Intrathecal baclofen in current neuromodulatory practice: established indications and emerging applications.

Intrathecal baclofen (ITB) has evolved into a standard treatment for severe spasticity of both spinal and cerebral origin. The accumulated promising data from reported series of patients receiving ITB therapy together with the fact that spastic hypertonia commonly coexists with other neurological disorders have constituted a solid basis for offering this kind of treatment to patients suffering from other movement disorders. These include motor disorders such as dystonia, amyotrophic lateral sclerosis, status dystonicus, Hallervorden-Spatz disease, Freidreich's ataxia, "stiff-man" syndrome, but also vegetative states after revere brain trauma, anoxic encephalopathy or other pathology and more recently, various chronic pain syndromes. In this article, on the basis of the established applications of ITB therapy, we review the important emerging indications of this rewarding neuromodulation method and attempt to identify its future potential beneficial role in other chronic and otherwise refractory neurological disorders.

An introduction to neural networks surgery, a field of neuromodulation which is based on advances in neural networks science and digitised brain imaging.

Operative Neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. The present article reviews relevant literature on procedures or devices applied either in contact with the cerebral cortex or cranial nerves or in deep sites inside the brain in order to treat various refractory neurological conditions such as: a) chronic pain (facial, somatic, deafferentation, phantom limb), b) movement disorders (Parkinson's disease, dystonia, Tourette syndrome), c) epilepsy, d) psychiatric disease, e) hearing deficits, and f) visual loss. These data indicate that in operative neuromodulation, a new field emerges that is based on neural networks research and on advances in digitised stereometric brain imaging which allow precise localisation of cerebral neural networks and their relay stations; this field can be described as Neural networks surgery because it aims to act extrinsically or intrinsically on neural networks and to alter therapeutically the neural signal transmission with the use of implantable electrical or electronic devices. The authors also review neurotechnology literature relevant to neuroengineering, nanotechnologies, brain computer interfaces, hybrid cultured probes, neuromimetics, neuroinformatics, neurocomputation, and computational neuromodulation; the latter field is dedicated to the study of the biophysical and mathematical characteristics of electrochemical neuromodulation. The article also brings forward particularly interesting lines of research such as the carbon nanofibers electrode arrays for simultaneous electrochemical recording and stimulation, closed-loop systems for responsive neuromodulation, and the intracortical electrodes for restoring hearing or vision. The present review of cerebral neuromodulatory procedures highlights the transition from the conventional neurosurgery of resective or ablative techniques to a highly selective "surgery of networks". The dynamics of the convergence of the above biomedical and technological fields with biological restorative approaches have important implications for patients with severe neurological disorders.

Neurosurgery for psychiatric disorders: from the excision of brain tissue to the chronic electrical stimulation of neural networks.

Neurosurgical treatment for psychiatric disorders has a long and controversial history dating back to antiquity. Both enthusiastic reports and social outcry have accompanied psychosurgical practice, particularly over the last century. Frontal lobotomy has probably been the only medical advance which was first awarded a Nobel prize in medicine and then irreparably stigmatized by scientific rejection and public criticism. In the present paper, the historical milestones of psychosurgery are briefly overviewed. The particular circumstances of the rise and fall of frontal lobotomy are also discussed. Furthermore, the clinical and surgical considerations of the four major psychosurgical procedures which are still in practice are presented. Over the last fifteen years, the advent of deep brain stimulation (DBS) methodology coupled with accurate stereotactic techniques and guided by elaborate neuroimaging methods have revolutionized neurosurgery, particularly for the alleviation of certain disabling movement disorders. Investigationally, chronic electrical stimulation of selected brain structures, clearly implicated in the pathophysiology of neuropsychiatric disorders, has already been applied with promising results. Given the tainted past of psychiatric neurosurgery, modern neuroscientists have to move forward cautiously, in a scientifically justified and ethically approved framework. The transition from the indiscriminate destruction of brain structures to the selected electrical modulation of neural networks lies ahead; contemporary neuroscientists would substantiate this aim but should remind the controversial history of the field.

Brain-computer interface: a reciprocal self-regulated neuromodulation.

