How I do it: neuromonitoring-guided clipping of high-riding basilar tip aneurysm.

BACKGROUND: Clipping of basilar tip aneurysms presents unique challenges due to the risk of perforator compromise and subsequent disabling stroke. METHOD: Herein, we describe the correct trajectory of the clip applier to clip basilar tip aneurysms through an orbitozygomatic approach to prevent perforator injury and discuss management of intraoperative neuromonitoring changes. CONCLUSION: We anticipate that this video and illustration will aid surgeons as they treat complex wide-necked basilar tip aneurysms with microsurgical clipping.

Mechanical injury and blood are drivers of spatial memory deficits after rapid intraventricular hemorrhage.

Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks.

mRNA Expression Profiles from Whole Blood Associated with Vasospasm in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Though there are many biomarker studies of plasma and serum in patients with aneurysmal subarachnoid hemorrhage (SAH), few have examined blood cells that might contribute to vasospasm. In this study, we evaluated inflammatory and prothrombotic pathways by examining mRNA expression in whole blood of SAH patients with and without vasospasm. METHODS: Adult SAH patients with vasospasm (n = 29) and without vasospasm (n = 21) were matched for sex, race/ethnicity, and aneurysm treatment method. Diagnosis of vasospasm was made by angiography. mRNA expression was measured by Affymetrix Human Exon 1.0 ST Arrays. SAH patients with vasospasm were compared to those without vasospasm by ANCOVA to identify differential gene, exon, and alternatively spliced transcript expression. Analyses were adjusted for age, batch, and time of blood draw after SAH. RESULTS: At the gene level, there were 259 differentially expressed genes between SAH patients with vasospasm compared to patients without (false discovery rate < 0.05, |fold change| ≥ 1.2). At the exon level, 1210 exons representing 1093 genes were differentially regulated between the two groups (P < 0.005, ≥ 1.2 |fold change|). Principal components analysis segregated SAH patients with and without vasospasm. Signaling pathways for the 1093 vasospasm-related genes included adrenergic, P2Y, ET-1, NO, sildenafil, renin-angiotensin, thrombin, CCR3, CXCR4, MIF, fMLP, PKA, PKC, CRH, PPARα/RXRα, and calcium. Genes predicted to be alternatively spliced included IL23A, RSU1, PAQR6, and TRIP6. CONCLUSIONS: This is the first study to demonstrate that mRNA expression in whole blood distinguishes SAH patients with vasospasm from those without vasospasm and supports a role of coagulation and immune systems in vasospasm.

Morphometric Analysis of Predictors of Cervical Syrinx Formation in the Setting of Chiari I Malformation.

BACKGROUND/AIMS: We performed a morphometric analysis of Chiari I malformations to look for predictors of cervical syrinx formation. METHODS: Eighteen patients with Chiari I malformation and associated cervical syrinx and 16 patients with Chiari I malformation without associated cervical syrinx were included in the study. Chiari I size was obtained from the radiology report; foramen magnum diameter, cerebellar volume, posterior fossa volume and intracranial volume were calculated using OsiriX software, and average measurements were compared between the two groups. RESULTS AND CONCLUSION: Patients with Chiari I with syrinx had an average tonsillar descent of 13.03 ± 5.31 mm compared to 9.25 ± 3.31 mm in the Chiari I without syrinx group (p < 0.05). Patients with Chiari I and syrinx also showed increased cerebellar crowding with a higher cerebellar volume to posterior fossa volume ratio; however, this difference was not significant (0.83 vs. 0.81; p = 0.1872). No difference between groups was found in posterior fossa volume, intracranial volume and foramen magnum diameter. Therefore, only Chiari I size based on the extent of tonsillar herniation was found to be a determinant of cervical syrinx formation.

CrossFit-related cervical internal carotid artery dissection.

CrossFit is a high-intensity strength and conditioning program that has gained popularity over the past decade. Potential injuries associated with CrossFit training have been suggested in past reports. We report three cases of cervical carotid dissection that are associated with CrossFit workouts. Patient 1 suffered a distal cervical internal carotid artery (ICA) dissection near the skull base and a small infarct in Wernicke's area. He was placed on anticoagulation and on follow-up has near complete recovery. Patient 2 suffered a proximal cervical ICA dissection that led to arterial occlusion and recurrent middle cerebral artery territory infarcts and significant neurological sequelae. Patient 3 had a skull base ICA dissection that led to a partial Horner's syndrome but no cerebral infarct. While direct causality cannot be proven, intense CrossFit workouts may have led to the ICA dissections in these patients.

Prominin-1 allows prospective isolation of neural stem cells from the adult murine hippocampus.

