The Spaghetti Sign: Nerve Root Redundancy in Lumbar Spinal Stenosis.

OBJECTIVE: Redundant nerve roots (RNRs) seen in conjunction with lumbar spinal stenosis (LSS) are well-described radiographic findings. Several studies suggest their presence may be a negative prognostic indicator of postoperative outcome. Our hypothesis was that severe RNR (informally known as the spaghetti sign [SS]) can serve as a reliable marker of LSS that would benefit from surgical decompression. We sought to evaluate a grading scale for RNR, characterize the association with stenosis, and investigate the clinical implications of RNR. METHODS: We conducted a retrospective chart review of 72 patients who underwent lumbar spine surgery from 2016 to 2018 at 1 institution. Preoperative T2 magnetic resonance imaging scans were graded by 3 reviewers for severity of stenosis (0-4), severity of RNR (0-3), and rostral versus caudal RNR. SS was defined as RNR score ≥2 (clear-cut or marked nerve root irregularity). Preoperative and postoperative Oswestry Disability Index scores were analyzed by stenosis and RNR severity. RESULTS: Seventy-one (98%) patients had severe stenosis (score ≥3) and 25 (35%) had a SS. SS was 100% specific for high-grade stenosis. If patients had a SS, it was more likely rostral (P=0.02). Postoperative Oswestry Disability Index scores improved significantly, but there were no differences related to RNR score, presence of SS, or stenosis severity. CONCLUSIONS: The study demonstrated that there is a significant association between SS and severe LSS and that presence of RNR is not a negative prognostic indicator for postoperative outcomes.

Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown. METHODS: This multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed. RESULTS: Engel I seizure freedom was achieved in 55.8% (149/267) at 1 year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1 year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1 year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1 year. CONCLUSIONS: MRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT.

Cochlear implants and deep brain stimulators.

OBJECTIVE AND IMPORTANCE: With an aging population and increasing utilization of both cochlear implants (CI) to treat hearing loss and deep brain stimulation (DBS) to treat neurodegenerative movement disorders, more patients will be sequentially implanted with the two devices. As such, understanding both presurgical evaluations and surgical procedures will be of great importance to the treating cochlear implant surgeon and neurosurgeon in optimizing outcomes for both conditions. CLINICAL PRESENTATION: Two illustrative cases of sequential CI followed by DBS are reviewed. Relevant pre-, intra-, and postoperative issues are discussed for both DBS following CI surgery and CI following DBS surgery. CONCLUSION: Despite the potential for challenges, sequential CI and DBS (and vice versa) can provide substantial benefit to those individuals with severe hearing loss and movement disorders. A thorough understanding of both devices is critical to ensuring optimal outcomes.

Use of a Pericranial Flap Technique for Deep Brain Stimulation Hardware Protection and Improved Cosmesis.

OBJECTIVES: Deep brain stimulation (DBS) has become an established neuromodulation therapy; however, surgical site complications such as hardware skin erosion remain an important risk and can predispose to infection, requiring explantation of the system. Nuances of surgical technique can affect wound healing, cosmetic outcome, comfort, and risk of infection. In this study, we describe our experience with a layered closure technique using a vascularized pericranial flap for improving cosmesis and protection of the implanted hardware against skin erosion and infection. MATERIALS AND METHODS: We retrospectively reviewed 636 individuals (746 lead implantations) who underwent DBS surgery by a single academic neurosurgeon between 2001 and 2020. A layered pericranial flap closure technique for the burr-hole and connector sites was instituted in 2015. We assessed the effects of a multimodal infection prevention approach that included the pericranial flap on hardware complication rates compared with the premultimodality cohort, and we report the nuances of the technique. RESULTS: In our institutional experience, we found that implementation of a pericranial flap closure technique can enhance the subjective cosmetic result at the burr-hole cover site and increase patient comfort and satisfaction. In addition, we found a decrease in hardware infection rates in the current cohort with a multimodal infection prevention regimen that includes the pericranial-flap technique (n = 256, 2015-2020 period) to 1.2% (p = 0.006), from 6.9% in the earlier cohort (n = 490, 2001-2015 period). CONCLUSIONS: The report highlights the potential of a pericranial-flap closure technique as a surgical adjunct to improve DBS surgical site healing and cosmesis and may, as part of a multimodal strategy, contribute to decreased risk of skin breakdown and hardware infection.

