Spinal intradural microsurgery in a nascent neurosurgical department: Lessons learned from the first 25 cases.

BACKGROUND: Between 2017 and 2021, the newly established Department of Neurosurgery at Shaare Zedek Medical Center in Jerusalem, a high volume metropolitan hospital, operated on 25 intradural lesions in 24 patients (one patient had multiple tumors). In this retrospective study, we review results and lessons learned as experienced surgeons opened a new service line. METHODS: A multidisciplinary team was assembled and led by experienced neurosurgeons with skills in both microneurosurgery and complex spine care. Standard operative techniques were used. A chart review was done to assess complications and outcome. RESULTS: 25 lesions were reviewed in 24 patients (14 female; 10 male) between the ages of 11-82 years of age. In 14 cases, gross total resection (GTR) was achieved; 11 cases underwent partial resection. Of the 11 non-GTR cases, 3 were initially planned as biopsies. In one case, there was a significant neurologic decline directly related to surgery. In a separate case, there was iatrogenic instability, necessitating further treatment. CONCLUSIONS: We identify six lessons learned in a nascent neurosurgical department, noting that surgical excellence is of paramount importance, but that the surgeon must also expand his/her role from master technician to team leader. Both microsurgical expertise for neural anatomy and understanding of spinal biomechanics for osseous anatomy is mandatory for surgery of SIDT. This retrospective analysis of our case series demonstrates experienced neurosurgeons can successfully deploy a new service line for challenging cases to the benefit of the hospital and local community.

[COMPARISON OF HIGH GAMMA ELECTROCORTICOGRAPHY AND DIRECT CORTICAL STIMULATION MAPPING OF CORTICAL FUNCTION IN AWAKE CRANIOTOMY: INITIAL EXPERIENCE].

INTRODUCTION: The use of intraoperative electrical cortical stimulation (ECS) to map function is the standard of care in modern neurosurgery. Recently, high gamma electrocorticography (hgECOG) mapping has had encouraging results. In this study we aim to compare hgECOG and fMRI with ECS for motor and language mapping. METHODS: We retrospectively evaluated medical records of patients who underwent awake surgery for tumor resection between January 2018 and December 2021. The first 10 consecutive patients who underwent ECS and hgECOG for mapping of motor and language functions were defined as the study group. Pre- and intra-operative imaging and electrophysiology data were used for analysis. RESULTS: ECS and hgECOG motor mapping demonstrated functional motor areas in 71.4% and 85.7% of patients, respectively. All motor areas identified with ECS were also demonstrated using hgECOG. In 2 patients, hgECOG-based mapping demonstrated motor areas not demonstrated with ECS but present in preoperative fMRI imaging. Of the 15 hgECOG tasks performed for language mapping, the findings of 6 (40%) were in accordance with the ECS mapping. Two (13.3%), showed language areas that were demonstrated using ECS and in addition, showed areas that were not. Four mappings (26.7%) showed language areas that were not demonstrated using ECS. In 3 mappings (20%), the functional areas identified by ECS were not demonstrated by hgECOG. CONCLUSIONS: Intraoperative hgECOG for mapping of motor and language functions provide a fast and reliable method without the risk of stimulation-induced seizures. Further studies are needed to assess functional outcome of patients undergoing hgECOG-guided tumor resection.

[INTRAOPERATIVE ELECTROPHYSIOLOGY MAPPING OF CORTICAL FUNCTION: A BRIEF HISTORY AND EVOLVING ALTERNATIVE].

INTRODUCTION: Multiple studies have demonstrated that the improved extent of resection for patients with glioma is associated with improved survival. The use of intraoperative electrophysiology cortical mapping to demonstrate function became a standard of care in modern neurosurgery and an indispensable tool to achieve the goal of maximal safe resection in tumor surgery. In this study, we review the brief history of intraoperative electrophysiology cortical mapping from the first cortical mapping study back in 1870 to the innovative tool of broad gamma cortical mapping used today.

Intraoperative Deterioration of Neurophysiological Potentials of the Spinal Tracts in Cervical Spine Surgery: Correlation With Patient-Related and Procedure-Related Variables.

