A. L. Benabid

Mechanisms of deep brain stimulation

The mechanism of action of high frequency deep brain stimulation is still unknown. However, in all circumstances and in all target nuclei so far stimulated, the effects mimic those of lesions previously made during thalamotomies, pallidotomies or even subthalamotomies, suggesting an inhibition of at least the neuronal network containing the target, if not of the target itself. On the contrary, fiber bundles are consistently activated at low or high frequencies. The hypothetical mechanisms envisioned should therefore be compatible and even produce these observed effects, to be acceptable as hypotheses. The mechanism could be either one or a combination of several causes: jamming of a feedback loop, activation of inhibitory structures included in a more complex network, blockade of membrane ion channels, deplorisation blockade, synaptic exhaustion, induction of early genes, changes in local blood flow, neuroplasticity, etc. It is probable that some are more involved in the acute effects and others in the long term changes, close to neuroplasticity. It is clear that the understanding of this strange and powerful phenomenon will profit from both clinical observation and well designed animal experiments.

Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease.

Recent pathophysiological models of Parkinsons disease have led to new surgical approaches to treatment including deep brain stimulation (DBS) and lesioning of basal ganglia structures. Various measures of upper limb akinesia were assessed in 6 patients with bilateral DBS of the internal pallidum and 6 with DBS of the subthalamic nucleus. Stimulation improved a number of aspects of motor function, and particularly movement time, and force production. Time to initiate movements, and to perform repetitive movements also improved but less dramatically. Processes indicating preparatory motor processes showed no significant change. Few significant differences were found between the internal pallidum and subthalamic nucleus groups. In general, the effects of DBS closely parallel previous reports of the effects of dopaminergic medication. It is suggested that disrupted pallidal output in Parkinsons disease interferes with the rate, level, and coordination of force production but has little effect on preparatory processes. The similarity of the effects of subthalamic nucleus and internal pallidum stimulation suggests this disrupted outflow is the most important determinant of upper limb akinesia in Parkinsons disease. The effects of DBS were similar to the effects of unilateral pallidal lesions reported elsewhere. Ann Neurol 1999;45:473–488

Potential Use of Robots in Endoscopic Neurosurgery

A 6-axis stereotactic robot has been designed and linked to a stereotactic frame for routine use. Robot software allows the positioning of a probe holder in order to reach a given target. A calibration step enables the robot to compute the position of the x-ray beam and correct its final position to avoid parallax errors. The co-ordinates of the target are presently taken from anteroposterior and lateral X-rays using a digitizing table. Connection with a digitized angiography system is in progress and will allow direct sampling of numerical data from the x-ray data. Further steps will include connections with a 3D-reconstructed image from MRI and CAT as well as with a resident computerized atlas. Present experience after 14 months of daily practice represents 140 stereotactic procedures which can be extended to any special use, including endoscopic approaches.

Is there any future for robots in neurosurgery

Since the first conception of machines that could replace humans for tasks they used to perform, the development of increasingly intelligent machines, later called robots, led to the science of synnoetics’ implying the perfect integration of humans and robots in an harmonious society. Science-fiction literature has helped us grow accustomed to the idea and the theme of mankind threatened by dominating robotic creatures has rapidly gone out of style. The prospect of an increasingly robotized society is becoming more acceptable and the recent experience of robots entering the exclusivedomain of medicine has proven that they are regarded as an addition to skill and safety rather than as a danger. Incredibly rapid progress in computer science, artificial intelligence, biomedical engineering and medical imaging, together with our society’s never ending pursuit of higher medical standards and achievements willundoubtedly foster advancements in medical robotics far beyond the scope of present-day capabilities. However, before a time has come when intelligent and flexible robots will be able to integrate the sum of clinical and paraclinical data, state a diagnosis, make a decision, and then perform a therapeutic (including surgical) procedure, not in a completely pre-programmed but in an adaptative manner based on the immediate knowledge provided by their own sensors, a considerable amount of work remains to be done well beyond the current state of the art.

Chronic Deep Brain Stimulation for Movement Disorders

The surgical treatment of movement disorders has evolved continuously over the course of the twentieth century, not only because of technical progress in neurosurgery but also because of improved recognition of the signs and symptoms of these disorders, and because of a progressive refinement of surgical indications, based on a better understanding of the relevant neuroanatomy and pathophysiology.

External and Implanted Pumps for Apomorphine Infusion in Parkinsonism

Continuous delivery of dopaminergic agents to the striatum is a major challenge to improve the treatment of Parkinsons disease. Apomorphine is one of the best candidates because of its solubility and its D1 and D2 receptor agonist properties. Seventeen Parkinsonian patients suffering from severe L-dopa-induced on-off effects were treated by continuous subcutaneous (SC) infusion with a portable minipump. Administration of intracerebroventricular (ICV) apomorphine was carried out in 7 macaca fascicularis monkeys using implanted programmable pumps. Four of the monkeys were made Parkinsonian by MPTP injections. In patients receiving apomorphine, the mean duration of daily off periods was reduced by 61%. Psychiatric side effects were rare but SC nodules occurred in all patients and the external infusion method was therefore difficult to implement. In monkeys, the implanted system was well tolerated. ICV apomorphine infusion led to CSF apomorphine concentrations higher than the same apomorphine dose infused i.m. Motor function was considerably improved in two MPTP monkeys during the time of ICV infusion and 30 min after its arrest. Long-term ICV administration could not be carried out because of catheter blockage and/or apomorphine toxicity. SC and ICV apomorphine infusions are efficient for controlling motor activity in Parkinsonism but long-term toxicity remains to be studied further.

How are We Inhibiting Functional Targets with High Frequency Stimulation

It is commonly accepted that high frequency stimulation (HFS) inhibits neuronal somatic structures. HFS has been used to treat a variety of conditions, but its primary use has been to treat movement disorders by targeting different basal ganglia and thalamic nuclei. The basal ganglia circuitry is didactically described by the parallel pathway model (Alexander and Crutcher, 1990; Albin et al., 1989; DeLong, 1990). Three principal areas of the basal ganglia are targeted for therapeutic purposes: the thalamic ventralis intermedialis nucleus (Vim), the internal pallidum (GPi), and the subthalamic nucleus (STN). The substantia nigra lies below these three nuclei within the stereotactic coordinate system. Degeneration of the pars compacta of substantia nigra (SNc) is the cause of Parkinson’s Disease, while the substantia nigra reticulata (SNr), which is more anterior and dorsal to it, is considered an equivalent of GPi in the model, because these two nuclei receive common afferents from both the STN and direct pathway, and the efferent output of both nuclei is GABAergic.