Diaphragm Pacing After Spinal Cord Injury

Subject recruitment. Patients with acute, traumatic C-SCIs, scheduled to receive
intramuscular diaphragm pacing OR who have recently received a diaphragm pacer (within past
5-days) will be recruited from two Level-1 trauma hospitals serving North Florida - UF Health
Shands Hospitals in Gainesville and Jacksonville, Florida.

Enrollment. Patients with acute, traumatic C-SCIs (AIS A-C, affecting C1-C6 segments) who are
scheduled to undergo or who have recently received implantation of diaphragm pacing
electrodes (within recent 5-days) will be identified by the investigators.

After obtaining informed consent for participation in the study, members of the study team
will review the participant's medical records to obtain study-related data and verify that
the participant meets the study criteria. Clinical tests of sensory and motor function also
may be conducted to verify the participant's SCI classification and extent of SCI. The tests
of sensory and motor function are part of the American Spinal Injury Association (ASIA)
Impairment Scale and the International Standards for Neurological Classification of Spinal
Cord Injury. These clinical assessments are part of standard clinical care and include tests
of sensation (dermatomes) and muscle strength via manual muscle testing (myotomes). These
tests are done to clinically determine which segmental levels of the spinal cord demonstrate
normal or impaired function. These tests also aid in determining if the SCI is clinically
complete or incomplete. Determination of complete versus incomplete is based on the sensory
and motor function in the lowest sacral segments which control sensation and motor function
at the anal sphincter. Respiratory function will be assessed by measurement of maximal
expiratory pressures and standard spirometry (tidal breathing, maximal voluntary ventilation
and flow-volume curves).

Following enrollment and implantation of diaphragm pacing electrodes, individuals will be
assessed at regular intervals. Assessments will include: a.) clinical ASIA neurologic
examination of sensory and motor function (as described above) b.) recording of intramuscular
diaphragm EMGs c.) measurement of diaphragm muscle strength via standard clinical assessment
of maximal inspiratory pressures and d.) standard clinical measures of respiratory function.

Up to 5 assessments will be conducted in the acute hospital setting; up to 5 assessments
during inpatient rehabilitation (Brooks Rehabilitation); up to 4 assessments will be
conducted after discharge to the home setting.

ASSESSMENT OVERVIEW: The examination will allow investigators to characterize longitudinal
changes in segmental sensory and motor function. Diaphragm electromyogram (EMG) will be
recorded from the intramuscular diaphragm pacing electrodes and respiratory function will be
assessed during non-stimulated respiration (diaphragm pacing unit turned off). Diaphragm EMGs
will be recorded from the intramuscular pacing electrodes with a custom connector that
attaches to the external pacing electrode wires and interfaces with an EMG acquisition
system. Concurrent with EMG recordings, each assessment will include tests of maximal
inspiratory pressures to assess diaphragm muscle strength.

Assessment of the neuromuscular activation of the diaphragm will be performed. Neuromuscular
activation of the diaphragm will be assessed by recording diaphragm EMGs from the
surgically-implanted intramuscular stimulating electrodes. This approach will allow for
comparisons of EMG recordings across time and reduces the methodological limitations
associated with surface or percutaneous EMG approaches. EMGs will be recorded during
non-stimulated respiration (diaphragm pacer turned off) and simultaneously with assessments
of respiratory function. These assessments may include maximal inspiratory pressures; sniff
nasal inspiratory pressure, maximal expiratory pressure, assessments of resting tidal
breathing, inspiration to total lung capacity, maximal voluntary ventilation and measurement
of flow volumes using standard spirometry.

During the assessments, photographs and/or video recordings may be obtained. These recordings
will be done with the participant's knowledge and consent for the type of recording being
obtained. Photographs and video recordings will be used to communicate study procedures with
the study team and to monitor the assessment process. Video and photographic data will be
used to assess how individuals with SCIs perform and respond to the testing and to
communicate the study procedures. Video and photographic information will be used in a manner
based on the level of consent obtained from each participant.

Primary outcomes to characterize neuromuscular activation of the diaphragm and assess changes
in diaphragm activation associated with intramuscular diaphragm stimulation will include:
amplitude and timing characteristics (raw, filtered EMGs and normalized); neural respiratory
drive to evaluate diaphragm muscle activation during tidal breathing relative to activation
capacity during maximal inspiratory maneuvers; and time-frequency characteristics of the
diaphragm EMGs (wavelet analysis).

Inclusion Criteria:

- Acute, traumatic cervical spinal cord injuries (C-SCIs), classified according to the
American Spinal Injury Association (ASIA) Impairment Scale (AIS) as A-C (complete SCI
(A); motor complete SCI (B); motor incomplete with minimal motor function (C)),
affecting C1-C6 spinal cord segments

- Scheduled to undergo implantation of a diaphragm pacer, or who have recently received
(in past 5-days) implantation of intramuscular diaphragm pacing electrodes due to
severe respiratory impairments and dependence on mechanical ventilation.

Exclusion Criteria:

- Progressive neuromuscular diseases such as multiple sclerosis and myasthenia gravis

- History of neurologic injuries such as stroke or prior SCI

- Chest wall injuries or deformities likely to influence breathing

- Pulmonary infection

- Pregnancy

- Cognitive impairments limiting study participation