Overall, the results of internal globus pallidus (GPi) DBS in dystonia appear clearly dependent on the type of dystonia, with a clear cutoff between primary and secondary dystonia.
Primary Generalized Dystonia
These forms of dystonia represent the best indications of GPi DBS. In primary generalized dystonia (associated and unassociated with DYT1 mutations), the improvement of motor symptoms is usually approximately 50% but depends on the experience of the teams.[3–16] These results have been first obtained in open-label studies but later confirmed in large controlled studies.[6,7,16] The benefit of this surgery is maintained in the long term, although worsening and spreading of the dystonia to other body parts have been observed,[8,11] raising the issue of a second implantation to expand the area covered by the stimulation (see the 'Future perspective' section). This beneficial effect on motor function after GPi DBS is accompanied by a clear improvement of the quality of life going beyond the physical domains.[6,14,15,17,18]
Factors of positive outcome are represented by younger age at the time of surgery and shorter duration of symptoms.[11,19,20] On the other hand, the presence of fixed orthopedic deformations or cervical myelopathy are factors of poorer outcome after GPi DBS.[21,22]
Furthermore, GPi DBS for primary generalized dystonia appears as a very well-tolerated treatment from cognitive and behavioral points of view.[6,7,14,17,23,24] Mood is also, in general, slightly improved or unchanged, although some rare cases of suicide have been reported, rending a close follow-up of these patients mandatory. On the other hand, GPi DBS can induce bradykinesia and freezing of gait in some patients (8% in this series), but this side effect can be reversed by optimization of stimulation parameters. More detailed results are presented in Table 1.
Focal & Segmental Primary Dystonias
Most of the results concern cervical dystonia. Several studies, including controlled ones, have demonstrated a mean 50% improvement in cervical dystonia.[15,27,28] This benefit is preserved over time (up to 10 years after surgery).[29–33] Pain and depression are also improved.[27,33] Again, as for generalized dystonia, some degree of bradykinesia and micrographia have been noted after GPi DBS for cervical dystonia.[33,34]
Available information on GPi DBS for other forms of segmental or focal dystonia are much more limited and often consist of uncontrolled small series or case reports. Improvement has been noted; for example, for Meige syndrome.[35–40] Improvement has also been noted for limb or axial dystonia.[41,42] Finally, dystonia with prominent cranial involvement due to DYT6 mutation has also been shown to respond partly to GPi DBS.[43,44] More detailed results are presented in Table 2.
Other Recognized Indications of Pallidal Stimulation in Dystonia
Myoclonus dystonia represent one of the best indications of GPi DBS, with an improvement of both the myoclonus and the dystonic features of the disease.[45,46] However the natural evolution of the disease with, in some cases, the spontaneous regression of the dystonia, should prevent a too-early surgery in childhood.
Tardive dystonia, due to prolonged neuroleptics exposure, is another excellent indication of pallidal stimulation. In this case, the improvement concerns the dystonia but also the other abnormal movements seen in this disorder, as demonstrated in controlled but also uncontrolled studies.[48–50] The benefit is maintained over time and quality of life is also clearly improved. More detailed results are presented in Table 3.
Many small series or single case reports have been published about GPi DBS and secondary dystonia. The evidence of favorable outcome is, overall, much more limited than for primary dystonia. One of the best studied examples is postanoxic dystonia, for which some patients may respond significantly to the surgery, while others do not, thus making any prediction of outcome very difficult.
Dystonia due to PKAN2 mutations may also inconstantly be improved by GPi DBS but this effect tends to vanish with disease progression.[53–55]
Finally, some case reports have shown some improvement after GPi DBS in Lesch–Nyhan disease, dystonia-deafness, X-linked dystonia–parkinsonism[58–60] and GM1 type 3 gangliosidosis. Furthermore, a recent publication demonstrated a very mild beneficial effect of GPi DBS for Wilson's disease. More detailed results are presented in Table 4.
Future Neurology. 2014;9(1):77-87. © 2014 Future Medicine Ltd.