Looking At The Literature

While FES has been around for some time, the research into the affect of electrical stimulation on denervated muscle is not as extensive as we thought and as such a definitive ‘body of proof’ for its use is not present. The following table provides a summary of some of the literature to date and we encourage you to interpret the findings with an objective mind set.

Study	Purpose	Parameters	Findings
S1: Kern, H., Boncompagni, S., Rossini, K., Mayr, W., Fano, G., Zanin, ME., Podhorska-okolow, M., Protasi, F. & Carraro, U. (2004). Long-Term Denervation in Humans Causes Degeneration of Both Contractile and Excitation- Contraction Coupling Apparatus, Which Is Reversible by Functional Electrical Stimulation (FES): A Role for Myofiber Regeneration? Journal of Neuropathology and Experimental Neurology, 63(9): 919-931 S2: Kern, H., Salmons, S., Mayr, W., Rossini, K. & Carraro, U. (2005). Recovery of Long Term Denervated Human Muscles Induced by Electrical Stimulation. Muscle Nerve, 31: 98-101 S3: Modlin, M., Forstner, C., Hofer, C., Mayr, W., Ritcher, W., Cararro, U., Protasi, F. & Kern, H. (2005). Electrical Stimulation of Denervated Muscles: First Results of a Clinical Study. Artificial Organs 29(3): 203-206	S1: Investigated the effect of electrostimulation on long term denervated muscle as a consequence of SCI and the structural changes that occur after FES (myofiber regeneration). S2: Investigated the effects of an intense electrical stimulation program on denervated quadriceps muscle as a result of a traumatic cauda equine lesion at T12. Commencing program 18 months post incident, with a one subject focus, looking at changes in muscle fibre size, excitability and force generating capacity. S3: Evaluated the effects of electrical stimulation on denervated muscles in people with spinal cord injuries.  All patients had either a cauda or conus lesions and had been suffering complete denervation of the quadriceps femoris muscle for at least 6-12 months.	S1, S2, S3 all collected data from the same study, consisted of 4 phases throughout study. Phase 1: Initial 1-3 months. Biphasic stimulation impulses, very long duration and high intensity. Muscle twitch was elicited by impulses lasting 150 to 200ms with amplitudes up to ±200 mA. Stimulation frequency was slightly less than 2Hz. Duration:  15 min/day (4 secs on2 sec off) Frequency: 5 days/ week. Electrodes made of conductive silicone rubber were used for surface stimulation. Phase 2: After 3-6 months Previous high pulse intervals were shortened to 50ms and then to 40ms to achieve a higher stimulation frequency. Phase 3: After 4-6 months.  the protocol was changed to a tetanic pattern (40ms pulse and 10ms  pause) delivered at 20Hz for 2s “on and 2s “off”, twice a day 3 times a day. Phase 4: Repeats were increased to 15-30 reps per set, 2min rest and 6-8 sets twice a day. Force training sessions were implemented. Force training sessions were also introduced with tetanic contractions against 70-80% of maximum load, 8-12 repetitions, 4-6 sets with a 2 minute rest once a day.	S1: Post electrical stimulation program the size of the myofibril increased, adipocytes were absent and collagen was present in normal amounts. They concluded that FES training could reverse muscle fibre degeneration. S2: After 26 months of  stimulation the subjects quadriceps muscles had increased in size and resembled those of a healthy sedentary individual (Muscle cross-sectional areas increased from 36.0 cm2 to 57.9cm2 (right) and from 36.1cm2 to 52.4cm2 (left). The intense stimulation regime also produced increases in excitability and force generating capacity of the muscles. S3: After one year of electrical stimulation a marked increase in CSA of the quadriceps muscle (mean: +29.74%) and also the hamstrings was observed. They concluded that appropriate electrical stimulation protocol can reverse the structural and functional changes that occur in denervated muscle. Moreover they concluded that it is possible to increase muscle mass and decrease the changes due to interrupted nerve supply, therefore reducing secondary problems.
Cakmak, A. (2004). Electrical Stimulation of Denervated Muscles. Disability and Rehabilitation26(7): 432-433	An ongoing study of the effectiveness of electrical stimulation on denervated muscle in  a man who suffered a pelvic ‘open book’ fracture, lumbosacral plexus avulsion and right lower extremity paralysis.	No parameters were specified	After 3 years of rehabilitation Cakmak concluded that electrical stimulation for denervated muscle be continued
Kern, H., Carraro, U., Adami, N., Biral, D., Hofer, C., Forstner, C., Modlin, M., Vogelauer, M., Pond, A., Boncompagni, S., Paolini, C., Mayr, W., Protasi, F. & Zampieri, S. (2010). Home-Based Functional Electrical Stimulation Rescues Permanently Denervated Muscles in Paraplegic Patients With Complete Lower Motor Neuron Lesion. Neurorehabilitation and Neural Repair, 24(8): 709-721	Investigation into the effect of home based functional electrical stimulation (h-bFES) to confirm a previous studies findings that h-bFES can rescue long term denervated muscle in patients with complete conus/cauda equina lesions. Muscle mass, force, and structure were determined before and after 2 years of h-bFES.	Stimulation therapy consisted of 4 combined programs 1: Biphasic stimulation impulses of very long duration(120-150 ms, 60-75 ms per phase) at high intensity (up to ±80 V and up to ±250 mA). 2,3&4: A combination of twitch and tetanic stimulation in consecutive sessions with a duration of up to 30min for each group of muscles (thigh, lower leg, glutes).	Post 2 year treatment there was a 35% CSA increase of the quadriceps muscle, an increase in the mean diameter of muscle fibres (16.6 ± 14.3 to 29.1 ± 23.3 mm), and a 1187% increase in force output during electrical stimulation from 0.8 ± 1.3 to 10.3 ± 8.1 N m (P < .001). Concluded that h-bFES of denervated muscle is an effective home therapy.
Gigo-Benato, D., Russo, T. L., Geuna, S., Domingues, N. R. S. R., Salvina, T. F., & Parizotto, N. A., (2010). Electrical stimulation impairs early functional recovery and accentuates skeletal muscle atrophy after sciatic nerve crush injury in rats. Nerve and Muscle 41(5), 685 – 693.	Examined the neuromuscular recovery in rats after a peripheral nerve lesion through the use of functional electrical stimulation, and to determine the functional rehabilitation of denervated muscle.	No parameters were specified. Electrical stimulation was applied to the tibialis anterior for six sessions following the crush injury to the sciatic nerve.	The results of this study did not support the use of electrical stimulation for denervated muscle as it was documented that electrical stimulation caused an increase in muscle atrophy.