Recrudescent infection after deep brain stimulator reimplantation.

OBJECTIVE: The efficacy of deep brain stimulation (DBS) in treating the symptoms of movement disorders can be life changing for patients. Thus, the 5%-15% incidence of stimulator-related infection requiring removal of the device can be particularly disheartening. Although DBS system reimplantation is generally successful, this is not always the case. The literature is replete with publications describing the incidence of infection and the associated features. However, the literature is sparse in terms of information on the incidence of recurrent or recrudescent infection after system reimplantation. The goal of this paper was to evaluate factors leading to unsuccessful reimplantation of a DBS system following initial infection. METHODS: Data were reviewed for all DBS procedures performed by one surgeon (K.L.H.) over 19 years including the infectious agent, location of infection, treatment regimen, and subsequent reimplantation of a DBS system and long-term outcome. RESULTS: In this series of 558 patients who had undergone DBS surgery, 37 (6.6%) subsequently developed an infection. Infections with methicillin-sensitive Staphylococcus aureus, Enterobacter species, or coagulase-negative staphylococci were predominant. Four patients had cerebritis, one had meningitis, and the rest had soft tissue infections of the pocket or scalp. All had their entire DBS system explanted, followed by 4-6 weeks of intravenous antibiotics and surveillance for recrudescence for an additional period of at least 30 days. Twenty-five patients subsequently underwent DBS system reimplantation, and the procedure was successful in 22. Three of the 4 patients with cerebritis developed a subsequent wound infection after system reimplantation. None of the other 22 patients developed a recurrence. The odds ratio for developing a recurrent infection after cerebritis was 28.5 (95% CI 1.931-420.5, p = 0.007). CONCLUSIONS: This study, the largest series of DBS system reimplantations following infection, demonstrated that most patients can have successful reimplantations without recurrent infection. However, patients who have had DBS-related cerebritis have a nearly 30-fold increased risk of developing reinfection after reimplantation. Alternative strategies for these patients are discussed.

Utility of GPI+VIM dual-lead deep brain stimulation for Parkinson's disease patients with significant residual tremor on medication.

OBJECTIVE: Randomized controlled trials have demonstrated that deep brain stimulation (DBS) of both the globus pallidus internus (GPI) and subthalamic nucleus (STN) for Parkinson's disease (PD) is superior to the best medical therapy. Tremor is particularly responsive to DBS, with reports of 70%-80% improvement. However, a small number of patients do not obtain the expected response with both STN and GPI targets. Indeed, the authors' patient population had a similar 81.2% tremor reduction with a 9.6% failure rate. In an analysis of these failures, they identified patients with preoperative on-medication tremor who subsequently received a GPI lead as a subpopulation at higher risk for inadequate tremor control. Thereafter, STN DBS was recommended for patients with on-medication tremor. However, for the patients with symptoms and comorbidities that favored GPI as the target, dual GPI and ventral intermediate nucleus of the thalamus (VIM) leads were proposed. This report details outcomes for those patients. METHODS: This is a retrospective review of patients with PD who met the criteria for and underwent simultaneous GPI+VIM DBS surgery from 2015 to 2020 and had available follow-up data. The preoperative Unified Parkinson's Disease Rating Scale scores were obtained with the study participants on and off their medication. Postoperatively, the GPI lead was kept on at baseline and scores were obtained with and without VIM stimulation. RESULTS: Thirteen PD patients with significant residual preoperative tremor on medication underwent simultaneous GPI+VIM DBS surgery (11 unilateral, 2 bilateral). A mean 90.6% (SD 15.0%) reduction in tremor scores was achieved with dual GPI+VIM stimulation compared to a 21.8% (SD 71.9%) reduction with GPI stimulation alone and a 30.9% (SD 37.8%) reduction with medication. Although rigidity and bradykinesia reductions were accomplished with just GPI stimulation, 13 of the 15 hemispheres required VIM stimulation to achieve excellent tremor control. CONCLUSIONS: GPI+VIM stimulation was required to adequately control tremor in all but 2 patients in this series, substantiating the authors' hypothesis that, in their population, medication-resistant tremor does not completely respond to GPI stimulation. Dual stimulation of the GPI and VIM proved to be an effective option for the patients who had symptoms and comorbidities that favored GPI as a target and had medication-resistant tremor.