Brain-computer interface (BCI) is a system that records brain activity and process it through a computer, allowing the individual whose activity is recorded to monitor this activity at the same time. Applications of BCIs include assistive modules for severely paralyzed patients to help them control external devices or to communicate, as well as brain biofeedback to self regulate brain activity for treating epilepsy, attention-deficit hyperactivity disorder (ADHD), anxiety, and other psychiatric conditions, or to enhance cognitive performance in healthy individuals. The vast majority of BCIs utilizes non-invasive scalp recorded electroencephalographic (EEG) signals, but other techniques like invasive intracortical EEG, or near-infrared spectroscopy measuring brain blood oxygenation are tried experimentally.

Connections of the basal ganglia with the limbic system: implications for neuromodulation therapies of anxiety and affective disorders.

The basal ganglia are best known for their role in motor planning and execution. However, it is currently widely accepted that they are also involved in cognitive and emotional behaviors. Parts of the basal ganglia play a key role in reward and reinforcement, addictive behaviors and habit formation. Pathophysiological processes underlying psychiatric disorders such as depression, obsessive compulsive disorder and even schizophrenia involve the basal ganglia and their connections to many other structures and particularly to the prefrontal cortex and the limbic system. In this article, we aim, on the basis of current research, to describe in a succinct manner the most important connections of the basal ganglia with the limbic system which are relevant to normal behaviors but also to psychiatric disorders. Currently, we possess sufficiently powerful tools that enable us to modulate brain networks such as cortex stimulation (CS) or deep brain stimulation (DBS). Notably, neuromodulation of basal ganglia function for the treatment of movement disorders has become a standard practice, which provides insights into the psychiatric problems that occur in patients with movement disorders. It is clear that a sound understanding of the currently available knowledge on the circuits connecting the basal ganglia with the limbic system will provide the theoretical platform that will allow precise, selective and beneficial neuromodulatory interventions for refractory psychiatric disorders.

An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology.

Operative neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. It is a rapidly evolving biomedical and high-technology field on the cutting-edge of developments across a wide range of scientific disciplines. The authors review relevant literature on the neuromodulation procedures that are performed in the spinal cord or peripheral nerves in order to treat a considerable number of conditions such as (a) chronic pain (craniofacial, somatic, pelvic, limb, or due to failed back surgery), (b) spasticity (due to spinal trauma, multiple sclerosis, upper motor neuron disease, dystonia, cerebral palsy, cerebrovascular disease or head trauma), (c) respiratory disorders, (d) cardiovascular ischemia, (e) neuropathic bladder, and (f) bowel dysfunction of neural cause. Functional neuroprosthetics, a field of operative neuromodulation, encompasses the design, construction and implantation of artificial devices capable of generating electrical stimuli, thereby, replacing the function of damaged parts of the nervous system. The present article also reviews important literature on functional neuroprostheses, functional electrical stimulation (FES), and various emerging applications based on microsystems devices, neural engineering, neuroaugmentation, neurostimulation, and assistive technologies. The authors highlight promising lines of research such as endoneural prostheses for peripheral nerve stimulation, closed-loop systems for responsive neurostimulation or implanted microwires for microstimulation of the spinal cord to enable movements of paralyzed limbs. The above growing scientific fields, in combination with biological regenerative methods, are certainly going to enhance the practice of neuromodulation. The range of neuromodulatory procedures in the spine and peripheral nerves and the dynamics of the biomedical and technological domains which are reviewed in this article indicate that new breakthroughs are likely to improve substantially the quality of life of patients who are severely disabled by neurological disorders.

The phenomenon of spasticity: a pathophysiological and clinical introduction to neuromodulation therapies.

Spasticity is part of the complex clinical picture which results from the upper motor neuron impairment. The underlying mechanisms that produce the automatic overactivity of the muscle groups may manifest themselves as either passive movements dependent on the exerted velocity or persistent muscle overactivity in the form of spastic dystonia. The therapeutic management of spasticity is closely related to the aims of rehabilitation; these include avoidance of complications, restoration of movement, re-education of motion and gait, development of self-dependency, and social integration, as well as modification and reorganization of the cortical brain map. The latter is achieved through long-term learning processes which are subserved by new neurophysiological dynamics. and the mechanisms of neuroplasticity which develop during neural regeneration.

The importance of neurorehabilitation to the outcome of neuromodulation in spasticity.

