Neurosurgical convection-enhanced delivery of treatments for Parkinson’s disease

Lam, Miu Fei; Thomas, Meghan; Lind, Christopher R. P.

doi:10.1016/j.jocn.2011.01.012

Cited by 29 publications

(13 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, atypically small PLGA nanoparticles can be transported large distances from the site of infusion via convection 23 . The invasiveness of this delivery method will limit its broad application, but it is potentially useful for the delivery of agents that reverse Parkinson’s disease 28 or Huntington’s disease 29 . In addition, this approach can be extended to other parts of the nervous system, as shown in the injection of protein growth factor-loaded nanoparticles for treatment of spinal cord injury 30 or the injection of various nanoparticles into the eye for treatment of retinal diseases 31, 32 .…”

Section: Anatomical Targetingmentioning

confidence: 99%

A holistic approach to targeting disease with polymeric nanoparticles

Cheng

Tietjen

Saucier-Sawyer

et al. 2015

Nat Rev Drug Discov

394

278

View full text Add to dashboard Cite

PREFACE The primary goal of nanomedicine is to improve clinical outcomes. Toward this end, targeted nanoparticles are engineered to reduce non-productive distribution while improving diagnostic and therapeutic efficacy. Paradoxically, as this field has matured, the notion of ‘targeting’ has been minimized to the concept of increasing affinity of a nanoparticle for its target. This review outlines a holistic view of nanoparticle targeting, in which nanoparticle route of administration, molecular characteristics, and temporal control are potential design variables that must be considered simultaneously. This comprehensive vision for nanoparticle targeting will hasten the integration of nanomedicines into clinical practice.

show abstract

Section: Anatomical Targetingmentioning

confidence: 99%

A holistic approach to targeting disease with polymeric nanoparticles

Cheng

Tietjen

Saucier-Sawyer

et al. 2015

Nat Rev Drug Discov

394

278

View full text Add to dashboard Cite

show abstract

“…Thus although PSA is a more accurate term to describe the DBS intervention centred on the caudal zona incerta, or even its border with the subthalamic nucleus, precise specification of the caudal zona incerta is important for mechanistic advances which may in the future be exploited by new technologies such as the use of stereotactically targeted neurotransmitter‐specific infusions (Lam et al. ).…”

Section: Discussionmentioning

confidence: 99%

The anatomy of the caudal zona incerta in rodents and primates

2013

Self Cite

View full text Add to dashboard Cite

SummaryThe caudal zona incerta is the target of a recent modification of established procedures for deep brain stimulation (DBS) for Parkinson's disease and tremor. The caudal zona incerta contains a number of neuronal populations that are distinct in terms of their cytoarchitecture, connections, and pattern of immunomarkers and is located at a position where a number of major tracts converge before turning toward their final destination in the forebrain. However, it is not clear which of the anatomical features of the region are related to its value as a target for DBS. This paper has tried to identify features that distinguish the caudal zona incerta of rodents (mouse and rat) and primates (marmoset, rhesus monkey, and human) from the remainder of the zona incerta. We studied cytoarchitecture, anatomical relationships, the pattern of immunomarkers, and gene expression in both of these areas. We found that the caudal zona incerta has a number of histological and gene expression characteristics that distinguish it from the other subdivisions of the zona incerta. Of particular note are the sparse population of GABA neurons and the small but distinctive population of calbindin neurons. We hope that a clearer appreciation of the anatomy of the region will in the end assist the interpretation of cases in which DBS is used in human patients.

show abstract

“…Current PD therapy may reduce symptoms, primarily through the use of dopaminergic agonists, but delivery is primary limited due to the inability of these agents to penetrate the blood-brain barrier (BBB). 4 The development of techniques that involve bypassing the BBB to deliver dopaminergic-restoring medications, including CED, is desired. 5 Direct brain infusion via CEDhas the additional benefit of reducing systemic toxicity of the therapeutics.…”

Section: Introductionmentioning

confidence: 99%

“…In the prototypical infusion, the infusate is symmetrically delivered in a spherical distribution pattern. 4 Occasionally, the infusate refluxes proximally up the cathetertip, a phenomenon known as backflow [Figure 1]. The potential for undesired effects is minimized if backflow can be prevented or contained within the target region.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ramped-rate vs. continuous-rate infusions: An in vitro comparison of Convection Enhanced Delivery protocols

Schomberg

Wang

Marshall

et al. 2013

ANS

View full text Add to dashboard Cite

BackgroundConvection enhanced delivery (CED) is a technique using infusion convection currents to deliver therapeutic agents into targeted regions of the brain. Recently, CED is gaining significant acceptance for use in gene therapy of Parkinson’s disease (PD) employing direct infusion into the brain. CED offers advantages in that it targets local areas of the brain, bypasses the blood-brain barrier (BBB), minimizes systemic toxicity of the therapeutics, and allows for delivery of larger molecules that diffusion driven methods cannot achieve. Investigating infusion characteristics such as backflow and morphology is important in developing standard and effective protocols in order to successfully deliver treatments into the brain. Optimizing clinical infusion protocols may reduce backflow, improve final infusion cloud morphology, and maximize infusate penetrance into targeted tissue.PurposeThe purpose of the current study was to compare metrics during ramped-rate and continuous-rate infusions using two different catheters in order to optimize current infusion protocols. Occasionally, the infusate refluxes proximally up the catheter tip, known as backflow, and minimizing this can potentially reduce undesirable effects in the clinical setting. Traditionally, infusions are performed at a constant rate throughout the entire duration, and backflow is minimized only by slow infusion rates, which increases the time required to deliver the desired amount of infusate. In this study, we investigate the effects of ramping and various infusion rates on backflow and infusion cloud morphology. The independent parameters in the study are: ramping, maximum infusion rate, time between rate changes, and increments of rate changes.MethodsBackflow was measured using two methods: i) at the point of pressure stabilization within the catheter, and ii) maximum backflow as shown by video data. Infusion cloud morphology was evaluated based on the height-to-width ratio of each infusion cloud at the end of each experiment. Results were tabulated and statistically analyzed to identify any significant differences between protocols.ResultsThe experimental results show that CED rampedrate infusion protocols result in smaller backflow distances and more spherical cloud morphologies compared to continuous-rate infusion protocols ending at the same maximum infusion rate. Our results also suggest internal-line pressure measurements can approximate the time-point at which backflow ceases.ConclusionOur findings indicate that ramping CED infusion protocols can potentially minimize backflow and produce more spherical infusion clouds. However, further research is required to determine the strength of this correlation, especially in relation to maximum infusion rates.

show abstract

Neurosurgical convection-enhanced delivery of treatments for Parkinson’s disease

Cited by 29 publications

References 63 publications

A holistic approach to targeting disease with polymeric nanoparticles

A holistic approach to targeting disease with polymeric nanoparticles

The anatomy of the caudal zona incerta in rodents and primates

Ramped-rate vs. continuous-rate infusions: An in vitro comparison of Convection Enhanced Delivery protocols

Contact Info

Product

Resources

About