Deep Brain Stimulation of the Pedunculopontine Nucleus Area in Parkinson Disease: MRI-Based Anatomoclinical Correlations and Optimal Target.

BACKGROUND: Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE: To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS: We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS: Most effective DBS electrode contacts to treat FOG in PD patients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION: In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF.

The laser shoes: A new ambulatory device to alleviate freezing of gait in Parkinson disease.

OBJECTIVE: To assess, in a cross-sectional study, the feasibility and immediate efficacy of laser shoes, a new ambulatory visual cueing device with practical applicability for use in daily life, on freezing of gait (FOG) and gait measures in Parkinson disease (PD). METHODS: We tested 21 patients with PD and FOG, both "off" and "on" medication. In a controlled gait laboratory, we measured the number of FOG episodes and the percent time frozen occurring during a standardized walking protocol that included FOG provoking circumstances. Participants performed 10 trials with and 10 trials without cueing. FOG was assessed using offline video analysis by an independent rater. Gait measures were recorded in between FOG episodes with the use of accelerometry. RESULTS: Cueing using laser shoes was associated with a significant reduction in the number of FOG episodes, both "off" (45.9%) and "on" (37.7%) medication. Moreover, laser shoes significantly reduced the percent time frozen by 56.5% (95% confidence interval [CI] 32.5-85.8; p = 0.004) when "off" medication. The reduction while "on" medication was slightly smaller (51.4%, 95% CI -41.8 to 91.5; p = 0.075). These effects were paralleled by patients' positive subjective experience on laser shoes' efficacy. There were no clinically meaningful changes in the gait measures. CONCLUSIONS: These findings demonstrate the immediate efficacy of laser shoes in a controlled gait laboratory, and offer a promising intervention with potential to deliver in-home cueing for patients with FOG. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PD, laser shoes significantly reduce FOG severity (both number and duration of FOG episodes).

Identifying freezing of gait in Parkinson's disease during freezing provoking tasks using waist-mounted accelerometry.

BACKGROUND: Freezing of gait (FOG) is a common and debilitating phenomenon in Parkinson's disease (PD). Wearable accelerometers might help to assess FOG in the research setting. Here, we evaluate whether accelerometry can detect FOG while executing rapid full turns and while walking with rapid short steps (the two most common provoking circumstances for FOG). METHODS: We included 23 PD patients, who all had objective FOG. Participants performed several walking tasks, including walking rapidly with short steps and rapid full turns in both directions with a triaxial linear waist-mounted accelerometer. Two independent experts identified FOG episodes using off-line video-analysis (gold standard). A validated algorithm [ratio between pathological freezing (3-8 Hz)-and normal locomotor frequencies (0.5-3 Hz)] was applied on the accelerometer data to detect FOG episodes. RESULTS: Clinically, FOG was most often observed during full rapid turns (81% of all episodes), followed by walking with short rapid steps (12% of all episodes). During full rapid turns, accelerometry yielded a sensitivity of 78% and specificity of 59%. A sensitivity of 64% and specificity of 69% was observed during walking rapidly with small steps. Combining all tasks rendered a sensitivity of 75% and specificity of 76%. CONCLUSION: Our results suggest that FOG can be detected from a single lumbar accelerometer during several walking tasks, including full rapid turns and walking with short steps rapidly, with reasonable sensitivity and specificity. This approach holds promise for possible implementation as complementary objective outcome in a research setting, but more work remains needed to improve the sensitivity and specificity.

Deep brain stimulation effect on freezing of gait.

The majority of patients with Parkinson's disease suffer from freezing of gait (FOG), which responds more or less to levodopa. Thalamic stimulation, mainly used in the treatment of tremor dominant Parkinson's disease is ineffective in FOG. GPi stimulation moderately improves FOG, but this effect may abate in the long term. STN stimulation was reported to improve levodopa-responsive FOG. In some patients, the benefit from levodopa is greater than that from STN stimulation, and levodopa and STN stimulation can have additive effects. On the contrary, STN stimulation is ineffective on levodopa-resistant FOG. In the few cases of levodopa-induced FOG, STN stimulation can indirectly be effective, thanks to a great decrease or arrest of levodopa. Stimulation of the pedunculopontine nucleus has recently been performed in small groups of patients suffering from both off- and on-levodopa gait impairments. The first results appear encouraging, but they need to be confirmed by controlled studies in larger series of patients.