The Poised Cannula Technique Reduces the Stereotactic Error of the Fiducial-Less Frameless DBS Procedure.

BACKGROUND: In this study, we describe a technique of optimizing the accuracy of frameless deep brain stimulation (DBS) lead placement through the use of a cannula poised at the entry to predict the location of the fully inserted device. This allows real-time correction of error prior to violation of the deep gray matter. METHODS: We prospectively gathered data on radial error during the operative placements of 40 leads in 28 patients using frameless fiducial-less DBS surgery. Once the Nexframe had been aligned to target, a cannula was inserted through the center channel of the BenGun until it traversed the pial surface and a low-dose O-arm spin was obtained. Using 2 points along the length of the imaged cannula, a trajectory line was projected to target depth. If lead location could be improved, the cannula was inserted through an alternate track in the BenGun down to target depth. After intraoperative microelectrode recording and clinical assessment, another O-arm spin was obtained to compare the location of the inserted lead with the location predicted by the poised cannula. RESULTS: The poised cannula projection and the actual implant had a mean radial discrepancy of 0.75 ± 0.64 mm. The poised cannula projection identified potentially clinically significant errors (avg 2.07 ± 0.73 mm) in 33% of cases, which were reduced to a radial error of 1.33 ± 0.66 mm (p = 0.02) after correction using an alternative BenGun track. The final target to implant error for all 40 leads was 1.20 ± 0.52 mm with only 2.5% of errors being >2.5 mm. CONCLUSION: The poised cannula technique results in a reduction of large errors (>2.5 mm), resulting in a decline in these errors to 2.5% of implants as compared to 17% in our previous publication using the fiducial-less method and 4% using fiducial-based methods of DBS lead placement.

Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. METHODS: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. RESULTS: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. SIGNIFICANCE: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

A Comparative Study of Fiducial-Based and Fiducial-Less Registration Utilizing the O-Arm.

BACKGROUND: Frameless stereotactic surgery utilizing fiducial-based (FB) registration is an established tool in the armamentarium of deep brain stimulation (DBS) surgeons. Fiducial-less (FL) registration via intraoperative CT, such as the O-arm, has been routinely used in spine surgery, but its accuracy for DBS surgery has not been studied in a clinical setting. OBJECTIVE: We undertook a study to analyze the accuracy of the FL technique in DBS surgery and compare it to the FB method. METHODS: In this prospective cohort study, 97 patients underwent DBS surgery using the NexFrame and the O-arm registration stereotactic system. Patients underwent FB (n = 50) registration from 2015 to 2016 and FL (n = 47) O-arm registration from 2016 to 2017. RESULTS: The radial errors (RE) and vector/euclidean errors of FB and FL registration were not significantly different. There was no difference in additional passes between methods, but there was an increase in the number of RE ≥2.5 mm in the FL method. CONCLUSION: Although there was no statistically significant difference in RE or the need for additional passes, the increased number of errors ≥2.5 mm with the FL method (17 vs. 4% in FB) indicates the need for further study. We concluded that O-arm images of the implants should be utilized to assess and correct for this error.

Frameless Functional Stereotactic Approaches.

The stereotactic frame has served as the gold standard apparatus for accurate and precise targeting of deep brain structures since 1947. Despite passing the test of time, the stereotactic frame has several limitations from the perspective of both neurosurgeons and patients. Therefore, there was a need to develop a frameless system that had equivalent accuracy and reliability to the frame. This need was met with 3 commercially available frameless stereotactic systems designed specifically for deep brain stimulation surgery: Nexframe, STarFix, and ClearPoint. Over the past decade, the frameless and frame-based systems have been extensively investigated by numerous studies and found to be equivalent in experimental and clinical accuracy as well as in clinical outcomes. This chapter summarizes the findings of those studies along with the discussion of sources of stereotactic errors. The procedural aspects, advantages, and disadvantages of each frameless system are reviewed. Frameless stereotaxy is a safe, accurate, and effective technique for functional stereotactic approaches and provides a viable alternative to the frame-based systems.

