Pedunculopontine Nucleus Deep Brain Stimulation in a Patient with Primary Progressive Freezing Gait Disorder

Department of Neurology, University of California San Francisco, Center for the Surgical Treatment of Movement Disorders, San Francisco, CA 94143, USA.
Stereotactic and Functional Neurosurgery (Impact Factor: 2.02). 01/2010; 88(1):51-5. DOI: 10.1159/000268742
Source: PubMed


Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) has recently been suggested for treatment of medication-unresponsive gait and axial symptoms in Parkinson's disease. Patients with the rare primary progressive freezing gait disorder (PPFG) have similar disabling symptoms and few therapeutic options. We report here on our experience with PPN DBS in treating a 76-year-old man with medication-refractory PPFG.
The patient was treated with staged PPN DBS and underwent careful pre- and postoperative clinical evaluations up to 12 months after surgery.
PPN DBS resulted in only mild improvement in symptoms after 12 months of stimulation.
In this single case of a patient with PPFG, PPN DBS served only a limited role in treating his symptoms and adds to the very limited published literature describing patients treated with DBS at this brain target.

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    • "Alternatively, the lack of freezing could have reflected failure of stimulation 'washout', as studies have suggested that therapeutic effects may sometimes persist beyond the period of pedunculopontine nucleus stimulation for up to several days (Ostrem et al., 2010; Thevathasan et al., 2011a). Exclusion of PD-FOG patients without baseline freezing was necessary for freezing related deficits to be accurately captured in the baseline condition and to avoid the introduction of floor effects, whereby the intervention (pedunculopontine nucleus stimulation) could not possibly yield Table 3 Straight task outcomes for the three subject groups, including patients in the PD-FOG group in all conditions of stimulation, mean (SD) "
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    ABSTRACT: Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson's disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients' usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral.
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    ABSTRACT: To assess the efficacy of bilateral pedunculopontine nucleus (PPN) deep brain stimulation (DBS) as a treatment for primary progressive freezing of gait (PPFG). A patient with PPFG underwent bilateral PPN-DBS and was followed clinically for over 14 months. The PPFG patient exhibited a robust improvement in gait and posture following PPN-DBS. When PPN stimulation was deactivated, postural stability and gait skills declined to pre-DBS levels, and fluoro-2-deoxy-d-glucose positron emission tomography revealed hypoactive cerebellar and brainstem regions, which significantly normalised when PPN stimulation was reactivated. This case demonstrates that the advantages of PPN-DBS may not be limited to addressing freezing of gait (FOG) in idiopathic Parkinson's disease. The PPN may also be an effective DBS target to address other forms of central gait failure.
    Journal of neurology, neurosurgery, and psychiatry 10/2010; 82(11):1256-9. DOI:10.1136/jnnp.2010.213462 · 6.81 Impact Factor
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