Multi-functional Neuroprosthetic System for Restoration of Motor Function in Spinal Cord Injury

The goal of this project is to restore these multiple functions to these individuals through
a comprehensive neuroprosthetic approach that addresses the overall needs of the individual.
This approach involves all aspects of the implementation, including the implanted technology,
the surgical installation, and the outcomes assessment through a coordinated team approach in
order to maximize the functional independence gained by the individual. With this system, we
propose that individuals who have a mid-cervical-level spinal cord injury will regain control
over multiple functions, including grasp, reach, bed mobility, seated posture, restoration of
an effective cough and bladder function. This ambitious and exciting goal is made possible by
the culmination of our research and clinical deployment of neuroprosthetic systems for spinal
cord injured subjects over the past 30 years. We anticipate that this system will not only
provide increased independence in each of the targeted body functions, but will provide
enough of an overall benefit to demonstrate significant improvements in quality of life and
health outcomes.

In clinical feasibility studies with spinal cord injured subjects, our clinical research
teams have demonstrated the control of bilateral hand function, bed mobility, postural
control, restoration of an effective cough, and bladder control using chronically implanted
neuroprostheses. Outcomes from each clinical study demonstrate that each system provides
increased functional independence to the individual. Initially, only a single type of
implanted system was implemented in any one individual, resulting in restoration of a single
bodily function. Thus, it has been necessary for subjects to choose between available
functions and select only one, despite the fact that each subject had multiple disabilities.
In the past few years, we have progressed to implementing a few subjects with more than one
system, such as providing both hand function and trunk stability. However, the fundamental
limitation of the current approach has been technological; i.e. each implanted system is
completely independent (both technically and programmatically), requiring separate technology
to be developed for each function, and these systems are implemented by separate teams in
separate surgical procedures. Thus, to this point, it has not been possible to address each
individual's comprehensive needs and tailor an overall approach that maximizes their
functional gains.

The proposed approach depends on the availability of a foundational platform technology that
is capable of meeting our broad specifications. We have now achieved this milestone under
separate funding, creating a revolutionary new implantable neuroprosthetic technology that is
fully capable of providing the necessary technological base for our proposed research. This
system, the Networked Neuroprosthetic System (NNPS), is a modular, scalable, and configurable
network of fully implanted, networked modules capable of meeting or exceeding the needs of
all of these neuroprosthetic applications. The NNPS provides a foundation which enables
efficient technical refinements that optimize implementation of the system for each targeted
application. The NNPS technology is currently operational and is undergoing fabrication and
testing in preparation for final pre-clinical studies and human implantation.

Inclusion Criteria:

- Diagnosis of cervical level spinal cord injury, either complete or incomplete;
International Standards for Neurological Classification of Spinal Cord Injury (INCSCI)
motor level of C4 through C8; American Spinal Injury Impairment Scale (AIS) grade A,
B, C, or D; six months or more post-injury

- Biceps/brachialis/brachioradialis strength of 2/5 or higher on Manual Muscle Test

- Peripheral nerve innervation to upper extremity and trunk muscles, including a grade
3/5 or higher stimulated strength (Manual Muscle Test) in at least two of the
following muscles in one arm: adductor pollicis, abductor pollicis brevis, flexor
pollicis longus, extensor pollicis longus, extensor digitorum communis, flexor
digitorum superficialis, flexor digitorum profundus, pronator quadratus, extensor
carpi ulnaris, extensor carpi radialis brevis, extensor radialis longus, flexor carpi
ulnaris, flexor carpi radialis, first dorsal interosseous; and in at least two of the
following muscles: left/right gluteus maximus, left/right erector spinae, left/right
quadratus lumborum,

- Age > 16 years

- Medically stable - cleared for surgery

- Able and willing to take part in study

Exclusion Criteria:

- Currently pregnant (neuroprosthesis implantation delayed until no longer pregnant)

- Other neurological conditions (multiple sclerosis, diabetes with peripheral nerve
involvement)

- History of coagulopathy, HIV, severe cardiopulmonary disease, severe bradycardia,
severe autonomic dysreflexia, or chronic obstructive pulmonary disease.

- Active untreated infection such as decubitus ulcer, urinary tract infection, pneumonia

- Presence of other active implantable medical devices with unknown or untested
interaction with the NNP implant

- Active implantable medical device (AIMD) such as a pacemaker or defibrillator, with
the exception of the implanted stimulator-telemeter (IST) or implanted receiver
stimulator (IRS) systems developed by the Cleveland Functional Electrical Stimulation
Center

- Unhealed fractures that prevent functional use of arm or trunk

- Less than six months post-injury (neuroprosthesis implantation delayed until criteria
met)

- Extensive upper extremity denervation (fewer than two stimulatable hand muscles and
two stimulatable trunk muscles)

- Involvement in other ongoing clinical studies that exclude concurrent until criteria
met)

- Disorder or condition that require MRI monitoring

- Mechanical ventilator dependency

- Progressive SCI In subjects who are undergoing bilateral implantation, subjects should
not have a history of autonomic dysreflexia, hypertension, diabetes or any condition
which requires frequent blood pressure monitoring or frequent venipuncture.

- Adverse interaction between system components and typical electromagnetic (EM) sources
in subject's home and work environments, including wheelchair or other active
implantable devices.