The neuromodulation specialist who is involved in the management of spasticity should not be interested only in the technical aspects of the implantation of a device. It is important that (s)he has a sound understanding of all aspects of this serious disability in order to determine appropriately whether an ablative or a neuromodulatory intervention (intrathecal baclofen administration, spinal cord stimulation, peripheral nerve stimulation) is best for the patient. It is also important that s(he) is able to collaborate effectively with the physiatrists, othopaedic surgeons, neurologists, physiotherapists, neuropsychologists, and care counselors. In this article, we review our approach to the neurorehabilitation of patients with spasticity due to multiple sclerosis, spinal cord injury, cerebrovascular disease or head injury and, on the basis of our experience, we highlight the importance of the integrated management that combines both rehabilitation and neuromodulation methods in order to ensure the maximum benefits for the patients.

Management and rehabilitation of neuropathic bladder in patients with spinal cord lesion.

The patients with spinal cord lesion (SCL) develop problems of urination due to impaired neural control of the lower urinary tract, such as incontinence or retention; these conditions constitute risks for the upper urinary tract and should be treated appropriately over the various phases of the disease. The therapeutic approach in the acute and subacute post-traumatic phase is of particular importance for the early and late management of the subsequent urinary disturbances. When the rehabilitation program is completed, it is estimated that deficiencies in sphincter control have greater impact on personal and social life of individuals than the movement disability. Currently, as the number of sufferers from SCLs is constantly increasing, medical science faces two great challenges: (i) to develop and apply modern treatment modalities in the framework of advanced neurorehabilitation programs, and (ii) to provide well-organized follow-up management. All efforts should be directed towards the functional integrity of the upper urinary tract and the acquirement of the greatest possible independence for the patient.

The current range of neuromodulatory devices and related technologies.

The pace of technology dictates changes in every aspect of human life. Medical profession is not an exception. The development of sophisticated electronic devices has radically influenced diagnosis and therapy. Today neurosurgical science is revolutionized with numerous implanted and non-implanted devices that modulate and stimulate the nervous system. Physicians, patients and non-technical experts involved in this field need to understand the core mechanisms and the main differences of this technology so that they can use it effectively. It will take years until clinicians reach a "consensus" about the use of these devices, but in the course of action objective information about the current status of the methods and equipment, and the technical, biological, and financial complications that arise in practice will speed up their public approval and acceptance.

Technical aspects and considerations of deep brain stimulation surgery for movement disorders.

Deep brain stimulation (DBS) represents one of the more recent advancements in Neurosurgery. Even though its most successful applications evolved in movement disorders (MDs), indications now include pain, psychiatric disorders, epilepsy, cluster headaches and Tourette syndrome. As this type of surgery gains popularity and the indications for DBS surgery increase, so it will certainly increase the number of neurosurgeons who will use this neuromodulatory technique. A detailed description of the technical aspects of the DBS procedure, as it is performed in our department, is presented. In our opinion, our method is a good combination of all the well-established necessary techniques in a cost-effective way. This technical article may be helpful to neurosurgeons considering to start performing this type of surgery. It could also prompt others who perform DBS regularly to express their views, and hence, lead to further refinement of this demanding procedure.

Vagus nerve stimulation for intractable epilepsy: outcome in two series combining 90 patients.

Vagus nerve stimulation (VNS) is the most widely used non-pharmacological treatment for medically intractable epilepsy and has been in clinical use for over a decade. It is indicated in patients who are refractory to medical treatment or who experience intolerable side effects, and who are not candidates for resective surgery. VNS used in the acute setting can both abort seizures and have an acute prophylactic effect. This effect increases over time in chronic treatment to a maximum at around 18 months. The evidence base supporting the efficacy of VNS is strong, but its exact mechanism of action remains unknown. A vagus nerve stimulator consists of two electrodes embedded in a silastic helix that is wrapped around the cervical vagus nerve. The stimulator is always implanted on the left vagus nerve in order to reduce the likelihood of adverse cardiac effects. The electrodes are connected to an implantable pulse generator (IPG) which is positioned subcutaneously either below the clavicle or in the axilla. The IPG is programmed by computer via a wand placed on the skin over it. In addition, extra pulses of stimulation triggered by a hand-held magnet may help to prevent or abort seizures. VNS is essentially a palliative treatment and the number of patients who become seizure free is very small. A significant reduction in the frequency and severity of seizures can be expected in about one third of patients and efficacy tends to improve with time. Vagus nerve stimulation is well tolerated and has few significant side effects. We describe our experience on the use of VNS on drug-resistant epilepsy in 90 patients treated in two departments (in Athens, Greece and Newcastle, England).