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial.

BACKGROUND: Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. METHODS: Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. FINDINGS: Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. INTERPRETATION: This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. FUNDING: Abbott (previously St Jude Medical).

Extracorporeal irradiation of tumorous calvaria: a case series.

OBJECT When intracranial tumors invade the overlying skull, gross resection typically includes removal of the involved bone. Methods used to repair the resulting structural defect in the cranium include artificial prostheses, allogeneic bone grafts, and autoclaving the autologous graft. The authors have previously reported a case involving high-dose extracorporeal ionizing radiation to treat the tumorous calvaria intraoperatively, followed by reimplantation of the treated bone flap. In this paper the authors report the long-term follow-up of that case, as well as results of using extracorporeal irradiation of tumorous calvaria (EITC) for an additional 20 patients treated similarly. METHODS The decision to undergo EITC was typically anticipated preoperatively, but determined intraoperatively, if upon inspection the bone flap was invaded by tumor. The bone flap was then delivered to the radiation oncology department, where a total dose of 120 Gy was delivered, using a clinical linear accelerator, over a period of approximately 15 minutes. After the intracranial tumor resection was completed, the irradiated craniotomy bone flap was reimplanted and the wound was closed in a standard fashion. A retrospective review of patients who had undergone EITC was performed for evidence of calvarial tumor recurrence or other complications. RESULTS Since the originally reported case, 20 additional patients have received EITC during craniotomy for invasive tumors. Eighteen (86%) of 21 patients were diagnosed with meningioma: 12 (67%) with WHO Grade I, 5 (28%) with WHO Grade II, and 1 with WHO Grade III (6%). The remaining 3 patients presented with dural-based B-cell lymphoma with extensive adjacent bone invasion (n = 2) and metastatic adenocarcinoma of the lung (n = 1). Follow-up of the 21 patients ranged from 1 to 132 months, with a mean of 41 months and a median of 23 months. No patients have experienced tumor recurrence, infection associated with the treated calvaria, or evidence of bone flap resorption. CONCLUSIONS Calvaria reconstructions represent an important component in structural and cosmetic outcome following craniectomy for tumorous bone. The authors' long-term experience with EITC has been excellent with no local tumor recurrence or complications. Therefore, EITC represents an excellent and efficient option for cranial reconstruction in such patients.

Image-guided deep brain stimulation.

Advances in deep brain stimulation (DBS) surgery have been achieved through the use of stereotactic targeting of key tracks in patients undergoing awake surgery. Intraoperative detection of track location has been useful in interpreting physiologic results, has limited the number of brain penetrations, and has decreased the incidence of reoperations. Alternatively, some centers are gaining experience with placement of the lead under general anesthesia using a purely anatomic approach, for which both computed tomography and magnetic resonance imaging have proved useful. In this article, the use of image guidance with both the anatomic and physiologic approaches is described.

Deep brain stimulation for dystonia: a meta-analysis.

Objective. To use a meta-analysis on all reported cases of deep brain stimulation (DBS) for dystonia to determine which factors significantly influence outcome. The Burke-Fahn-Marsden (BFM) movement scale, the most reported measure, was chosen as the primary outcome measure for this analysis. Methods. A MEDLINE search identified 137 patients who underwent DBS for dystonia in 24 studies that had individual BFM scores. Individual patient data, including age at onset of dystonia, age at surgery, gender, distribution of dystonia, etiology of dystonia, presence of associated features, abnormality of preoperative imaging, prior stereotactic surgeries, nucleus stimulated, type of anesthesia used, use of physiologic monitoring, type of imaging used for localization, stimulation parameters used, time of response to stimulation, and timing of outcome assessment were entered into an SPSS database for statistical analysis. Results. The mean BFM percentage change (improvement in postoperative score from baseline) was 51.8% (range -34% to 100%). Significantly better outcomes were achieved with stimulation of the globus pallidus internus (GPi) than with stimulation of the posterior portion of the ventral lateral (VLp) nucleus of the thalamus (p = 0.0001). The etiology of the dystonia also had a significant effect on outcomes. Statistically significant improvements in outcomes were seen for all etiologic categories, except encephalitis. Dystonia due to birth injury and encephalitis had significantly worse outcomes when compared to other etiologies. However, there were no significant differences in the outcomes of patients who were DYT1 (DYT1 is the gene associated with the disorder Dystonia Musculorum Deformans) gene positive, DYT1 gene negative, or had pantothenate kinase-associated neurodegeneration (PKAN), tardive dyskinesia, and idiopathic and posttraumatic dystonias. Longer duration of dystonia symptoms correlated negatively with surgical outcome. A regression model using the three variables-stimulation site, etiology of dystonia, and duration of dystonia symptoms-explained 51% of the variance in outcomes. Conclusion. Deep brain stimulation of the GPi provides significant improvement in BFM scores in a variety of dystonic conditions.

