. Optimized temporal pattern of brain stimulation designed by computational evolution. Sci Transl Med. 2017 Jan 4;9(371) PubMed.

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  1. This study by Brocker et al. reveals an interesting finding of beneficial effects on PD motor symptoms when using an optimized stimulation sequence with lower average frequency (45 Hz) than the traditional DBS settings (130 to 185 Hz).

    It is, however, important to note that the results are rather preliminary, especially in relation to three points.

    First, in relation to validation of the effects in proper PD cohorts, this is more of a pilot study since only four bradykinesia-dominant and four tremor-dominant PD patients were tested. Hence, it is difficult to predict whether the reported effects of the optimized stimulation sequence would generalize to full-sized PD cohorts.

    Second, the “traditional” stimulation parameters used for comparison (and hence also for calculation of improved battery longevity) were not representative of the general DBS-treated PD population, in which monopolar stimulation of one contact at 130 Hz is the standard and most common setting (Volkmann et al., 2006; Picillo et al., 2016). In this study, six out of eight patients were stimulated at 180 or 185 Hz, which wears battery life considerably more than the more common setting at 130 Hz. Hence, the reported gain of 3.9 years in battery life on average should be read with some caution.

    Furthermore, seven of eight patients, treated with either monopolar or bipolar stimulation, all received stimulation on two or three negative contacts (cathodes) compared with the normal one negative contact, which suggests that electrode placement is not optimal in these patients. This was further underlined by the fact that five of 17 consented subjects failed to demonstrate any beneficial effect of high-frequency DBS compared with DBS off, indicating that the cohort is not particularly representative of the general DBS-treated PD population.

    Third, the reported alleviations of PD motor symptoms are estimated on the basis of only one aspect of these in the two sub-cohorts, namely finger tapping (bradykinesia) and tremor, respectively, rather than the full range of the cardinal motor symptoms as tested with the UPDRS-III. Hence, the effects of the optimized sequence on gait and balance were not tested at all, which makes it difficult to assess the relevance of the optimized sequence as a viable treatment alternative.

    Finally, the premise of the study is to investigate potentially battery saving optimizations to the stimulation protocol to mitigate increased risk of infections, etc., due to increasing numbers of IPG replacement surgeries. While this is still relevant for a substantial number of PD patients implanted with non-rechargeable IPGs, this risk is much less prevalent for the many PD patients who receive rechargeable IPGs with longevities ranging from nine to 25 years with standard DBS settings.

    Hence, these preliminary findings call for validation in full-sized and representative PD cohorts using the full UPDRS-III assessment.

    Nonetheless, from a basic science perspective it seems very relevant to further investigate what aspects of the optimized sequence led to the reported beneficial effects on PD motor symptoms, since this may open up a new window into the effect mechanism of DBS in PD.

    References:

    . Programming Deep Brain Stimulation for Parkinson's Disease: The Toronto Western Hospital Algorithms. Brain Stimul. 2016 May-Jun;9(3):425-37. Epub 2016 Feb 12 PubMed.

    . Basic algorithms for the programming of deep brain stimulation in Parkinson's disease. Mov Disord. 2006 Jun;21 Suppl 14:S284-9. PubMed.

    View all comments by Karen Østergaard

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