Publications by authors named "Stephano J Chang"

6 Publications

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Deep brain stimulation of midbrain locomotor circuits in the freely moving pig.

Brain Stimul 2021 Feb 27;14(3):467-476. Epub 2021 Feb 27.

Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address:

Background: Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson's disease as a therapy for gait dysfunction, with mixed reported outcomes. Recent studies suggest that optimizing the MLR target could improve its effectiveness.

Objective: We sought to determine if stereotaxic targeting and DBS in the midbrain of the pig, in a region anatomically similar to that previously identified as the MLR in other species, could initiate and modulate ongoing locomotion, as a step towards generating a large animal neuromodulation model of gait.

Methods: We implanted Medtronic 3389 electrodes into putative MLR structures in Yucatan micropigs to characterize the locomotor effects of acute DBS in this region, using EMG recordings, joint kinematics, and speed measurements on a manual treadmill.

Results: MLR DBS initiated and augmented locomotion in freely moving micropigs. Effective locomotor sites centered around the cuneiform nucleus and stimulation frequency controlled locomotor speed and stepping frequency. Off-target stimulation evoked defensive and aversive behaviors that precluded locomotion in the animals.

Conclusion: Pigs appear to have an MLR and can be used to model neuromodulation of this gait-promoting center. These results indicate that the pig is a useful model to guide future clinical studies for optimizing MLR DBS in cases of gait deficiencies associated with such conditions as Parkinson's disease, spinal cord injury, or stroke.
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http://dx.doi.org/10.1016/j.brs.2021.02.017DOI Listing
February 2021

Commentary: Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study.

Neurosurgery 2021 03;88(4):E310-E311

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida.

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http://dx.doi.org/10.1093/neuros/nyaa543DOI Listing
March 2021

Freezing of Gait in Parkinson's Disease: Invasive and Noninvasive Neuromodulation.

Neuromodulation 2020 Dec 26. Epub 2020 Dec 26.

Department of Neurological Surgery, University of California, San Francisco, CA, USA.

Introduction: Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life.

Materials And Methods: Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders.

Conclusion: Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.
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http://dx.doi.org/10.1111/ner.13347DOI Listing
December 2020

Population Averaged Stereotaxic T2w MRI Brain Template for the Adult Yucatan Micropig.

Front Neuroanat 2020 13;14:599701. Epub 2020 Nov 13.

Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, United States.

Population averaged brain templates are an essential tool for imaging-based neuroscience research, providing investigators with information about the expected size and morphology of brain structures and the spatial relationships between them, within a demographic cross-section. This allows for a standardized comparison of neuroimaging data between subjects and provides neuroimaging software with a probabilistic framework upon which further processing and analysis can be based. Many different templates have been created to represent specific study populations and made publicly available for human and animal research. An increasingly studied animal model in the neurosciences that still lacks appropriate brain templates is the adult Yucatan micropig. In particular, T2-weighted templates are absent in this species as a whole. To address this need and provide a tool for neuroscientists wishing to pursue neuroimaging research in the adult micropig, we present the construction of population averaged ( = 16) T2-weighted MRI brain template for the adult Yucatan micropig. Additionally, we present initial analysis of T1-weighted ( = 3), and diffusion-weighted ( = 3) images through multimodal registration of these contrasts to our T2 template. The strategies used here may also be generalized to create similar templates for other study populations or species in need of template construction.
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http://dx.doi.org/10.3389/fnana.2020.599701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691581PMC
November 2020

Dissecting Brainstem Locomotor Circuits: Converging Evidence for Cuneiform Nucleus Stimulation.

Front Syst Neurosci 2020 21;14:64. Epub 2020 Aug 21.

Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, United States.

There are a pressing and unmet need for effective therapies for freezing of gait (FOG) and other neurological gait disorders. Deep brain stimulation (DBS) of a midbrain target known as the pedunculopontine nucleus (PPN) was proposed as a potential treatment based on its postulated involvement in locomotor control as part of the mesencephalic locomotor region (MLR). However, DBS trials fell short of expectations, leading many clinicians to abandon this strategy. Here, we discuss the potential reasons for this failure and review recent clinical data along with preclinical optogenetics evidence to argue that another nearby nucleus, the cuneiform nucleus (CnF), may be a superior target.
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http://dx.doi.org/10.3389/fnsys.2020.00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473103PMC
August 2020

Nicotine replacement therapy in patients with aneurysmal subarachnoid hemorrhage: Systematic review of the literature, and survey of Canadian practice.

J Clin Neurosci 2017 Aug 22;42:48-53. Epub 2017 Mar 22.

Division of Neurosurgery, Vancouver General Hospital, 899 West 12th Avenue, Vancouver, BC V5Z 1M9, Canada.

Tobacco smoke increases the risk of aneurysmal subarachnoid hemorrhage (SAH), as well as complications such as vasospasm. Most patients presenting with aneurysmal SAH smoke, and many survivors continue to smoke after discharge. Neurosurgeons often hesitate to use nicotine replacement therapy (NRT) during hospitalization of patients with SAH due to concerns of inducing vasospasm. We aimed to evaluate the safety and efficacy, and patterns of use of NRT in smokers hospitalized for SAH. We performed a systematic review of MEDLINE, CENTRAL, Embase, and unpublished sources of literature to October 2016 for randomized and observational studies comparing exposure to non-exposure of smoking cessation products in the acute phase of aneurysmal SAH. Additionally, we surveyed 50 Canadian vascular neurosurgeons to evaluate patterns of NRT use in SAH. Four cohort studies (n=1210) met our eligibility criteria. Three studies enrolled patients with aneurysmal SAH, and one study enrolled all neurocritically ill patients. We rated the quality of evidence as very low using the GRADE approach. We could not meta-analyze studies due to methodological heterogeneity. Individual studies reported beneficial or neutral effects of NRT on functional outcome, death, and clinical or radiographic vasospasm. None of the studies assessed long-term abstinence from tobacco. Of the 14 vascular neurosurgeons responding to our survey, most never used NRT in patients hospitalized with SAH, often citing training or standard of practice as the reason. Current evidence suggests that NRT does not induce vasospasm, and is associated with improved outcomes in smokers hospitalized for SAH. Protocol registered in PROSPERO, available at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016037200.
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http://dx.doi.org/10.1016/j.jocn.2017.03.014DOI Listing
August 2017