Cell replacement efforts to repair neuronal injury: a potential paradigm for the treatment of Parkinson's disease.

Much has been learned from recent clinical trials exploring cell transplantation as a means to treat Parkinson's disease. Additionally, much information is being gathered in the science arena on the method of cultivation and expansion of neural stem/progenitor cells as well as catheter and cell delivery methodology. Cell replacement remains a potential promising treatment option for Parkinson's disease, however several obstacles must be overcome in order to achieve successful outcomes in future clinical trials. Hurdles include but are not limited to the identification of a reliable method of cultivation and expansion of neural stem/progenitor cells, the optimization of methods for cell delivery and the optimization of location or locations for transplantation.

Frameless stereotaxy using bone fiducial markers for deep brain stimulation.

OBJECT: Functional neurosurgical interventions such as deep brain stimulation (DBS) are traditionally performed with the aid of a stereotactic frame. Although frameless techniques have been perceived as less accurate, data from a recent phantom study of a modified frameless approach demonstrated a laboratory accuracy exceeding that obtained using a common frame system. The present study was conducted to evaluate the accuracy of a frameless system in routine clinical use. METHODS: Deep brain stimulation leads were implanted in 38 patients by using a skull-mounted trajectory guide and an image-guided workstation. Registration was accomplished with bone fiducial markers. Final lead positions were measured on postoperative computerized tomography scans and compared with the planned lead positions. The accuracy of the Leksell frame within the clinical situation has been reported on in a recent study; these raw data served as a comparison data set. The difference between expected and actual lead locations in the x plane was 1.4 mm in the frame-based procedure and 1.6 mm in the frameless procedure. Similarly, the difference in the y plane was 1.6 mm in the frame-based system and 1.3 mm in the frameless one. The error was greatest in the z plane, that is, 1.7 mm in the frame-based method and 2 mm in the frameless system. Multivariate analysis of variance demonstrated no statistically significant difference in the accuracy of the two methods. CONCLUSIONS: The accuracy of the frame-based and frameless systems was not statistically significantly different (p = 0.22). Note, however, that frameless techniques offer advantages in patient comfort, separation of imaging from surgery, and decreased operating time.

Heterotypic neuronal differentiation of adult subependymal zone neuronal progenitor cells transplanted to the adult hippocampus.

Neuronal progenitor cells (NPCs) residing in the adult subependymal zone (SEZ) are a potential source of expandable cells for autologous transplantation to replace neurons lost in multiple types of brain injury. To characterize the capacity of these cells for neuronal differentiation in a mature ectopic environment, NPCs expanded from the SEZ of adult rats were transplanted to the adult dentate gyrus. Cultures comprised a heterogeneous population of proliferating cells, which expressed nestin (47%) and GFAP (37%), with many cells expressing both progenitor cell markers (31%). In grafts of undifferentiated cells, as well as in grafts of cells that were induced to differentiate in vitro with retinoic acid, 35% of the transplanted SEZ-derived cells exhibited immunohistochemical and morphological features characteristic of hippocampal granule cell neurons. These novel results indicate that in vitro expanded adult SEZ NPCs are capable of heterotypic neuronal differentiation in a neurogenic region of the adult brain.

