The main indication for deep brain surgery soon became the alleviation of movement disorders. In 1935 Russell Meyer had discovered that destroying movement centres in and around the basal ganglia, particularly the globus pallidus, could greatly reduce the tremor and rigidity of Parkinson's disease without causing paralysis. However, these open operations killed up to one in five patients (!), and it was soon shown that stereotactic surgery was much safer. Speigel found that most patients who had lost the ability to move after carbon monoxide poisoning showed damage in the globus pallidus. Since he considered most Parkinson's disease symptoms to be caused by uncontrolled release of movements, like Meyer he inferred that destroying the pallidum could help these people. Using his frame to target and destroy the pallidum in Parkinsonian patients that is what he confirmed. Even better, using the stereotactic technique only one in every 100 patients died from complications. Stereotactic lesioning of the globus pallidus or its target in the ventral thalamus became the standard treatment for Parkinson's disease. Various methods were used to destroy the target areas such as passing currents down the electrode to heat the area, injections of pure alcohol into the target, or cutting around it with a wire. Today, very high-frequency currents are used to heat the targets to destroy them in a controlled fashion.
In the 1960s, however, Horniecywicz discovered that Parkinson's disease was due to degeneration of the dopamine-containing cells of the substantia nigra pars compacta, and soon afterwards it became clear that treatment with the dopamine precursor l-dopa could alleviate all the symptoms of Parkinson's disease without the need for surgery. As a result stereotactic surgery was generally abandoned, even for non-Parkinsonian movement disorders, in the hope that other new drugs were just around the corner.
But a few centres continued to offer such surgery for tremulous disorders and pain. Also the requirement to be able to biopsy deep brain tumours in order to determine their malignancy and susceptibility to cytotoxic drugs and radiotherapy kept stereotactic technology advancing. It was rapidly realized that CT and MRI scans taken with the patient's head in a frame could allow surgeons to directly access tumours using fine cannulae to target and biopsy them via small holes in the skull. Previously surgeons had to use patient symptoms and signs to best guess the location of a brain tumour and then explore a large area of the brain to find it, with predictably high complication rates. Tumour biopsy remained the main indication for stereotactic brain surgery for over a decade. Better imaging technology to study the structure of the brain, beginning with CT scans using X-rays and then MRI using superconducting magnets yielded pictures that provided detail of deep brain structures that could not have been imagined at the birth of stereotactic surgery. Radiolucent and non-magnetic frames were designed to be compatible with CT and MRI imaging, and software was developed to fuse CT and MRI images together to gain the advantages of both. All these were available by the end of the 1980s.
By the 1990s the wheel had turned full circle, however, back to stereotactic surgery for treating movement disorders because it had become clear that long-term l-dopa therapy often has very serious side effects. After about five years' treatment half of all Parkinson's patients develop severe 'dyskinesias' when they take the drug; these are wild flailing involuntary movements, 'chorea', and/or contorted postures, dystonias, that are completely disabling. They are resistant to most drug therapy but can be greatly reduced or even completely eliminated by lesions or high-frequency electrical stimulation in the globus pallidus or subthalamic nucleus of the basal ganglia.
The rationale for these stereotactic treatments of movement disorders derive from the great advances that had been made in our understanding of the neural mechanisms underlying Parkinsonism. This was made possible by the introduction of a good animal model of the disease. In 1978 young drug users in San Francisco unexpectedly began to develop Parkinsonism, which is most unusual under the age of 40. They had been injecting themselves with a home-made recreational drug which was found to be contaminated with a substance, MPTP, that is highly selectively toxic to the dopaminergic neurons in the substantia nigra. Monkeys injected with MPTP develop all the symptoms of Parkinson's disease, so that changes in basal ganglia function in the disease could now be studied in detail using this animal model. This work has revealed that in Parkinson's disease motor control circuits in the basal ganglia get out of control. The subthalamic nucleus (STN) becomes spontaneously overactive and drives the inner half of the pallidum, the medial globus pallidus or GPm, to overinhibit thalamocortical production of motor programmes. This explains why inactivating either the STN or the globus pallidus can reverse most Parkinson's symptoms.
Hence stereotactic lesions of the globus pallidus, pallidotomies, have been reintroduced for the treatment of Parkinsonian dyskinesias, and their success is often dramatic. Many patients who were wheelchair bound and required 24-hour care have been rescued by these operations and restored to useful lives. Lesioning the STN has turned out to be too risky, however, since it is very small and lesions following strokes in this area can cause even worse wild thrashing movements of the whole limb, called hemiballismus. Instead it has been found that electrically stimulating STN neurons at frequencies far higher than their natural rate of discharge, around 100 impulses per second, effectively inactivates them and is comparatively safe. Such stimulation can therefore alleviate all the symptoms of Parkinson's disease with results comparable to those of pallidotomy. Now therefore programmable stimulators connected to electrodes situated in the STN are often implanted subcutaneously, and hundreds of patients have thus been restored to near normal lives.
Thus stereotactic thalamotomy, pallidotomy, or STN stimulation is now routinely used for the treatment of advanced Parkinson's disease. Implantable stimulators in these areas are also increasingly used for other movement disorders that are resistant to drug treatment. These include the ataxic tremors that develop in nearly half of all patients with the demyelinating disease multiple sclerosis. Also childhood contorting body dystonias and the uncontrollable head turning that occurs in 'spasmodic torticollis' are now being treated with stimulators implanted in the basal ganglia.
The alleviation of intractable pain, another of the original indications for stereotactic surgery, is also now being reinvestigated. Many patients, after amputation of a limb, experience severe pain in the absent limb, 'phantom limb pain' that is resistant to all analgesics. Often this is caused by the phantom limb feeling unbearably contorted, and the pain can often be relieved if the patient can gain control over the phantom's movements. This can be achieved by electrically stimulating the contralateral arm area of the motor cortex, and implantable stimulators have been used successfully to relieve the pain.
Phantom limb pain is an example of pain spontaneously generated within the central nervous system, collectively known as 'central' or 'neuropathic' pains. Another way of relieving these is to stimulate the body's own pain control system, which originates in the upper brain-stem periacqueductal grey region. Stimulators are therefore being implanted there with great success at alleviating neuropathic pain. At the same time recording has suggested that the pain is associated with slow frequency spontaneous neuronal activity in the sensory thalamus that correlates with the pain. If the activity is damped down the pain disappears.
Stereotactic surgery is also now being used to implant fetal stem cells, or growth factors into the basal ganglia to attempt to repair the degeneration caused by Parkinson's disease or Huntington's disease. Although even after two decades of experience these procedures have not been very successful, it is clear that this approach offers the best chance of actually curing these diseases. Moreover there is no doubt that stereotactic implantation of repair molecules or stem cells into appropriate sites will become increasingly important for treating a wide range of other diseases, such as Alzheimer's disease, epilepsy, and stroke.
Thus the technique of targeting the deep internal structures of the brain using a stereotactic approach has expanded from a research tool in animals to one with very wide-reaching therapeutic applications in the world of neurology, neurosurgery, and the neurosciences.
(Published 2004)
See also brain theorizing.
— T. Z. Aziz/J. F. Stein