Prominin-1 (CD133) is commonly used to isolate stem and progenitor cells from the developing and adult nervous system and to identify cancer stem cells in brain tumors. However, despite extensive characterization of Prominin-1(+) precursor cells from the adult subventricular zone, no information about the expression of Prominin-1 by precursor cells in the subgranular zone (SGZ) of the adult hippocampus has been available. We show here that Prominin-1 is expressed by a significant number of cells in the SGZ of adult mice in vivo and ex vivo, including postmitotic astrocytes. A small subset of Prominin-1(+) cells coexpressed the nonspecific precursor cell marker Nestin as well as GFAP and Sox2. Upon fluorescence-activated cell sorting, only Prominin-1/Nestin double-positive cells fulfilled the defining stem cell criteria of proliferation, self-renewal, and multipotentiality as assessed by a neurosphere assay. In addition, isolated primary Prominin-1(+) cells preferentially migrated to the neurogenic niche in the SGZ upon transplantation in vivo. Finally, despite its expression by various stem and progenitor cells, Prominin-1 turned out to be dispensable for precursor cell proliferation in vitro and in vivo. Nevertheless, a net decrease in hippocampal neurogenesis, by ∼30% was found in Prominin-1 knock-out mice, suggesting other roles in controlling adult hippocampal neurogenesis. Remarkably, an upregulation of Prominin-2 was detected in Prominin-1-deficient mice highlighting a potential compensatory mechanism, which might explain the lack of severe symptoms in individuals carrying mutations in the Prom1 gene.

A technical guide to robotic-assisted carotid angioplasty and stenting with the Corindus CorPath GRX system.

Robotic-assisted carotid artery angioplasty and stenting is becoming more popular due to its precision and radiation safety. In this video, we present a case using the CorPath GRX Robotic System (Corindus, a Seimens Healthineers Company, Waltham, Massachusetts, USA) with step-by-step procedure process and technical nuances (video 1). We demonstrate that cervical carotid angioplasty and stenting can be safely performed using the robotic system with efficiency and accuracy.

Transvenous embolization of a carotid-cavernous fistula via the inferior ophthalmic vein: illustrative case.

BACKGROUND: A 49-year-old woman with a history of hypertension presented to the emergency department with right eye redness, proptosis, orbital fullness, and blurry vision. She had initially been diagnosed with an orbital pseudotumor, and the symptoms worsened over a course of steroids. Computed tomography angiography raised concern for a carotid-cavernous fistula (CCF), which was subsequently confirmed by digital subtraction angiography. OBSERVATIONS: She underwent fistula coil embolization via the internal maxillary artery and inferior ophthalmic vein (IOV). At the 2-month follow-up, she reported complete resolution of diplopia, orbital fullness, and proptosis. An ophthalmology examination revealed normal visual fields bilaterally. LESSONS: CCF embolization is rarely performed through the IOV, with only 5 reported cases in the literature. This case demonstrates that the procedure can be easily performed if the anatomy is favorable over the superior ophthalmic vein, with the illustration of good cosmetic outcomes. https://thejns.org/doi/10.3171/CASE24183.

Factors Affecting Selection of TraineE for Neurointervention (FASTEN).

BACKGROUND AND IMPORTANCE: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. METHODS: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs' characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. CONCLUSION: Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

Transient complete lower facial nerve palsy after craniotomy for aneurysm clipping.

We present the case of a 41-year old female who developed a complete facial nerve palsy after an interhemispheric approach for clipping of a distal anterior cerebral artery aneurysm. Work-up revealed that she had developed acute parotitis during surgery, possibly from obstruction of the parotid duct by the tracheal tube.

Cosmetic Outcomes of Supraorbital Keyhole Craniotomy Via Eyebrow Incision: A Systematic Review and Meta-Analysis.