Penetrating craniocerebral injury caused by a pneumatic nail gun: an unsuccessful attempt of suicide.

Nail guns are powerful tools commonly used in the building industry. As a result of their improper use, many accidents of bodily injury, including death, have already been reported over the last 50 years; their use in suicide attempts, however, is rare. In this paper, an unusual case of unsuccessful suicidal craniocerebral penetrating injury committed with a pneumatic nail gun by a 23-year-old man is presented. The particular findings that suggest a suicidal attempt are also discussed.

The expression of the epitope H recognized by the monoclonal antibody H is higher in astrocytomas compared to anaplastic astrocytomas and glioblastomas.

The epitope H contains an O-linked N-acetylglucosamine residue in a specific conformation and/or environment recognized by the monoclonal antibody H (mAbH). mAbH stains two bands with Mr x0.001 of 209 and 62 in lysates of cultured rat astrocytes. In normal human brains epitope H is absent from the overwhelming majority of normal astrocytes and only sparse reactivity is observed, confined mostly to fibrous astrocytes. Upregulation of the epitope H takes place in reactive astrocytes. In the present study we used the mAbH to investigate the immunohistochemical expression of the epitope H in 41 cases of astrocytic tumors including 19 cases of astrocytomas, 8 cases of anaplastic astrocytomas and 14 cases of glioblastomas. Seven out of 19 cases (37%) of astrocytomas showed weak staining, 10 cases (53%) moderate staining and 2 cases (10%) intense staining. Two out of 8 cases (25%) of anaplastic astrocytomas appeared negative, 3 cases (37.5%) showed weak staining and 3 cases (37.5%) moderate staining. Four out of 14 cases (28.5) of glioblastomas appeared negative, 7 cases (50%) showed weak staining, 2 cases (14%) showed moderate staining and only one case (7.5%) showed intense staining. There was a statistically significant elevation of the expression of the epitope H in astrocytomas compared to anaplastic astrocytomas and glioblastomas (p=0.047). These results indicate that the expression of the epitope H decreases in parallel with the increase of the grade of astrocytic tumors from low to higher grade neoplasms. This could be of interest for predicting the progression of an astrocytic tumor since it is documented that astrocytomas progress to tumors of higher grade of malignancy. Further investigation of the antigens bearing the epitope H might help to gain further insight into the mechanisms which regulate the progression of astrocytic tumors and to examine the relevance of the mAbH staining with respect to the prognosis of these neoplasms.

Current concepts on the mechanisms of dystonia and the beneficial effects of deep brain stimulation.

The application of lesioning procedures in the basal ganglia and, more recently, of deep brain stimulation (DBS) has revolutionalized dystonia treatment. However, our understanding of the mechanism of action of DBS is only minimal. This is largely due to a rudimentary understanding of dystonia pathophysiology itself, which in turn reflects an insufficient understanding of the functional significance of the cortico-striato-pallido-thalamocortical loops. The initial dystonia pathophysiology concept was one of changes in oscillation rate. Soon, it was realized that not only rate but also the pattern of basal ganglia activity is crucial in the etiology of the disease. The observations of altered somatosensory responsiveness and cortical neuroplasticity, along with the vast array of clinical phenotypes, imply the need for a wholistic neuronal pathophysiology model; one in which an underlying defect of basal ganglia function results in increased cortical excitability, misprocessing of sensory feedback, aberrant cortical plasticity, and ultimately clinical dystonia. This unified dystonia pathophysiology model, although simplistic, may provide the scaffold on which all incoming research and clinical data becomes united in a meaningful and practical way. In light of this model, the dramatic response of some forms of dystonia to pallidal stimulation, the time latency for the beneficial effect and even the presence of non-responders may be explained. Additionally, it may help in developing a rationale for more efficacious DBS programming, better selection of the timing of surgery, and more successful identification of those candidates that are most likely to respond to DBS.