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| Study | Number of Patients | Inclusion criteria | Study design | Stimulation target | Stimulation parameters | Outcomes | Adverse events | Comments |
|
| Mazzone et al. [39] | 2 | FoG | Open label | Bilateral PPN | Bipolar; 10 Hz | Intraoperative improvement of UPDRS III score | NR | First human study to demonstrate the potential efficacy of PPN-DBS in PD |
|
| Plaha and Gill [40] | 2 | FoG, PI, and frequent falls | Open label | Bilateral PPN | Bipolar; 20–25 Hz | UPDRS improved by 53%; UPDRS III by 57% | Certain stimulation frequencies can exacerbate gait | Short follow-up, 42 days for patient 1 and 16 days for patient 2 |
|
| Stefani et al. [41] | 6 | FoG, 3 had “on” FoG, UPDRS-III > 70, and levodopa-induced dyskinesias | Open label | Bilateral STN and PPN | Bipolar; 25 Hz at PPN | PPN stimulation showed more benefit on posture and gait items compared to STN stimulation; UPDRS III improved by 32%; axial symptoms (UPDRS 27–30) by 60% | Paresthesia | Total length of study was 6 months; noted decline in motor benefit; trend of improved UPDRS scores with both STN and PPN stimulation |
|
| Strafella et al. [42] | 1 | Advanced PD, FoG, PI | Open label | Unilateral PPN | 70 Hz | UPDRS improved by 19%, mainly in relation to gait, tremor, and bradykinesia | NR | PET studies showed increased rCBF in different subcortical areas, most notably in the thalamus bilaterally |
|
| Ferraye et al. [43] | 6 | Severe FoG unresponsive to levodopa and STN stimulation | Double-blinded assessment | Bilateral STN and PPN | Bipolar; 15–25 Hz | Only FoG showed clear improvement; gait and PI scores did not improve; falls unrelated to FoG were unchanged in 5/6 | Seizure in 1 patient; stimulation frequency dependent oscillopsia; paresthesias; limb myoclonus | The total length of the study was 1 year; objective improvement of FoG in 2 patients |
|
| Moro et al. [44] | 6 | Age < 70, severe “off” FoG and PI; no dementia | Double-blinded assessment | Unilateral PPN | Bipolar; chronic stimulation frequency of 67 Hz | Improvement in UPDRS item 13 (falling) by 75% at 3 and 12 months | Stimulation frequency dependent oscillopsia and paresthesias | First double-blinded study to investigate unilateral PPN stimulation; total study length was 1 year |
|
| Thevathasan et al. [45] | 11 | Severe FoG and PI, in addition to falls both in the “on” and “off” states | Open label | Bilateral PPN in 8 patients, bilateral PPN and ZI in 2 patients, and unilateral PPN and bilateral ZI in 1 patient | Bipolar; 20–35 Hz | Improvement in frequency of falls and gait | NR | Follow-up 3–38 months |
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| Thevathasan et al. [46] | 5 | Severe FoG and PI, in addition to falls persisting in the “on” state | Open label | Bilateral PPN | Monopolar; 35 Hz; PPN target more caudal than previous | Improvement in all by FoG and falls questionnaire at 3 months and 2 years | Stimulation frequency dependent decline in motor function and gait; oscillopsia | Total study length was 2 years; assessments at 3 months and 2 years |
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| Khan et al. [47] | 7 | PD patients with severe FoG, PI, falls during “on” and “off” states | Open label | Bilateral PPN, in combination with cZi stimulation | Bipolar; 60 Hz (PPN) | Improvement in UPDRS III score (18.8%) and axial symptoms score (26.3%) | Akinesia in 2 patients | Follow-up 12 months; similar benefit with ZI stimulation versus ZI and PPN “on” |
|
| Thevathasan et al. [48] | 7 | PI, severe FoG, and falls during “on” state | Open label | 5 bilateral and 2 unilateral | Bipolar; 35 Hz | Improvement in freezing of gait questionnaire, turn task duration, and cadence | NR | First study to directly compare unilateral versus bilateral stimulation; less robust result in unilateral PPN |
|
| Mazzone et al. [49] | 28 | 24 patients had PD and 4 had PSP | Open label | Both bilateral (6) and unilateral (22) PPN | Bipolar; unilateral (40 Hz) and bilateral (25 Hz) | Improvement in UPDRS III score in “off” medication and “on” stimulation | None | The largest and longest study of PPN DBS to date with a mean follow-up of 3.8 years; included patients from prior studies |
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