Contralaterally Controlled FES of Arm & Hand for Subacute Stroke Rehabilitation

Loss of arm and hand function is a severely disabling condition that occurs in nearly 75% of
the estimated 795,000 Americans who have a new or recurrent stroke each year [Roger 2011].
Upper limb impairment is often characterized by inability to extend the elbow and open the
hand. The hope of regaining lost motor function after stroke has been fueled in recent years
by the development of new rehabilitation therapies and devices that are aimed at promoting
the brain's capacity to reorganize after injury in such a way that restores motor control of
paretic limbs [Nudo 2001]. The Investigators' long-term objective is to develop stroke
rehabilitation treatments for the hemiparetic upper limb that are optimized for
effectiveness, applicability, and deployability.

The primary objective of this project is to estimate the effect of Arm+Hand Contralaterally
Controlled Functional Electrical Stimulation (CCFES) in reducing upper limb motor impairment
and activity limitation in subacute hemiplegia. CCFES is a treatment aimed at improving
recovery of volitional motor function in stroke survivors [Knutson 2007; Knutson 2009;
Knutson 2010]. Hand CCFES activates finger and thumb extensors with an intensity of
electrical stimulation that is proportional to the degree of opening of the contralateral
unimpaired hand wearing an instrumented glove. Thus, volitional opening of the nonparetic
hand produces stimulated opening of the paretic hand. The Hand CCFES system enables stroke
patients to use their impaired hand to practice functional tasks in therapy sessions. CCFES
incorporates the following features considered to be important to motor recovery and
promoting neuroplasticity: synchronization of motor intent with motor execution of paretic
hand opening [Rushton 2003; Kimberley 2004], bilateral symmetric movement [Luft 2004],
intensive repetitive hand opening exercises [Lang 2009], and the practice of functional tasks
[Nudo 2003]. In a pilot case series study of patients with chronic (> 6 months) post-stroke
hemiplegia, all 6 participants experienced some reduction of upper limb motor impairment
after several weeks of Hand CCFES [Knutson 2007; Knutson 2009]. The results of a Phase I
randomized clinical trial (RCT) of Hand CCFES in 21 patients with subacute (≤ 6 months)
hemiplegia suggested that Hand CCFES may be superior to cyclic neuromuscular electrical
stimulation (NMES) in reducing upper extremity impairment and activity limitation [Knutson
2011].

In this study, added to the Hand CCFES treatment is stimulated elbow extension controlled by
the contralateral elbow. This "next generation" CCFES treatment is called Arm+Hand CCFES.
Arm+Hand CCFES therapy is intended to strengthen and improve the motor control of the
proximal upper limb as well as the hand, to improve simultaneous reaching and hand opening, a
functionally critical movement pattern that is often prevented by paresis and post-stroke
flexor synergies. The secondary objective of this project is to evaluate the effect of adding
elbow extensor stimulation to the Hand CCFES treatment.

A sample of 108 stroke survivors with acute/subacute (≤ 6 months) upper limb hemiplegia will
be randomly assigned in equal proportions to receive 12 weeks of either Arm+Hand CCFES
(stimulates elbow extension and hand opening), Hand CCFES (stimulates hand opening), or
Arm+Hand Cyclic NMES (stimulates elbow extension and hand opening but with pre-set timing and
intensity, i.e., not intention-driven), plus lab-based therapist-guided task practice. Upper
limb impairment and activity limitation will be assessed at baseline, 6, 12, 20, 28, and 36
weeks.

This is the first randomized controlled trial of Arm+Hand CCFES in subacute upper extremity
hemiplegia. Ultimately, the information learned in this study will serve to accelerate the
development of a new treatment for reducing post-stroke disability.

Inclusion Criteria:

- Age ≥ 21 and ≤ 80

- ≤ 6 months of first clinical hemorrhagic or nonhemorrhagic stroke

- Skin intact on hemiparetic arm and hand

- Able to follow 3-stage commands

- Able to recall 2 of 3 items after 30 minutes

- Medically stable

- MRC ≤ 4 for finger extensors on paretic side

- Adequate movement of shoulder and elbow to position the paretic hand in the workspace
for table-top task practice

- Caregiver available to assist with device daily - OR - able to independently don elbow
cuff on unaffected arm

- Full volitional elbow extension/flexion and hand opening/closing of unaffected limb

- Upper extremity hand section of FMA ≥ 1 AND ≤ 11/14

- Unable to simultaneously fully extend the elbow and fully open the hand toward
tabletop object with arm unsupported (i.e. cannot voluntarily achieve the maximum PROM
available)

- Functional PROM (minimal resistance) at shoulder, elbow, wrist, and hand
simultaneously on affected side (i.e., there exists enough PROM to reach and acquire
table-top objects).

- Able to hear and respond to stimulator cues

- While relaxed, surface NMES of finger extensors and thumb extensors and/or abductors
produces a functional degree of hand opening without pain.

- While relaxed with the forearm supported with a mobile arm support, surface NMES of
elbow extensors (triceps) produces functional elbow extension without pain.

- Patient must be able to sit unassisted in an armless straight-back chair for the
duration of the screening portion of the eligibility assessment.

Exclusion Criteria:

- Co-existing neurological condition other than prior stroke involving the hemiparetic
upper limb (e.g., peripheral nerve injury, PD, SCI, TBI, MS).

- Severely impaired cognition and communication

- Uncontrolled seizure disorder

- History of cardiac arrhythmias with hemodynamic instability

- Cardiac pacemaker or other implanted electronic device

- Pregnant

- IM Botox injections in any UE muscle in the last 3 months

- Insensate arm, forearm, or hand

- Uncompensated hemi-neglect (extinguishing to double simultaneous stimulation)

- Severe shoulder or hand pain

- Severe depression on Beck Depression Inventory (>=13 on BDI-fast screen)