Surgical Treatment Of Parkinson's Disease
The first surgical operation for Parkinson's disease were performed in 1952 following the introduction of stereotactic system by Spiegel and Wycis in 1947. During 1950's and 1960's, thousands of surgeries were performed for this debilitating disease for which no effective medical treatment was available. However in 1960's, discovery of levodopa made the surgical treatment redundant. Levodopa was found to be very effective in alleviating parkinsonian symptoms. However few years later, side effects of levodopa started appearing in the patients who had been on long term levodopa treatment. This led to rethinking about the surgical option. During the last decade there has been resurgence in the interest of neurosurgical treatment of Parkinson's disease due to simultaneous advances in the clinical neurosurgery and basic neurosciences. The current model of basal ganglia connections and their role in movement disorders provide a rational basis for the neurosurgical treatment of Parkinson's disease. There are three targets for neurosurgical treatment of Parkinson's disease: 1) Globus Pallidus Interna (Gpi), 2) Subthalamic Nucleus (STN) and 3) VIM Nucleus of the thalamus. Options of treatment include implantation of deep brain stimulators in one or more of these areas (Gpi, STN & VIM) or the creation of new lesion in Gpi (Pallidotomy) or VIM nucleus of the thalamus (Thalamotomy). The choice of which treatment and the best target for treatment is based on the careful evaluation of each patient by our movement disorder team. Currently the GPi & STN are the preferred targets for the treatment of Parkinson's disease.
Basal Ganglia Anatomy:
Basal ganglia are group of cells located deep within the brain.
Fig. 1. Coronal section through the brain showing various surgical targets for Parkinson's disease surgery.
They are responsible for the extra pyramidal function of the brain. Basal ganglia normally comprise of five nuclei i.e. caudate, putamen, globus pallidus, substantia nigra and subthalamic nucleus. The globus pallidus is further divided into globus pallidum externus(Gpe) and globus pallidum internus(GPi). The caudate and putamen together are also called striatum whereas putamen and globus pallidum are called the lentiform nucleus. The main outflow of the basal ganglia is through the globus pallidum. To explain the functioning of the basal ganglia in normal and parkinsonian state we need to understand its connections and their relative functions. The present basal ganglia model explains the intricate connections between the cortex and the basal ganglia by direct and indirect pathways.
There are projections from the cortex to the putamen, which in turns connects to the GPi. The GPi projects to the thalamus which in turn projects back to the cortex. In this loop, the projections from cortex to the putamen are excitatory (Glutamate). The projection from the putamen to GPi and from GPi to the thalamus are inhibitory (Gamma amino butyric acid (GABA)). Again the projections from the thalamus to the cortex are excitatory. When the cortex is stimulated it excites the putamen, the putamen in turn inhibits the GPi, which in turn inhibits the thalamus. The thalamus is in a chronically inhibited state by the excitatory impulses from the GPi and hence following cortical excitation when the inhibitory inputs travel from GPi to thalamus, the thalamus is released, resulting in the excitatory stimulation from the thalamus to travel to the cortex thereby re-enforcing the direct movements.
In indirect pathway, projections from the cortex project to the putamen which in turn projects to the GPe and GPe projects to the subthalamic nucleus and subthalamic nucleus in turn projects back to the GPi which again projects to the thalamus and thalamus projects to the cortex. The projections from the Putamen to GPe and from GPe to STN use GABA and are inhibitory, where as the projections from the STN to Gpi is excitatory. Once again excitatory stimulation from the cortex causes excitation of the putamen which inhibits GPe. Since GPe is normally inhibitory to the STN, the STN is released and it excites the GPi, which in turns reinforces the inhibition over thalamus which then, inhibits the cortex. In this way, the activation of the indirect pathway causes relative inhibition of movements. The result of direct and indirect pathway is a smooth coordinated movement.
The primary derangement in Parkinson's disease is a loss of dopaminergic neurons in substantia nigra. The loss of dopamine results in derangement of both direct and indirect pathways. In Parkinson's disease the dopaminergic input is less in both the pathways. Therefore direct pathway becomes less active and indirect pathway becomes more active. In indirect pathway, the loss of dopamine results in the excessive activity of subthalamic nucleus which leads to excessive activity in GPi. In both cases, there is excessive inhibition of thalamus by the GPi which then presumably leads to the observed paucity of movements in Parkinson's disease. The important point is that since both the GPi and the subthalamic nucleus are over active in Parkinson's disease, both these nuclei are potential targets for surgical therapy when medical treatment has reached its limits.
Based on this patho-physiological explanation of evolution of Parkinson's disease symptoms, one can conclude that there are three suitable anatomical targets for the surgical treatment of Parkinson's disease. These are thalamus (VIM), pallidum (Gpi) and subthalamic nucleus (STN). The rationality of selecting each target depends on the specific symptomatology of each patient and his expectations about the clinical outcome.
Type of DBS
Effective for tremor Useful for unilateral tremor dominant disease
Thalamotomy can only be performed on one side. Bilateral thalamotomy is contraindicated. Bilateral thalamic DBS can be performed but again it offers limited benefit, i.e. tremor control only. Other Parkinsonian symptoms would progress over time.
The most potent as measured by ability of patients to reduce their medications. Effective in controlling essentially all the symptoms of Parkinson's disease.
Only DBS can be performed for this site. Lesional surgeries are still under research. Requires close medical supervision for programming.
Particularly effective for drug-induced dyskinesia. Also helps control tremor and benefits bradykinesia. Pallidotomy is most beneficial to the patients having predominantly unilateral dyskinesias. Pallidal stimulation can be performed for bilateral advanced disease.
Not very effective for gait and postural abnormalities. There is no associated drug reduction that is seen with STN surgery.