic craniopharyngiomas are difficult to treat due to their close proximity to critical neurovascular structures. Several surgical approaches with distinct advantages and limitations have been described to access these tumors, including extended transnasal endoscopic approach (ETEA), subtemporal, translamina terminalis, and transpetrosal approach.1-3  We present a 51-yr-old male with a large retrochiasmatic craniopharyngioma extending into the third ventricle, causing obstructive hydrocephalus. Preoperative magnetic resonance imaging (MRI) showed a tumor cyst abutting the fornices expanding the space between two internal cerebral veins (ICV). After surgical consent, we decided to take advantage of this corridor to approach the tumor in its long axis. Surgical goal was to achieve cyst decompression with “safe maximal” resection of the solid component at last to preserve the pituitary function. Though the long axis of the tumor could be approached using ETEA, we preferred this approach in view of cyst decompression early in the surgery while completely avoiding risks such as cerebrospinal fluid (CSF) rhinorrhea, internal carotid artery (ICA) injury, and sinonasal complications. We utilized a 3-dimensional 4 K exoscope, which provides an excellent ergonomic position, and a high-resolution immersive view compared to a microscope or endoscope. Cyst decompression and near-total resection of the solid component was achieved. Postoperatively, his headaches improved and he was neurologically intact with intact neuroendocrine function. Approach-related risks may include but not limited to hemorrhage due to the rupture of venous sinuses or ICV, stalk or hypothalamus injury, and memory disturbances due to forniceal injury. To conclude, the transcallosal, interforniceal approach to retrochiasmatic craniopharyngiomas may provide a safe surgical corridor in select cases.  Patient consented to the proposed procedure. All radiological images have been anonymized. IRB/ethics committee approval was not required.

Fusiform aneurysms remain challenging entities to treat, as maintenance of flow and prevention of branch occlusion are concerns. Use of endovascular stents may risk nearby branch occlusion. We present a 31-yr-old male with a prior subarachnoid hemorrhage from a left middle cerebral artery (MCA) M1 aneurysm. Informed consent for use of the operative video and information was obtained from the patient. Initially, open clipping was performed with noted residual because of risk of nearby branches. On angiography, a growing fusiform segment distal to the initial aneurysm was noted. The patient was referred to our institution for this finding, and a multidisciplinary team reviewed the case. Endovascular treatment was felt to be risky, as stenting could jail nearby MCA branches. Clipping would also risk occlusion because of scaring from previous hemorrhage. Sufficient flow would be needed, and because the ipsilateral superficial temporal artery was sacrificed in the initial craniotomy, the internal maxillary artery (IMAX) was chosen as the bypass source. A cerebrovascular neurosurgeon, skull base otolaryngologist, and vascular surgeon worked together to perform a left-side IMAX to MCA bypass using an anterior tibial artery graft under 3-dimensional exoscopic visualization. Specifically, a 9-0 nylon suture on a BV-130 needle along with straight and tying forceps were used along with heparinized saline. The bypass was noted to be of robust flow, and the patient did very well on postoperative follow-up. The utilization of an anterior tibial artery graft, IMAX exposure, and corresponding bypass provides educational value, as there are only a limited number of videos on this topic.

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