Background Supraorbital eyebrow craniotomy is a minimally invasive alternative to a frontotemporal craniotomy and is often used for tumor and vascular pathologies. The purpose of this study was to investigate how patient cosmetic outcomes are affected by technique variations of this approach. Methods PubMed, Embase, and Scopus databases were systematically searched, and results were reported according to PRISMA guidelines. For the meta-analysis portion, the DerSimonian-Laird random effects model was used, and the primary end points were patient satisfaction and percentage of permanent cosmetic complications. Results A total of 2,629 manuscripts were identified. Of those, 124 studies (8,241 surgical cases) met the inclusion criteria. Overall, 93.04 ± 11.93% of patients reported favorable cosmetic outcome following supraorbital craniotomy, and mean number of cases with permanent cosmetic complications was 6.62 ± 12.53%. We found that vascular cases are associated with more favorable cosmetic outcomes than tumor cases ( p = 0.0001). Addition of orbital osteotomy or use of a drain is associated with adverse cosmetic outcomes ( p = 0.001 and p = 0.0001, respectively). The location of incision, size of craniotomy, utilization of an endoscope, method of cranial reconstruction, skin closure, use of antibiotics, and addition of pressure dressing did not significantly impact cosmetic outcomes ( p > 0.05 for all). Conclusions Supraorbital craniotomy is a minimally invasive technique associated with generally high favorable cosmetic outcomes. While certain techniques used in supraorbital keyhole approach do not pose significant cosmetic risks, utilization of an orbital osteotomy and the addition of a drain correlate with unfavorable cosmetic outcomes.

Successful mechanical thrombectomy for terminal ICA bullet embolism: A case report.

Bullet embolism after high velocity penetrating trauma is a rare event that can have devastating and wide-ranging effects distant from the original site of injury. A 29-year-old presented with multiple gunshot wounds to the chest, back, abdomen, and lower extremities but no penetrating head injury. After proper resuscitation, the patient was noted to have left-sided hemiparesis and computed tomography angiography of the head showed a bullet fragment that had traveled to the right M1 segment of the middle cerebral artery resulting in occlusion of the vessel. Mechanical thrombectomy was performed in an attempt to remove the bullet fragment but this was unsuccessful as the fragment was firmly lodged in the blood vessel. Aspiration of clot distal to the fragment was then performed in hopes of preventing a large volume ischemic event which was angiographically successful resulting in TICI 2c revascularization. This case demonstrates that thrombectomy can be safely and successfully performed distal to a lodged foreign body.

Sustained ICP Elevation Is a Driver of Spatial Memory Deficits After Intraventricular Hemorrhage and Leads to Activation of Distinct Microglial Signaling Pathways.

The mechanisms of cognitive decline after intraventricular hemorrhage (IVH) in some patients continue to be poorly understood. Multiple rodent models of intraventricular or subarachnoid hemorrhage have only shown mild or even no cognitive impairment on subsequent behavioral testing. In this study, we show that intraventricular hemorrhage only leads to a significant spatial memory deficit in the Morris water maze if it occurs in the setting of an elevated intracranial pressure (ICP). Histopathological analysis of these IVH + ICP animals did not show evidence of neuronal degeneration in the hippocampal formation after 2 weeks but instead showed significant microglial activation measured by lacunarity and fractal dimensions. RNA sequencing of the hippocampus showed distinct enrichment of genes in the IVH + ICP group but not in IVH alone having activated microglial signaling pathways. The most significantly activated signaling pathway was the classical complement pathway, which is used by microglia to remove synapses, followed by activation of the Fc receptor and DAP12 pathways. Thus, our study lays the groundwork for identifying signaling pathways that could be targeted to ameliorate behavioral deficits after IVH.

Robotic Diagnostic Cerebral Angiography: A Multicenter Experience of 113 Patients.

BACKGROUND: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography. METHODS: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF). The equipment used was the CorPath GRX Robotic System (Corindus, Waltham, MA). RESULTS: A total of 113 cases were analyzed who underwent robot-assisted diagnostic cerebral angiography from September 28, 2020 to October 27, 2022. There were no significant complications related to use of the robotic system including stroke, arterial dissection, bleeding, or pseudoaneurysm formation at the access site. Using the robotic system, 88 of 113 (77.9%) cases were completed successfully without unplanned manual conversion. The principal causes for unplanned manual conversion included challenging anatomy, technical difficulty with the bedside robotic cassette, and hubbing out of the robotic system due to limited working length. For robotic operation, average fluoroscopy time was 13.2 min (interquartile range (IQR), 9.3 to 16.8 min) and average cumulative air kerma was 975.8 mGY (IQR, 350.8 to 1073.5 mGy). CONCLUSIONS: Robotic cerebral angiography with the CorPath GRX Robotic System is safe and easily learned by novice users without much prior manual experience. However, there are technical limitations such as a short working length and an inability to support 0.035" wires which may limit its widespread adoption in clinical practice.

Intentional partial coiling dome protection of complex ruptured cerebral aneurysms prevents acute rebleeding and produces favorable clinical outcomes.

