Objective: The study of the benefit of intestinal levodopa/carbidopa infusion(LCIG) in resistant ON-freezing of gait(FOG-ON) that appears after Subthalamic Nucleus Deep Brain Stimulation(NST-DBS) in Parkinson’s disease(PD).

Background: Different strategies are proposed for the treatment of FOG(1). DBS can induce FOG in PD patients who never had gait symptoms before(2,3). Recently, LCIG has shown positive effects in FOG resistant to oral therapies(4). However, its utility in the scenario of FOG-ON after NST-DBS, has not been reported yet.

Method: We report data from 5 out of 48 PD patients with NST-DBS performed in our hospital between 2010 and 2018, who developed resistant FOG-ON after surgery. These patients were treated with LCIG as an alternative therapy. FOG-ON was considered resistant after trying both all posible adjustments of DBS and combinations of conventional medication. LCIG was administered following a protocol. DBS was switched OFF and medication was converted to total equivalent dose of L-dopa(LEDD) to be administered as L-dopa gel during daytime. Data was retrospectively collected: sex, age of disease onset, age at the time of surgery, time between surgery and FOG-ON, positioning of electrodes within NST, surgery complications, FOG scores pre/post LCIG based on item 14 in the Unified Parkinson’s Disease Rating Scale(UPDRS); pre/post LCIG LEDD and the duration of any improvement after LCIG.

Results: Five out of 48 patients(10%) developed resistant FOG-ON after surgery. All the patients(PC1-5) were women. The mean age at the time of surgery was 65.5 years(57-69) with an average of 9 years(4-12) since disease onset. The electrodes were correctely placed in the dorsolateral NST in all cases. The period from surgery to FOG-ON was greater than 6 months in all but one patient(PC1). Only PC2 had an infection in the left electrode after 2.5 months that was replaced without incidences. Mean age at the beginning of LCIG was 70.4 years(63-74) and the interval between NST-DBS and the begginig of LCIG was 18.5 months(8-36). Four patients(80%) improved FOG with LCIG in 2 or more points in item 14 of the UPDRS scale. This benefit was maintained at least for 16 months in all patients. It was not related with a higher LEDD with LCIG.

Conclusion: LCIG might be a valuable therapeutic option for FOG-ON after NST-DBS. Future larger trials should be conducted to confirm these findings.

References: 1. Nonnekes, J., Snijders, A., Nutt, J., Deuschl, G., Giladi, N. and Bloem, B. (2015). Freezing of gait: a practical approach to management. The Lancet Neurology, 14(7), pp.768-778. 2. Collomb-Clerc, A. and Welter, M. (2015). Effects of deep brain stimulation on balance and gait in patients with Parkinson’s disease: A systematic neurophysiological review. Neurophysiologie Clinique/Clinical Neurophysiology, 45(4-5), pp.371-388. 3. Buhmann, C., Huckhagel, T., Engel, K., Gulberti, A., Hidding, U., Poetter-Nerger, M., Goerendt, I., Ludewig, P., Braass, H., Choe, C., Krajewski, K., Oehlwein, C., Mittmann, K., Engel, A., Gerloff, C., Westphal, M., Köppen, J., Moll, C. and Hamel, W. (2017). Adverse events in deep brain stimulation: A retrospective long-term analysis of neurological, psychiatric and other occurrences. PLOS ONE, 12(7), p.e0178984. 4. Rispoli, V., Golfrè Andreasi, N., Penna, G., Preda, F., Contini, E. and Sensi, M. (2018). Levodopa/Carbidopa Intestinal Gel Infusion Therapy: Focus on Gait and Balance. Movement Disorders Clinical Practice, 5(5), pp.542-545.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intestinal-levodopa-carbidopa-infusion-as-a-therapeutic-option-for-freezing-of-gait-after-deep-brain-stimulation-in-parkinsons-disease/