Figure 5 - Comparison of light microscopy taken of a denervated quadriceps femoris muscle beofre (left) and after (right) electrical stimulation training (Kern et al, 2004).



For further interest in the use of FES with OTHER nerve injuries/pathologies the following references are a good source of further information.

Everaert, D.G., Thompson, A.K., Chong, S.L. & Stein, R.B. (2010) Does Functional Electrical Stimulation for Foot Drop Strengthen Corticospinal Connections? Neurorehabilitation and Neural Repair, 24 (2), 168– 177.

Paul, L., Rafferty, D., Young, S., Miller, L., Mattison P. & McFadyen, A. (2008). The effect of functional electrical stimulation on the physiological cost of gait in people with multiple sclerosis. Multiple Sclerosis, 14: 954–961

Stein, R.B., Everaert, D.G., Thompson, A.K., Chong, S.L., Whittaker, M., Robertson, J. & Kuether, G. (2010). Long-Term Therapeutic and Orthotic Effects of a Foot Drop Stimulator on Walking Performance in Progressive and Nonprogressive Neurological Disorders. Neurorehabilitation and Neural Repair 24(2) 152– 167.

Thompson, A.K., Estabrooks, K.L., Chong S. & Stein, R.B. (2009). Spinal reflexes in ankle flexor and extensor muscles after chronic central nervous system lesions and functional electrical stimulation, Neurorehabilitation and Neural Repair.  23 (2), 133-142

Not So Fast!

Before you jump into electrical stimulation, you need to consider the risks and contraindications for its use, for both externally applied and implanted FES systems. Although there are no absolute contraindications for externally applied FES, patients with a cardiac pacemaker or an automatic implanted defibrillator should be approached with extreme caution (Vernon, 2003). Electrical simulation applied to areas anywhere on the body has been found to in some instances to potentially interfere with the sensing portion of the pacemaker. Relative contraindications for FES include pregnancy, electrical sensitivity, healing wounds and patients with congestive heart failure or at risk of cardiac arrhythmias.  

