A New Era for Surgical Neurotherapeutics
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Surgical interventions now have the potential to outperform traditional drug treatments in the management of many different neurological disorders. For example, in epilepsy, despite the introduction of more than a dozen new anti-epileptic medications over the past two decades, the overall rates of seizure freedom are unchanged [1, 2], whereas responsive neurostimulation is now known to confer significant improvements in seizure reduction and quality of life in these same medically refractory patients [3, 4]. Thus, modern neurosurgical techniques and devices, having low morbidity and, in many cases, excellent efficacy, are increasingly seen as part of a normal spectrum of treatment that includes medications, rather than existing in a separate dimension. In this issue of Neurotherapeutics, an international group of expert authors describe this new era for therapies delivered via neurosurgery, in which advances in neuroscience, computational biology, and imaging are driving both the evolution of traditional strategies and the initiation of novel approaches.
Evolution of Traditional Surgeries and Novel Adjuvants
First, Enslin and colleagues  describe the evolution of selective dorsal rhizotomy, one of the most commonly performed operations to treat spasticity in children with cerebral palsy. Poppler and colleagues  then review the state of the art for four types of chronic pain amenable to surgical treatment. Wilson and colleagues  next describe novel uses of nerve transfers, including nerve transfers for sensory reinnervation, nerve transfers for spinal cord injury and stroke patients, supercharge end-to-side nerve transfers, and targeted muscle reinnervation for the prevention and treatment of post-amputation neuroma pain. Switching gears to adjuvant techniques, Fernandez-Miranda and colleagues  provide an overview of high-definition fiber tractography, an advanced imaging technique that they developed, and have pioneered in neurosurgical planning to optimize functional outcomes in tumor surgery. Yeh and colleagues  then tackle the false connection problem in tractography imaging, describing topology-informed pruning (TIP), a method that automatically identifies singular tracts and eliminates them to improve fiber tracking accuracy. Continuing a computational theme, in an original research article, Vakharia and colleagues  describe machine learning approaches for predicting trajectories that optimize the extent of mesial temporal lobe ablations during laser interstitial thermal therapy of epilepsy. Katz and Abel  provide an overview of the modern use of intracranial monitoring techniques for identifying epileptic foci in medically intractable epilepsy. Addressing a field about which there is currently much buzz, Prada and colleagues  discuss the evolution of high-intensity focused ultrasound, providing an overview of current and future ablative applications in oncology and cerebrovascular neurology. Darrow  then describes the potential for low-intensity focused ultrasound, which can both excite and inhibit neural activity reversibly to deliver a range of reversible neuromodulation therapies.
Brain–Computer Interfaces for Restoring Movement, Seizure Control, Vision, and Speech
Brain–computer interfaces span from approaches that have been FDA-approved for decades to those on the verge of clinical application. Steigerwald and colleagues  begin this section by describing new deep brain stimulation electrode designs to control the direction of current flow and implications for DBS programming and improved patient outcomes. Neumann and colleagues  then go to the next level by providing detailed insight into factors that affect the development of intelligent, adaptive DBS that can deliver highly individualized treatment to patients with movement disorders. Along the same lines, Sisterson et al.  review the evolution of closed-loop brain stimulation for epilepsy, proposing an evidence-based solution for individualizing therapy that is driven by a bottom-up informatics approach. Focusing on pediatrics, Ibrahim and colleagues  address neuromodulatory strategies for the treatment of intractable epilepsy in children, including putative mechanisms of action and biomarkers for treatment success. Addressing vision restoration, Niketeghad and Pouratian  describe the historical thinking on cortical visual prosthetics, as well as the current state of the art, explaining the design of current devices that are either under development or in the clinical testing phase. Rabbani and colleagues  then complete this section by introducing us to the field of neural speech decoding using electrocorticography, exploring what a brain–computer interface for speech might entail.
In the single paper describing the neurosurgical application of biologics, Sudhakar and Richardson  describe the gene therapy field’s entry into a new technological era, in which interventional-MRI-guided convection-enhanced delivery (iMRI-CED) is the gold standard for verifying accurate vector delivery in real-time. This paradigm shift has the potential to accelerate the translation of therapies for neurodegenerative disorders that require direct delivery of the therapeutic agent into the brain parenchyma.
In all, the editors believe this collection of articles reflects a remarkable moment in the history of clinical neuroscience in which existing neurosurgical therapies continue to be fine-tuned whereas novel approaches break exciting ground.
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- 5.Enslin JMN, Langerak NG, Fieggen AG. The Evolution of Selective Dorsal Rhizotomy for the Management of Spasticity in Children. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00690-4.
- 6.Poppler LH, Mackinnon SE. The Role of the Peripheral Nerve Surgeon in the Treatment of Pain. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00695-z.
- 7.Wilson TJ. Novel Uses of Nerve Transfers. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-0664-x.
- 8.Panesar SS, Abhinav K, Yeh FC, Jacquesson T, Collins M, Fernandez-Miranda JC. Tractography for Surgical Neuro-Oncology. Planning: Towards a Gold Standard. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00697-x.
- 9.Panesar S, Abhinav K, Yeh FC, , Barrios J, Fernandes D Meola A, Fernandez-Miranda JC. Improved Accuracy of Diffusion MRI Tractography Using Topology-Informed Pruning (TIP). Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-0663-y.
- 10.Vakharia VN, Li K, Sparks R, França LGS, Granados A, McEvoy AW, Miserocchi A, Wang M, Ourselin S, Duncan JS. Optimizing Trajectories for Cranial Laser Interstitial Thermal Therapy Using Computer-Assisted Planning: A Machine Learning Approach. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00693-1.
- 11.Katz JS, Abel TJ. Stereoelectroencephalography and Subdural Electrodes for Identification of the Epileptogenic Zone. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00703-2.
- 12.Prada F, Kalani MYS, Yagmurlu K, Norat P, Del Bene M, DiMeco F, Kassell NF. FUS in Cerebrovascular Disease and Brain Tumors. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00683-3.
- 13.Darrow, David P. Focused Ultrasound for Neuromodulation. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00691-3.
- 14.Steigerwald F, Matthies C, Volkmann J. Directional Deep Brain Stimulation. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-0667-7.
- 15.Neumann J-W, Turner RS, Blankertz B, Mitchell T, Kuhn, A, Richardson RMR. Toward Electrophysiology-based Intelligent Adaptive Deep Brain Stimulation for Movement Disorders. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00705-0.
- 16.Sisterson ND, Wozny TA, Kokkinos V, Constantino A, Richardson RM. Closed-loop Brain Stimulation for Drug-Resistant Epilepsy: Towards an Evidence-Based Approach to Personalized Medicine. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00682-4.
- 17.Hachem LD, Yan H, Ibrahim G. Advances in Neuromodulation in Pediatric Epilepsy, Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00685-1.
- 18.Pouratian N, Niketeghad S. Brain Machine Interfaces for Vision Restoration: The Current State of Cortical Visual Prosthetics. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-0660-1.
- 19.Rabbani Q, Milsap G, Crone N. Brain Machine Interfaces for Motor Restoration, Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00692-2.
- 20.Sudhakar V, Richardson RM. Gene Therapy for Neurodegenerative Diseases. Neurotherapeutics 2019. https://doi.org/10.1007/s13311-018-00694-0.