Cervical Electrical Stimulation for ALS

Amyotrophic lateral sclerosis (ALS) reduces connections between the cortical motor neurons
that initiate movement and the spinal motor neurons that direct muscles to execute movement.
This situation shares many key features with incomplete spinal cord injury (SCI).
Accumulating evidence in SCI suggests that externally activating spared nerve circuits with
electromagnetic stimulation augments neural transmission.

With this goal, the investigators developed a novel method of noninvasive cervical electrical
stimulation (CES). CES activates multiple muscles on both upper limbs by triggering afferent
sensory or efferent motor nerve roots depending on stimulus intensity. This study will
investigate CES for its potential to strengthen residual circuits to the hands in ALS.

To the investigators' knowledge, electrical spinal stimulation for ALS has never been tested
or applied previously. Therefore, a pilot study is essential. This study will be performed in
two stages:

1. Map CES circuit and synaptic targets: The experiments share a common structure
comprising conditioning and test stimuli delivered at a range of intensities, sites, and
interstimulus intervals.

2. Determine parameters for combining CES with volitional movement: volitional limb
movements depend on the same corticospinal and motor neuron circuits as those activated
by TMS and F-waves. Since preliminary data shows that subthreshold CES facilitates TMS
responses, CES may also be able to facilitate volitional limb movements.

Successful completion of these experiments will: mechanistically elucidate CES circuit
interactions; investigate the potential for CES to enhance concurrent volitional muscle
activation; and establish CES as safe and feasible in the ALS population. Given the limited
treatment options for ALS, any amount of progress would represent a meaningful step forward.
Moreover, results of this pilot study could lead to direct translation for lasting clinical
benefit by combining repetitive subthreshold CES with repetitive task-oriented physical
exercise training in subsequent studies. CES would be compatible with other interventions,
including medications and cell-based treatments.

Inclusion Criteria:

- Age between 21 and 65 years

- Diagnosis of probable or definite ALS (or non-disabled volunteer)

- Incomplete weakness of left or right wrist or hand muscles:

- score of 2, 3, or 4 (out of 5) on manual muscle testing of wrist extension

- wrist flexion

- finger extension

- finger flexion

- or finger abduction

- Detectable F-wave responses of the left or right APB to median nerve stimulation
and/or ADM to ulnar nerve stimulation

- US Veteran or non-Veteran

Exclusion Criteria:

- History of other serious injury or disease of central or peripheral nervous system

- History of seizures

- Ventilator dependence or patent tracheostomy site

- Use of medications that significantly lower seizure threshold

- History of head trauma with evidence of brain contusion or hemorrhage or depressed
skull fracture on prior imaging

- History of implanted:

- brain/spine/nerve stimulators

- aneurysm clips

- ferromagnetic metallic implants

- or cardiac pacemaker/defibrillator

- Significant coronary artery or cardiac conduction disease

- History of bipolar disorder or suicide attempt or active psychosis

- Heavy alcohol consumption (> equivalent of 5 oz of liquor) within previous 48 hours

- Open skin lesions over the face, neck, shoulders, or arms

- Pregnancy

- Unsuitable for study participation as determined by study physician