For implanted FES systems, absolute contraindications encompass presence of an implanted cardiac pacemaker, active or recurrent sepsis, or uncontrolled spasticity (Vernon, 2003). With implanted FES systems antibiotic prophylaxis needs to be taken by individuals when undergoing invasive procedures (Vernon, 2003). There are no contraindications for the previous held concern with FES implants and MRI, which is reflected on the FDA-approved labels.

Caution has been raised in the use of other treatment modalities, short wave diathermy, microwave diathermy or therapeutic ultrasound diathermy with implanted FES, as there is a risk of heating at the electrode-tissue interface that could produce damage to tissue or nerve. NeuroControl Corporation indicated that these types of modalities should not be performed over implants to protect components of body tissue as well as the device (Vernon, 2003).

A risk of FES has been raised where the damaged nerve (thought to have been lost) can retard during the healing process with excessive use of FES. The long duration, high intensity pulse parameters used for denervated muscle can interfere with nerve sprouting as the nerve tries to regenerate, preventing the nerve from returning to its pre-injured state (Low & Reed, 2000). This is a precaution that has limited evidence, but it is still a worthwhile consideration to be aware of when applying FES. Hence, physiotherapist, patient and other health professionals involved should adhere to the recommended doses (not hammer the muscle/nerve too much) and should monitor/reassess the damage nerve to ensure true denervation.

FES is an electrical stimulatory device, so the general contraindications and precautions when apply such a device should not be neglected. The table below presents a general and encompassing list for the use electrical stimulatory devices:

CONTRINDICATIONS
Abdomen and lower back of pregnant women	Infective area
Active rheumatoid disease	Metallic implants
Acupuncture points in pregnancy	Morbid obesity
Acute inflammatory reaction	Obtunded reflexes
Anticoagulant therapy	Open epiphyses
Arrhythmia	Open wounds
Cancerous lesions	Plastic implants
Cardiac region of thorax	Pyrexia
Carotid sinus	Recent intake of analgesia
Cement for Arthroplasty	Recent radiotherapy
Deep Vein Thrombosis	Stellate ganglion
Demand type pacemakers	Sympathetic ganglia
Dermatological conditions	Thyroid gland
Excessive oedema	Tissues of the central nervous system
Eyes	Tubercular joints
Haemorrhagic regions	Underlying lung
Immune suppressant drugs	Unreliable patient
Implanted stimulators	Upper cervical spine where history of epilepsy
Impoverished circulation	Vagus nerve
Impoverished perception of pain	Wet dressings or adhesive tape

 

PRECAUTIONS

Fatigue of muscles being stimulated

The physiotherapist must check each subject’s FES equipment to ensure it is in working order and correct placement of the electrodes

The physiotherapist should also test the patients sensation by blunt and sharp differentiation

Cakmak, A. (2004). Electrical stimulation of denervated muscles. Disability and Rehabilitation 26(7), 432 – 433.

Low, J., & Reed, A. (2000). Electrotherapy explained: principles and practice. Oxford: Butterworth-Heinemann.

Vernon, W. (2003). Spinal cord medicine; principles and practice. New York, Demos medical publishing.

Parameters of FES for Denervated Muscle

So far we have outline the niche market that FES serves, as well as the degenerative muscle changes that result from denervation and how electrically induced isometrics contractions can help to prevent/slow and help reverse the severity of the dysfunctional tissue. Now we can look at more specifically at parameters used for FES for successful applicaiton.

To overcome the degenerative changes and produce a desirable contraction of a selected muscle/muscle groups (eg. peroneals), a slow-rising electrical pulse is required (Low & Reed, 2000). This slow rising pulse, also known as selective triangular or accommodation pulses, allows the stimulation to accumulate in the denervated muscle while innervated structures accommodate to the slow rising pulse (Kern et al., 2010). Interestingly, a square pulse was originally used for denervated muscle stimulation with long pulse durations of 30ms or more, before investigations found a slow rise time to be more effective.

FES provides a means of selectively stimulating different tissues (Low & Reed, 2000). Research has found that to stimulate muscle fibre but not nerve requires triangular pulses with a leading edge time of 50ms and pulse of 100ms. To stimulate denervated muscle fibre only, a rise time of longer than 100ms is best, with triangular pulses of 300 – 500ms (Low & Reed, 2000). Further research supports the use of long duration pulses that take a long time to reach peak amplitude and also highlighted in their findings that higher amplitudes are more effective as more current is needed (Cakmak, 2004 & Kern et al., 2010).