BACKGROUND: The coiling of ruptured cerebral aneurysms protects against acute rebleeding; however, whether partially coiling a ruptured cerebral aneurysm protects against acute rebleeding has never been demonstrated. OBJECTIVE: This study was performed to test our hypothesis that intentional partial coiling of complex ruptured cerebral aneurysms, which are unfavorable for clipping and cannot be completely coiled primarily, prevents acute rebleeding to allow for clinical and neurological recovery until definitive treatment and produces favorable clinical outcomes. METHODS: Data were collected from the prospective databases of three centers. Only subarachnoid hemorrhage patients that were treated with a strategy of intentional partial coiling for dome protection were included. This did not include patients in whom the goal was complete coiling but only subtotal coil occlusion was achieved. RESULTS: Fifteen patients [aged 51 ± 13 years; HH 3-5 (n = 7); Fisher 3-4 (n = 9)] were treated with intentional partial dome protection. Aneurysm size was 12.8 ± 5.4 mm; neck size 4.9 ± 3 mm; 12 anterior circulation. Four intentional partial coilings were performed with balloon assistance. Definitive treatment was performed 92 ± 90 days later, with no case of rebleeding. Definitive treatment was clipping (n = 8), stent-coiling (n = 5), Onyx (n = 1), further coiling (n = 1). Clinical outcome was favorable in 13 cases (GOS 4-5), fair in one (GOS 3), and death in one (GOS 1). CONCLUSIONS: Judicious use of a treatment strategy of intentional partial dome protection for complex aneurysms that are not favorable for clipping and in which complete coiling primarily is not possible may prevent acute rebleeding and produce favorable clinical outcomes.

Supraorbital Keyhole Craniotomy via Eyebrow Incision: A Systematic Review and Meta-Analysis.

BACKGROUND: Supraorbital eyebrow keyhole craniotomy is a minimally invasive alternative to a frontotemporal craniotomy and is often used for tumor resection and aneurysm clipping. The purpose of this study is to provide a contemporary review on the outcomes related to this approach and to determine whether they vary with the type of pathology and the addition of an endoscope. METHODS: PubMed, Embase, and Scopus databases were systematically searched, and results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the meta-analysis portion, the DerSimonian-Laird random effects model was used. RESULTS: A total of 2629 manuscripts were identified. of those, 124 studies (8241 surgical cases) met the inclusion criteria. Mean total complication rate was 26.7 ± 25.7% and the mean approach-related mortality rate was 1.3 ± 2.8%. Technical success, defined as gross total tumor resection or complete aneurysm clipping, was achieved in 83.6 ± 21.5% of the cases. Vascular pathologies were associated with greater technical success, lower total complications, and longer length of hospital stay compared with tumor cases (P < 0.05 for all). For vascular cases, addition of the endoscope yielded lower technical success (P = 0.001) and lower complication rate (P = 0.041). The use of the endoscope for tumor pathologies did not affect technical success, complications, mortality, length of hospital stay, operative time, or reoperation rate (P > 0.05). CONCLUSIONS: The supraorbital craniotomy via an eyebrow incision is a feasible minimally invasive approach with an overall high technical success rate for both vascular and tumor pathologies.

Intracranial Pressure Monitoring In Nontraumatic Intraventricular Hemorrhage Rodent Model.

Survivors of intraventricular hemorrhage are often left with significant long-term memory impairment; thus, research utilizing intraventricular hemorrhage animal models is essential. In this study, we sought out ways to measure intracranial pressure, mean arterial pressure, and cerebral perfusion pressure during nontraumatic intraventricular hemorrhage in rodents. The experimental design included three Sprague Dawley groups: sham, standard 200 µl intraventricular hemorrhage, and vehicle control groups. By introducing an intraparenchymal fiberoptic pressure sensor, precise intracranial pressure measurements were obtained in all groups. Cerebral perfusion pressures were calculated with the knowledge of intracranial pressure and mean arterial pressure values. As expected, the intraventricular hemorrhage and vehicle control groups both experienced a rise in the intracranial pressure and subsequent decline in cerebral perfusion pressure during intraventricular injection of autologous blood and artificial cerebrospinal fluid, respectively. The addition of an intraparenchymal fiberoptic pressure sensor is beneficial in monitoring precise intracranial pressure changes.

Mechanisms of memory impairment in animal models of nontraumatic intracranial hemorrhage: A systematic review of the literature.