Grafts of adult subependymal zone neuronal progenitor cells rescue hemiparkinsonian behavioral decline.

Neuronal progenitor cells (NPCs) residing in the adult subependymal zone (SEZ) are a potential source of expandable cells for autologous transplantation to treat Parkinson's Disease and other types of brain injury. We have previously demonstrated the capacity of transplanted adult SEZ NPCs for heterotypic differentiation in the hippocampus. To further characterize the therapeutic potential of these cells, NPCs expanded from the adult rat SEZ were grafted to the striatum of normal and 6-OHDA lesioned adult rats. Grafted cells were assessed for neuronal differentiation, and lesioned animals were tested for amphetamine-induced rotational asymmetry. In addition, the effect of inducing differentiation in vitro prior to transplantation was assessed. Although grafted cells survived after 2 weeks in all animals, neither striatal deafferentation nor in vitro induction of differentiation resulted in significant neuronal differentiation of transplanted cells. Grafts, however, did produce a behavioral effect. While sham animals exhibited increased rotational behavior (+67%) from 2 to 4 weeks post-lesioning, grafted animals did not (-21%). Grafted cells continued to express nestin at the survival time point, and dopamine transporter (DAT) immunoreactivity was restored in the graft body. These results suggest that although neither the normal nor the deafferented striatum alone support the neuronal differentiation of transplanted adult SEZ NPCs, grafts maintaining a progenitor phenotype may produce a therapeutic benefit.

Progress in cerebral transplantation of expanded neuronal stem cells.

OBJECT: Given the success and limitations of human fetal primary neural tissue transplantation, neuronal stem cells (NSCs) that can be adequately expanded in culture have been the focus of numerous attempts to develop a superior source of replacement cells for restorative neurosurgery. To clarify recent progress toward this goal, the transplantation into the adult brain of NSCs, expanded in vitro before grafting, was reviewed. METHODS: Neuronal stem cells can be expanded from a variety of sources, including embryos, fetuses, adult bone marrow, and adult brain tissue. Recent investigations of each of these expanded stem cell types have generated a large body of information along with a great number of unanswered questions regarding the ability of these cells to replace damaged neurons. Expanded NSCs offer many advantages over their primary tissue predecessors, but also may exhibit different functional abilities as grafted cells. Because expanded NSCs will most likely ultimately replace primary tissue grafting in clinical trials, this review was undertaken to focus solely on this distinct body of work and to summarize clearly the existing preclinical data regarding the in vivo successes, limits, and unknowns of using each expanded NSC type when transplanted into the adult brain. CONCLUSIONS: Embryonic stem cell-derived cells have demonstrated appropriate neuronal phenotypes after transplantation into nonneurogenic areas of the adult brain. Understanding the mechanisms responsible for this may lead to similar success with less studied adult neuronal progenitor cells, which offer the potential for autologous NSC transplantation with less risk of tumorigenesis.

The application accuracy of a skull-mounted trajectory guide system for image-guided functional neurosurgery.

OBJECTIVE: Frameless image guided systems have traditionally been perceived as being less accurate than stereotactic frames, limiting their adoption for trajectory-based procedures such as deep brain stimulator placement which require submillimetric accuracy. However, some studies have suggested that high degrees of accuracy are attainable with optical localization systems. We evaluated the application accuracy of a skull-mounted trajectory guide coupled to an optical image-guided surgery system in a laboratory setting. MATERIALS AND METHODS: A plastic skull phantom was fitted with five fiducial markers rigidly attached via self-drilling bone screws. Varying MRI and CT imaging protocols were obtained at 25 different centers. A metal disc marked in 1-mm increments was placed at the expected target point. Following registration and alignment of the trajectory guide, radial and depth localization errors were measured. A total of 560 measurements were obtained and detailed statistical analyses were performed. RESULTS: Mean localization error was 1.25 mm with a 95% confidence interval of 2.7 mm and a 99.9% confidence interval of 4.0 mm. These values were significantly lower than those published for the two most widely used frame systems (p<0.001). CONCLUSIONS: Accuracy of image-guided localization using a rigid trajectory guide can meet or exceed that achievable with a stereotactic frame.