Mark A. Liker

Human neural stem cell transplantation in the MPTP-lesioned mouse.

Human neural stem cells have exhibited a remarkable versatility to respond to environmental signals. Their characterization in models of neurotoxic injury may provide insight into human disease treatment paradigms. This study investigates the survival and migration of transplanted human stem cells and tyrosine hydroxylase immunoreactivity in the parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model, using antisera recognizing human nuclear protein (hNuc) and tyrosine hydroxylase (TH). Our results indicate long-term (up to 90 days) survival of human stem cell xenograft in the MPTP-lesioned mouse and the presence of hNuc-immunoreactive cells at sites distal to the transplant core. Few TH-positive cells are identified in the striatum by immunoperoxidase staining and using immunofluorescent double labeling, infrequent TH-immunoreactive, transplanted cells are identified.

Deep brain stimulation: a mechanistic and clinical update.

Deep brain stimulation (DBS), the practice of placing electrodes deep into the brain to stimulate subcortical structures with electrical current, has been increasing as a neurosurgical procedure over the past 15 years. Originally a treatment for essential tremor, DBS is now used and under investigation across a wide spectrum of neurological and psychiatric disorders. In addition to applying electrical stimulation for clinical symptomatic relief, the electrodes implanted can also be used to record local electrical activity in the brain, making DBS a useful research tool. Human single-neuron recordings and local field potentials are now often recorded intraoperatively as electrodes are implanted. Thus, the increasing scope of DBS clinical applications is being matched by an increase in investigational use, leading to a rapidly evolving understanding of cortical and subcortical neurocircuitry. In this review, the authors discuss recent innovations in the clinical use of DBS, both in approved indications as well as in indications under investigation. Deep brain stimulation as an investigational tool is also reviewed, paying special attention to evolving models of basal ganglia and cortical function in health and disease. Finally, the authors look to the future across several indications, highlighting gaps in knowledge and possible future directions of DBS treatment.

Deep Brain Stimulation: An Evolving Technology

Deep brain stimulation (DBS) is widely used as a safe and effective medical treatment for certain neurological disorders. It continues to evolve with improving techniques in functional neurosurgery and biomedical device engineering. This paper provides an overview of the enabling science and technology that have allowed DBS to successfully treat certain neurological disorders. It also points toward some of the engineering advances that will enable DBS to yield a more predictable outcome for current indications and to be systematically developed as a treatment for new indications.

Implantable Biomimetic Microelectronics Systems

This issue provides a comprehensive overview of state-of-the-art implantable biomimetic microelectronics systems, the diverse range of applications they serve, and the technologies enabling such systems. The 13 papers in this issue are summarized here.

Pediatric Deep Brain Stimulation Using Awake Recording and Stimulation for Target Selection in an Inpatient Neuromodulation Monitoring Unit

Deep brain stimulation (DBS) for secondary (acquired, combined) dystonia does not reach the high degree of efficacy achieved in primary (genetic, isolated) dystonia. We hypothesize that this may be due to variability in the underlying injury, so that different children may require placement of electrodes in different regions of basal ganglia and thalamus. We describe a new targeting procedure in which temporary depth electrodes are placed at multiple possible targets in basal ganglia and thalamus, and probing for efficacy is performed using test stimulation and recording while children remain for one week in an inpatient Neuromodulation Monitoring Unit (NMU). Nine Children with severe secondary dystonia underwent the NMU targeting procedure. In all cases, 4 electrodes were implanted. We compared the results to 6 children who had previously had 4 electrodes implanted using standard intraoperative microelectrode targeting techniques. Results showed a significant benefit, with 80% of children with NMU targeting achieving greater than 5-point improvement on the Burke⁻Fahn⁻Marsden Dystonia Rating Scale (BFMDRS), compared with 50% of children using intraoperative targeting. NMU targeting improved BFMDRS by an average of 17.1 whereas intraoperative targeting improved by an average of 10.3. These preliminary results support the use of test stimulation and recording in a Neuromodulation Monitoring Unit (NMU) as a new technique with the potential to improve outcomes following DBS in children with secondary (acquired) dystonia. A larger sample size will be needed to confirm these results.

Craniopharyngiomas: Surgical Management

Craniopharyngiomas are an unusual group of epithelial tumors thought to be derived from the embryonic remnants of an incompletely involuted hypophyseal-pharyngeal duct (Erdheim 1904). The name of the tumor was first introduced by Cushing in 1932, and has been considered by many to be a misnomer as Rathke’s pouch is actually an evagination of the primitive stomodeum and not the pharynx proper. They are encountered primarily in the sellar and parasellar regions but can be found anywhere along the developmental path of Rathke’s pouch (Podoshin et al. 1970). They occur with a peak incidence between 5 to 15 years of age but can present at any age (Sung et al. 1981). Visual loss and impairment, headache, apathy, depression, incontinence,hypersomnia, cognitive deficits, memory loss,sexual dysfunction, and growth failure are typical symptoms. Hydrocephalus and endocrine disorders are often present at the time of diagnosis (Carmel 1982). Due to the slow growth rate of these tumors,they are often quite large before becoming symptomatic.

Case Report: Targeting for Deep Brain Stimulation Surgery Using Chronic Recording and Stimulation in an Inpatient Neuromodulation Monitoring Unit, With Implantation of Electrodes in GPi and Vim in a 7-Year-Old Child With Progressive Generalized Dystonia

Background: Deep brain stimulation for secondary dystonia has been limited by unknown optimal targets for individual children. Objectives: We report the first case of a 7-year-old girl with severe generalized dystonia due to acquired striatal necrosis in whom we used a new method for identifying targets for deep brain stimulation. Methods: We implanted temporary depth electrodes in 5 different nuclei bilaterally in the basal ganglia and thalamus, with test stimulation and recording during 1 week while the child was an inpatient in a neuromodulation monitoring unit. Results: Single-unit activity in ventral intermedius Vim, internal globus pallidus (GPi), and subthalamic (STN) nuclei occurred during dystonic spasms and correlated with electromyography. Stimulation in Vim eliminated dystonic spasms. Subsequent implantation of 4 permanent deep brain stimulation electrodes in bilateral Vim and Gpi nuclei resolved dystonic spasms. Conclusion: The use of temporary stimulation and recording electrodes to identify deep brain stimulation targets is a promising new technique that could improve outcomes in children with acquired dystonia.

Neural interface technologies: applications of biomedical engineering to neurosurgery

The neurosurgical approach to diseases of the nervous system continues to evolve. As bioengineering technologies have advanced, an ally has been found to expand the role of the neurosurgeon in treating diseases not previously considered eligible for intervention. Not only are they purveyors of life-saving surgical treatments, but neurosurgeons have also embraced the application of new therapies for pain and disability, treating these as targeted disease entities in and of themselves. Consider the dramatic rise in implant technologies such as spinal pedicle screws and spinal cord stimulators to treat back pain, deep brain stimulators for functional disabilities, vagal nerve stimulators for epilepsy and depression, and peripheral nerve stimulators for pain and urinary incontinence. Sensory augmentation devices such as retinal prostheses and cochlear implant devices are in various stages of development by non-neurosurgeons and engineers. Technological developments have provided neuroscience-based clinicians with a venue to consider applications well beyond the purview of their predecessors. Many lessons can be gleaned from these and other “foreign” technologies, thereby accelerating the collaboration between the previously disparate disciplines of engineering and surgery and providing a venue for shared interests in the field of neural interface devices. In the future, leading neurosurgeons will continue to drive their craft forward by identifying the potential neurosurgical uses for emerging technology, directing engineering concepts toward surgical applications, and incorporating the technologies into daily practice.