Mechanisms underlying memory and cognitive dysfunction following spontaneous intracranial hemorrhage are diverse. The aim of this systematic review was to provide a contemporary review of the commonly reported mechanisms responsible for memory impairment following nontraumatic intracranial hemorrhage. PubMed, Embase, and Scopus databases were systematically searched for pre-clinical studies, and results were reported according to PRISMA guidelines. Methodological quality assessment was performed according to the SYRCLE's Risk of Bias tool. Ninety studies met the inclusion criteria. Most of animal studies reported on subarachnoid hemorrhage (48%), followed by intraparenchymal hemorrhage (44%), and intraventricular hemorrhage (8%). Most of subarachnoid hemorrhage studies (30%) reported neuronal apoptosis as a mechanism for memory dysfunction, whereas the most commonly described mechanism following intraparenchymal hemorrhage (40%) and intraventricular hemorrhage (23%) was a proinflammatory response. Based on SYRCLE's Risk of Bias assessment, the average methodological risk of bias of all studies was 56.83 ± 12.77% on a 0-100% scale. There is a great need not only for more preclinical studies with improved methodology, but also for studies reporting negative treatment effects and for multicenter animal studies. In vivo studies on non-rodent animal ICH models can also be helpful.

Incidence of Postoperative Cerebral Aneurysm Clip Slippage: Review of a Consecutive Case Series of 115 Clipped Aneurysms.

OBJECTIVE: Although delayed postoperative clip slippage has been reported in previous case reports and case series, its true incidence with high rate of follow-up imaging has not been reported. We attempted to determine the incidence of clip slippage in a cohort of consecutive aneurysm clippings. METHODS: We performed a retrospective review of a prospectively maintained database of 115 consecutive saccular aneurysm clippings at a single institution. Postoperative imaging was reviewed for clip slippage within 24 hours and at 3-12 months. Eighty-six aneurysms (75.8%) were exclusively clipped with Sugitaclip (Mizuho Medical, Tokyo, Japan) Titanium II clips, 16 aneurysms were exclusively clipped with Yasargil (Aesculap, Center Valley, PA) titanium clips (13.9%), 5 aneurysms were only clipped with Sugita aneurysm clips (4.3%), and 3 aneurysms were only clipped with Peter Lazic (Peter Lazic Microsurgical Innovations, Tuttlingen, Germany) clips (2.6%). RESULTS: In this cohort, 94.7% of clipped aneurysms had follow-up imaging within 24 hours, and 51.3% had delayed follow-up imaging within 3-12 months. We identified 3 cases of clip slippage in 115 consecutive aneurysm clippings, resulting in an incidence of 2.6%. The average cumulative closing force of clips per aneurysm across the study was 2.32 N, and the median number of clips placed was 1. Two of the 3 cases of clip slippage had a closing force <2.32 N and only placement of a single clip. CONCLUSIONS: Because our series showed a 2.6% incidence of clip slippage, clipped aneurysms should be monitored with early and delayed vascular follow-up imaging. Lower cumulative clip closing force, single clip placement, and oversized clip blade length may be risk factors for postoperative aneurysmal clip slippage.

Medial ganglionic eminence-derived neural stem cell grafts ease spontaneous seizures and restore GDNF expression in a rat model of chronic temporal lobe epilepsy.

Nearly 30% of patients with mesial temporal lobe epilepsy (TLE) are resistant to treatment with antiepileptic drugs. Neural stem cell (NSC) grafting into the hippocampus could offer an alternative therapy to hippocampal resection in these patients. As TLE is associated with reduced numbers of inhibitory gamma-amino butyric acid (GABA)-ergic interneurons and astrocytes expressing the anticonvulsant glial-derived neurotrophic factor (GDNF) in the hippocampus, we tested the hypothesis that grafting of NSCs that are capable of adding new GABA-ergic interneurons and GDNF-expressing astrocytes into the epileptic hippocampus restrains spontaneous recurrent motor seizures (SRMS) in chronic TLE. We grafted NSCs expanded in vitro from embryonic medial ganglionic eminence (MGE) into hippocampi of adult rats exhibiting chronic TLE with cognitive impairments. NSC grafting reduced frequencies of SRMS by 43% and stage V seizures by 90%. The duration of individual SRMS and the total time spent in seizures were reduced by 51 and 74%, respectively. Grafting did not improve the cognitive function however. Graft-derived cells (equivalent to approximately 28% of injected cells) were observed in various layers of the epileptic hippocampus where they differentiated into NeuN+ neurons (13%), S-100beta+ astrocytes (57%), and NG2+ oligodendrocyte-progenitors (3%). Furthermore, among graft-derived cells, 10% expressed GABA and 50% expressed GDNF. Additionally, NSC grafting restored GDNF in a vast majority of the hippocampal astrocytes but had no effect on neurogenesis. Thus, MGE-NSC therapy is efficacious for diminishing SRMS in chronic TLE. Addition of new GABA-ergic neurons and GDNF+ cells, and restoration of GDNF in the hippocampal astrocytes may underlie the therapeutic effect of MGE-NSC grafts.