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Merello et al reported a randomised study comparing bilateral simultaneous posteroventral pallidotomy (PVP) with a combination of unilateral PVP and contralateral pallidal stimulation.1 After having included three patients in each group, the study had to be aborted because of the severe complications encountered in the patients who had had bilateral pallidotomy.
This interesting paper raises some serious concerns.
First, the three patients who had bilateral PVP had a mean age of 67 years and those who had PVP and contralateral pallidal stimulation had a mean age of 55 years. This difference in age is said to be non-significant. As there are only three patients in each group it would perhaps have been more appropriate to have given the ages of the individual patients rather than the means.
Second, at three months after surgery, the patients who had bilateral PVP showed deterioration in parts I (mood) and II (activity of daily living) of the unified Parkinson's disease rating scale (UPDRS). The subscores of gait and postural instability worsened significantly. The patients showed deterioration in depression and apathy scores, and it was not possible to perform neuropsychological evaluation after surgery. The patients required feeding tube, their gait freezing deteriorated, and they had no benefit from increased levodopa doses. They suffered from severe loss of initiative and motivation. In my opinion, even though bilateral pallidotomy may increase the risks of complications,2–5 the disastrous outcome of the three patients described in Merello's paper poses serious questions as to the exact location of the lesions. I believe that in order to provoke the severe corticobulbar syndrome and “psychic akinesia” described, the pallidal lesions must have encroached on the internal capsule bilaterally, and also have included antero-dorso-medial parts of the GPi.
The authors wrote that “brain MRI three months after surgery showed that all nine lesions and the three electrodes were located entirely within the GPi. Coordinates of the lesion/lead as well as lesion volumes were not significantly different between the groups.” The authors concluded: “Our present findings argue against the possibility that lesion inaccuracy is responsible for the unacceptable rate of side effects of bilateral procedures as targets were confirmed by microrecording, lesions checked by MRI and the same criteria were followed either for lesioned or stimulated patients.”
It is indeed very fortunate that the authors did perform the postoperative MRI at three months after surgery—that is, when the surgical oedema that would disturb the interpretation of the lesion location had completely resolved. From a didactic point of view, and to allow the reader to learn more about the anatomical substrate of this rather catastrophic outcome in patients with bilateral PVP, the MRI scans should have been shown in this important paper. I invite Merello et al to publish relevant axial and coronal postoperative brain MRI scans of these three patients in their answer to this letter, showing the locations of the bilateral posteroventral GPi lesions that were responsible for the reported “corticobulbar syndrome and psychic akinesia.”
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Author's reply
We greatly appreciate the publication of the letter from Professor Hariz, which gives us occasion to provide more information about our paper and confirm the dangerous effect of simultaneous bilateral lesions within the GPi. We all know how limited the literature is on negative results of surgical procedures and how important they are. Surgery for Parkinson's disease is an extremely useful tool in a certain subgroups of patients, but it is not entirely risk-free and unfortunately many of the side effects seen at the bedside are poorly represented in published reports.
On the basis of unpublished descriptions by many neurosurgeons, bilateral procedures are performed by placing a normal lesion on one side, involving as much as possible of the motor portion of the GPi, followed by a smaller contralateral lesion. An excellent point arises from the concern expressed by Hariz: should both lesions be the same size? Perhaps staged asymmetric lesions could provide an alternative, but this was not the case in our report; we made simultaneous lesions which both involved as much as possible of the motor portion of the GPi, and our conclusions should not be extended to other surgical contexts.
As requested, we provide MRIs of our cases (fig 1) and fully agree that lesion placement is crucial, as Hariz is well aware, given his reported outcome of five of 13 patients (that is, almost 40%) who subsequently required seven further procedures, presumably because of initial lesion misplacement.1 Whatever the importance of descriptive photography, we believe it was more important that non-significant statistical differences were found in lesion/stimulation placement between the groups, and clinical psychic akinesia was only present in simultaneous bilaterally lesioned cases.
We are sure that Hariz must have already read a recent review by Laplane and Dubois,2 which clearly describes the psychic akinesia syndrome as a result of bilateral basal ganglia lesions, providing deep insight into the non-motor roles of the basal ganglia, such as behavioural activation, cognitive processing, affectivity, and conscious awareness, with which we fully agree.
Axial MRI scans with three month old bilateral pallidal lesion performed in the patients who underwent bilateral ablative procedures.