Eligibility for PD Surgery
Eligible for surgery are patients with incomplete effect of medications on their symptoms and disability and/or patients presenting side effects due to medication, such as dyskinesias. In general, the sooner the surgery the better outcome for the patient. High age, although not in itself a contraindication for operation may increase the risks. Besides, the “old” patient’s ability for regaining independency after successful surgery is not as good as that of the “younger” patient. Surgery is contraindicated in the following conditions:

1. Patients regularly taking anticoagulation drugs or who have blood coagulation deficiency
2. Severely hypertensive patients with uncontrolled blood pressure
3. Patients with cognitive decline (clinically relevant short-term memory deficit or dementia)

Pallidotomy and Pallidal DBS
Pathophysiological background: Dopamine deficiency in the putamen provokes through a GABAergic direct pathway to the globus pallidus internum (GPI) and a glutaminergic pathway from the subthalamic nucleus (STN), an over activity of the inhibitory GPI, acting on the thalamo-cortical circuitry, which provokes an inhibition of movement time and inhibition of initiation of movements. This inhibition may account for the development of akinesia, rigidity and tremor in PD. The dyskinesia seen in PD patients after long duration L-dopa treatment may also be mediated by a dysinhibition of the STN which provokes a decreased activity of the inhibitory globus pallidus and hence, the initiation of choreacthetotic movements and dystonias, ie. dyskinesias.

Indications for surgery: Patients with advanced PD suffering from on-off phenomena, dystonias, dyskinesias, muscular cramps, tremor, etc are suitable for surgery on the posteroventral pallidum. There is an impact profile of pallidal surgery: Dyskinesias respond best, followed by dystonias and muscular cramps, rigidity, tremor, and akinesia, while the so called freezing of the gait is worst in responding.(1) If needed, pallidotomy can be done bilaterally in two separate sessions with a minimum interval of 6 months between the two surgeries. Bilateral pallidotomy is contraindicated if there are significant speech or swallowing problems after the first surgery. The same applies if the patient has moderate memory problems. The risks of bilateral pallidotomies is decreased if the lesions are kept within the posteroventral part of the pallidum, avoiding any encroachment of the lesion on the internal capsule and inclusion of the antero-dorso-medial pallidum in the lesion.(7,13)

Pallidal DBS on the second side of the brain in patients who have already had a pallidotomy on one side may be preferred if the patient has significant speech and voice difficulties.

Side effects: The side effects of pallidotomy in experienced hands are rare and usually transient. a) Pallidotomy in either hemisphere may provoke worsening of memory, injury to optic tract, paresis, depression, stroke, increased salivation. b) Pallidotomy in dominant hemisphere may provoke confusion, dysarthria, dysphonia. c) Pallidal DBS may be complicated by infection, skin erosion, displacement of electrode, seroma in pacemaker pocket, reversible induction of visual, motor, gait and/or speech disturbances.

Results: The results of pallidal surgery depend on which symptoms are being treated. Furthermore, the degree and longevity of improvement of the symptoms, dyskinesias excepted, is quite variable. Dyskinesias decrease markedly in more than 80% of the patients, dystonic pain, muscular cramps and rigidity in about 70%. Tremor decreases significantly in about 65%.(8) Akinesia diminishes slightly or moderately but freezing of the gait generally does not improve. After pallidotomy, “on-off” fluctuations may still occur. However, the “on” periods generally last longer and provide better mobility without dyskinesias, and the “off” periods usually are not as profound and as long-lasting as before surgery. Quality of life is improved.(14) Pallidotomy seems to be more effective, less expensive and less laborious (for patient and doctor) than pallidal DBS. Unlike in other brain targets (see below), DBS in the pallidum has less to offer in terms of increased safety, compared to lesioning, at least when unilateral.

Thalamotomy and Thalamic DBS
Pathophysiological background: The ventralis intermedius (VIM) nucleus and, sometimes, the ventralis oralis posterior (VOP) (and part of the ventralis oralis anterior) nuclei in the ventrolateral thalamus are the main target area for alleviation of tremor. These nuclei occupy an area where dentate-thalamic VIM and pallido-thalamic VOP-VOA pathways converge. These pathways constitute the two adjacent pathways of the so called extra-pyramidal system: one pathway involves a loop connecting the following: cerebellar cortex – dentate – nucleus rubber – ventral thalamus – cerebral cortex - internal capsule – pons nuclei – cerebellar cortex; the other pathway involves a loop between the caudate – putamen – pallidum – ventral thalamus – motor cortex – caudate. In the VIM nucleus, kinaesthetic cells that respond to joint movements and so called tremor cells synchronous with the tremor are present which are believed to act as a “pacemaker” to tremor oscillations.