PURPOSE: To identify characteristics associated with higher incidence of intraoperative deterioration of neurophysiological potentials related to spinal tracts in cervical spine surgeries. METHODS: Electrophysiological raw data and neurophysiological case reports of 1,611 patients from multiple medical centers, who underwent cervical spine surgery for decompression and/or fusion, were retrospectively reviewed. Patient-related and procedure-related variables were identified and analyzed for correlation with intraoperative neurophysiological event of the spinal tracts. The neurophysiological events were analyzed for identification of collective characteristics. RESULTS: The study cohort presented consistent dominancy of male over female patients (67% vs. 33%). Intraoperative deterioration of spinal tract-derived potentials was noted in 10.5% of the total cases, which was not correlated with gender, age, or indication of the surgery. Higher incidence of neurophysiological events was noted in patients with impaired baseline of motor evoked potentials from the thenar muscle ( P = 0.01) or somatosensory evoked potentials of the posterior tibial nerve ( P = 0.0002). Procedures of circumferential approach or procedures that involved ≥3 spinal levels demonstrated higher incidence of neurophysiological events as well ( P = 0.0003 and 0.001, respectively). CONCLUSIONS: Patients with deteriorated neurophysiological baseline and procedures of extensive intervention are at higher risk of intraoperative neurophysiological event in cervical spine surgery. Inclusion of intraoperative neurophysiological monitoring should be encouraged in complicated cases of cervical spine surgeries.

Vestibular schwannoma manifesting with hemifacial spasm in a young woman: clinical considerations and tumor removal with hearing preservation. 2-Dimensional operative video.

Hemifacial spasm (HFS) is a rare presentation of vestibular schwannoma. The authors present their experience with a 27-year-old woman who presented with normal hearing and HFS, which was the single neurological manifestation of an 18-mm vestibular schwannoma. In this challenging situation, the treatment goals were maximal tumor removal with preservation of hearing and facial nerve function and cure of the HFS. The authors achieved these goals, performing complete tumor removal via a retrosigmoid approach, assisted with neurophysiological monitoring and a 45°-angle QEVO endoscope. In the video, they explain the clinical, radiological, and surgical considerations and demonstrate the surgical technique. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID2099.

Single root multiple spinal schwannomas: Case report, treatment strategy and review of literature.

INTRODUCTION: Schwannomatosis is defined as multiple schwannomas without presence of neurofibromatosis and is a rare pathology. In vast majority of cases the schwannomas grow from different nerve roots or peripheral nerves. PRESENTATION OF CASE: A 52-year-old woman presented with multiple intradural schwannomas arranged in a chain along the spinal canal causing significant compression. The lesions were successfully removed using a left side en-bloc hemilaminectomy technique in order to preserve maximal stability of the posterior column. Back and leg pain resolved completely. Tendon reflexes returned to normal shortly. There was decreased pain sensation in the distribution of the left L3 spinal root. DISCUSSION: The traditional surgical strategy for posterior approach by laminectomy or laminotomy is sometimes complicated with instability or deformation of the vertebral column that requires surgical stabilization. We performed a one side en-bloc hemilaminectomy thus maintaining the integrity of the muscles and ligaments on the opposite side and preserving maximal stability of the vertebral column. Densely adherent tumors required careful sharp dissection and separation under neurosurgical monitoring and stimulation for recognition and preservation of spinal roots. An additional tumor was discovered by exploration of the spinal canal using an endoscope. CONCLUSION: Multiple spinal cord schwannomas that are growing along the same part of the vertebral column can be safely removed by one-sided hemilaminectomy with preservation of the integrity of the muscles and ligaments on the opposite side and thus maintain spinal stability. The 30° endoscope can be a good tool for visual exploration of the spinal canal.

Intraoperative monitoring of corticospinal tracts in anterior cervical decompression and fusion surgery: Excitability differentials of lower extremity muscles.

OBJECTIVE: This study examines and compares excitability characteristics of tibialis anterior (TA) and abductor hallucis (AH) transcranial motor evoked potentials (tcMEP) during anterior cervical decompression and fusion (ACDF) surgery. METHODS: Electrophysiological and clinical data of 89 patients who underwent ACDF procedure were retrospectively reviewed. TcMEP data of TA and AH muscles from 178 limbs were analyzed for availability, robustness and stability during the procedure. RESULTS: TA tcMEP was available at 83% whereas AH tcMEP was available at 99% of the monitored lower limbs at preposition baseline. Availability of both TA and AH tcMEP was demonstrated in 147/178 limbs. The baseline amplitude of AH tcMEP was significantly greater than that of TA tcMEP recorded from the same limb (744.6 ±â€¯54.0 and 326.9 ±â€¯33.3 µV, respectively). Simultaneous deterioration of TA and AH tcMEP data was demonstrated in 10/147 limbs. Deterioration of either TA or AH tcMEP data accompanied by unchanged tcMEP data from the other lower limb muscle was noted in 32/147 compared to 1/147 limbs, respectively. The deteriorated TA and AH tcMEP data returned to baseline before closing at incidence of 17% compared to 46%, respectively. No new lower extremity (LE) neurological deficit was presented postoperatively in any patient. CONCLUSIONS: AH tcMEP is a more reliable candidate than TA tcMEP for intraoperative LE monitoring in ACDF procedure. SIGNIFICANCE: The excitability differentials in LE tcMEP in ACDF is a variable that need to be considered while interpreting intraoperative neurophysiological data.

Infantile spasms in down syndrome: Rescue by knockdown of the GIRK2 channel.

