Topics and Speakers Seth L. Pullman, MD
| ||||||
Synopsis
Insults to the basal ganglia can result in a variety of motor disorders, ranging from simple dyskinesias and dystonias to Parkinson's disease and Huntington's disease. In this lecture, Dr Seth Pullman discusses the general circuitry of the basal ganglia, the physiological consequences of injury to this circuitry, and how new techniques such as deep brain stimulation (DBS) can help treat such disorders.
The basal ganglia help program the scale, amplitude, and effort of motor movements by linking various aspects of the higher motor systems. They also deal with the circuits that come from and go to the cortical regions and down toward the cerebellum and brainstem. This group of subcortical nuclei is characterized by two pathways: one direct and one indirect. The direct pathway, which goes from the cortex to the striatum (mediated by D1 receptors) to the globus pallidus internus (GPi) and the substantia nigra pars reticulata (SNpr) to the thalamus and back to the cortex, is monosynaptic and facilitated by dopamine. The indirect pathway, which goes from the cortex to the striatum (mediated by D2 receptors) to the globus pallidus externus (GPe) to the subthalamic nucleus (STN) to the GPi to the thalamus and back to the cortex, is polysynaptic and inhibited by dopamine. Under normal conditions, these two pathways act in synchrony with each other keeping the excitatory and inhibitory aspects of dopamine in balance and allowing normal motor movements. Disruption of the synchrony of these pathways can result in either a hypokinetic condition, such as Parkinson's, or a hyperkinetic condition, such as Huntington's. An example of insult resulting in hypokinetic conditions are lesions in the substantia nigra (SN), which are the main characteristic of Parkinson's disease. This insult leads to inhibition of the direct pathway, alteration in the indirect pathway, and increased dopamine inhibition which results in decreased movement and hypokinesia.
Historically, targeting basal ganglia conditions like Parkinson's involved lesioning various parts of this system. Other methods included ablative surgery, such as pallidotomies and thalamotomies. Even though many patients improved with these methods, the mortality rate was very high. Only in 1997 did deep brain stimulation (DBS) emerge as a treatment for unilateral thalamic conditions, like tremor on one side of the body. Since then, it has been found that DBS can be very successful not only for movement disorders, like Parkinson's and Huntington's, but also for behavioral conditions, depression, and Tourette's syndrome. There are many advantages of DBS over ablative surgery. There is much less morbidity with the stimulation; the DBS is adjustable in accordance to changes in the patient's condition; and the equipment is removable, which allows for future surgical improvements. However, there are some patients where DBS is contraindicated. These include patients with coagulopathies, pacemakers, and dementia. The latter is important, since ideally, the patient should be awake during the implantation of the device in order to receive coherent feedback.
But what exactly is DBS? Deep brain stimulation is the implanting of an electronic device known as a "neurostimulator" into a brain region where it mimics cellular ablation. Its effect is understood in terms of "stunning" the brain with pulses (ranging from less than 10 Hz to greater than 60 Hz) and keeping the neurons from being active at 185 Hz on average, where motor disorders usually result. DBS does not actually drive anything directly. However, it has been noticed that neighboring nuclei in the DBS region,as well as their afferents, might actually be activated in some way how this happens is yet to be understood.
Depending on the condition, the DBS will be implanted in a particular brain region. The most typical place used for Parkinson's is the STN; for dystonia and Parkinson's, in which dystonia is a major issue, the most typical place is the GPi and the SNpr; for tremor-predominant Parkinson's, then the ventral intermediate nucleus is the place; for conditions like Tourette's or depression, then the limbic pallidum is the place. For Parkinson's, by placing the DBS in the STN, there can be a decrease in medication (i.e., levodopa) of up to 60%. This is very beneficial since levodopa has an array of unwanted side effects such as dyskinesias and changes in the sense of taste. The details of how the DBS is implanted, such as using a workstation and mapping the localization of the device using microelectrodes, is explained via slides. An interesting detail, mentioned above, is that ideally the patient must be awake in order for the operation to be more precise. For instance, when placing the DBS in the GPi, which is "literally just a millimeter from the optic track," the surgeon can elicit feedback from the patient to determine whether the device is too close to the optic track. While being stimulated with the microelectrode, the patient should report whether he or she sees phosphenes. If the patient answers affirmatively, the DBS has been planted too close to the optic track and should be moved back to the GPi.
Dr Pullman concludes with a discussion of the clinical efficacy of DBS and some complications resulting from the surgery. Tremor, rigidity, and anti-dyskenetic effects associated with disorders of the basal ganglia are very much helped by the device. After the operation, the patient works with a nurse to "troubleshoot" the device, changing the pulse with amplitude and frequency for hours, until the right pulse is reached. Complication rates are very low. Strokes and hemorrhages are very infrequent and seizures are few; whereas, hematomas are more common since the operation goes through the surface of the brain, as well as post-operation confusion. The worst problem may be a malfunction with the hardware, such as a battery issue. Even though it is unknown how DBS helps the symptoms of Parkinson's and other motor disorders, it has proven to be a proficient and beneficial assistant to medication.