Indications for surgery: The only indication for surgery on the ventrolateral thalamus is tremor, regardless of origin. Parkinsonian and essential tremor respond best. Rest and postural tremor respond better than action tremor. Distal arm tremor responds better than the proximal one and upper extremity tremor better than lower extremity tremor. Head and axial tremor respond least and so also ataxia and choreoathetotic movements and dystonias. Thalamotomy should not be done on both sides of the brain because of high risks of dysarthria and balance problems. Thalamic DBS is safer and may be chosen for the dominant brain while thalamotomy should be reserved for the non-dominant brain.(15) Bilateral thalamic DBS, however, is also considered quite safe, and has been increasingly used in the last decade. Thalamotomy on the other hand is nowadays more rarely done.

Side effects: Thalamotomy does harbour more risks and provokes more side effects than pallidotomy. Some of the side effects are generally transient.

a) Thalamotomy in either hemisphere may provoke hyptonia, balance problems, hemi-inattention, dyspraxia, paresis,    dysphonia, dysphagia, increased bradykinesia, sensory deficit.
b) Thalamotomy in dominant hemisphere may provoke confusion, memory deficit, dysarthria, dysphonia
c) Thalamic DBS may result in the same complications as for pallidal DBS. However, in the thalamus there may also    be risk for reversible induction of sensory, motor, gait, speech disturbances, ataxia or aggravation of akinesia.

Results: a) Thalamotomy provides in 75-85% of the cases good to excellent results for the tremors. Rigidity is frequently replaced by hypotonia, that may affect the gait negatively b) Thalamic DBS has the same figures as above.

DBS of Subthalamic Nucleus (STN)
Pathophysiological background: In Parkinson’s disease, the subthalamic nucleus (STN) exerts a strong glutaminergic excitatory effect on the GPI increasing thus the inhibitory effect of the GPI on movements. Therefore, the STN is a “logical” target to functionally neutralise (by chronic high frequency stimulation) in order to alleviate the akinesia including the freezing of gait in PD.

Indications for surgery: Patients with mainly akinetic symptoms, and also patients who have motor fluctuations, may benefit from bilateral simultaneous STN DBS. The STN should not be lesioned by radiofrequency coagulation because of risk for severe side effects, especially hemiballism and hypophonia. Therefore, only chronic stimulation with permanently implanted electrodes is advisable. DBS of the STN is a relatively recent procedure. Its long-term efficacy is not yet established nor its safety in terms of remote side effects, despite the fact that it is widely used nowadays. In the following will be listed what is already known about that surgery.

Side effects: Confusion, mostly transient, is frequently seen after bilateral STN DBS.(11) Also dysphonia and dysarthria may not be as uncommon as previously thought. Difficulties in opening eyelids, personality changes and thought disorders have also been mentioned (Volkmann J: Deep brain stimulation of globus pallidus internus and sub-thalamic nucleus in advanced Parkinson’s disease. Presentation of the results of the multicenter DBS in advanced Parkinson’s disease study at the Kinetra Launch meeting, Lausanne, Switzerland, February 4, 2000). The possible induction of dyskinesias, it not truly a side effect because after successful STN stimulation, the doses of L-dopa medication can often be reduced in most patients.(11)

Results: So far, it seems, that STN DBS benefits mostly for the akinetic patients, especially patients with gait freezing. In fact, it seems that this is the most powerful surgical procedure for genuine symptoms of PD, including the gait freezing, and it also affects positively the rigidity and the tremor as well.

Conclusion

Stereotactic surgery for Parkinson’s disease is, in experienced hands, a relatively safe operation. Surgery should be proposed for patients well before they reach end-stage of the disease and/or start to show signs of dementia. This would provide the patients with many years of improved quality of life despite the course of their chronic and progressive illness.

The choice of brain target to be lesioned or stimulated should be based on the analysis of the evolution of the specific symptoms of each patient and based on which impact these symptoms have on the disability of the patient. For patients with advanced PD, pallidotomy or STN DBS seems most appropriate. However, depending on bilaterally of symptoms, on availability of stimulators, on costs, and on availability of close follow-up of patients, one may choose between these two procedures, keeping in mind that pallidotomy is often done unilaterally and affects immediately, mainly but not solely, dyskinesias, while STN DBS can be done simultaneously bilateral and acts mainly on gait freezing and rigidity, but requires frequent and laborious follow-up before it reaches its full effect. In those (rare) patients with stable PD and where the tremor is the only symptom, or in patients where a previous pallidal (or STN) surgery did not affect the tremor, then radio-frequency lesion, or, rather, DBS in the ventro lateral thalamus may be indicated. Table 1 shows the characteristics, effects and side effect of the various procedures.

Abbreviations: VIM: ventral intermedius nucleus of thalamus. DBS: deep brain stimulation: STN: subthalamic nucleus. VOP: ventral oral posterior nucleus of thalamus

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