OBJECTIVE: The Ts65Dn (Ts) mouse model of Down syndrome (DS) is exquisitely sensitive to an infantile spasms phenotype induced by γ-aminobutyric acidB receptor (GABAB R) agonists. The Ts mouse contains the core genomic triplication of the DS critical region, which includes 3 copies of the Kcnj6 gene that encodes the GABAB R-coupled G protein-coupled inward rectifying potassium channel subunit 2 (GIRK2) channel. We test the hypothesis that GIRK2 is necessary for the GABAB R agonist-induced infantile spasms phenotype in Ts. METHODS: We assessed the result of either genetic or pharmacological knockdown of the GIRK2 channel in Ts brain upon the GABAB R agonist-induced infantile spasms phenotype in the Ts mouse model of DS. As well, we examined GABAB R currents in hippocampal neurons prepared from GIRK2-trisomic Ts control mice and GIRK2-disomic Ts mice in which Kcnj6 had been genetically knocked down from 3 to 2 copies. RESULTS: The reduction of the copy number of Kcnj6 in Ts mice rescued the GABAB R agonist-induced infantile spasms phenotype. There was an increase in GABAB R-mediated GIRK2 currents in GIRK2-trisomic Ts mouse hippocampal neurons, which were normalized in the GIRK2-disomic Ts mice. Similarly, pharmacological knockdown of the GIRK2 channel in Ts brain using the GIRK antagonist tertiapin-Q also rescued the GABAB R agonist-induced infantile spasms phenotype in Ts mutants. INTERPRETATION: The GABAB R-coupled GIRK2 channel is necessary for the GABAB R agonist-induced infantile spasms phenotype in the Ts mouse and may represent a novel therapeutic target for the treatment of infantile spasms in DS. Ann Neurol 2016;80:511-521.

Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure.

Excitatory synapses on dopamine (DA) neurons in the ventral tegmental area (VTA) are modulated following exposure to various addictive drugs, including cocaine. Previously we have shown that cocaine affects GABA(A) receptor (GABA(A)R)-mediated neurotransmission in VTA DA neurons. This finding led us to reexamine the modulation of the excitatory synapse on these neurons in response to cocaine exposure, while the activity of GABA(A)R is uninterrupted. Using rat brain slices, evoked post synaptic currents (ePSC) were monitored and inhibitors of NMDA receptor (NMDAR) and AMPA receptor (AMPAR) were gradually added to inhibitors-free bath solution. Modifications in the efficacy of the excitatory synapses were evaluated by comparing AMPAR-mediated and NMDAR-mediated currents (AMPA/NMDA ratio). The lack of GABA(A)R inhibitors enabled us to examine parallel changes in the relation between GABA(A)R-mediated and NMDAR-mediated currents (GABA(A)/NMDA ratio). First, we found that AMPA/NMDA ratio measured under complete availability of GABA(A)R, is significantly higher than the ratio measured under GABA(A)R blockade. In addition, GABA(A)/NMDA ratio, but not AMPA/NMDA ratio, is augmented a few hours following in vitro acute cocaine exposure. When measured 24 h after in vivo single cocaine injection, no change in GABA(A)/NMDA ratio was observed, however, the AMPA/NMDA ratio was found to be significantly higher. Finally, a decrease in both ratios was detected in rats repeatedly injected with cocaine. Taken together, these results lead to a better understanding of the means by which cocaine modifies synaptic inputs on VTA DA neurons. The parallel changes in GABA(A)/NMDA ratio may suggest an interaction between inhibitory and excitatory neural systems.

Dopamine-related drugs act presynaptically to potentiate GABA(A) receptor currents in VTA dopamine neurons.

Electrical activity of ventral tegmental area (VTA) dopamine (DA) neurons is immediately inhibited following in vivo administration of cocaine and other DA-related drugs. While various forms of synaptic modulation were demonstrated in the VTA following exposure to DA-related drugs, comprehensive understanding of their ability to inhibit the activity of DA neurons, however, is still lacking. In this study, using whole-cell patch-clamp recordings from rat brain slices, a novel form of synaptic modulation induced by DA-related drugs was isolated. DA exposure was shown to cause potentiation of γ-amino-butyric acid (GABA) receptor type A (GABA(A)R)-mediated evoked inhibitory postsynaptic currents (eIPSCs), recorded from VTA DA neurons, under conditions of potassium channels blockade. The potentiation of these eIPSCs lasted for more than twenty minutes, could be mimicked by activation of D2-like but not D1-like DA receptors, and was accompanied by an increase in the frequency of GABA(A)R-mediated spontaneous miniature inhibitory postsynaptic currents (mIPSCs). Furthermore, exposure to inhibitors of DA transporter (DAT) led to potentiation of GABA(A) currents in a manner similar to the DA-mediated potentiation. Finally, a prolonged presence of l-NAME, an inhibitor of nitric-oxide (NO) signaling was found to conceal the potentiation of GABA(A) currents induced by the DA-related drugs. Taken together, this study demonstrates a new modulatory form of VTA GABA(A) neurotransmission mediated by DA-related drugs. These results also suggest better understanding of the initial inhibitory action of DA-related drugs on the activity of DA neurons in the VTA.

