Multiple system atrophy (MSA) is a debilitating and fatal neurodegenerative disorder that
characterized pathologically by α-synuclein (aSyn) accumulation in oligodendrocytes, the
myelinating glial cells of the central nervous system (CNS), and symptomatic therapeutic
strategies are still limited.
The parkinsonian type of multiple system atrophy (MSA-P) has parkinsonian symptoms as its
prominent manifestation and may have an initial but short-lived response to levodopa
(L-dopa). Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or globus pallidus
interna(GPi) has been an established treatment for Parkinson's disease(PD) patients with
medically intractable fluctuations and has shown long-term efficacy to improve parkinsonian
motor symptoms, such as bradykinesia, rigidity and rest tremor. However, DBS therapy is
mostly ineffective in MSA patients. For the patients with MSA-P, improvement in motor
function is short-lasting and rapidly followed by the early appearance of freezing of gait
(FOG) and postural instability that counteracted DBS benefits and often leads to significant
disability and loss of quality of life. Dopaminergic therapy or other symptomatic medications
only offer limited alleviation of FOG and often lose their effect over time. Spinal cord
stimulation (SCS) is a well-established therapy for treating chronic lower back or low limb
pain neuropathic pain. Recently, some pilot studies demonstrated the safety and significant
therapeutic outcome of SCS for FOG in PD, MSA-P and primary progressive freezing
gait（PPFG）patients.
Can combined DBS with SCS be an alternative approach for symptomatic treatment of
parkinsonian symptoms and gait-associated problems in patients with MSA-P? The purpose of
this clinical study is to understand the combined treatment effectiveness for MSA-P.
It's a a multi-center, prospective, open label clinical study with a 12 months follow-up
period. The intended study population is individuals suffering from multiple system atrophy
with predominant parkinsonism. Each subject will complete an enrollment/screening/baseline
visit, an DBS&SCS implant and activation visit, and 3 months, and 12months follow-up visits.
Data collected at the enrollment visit after the consent process includes: demographics,
baseline clinical status, MSA-related medical history, and inclusion/exclusion criteria
assessment.Baseline assessment includes: Movement Disorder Society Sponsored Revision of the
Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III,New Freezing of Gait Questionnaire
(NFOGQ), Gait and Fall Questionnaire (GFQ), PD-related quality of life (PDQ-39) and Berg
Balance Scale(BBS). The participants will proceed to implantation after satisfying implant
inclusion and exclusion criteria. Medtronic Model 3389 DBS electrodes (Medtronic, U.S.A.)
will be implanted in the STN bilaterally using a stereotactic technique, connected to a
dual-channel ACTIVA Neurostimulator (Medtronic); Paddle-shaped SCS electrode with 16 contacts
(AdaptiveStim® 39, 565; Medtronic, USA) will be implanted into the epidural space at the
thoracic levels ranging from T10 to T12. Electrode positions of DBS will be verified by
postoperative CT-MRI image fusion and electrode position of SCS will be verified by X-ray.
The stimulators will be turned on within 1 month after electrode implantation surgery. The
stimulation parameters could vary freely, but medications will be kept constant during the
study period. At the end of month 12, participants will enter the long-term follow-up in
which medications could vary freely.