Comparison of the different parameters for nerve/innervated tissue vs. denervated muscle:

·         Nerve (innervated muscle) stimulation favours square pulses that reaches peak amplitude rapidly.

·         Denervated muscle stimulation prefers long duration, high amplitude electrical pulse that takes a long time to reach peak amplitude.

Figure 3. Comparison of square wave pulses (innervated muscle) and triangular wave pulses (denervated muscle).

Figure 4. Electrode Placement.

Electrode Placement

Optimal positioning of the stimulating electrodes is at each end of the muscle belly, allowing for the charge to travel down the long axis of the muscle fibers and thus an effective contraction. Implanted FES devises are also available, where muscle or nerve-based electrodes are installed surgically and connected to an implanted stimulation device, so no material crosses the skin. Implanted electrodes offer numerous advantages over surface and percutaneous stimulation for long-term clinical use, including improved convenience, cosmesis, reliability, and repeatability, where surface electrodes are more ideal for short-term therapeutic applications (Hardin, et al., 2007).

Figure 4. illustrates the the placement of the elctrodes on the antereior lateral shank. A) represents the electronic stimulator. B) and C) are surface electrode placed over the motor point of the peroneal nerve and the tibialis anterior muscle belly. D) is a sensory insole located within the shoe on the heel to detect impact.

Cakmak, A. (2004). Electrical Stimulation of Denervated Muscles. Disability and Rehabilitation26(7): 432-433

Hardin, E., Kobetic, R., Murray, L., Corado-Ahmed, M., Pinault, G., Sakai, J., Bailey, S.N., Ho, C. & Triolo, R.J. (2007). Walking after incomplete spinal cord injury using an implanted FES system: a case report. Journal of rehabilitation research and development. 44(3), 333-46.

Low, J., & Reed, A. (2000). Electrotherapy explained: principles and practice. Oxford: Butterworth-Heinemann.

Characteristics of Denervated Muscle

The denervated muscle is very different to that of an innervated muscle. When innervation is lost the muscle undergoes a progressive decay, where many morphological and physiological changes occur. These are principally (Robinson & Snyder-Mackler, 2008):

 

o Loss of voluntary and reflex activity

o Muscle Atrophy

§ Decrease in muscle weight, and muscle sarcoplasm

§ Decrease in myofibril (muscle contractile protein)

§ Decrease in the number of muscle fibres

o Replacement of muscle by fibrous and adipose tissue

o Changes in muscle excitability

§ Fibrillation: spontaneous contraction of muscle fibres

§ Oscillations in resting membrane potential

Figure 2. Comparison of (A) healthy muscle biopsy and a biopsy of a (E) denervated muscle as a result of a LMN lession (Kern et al., 2010)

These progressive internal changes to the muscle make denervated muscle tissue less excitable than healthy normal muscle, requiring a greater electric charge to cause a contraction. Electrical stimulation to these muscles produces a slow worm-like contraction (Low & Reed, 2000). The electrical charge slowly spreads through the muscle with a diminished rate of contraction compared with innervated muscle (Low & Reed, 2000). Studies have shown that using electrical stimulation to produce isometric contractions of denervated muscle can retard the atrophy process. As such, electrical stimulation treatment of denervated muscle should commence as soon as possible after the event of denervation (but not before axonal sprouting) to decrease the amount of atrophy that will ensue (Kern et al., 2010).  The best results are seen with vigorous isometric stimulation to the point of fatigue (three sessions per day for at least 10 minutes in duration) (Low & Reed, 2000). However, this treatment has shown that it cannot completely prevent the degenerative process (Low & Reed, 2000). Further studies have used large surface electrodes with high intensity, long-duration impulses to directly elicit contraction with the aim to reverse and treat denervated muscle that have the longstanding severe atrophy (Kern et al., 2010).

Robinson, A. J.  & Synder-Mackler, L. , 2008. Electrotherapy and electrophysiological testing. Clinical Electrophysiology 3^rd Edition.

Kern, H., Carraro, U., Adami N., Biral D., Hofer C., Frostner C., Modlin M., Vogelauer M., Pond A., Boncompagni S., Paolini C., Mayr W., Protasi F., & Zampieri S., (2010), Home-based functional electrical stimulation rescues permanently denervated muscles in paraplegic patients with complete lower motor neuron lesion. Neurorebilitation and Neural Repair, 24(8), 709 – 721.

Low, J., & Reed, A. (2000). Electrotherapy explained: principles and practice. Oxford: Butterworth-Heinemann