NR2A/B-containing NMDA receptors mediate cocaine-induced synaptic plasticity in the VTA and cocaine psychomotor sensitization.

Cocaine-induced modifications of glutamatergic synaptic transmission in the mesolimbic system play a key role in adaptations that promote addictive behaviors. In particular, the activation of ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR) in the ventral tegmental area (VTA) is critical for both cocaine-induced synaptic plasticity induced by a single cocaine injection and for the initiation of cocaine psychomotor sensitization. In this study, we set to determine whether the NR2 subunits of the NMDAR play a specific role in triggering cocaine-induced alterations in synaptic plasticity and the development of psychomotor sensitization. We found that inhibition of NR2A-containing NMDARs by NVP-AAM077, or NR2B-containing receptors by ifenprodil, blocked cocaine-induced increase in the AMPAR/NMDAR currents ratio, a measure of long-term potentiation (LTP) in vivo, in VTA neurons 24h following a single cocaine injection. Furthermore, inhibition of the NR2A subunit during the development of psychomotor sensitization attenuated the enhanced locomotor activity following repeated cocaine injections. Together, these results suggest that NR2-containing NMDA receptors play an important role in the machinery that triggers synaptic and behavioral adaptations to drugs of abuse such as cocaine.

Src-protein tyrosine kinases are required for cocaine-induced increase in the expression and function of the NMDA receptor in the ventral tegmental area.

Cocaine-induced long-term potentiation of glutamatergic synapses in the ventral tegmental area (VTA) has been proposed as a key process that contributes to the development of addictive behaviors. In particular, the activation of ionotrophic glutamate NMDA receptor (NMDAR) in the VTA is critical for the initiation of cocaine sensitization. Here we show that application of cocaine both in slices and in vivo induced an increase in tyrosine phosphorylation of the NR2A, but not the NR2B subunit of the NMDAR in juvenile rats. Cocaine induced an increase in the activity of both Fyn and Src kinases, and the Src-protein tyrosine kinase (Src-PTKs) inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), abolished both cocaine-induced increase in tyrosine phosphorylation of the NR2A subunit and the increase in the expression of NR1, NR2A, and NR2B in the VTA. Moreover, cocaine-induced enhancement in NMDAR-mediated excitatory post-synaptic currents was completely abolished by PP2. Taken together, these results suggest that acute cocaine induced an increase in the expression of NMDAR subunits and enhanced tyrosine phosphorylation of NR2A-containing NMDAR through members of the Src-PTKs. This in turn, increased NMDAR-mediated currents in VTA dopamine neurons. These results provide a potential cellular mechanism by which cocaine triggers NMDAR-dependent synaptic plasticity of VTA neurons that may underlie the development of behavioral sensitization.

RIC-3 affects properties and quantity of nicotinic acetylcholine receptors via a mechanism that does not require the coiled-coil domains.

Members of the RIC-3 gene family are effectors of nicotinic acetylcholine receptor (nAChR) expression in vertebrates and invertebrates. In Caenorhabditis elegans RIC-3 is needed for functional expression of multiple nAChRs, including the DEG-3/DES-2 nAChR. Effects of RIC-3 on DEG-3/DES-2 functional expression are found in vivo and following heterologous expression in Xenopus leavis oocytes. We now show that in X. leavis oocytes RIC-3 also affects the kinetics and agonist affinity properties of the DEG-3/DES-2 receptor. Because these effects are mimicked by increasing the ratio of DEG-3 subunits within DEG-3/DES-2 receptors, this suggests that RIC-3 may preferentially promote maturation of DEG-3-rich receptors. Indeed, effects of RIC-3 on functional expression of DEG-3/DES-2 positively correlate with the DEG-3 to DES-2 ratio. All RIC-3 family members have two transmembrane domains followed by one or two coiled-coil domains. Here we show that the effects of RIC-3 on functional expression and on receptor properties are mediated by the transmembrane domains and do not require the coiled-coil domains. In agreement with this, mammals express a RIC-3 transcript lacking the coiled-coil domain that is capable of promoting DEG-3/DES-2 functional expression. Last, we show that RIC-3 affects DEG-3 quantity, suggesting stabilization of receptors or receptor intermediates by RIC-3. Together our results suggest that subunit-specific interactions of RIC-3 with nAChR subunits, mediated by the transmembrane domains, are sufficient for the effects of RIC-3 on nAChR quantity and quality.