Attenuation of autonomic dysreflexia during functional electrical stimulation cycling by neuromuscular electrical stimulation training: case reports

Abstract

Introduction

Spinal cord injury (SCI) may cause impairments of the motor, sensory, and autonomic nervous systems, which result in adverse changes in body composition and cardiovascular health. Functional electrical stimulation (FES) cycling may provide an effective alternative approach to perform exercise and improve cardiovascular health after SCI. Persons with an injury at or above T6 level are at high risk of developing a life-threatening complication of autonomic dysreflexia (AD).

Case presentation

Two participants with motor-complete C6 SCI completed either 12 weeks of passive range of motion or surface neuromuscular electrical stimulation (NMES) resistance training, followed by 12 weeks of functional electrical stimulation (FES) lower extremity cycling for both participants. Systolic and diastolic blood pressure (BP) were measured to determine the effects of NMES-resistance training and FES-lower extremity cycling during rest and exercise.

Discussion

The difference between mean value of BP during FES-lower extremity cycling exercise and resting BP averaged for 24 sessions was smaller for participant A (31.25 mmHg for systolic BP and 10.44 mmHg for diastolic BP), who received NMES-resistance training, as compared with participant B (58.62 mmHg for systolic BP and 35.07 mmHg for diastolic BP). The results of these case reports suggest that 12 weeks of NMES-resistance training preceding FES-lower extremity cycling may attenuate the development of AD after SCI. Risk of AD, triggered by noxious stimuli, may be dampened with FES-lower extremity cycling training in persons with SCI.

Introduction

Spinal cord injury (SCI) is a devastating medical condition, which is characterized by impairments of motor, sensory, and autonomic nervous systems [1]. Motor and sensory impairments result in decreased physical activity causing dramatic changes in body composition, muscle atrophy, bone loss, and decline in cardiovascular health [2]. Functional electrical stimulation (FES) has been recognized as an effective rehabilitation intervention commonly used to stimulate the paralyzed musculature, to restore muscle size, and improve cardiovascular fitness. Other benefits include increased bone mass, reduced spasticity, prevention of venous thromboembolism, and decreased pressure injuries [3–7].

Dysfunction in the autonomic nervous system following SCI may also lead to number of life-threatening conditions, in particular due to postural hypotension and autonomic dysreflexia (AD). Postural hypotension may interfere with one’s ability to sustain activities of daily living, or safely participate in a standard rehabilitation program. On the other hand, AD represents a clinical emergency condition in those with SCI at the level of T6 or above. The incidence of AD may exceed 90% in those with mid-thoracic and cervical SCI. Episodes of AD can cause acute elevations of BP coupled with bradycardia. A systolic BP (SBP) rise >20–30 mmHg is typically considered an episode of AD [8], and BP has been reported to increase up to 300 mm Hg in some cases [9]. Symptoms during an episode of AD may represent mild discomfort and headache, while life-threatening symptoms include seizures, intracranial hemorrhage, and death have also been reported [9].

Applications of FES may lead to episodes of AD [7], which has been attributed to increased electrical charges that commonly developed underneath the stimulated electrodes and serve as a source of noxious stimuli. The use of large electrodes commonly applied to activate the large muscle groups are accompanied with flooding of electrical charges that stimulate the peripheral free nerve endings, and cause noxious stimuli below the level of injury. These noxious stimuli can generate sympathetic reflex at or below the level of injury, which can lead to an increase in blood pressure (BP) and the development of AD. Concerns over the development of episodes of AD may result in the exclusion of individuals with SCI from participation in FES-related clinical trials. As a result, these individuals are less likely to be considered for this important form of physical activity and exercise, which puts them at risk for the manifold side effects of immobility and inactivity.

As cardiovascular disease represents a paramount problem for the SCI population, and activities of daily living provide insufficient cardiovascular fitness to enhance wellness [10], identifying safe approaches to the use of FES-support exercise are needed. The two comparative case reports presented demonstrate that “priming” the nervous system with surface neuromuscular electrical stimulation (NMES) for 12 weeks may attenuate the response of the autonomic nervous system and decrease the likelihood of developing AD in individuals with SCI undergoing FES-based exercise.

Case presentation

Participants

Two participants with motor-complete, C6 SCI were recruited as part of the registered clinical trial (NCT02660073) to determine the effect of NMES-resistance training (NMES-RT) and FES-lower extremity cycling (FES-LEC) on body composition and cardio-metabolic health profile. The detailed protocol and primary and secondary outcomes of this trial have been published [11]. The study protocol and informed consent were approved by the McGuire VA Institutional Review Board (IRB) and Virginia Commonwealth University (VCU) IRB. The study procedure was explained to both participants prior to enrollment and both provided a verbal and written consent. A detailed physical examination was conducted prior to enrollment to rule out any preexisting medical conditions. This included American Spinal Injury Association (ASIA) classification Impairment Scale (AIS), modified Ashworth scale for grading spasticity, Penn Spasm Frequency Scale, the World Health Organization Quality of Life questionnaire covering four different domains of quality of life (physical health, psychological, social relationships, and environmental factors), leisure time of physical activity questionnaire, and demographics. The demographic characteristics of both the participants are presented in Table 1. Participant A reported that he experienced a rise in BP with stimuli below the level of the lesion, such as full bladder or constipation. Participant B did not report self-reported issues with BP.

Table 1.

Physical characteristic and skinfold thickness of both participants.

Characteristics	Participant A	Participant B
Age (yrs)	53	51
Sex	Male	Female
Ethnicity	Caucasian	African American
Weight (kg)	89.7	69.4
Height (cm)	178.7	164.1
BMI (kg/m2)	26.0	25.8
Level of injury	C6	C6
Time since injury (yrs)	26	13
AIS classification	A	A
Level of Paralysis	Tetraplegia	Tetraplegia
aSkinfold thickness
Abdominal (mm)	56.5	55.8
Suprailiac (mm)	22.2	48
Thigh (mm)	27	52

^aSkinfold thickness was measured as the average of three closest folds with difference <2 mm.

Procedure

Participants were randomly assigned either NMES-RT + FES-LEC training or passive movement (PM) + FES-LEC training. Participant A underwent 12 weeks of NMES-RT accompanied with ankle weights, twice weekly followed by 12 weeks of FES-LEC, twice weekly, using the RT300 bike. Participant B underwent 12 weeks of passive leg extension/flexion with no ankle weights, twice weekly, followed by 12 weeks of FES-LEC, twice weekly, using RT300 bike.

NMES-RT protocol (participant A)

A recent video publication provided full details on the NMES-RT protocol [12]. The participant was instructed to take off his shoes while sitting in a wheelchair. A pillow was placed behind the participant’s leg to cushion it during resting position. Two 8 × 10 cm² adhesive electrodes were placed on the skin over the knee extensor muscle group of each leg. The distal electrode was placed approximately one-third the distance between the patella and inguinal fold and medially over the vastus medialis muscle. The proximal electrode was placed laterally and adjacent to the inguinal fold over the vastus lateralis muscle. The stimulator frequency was set to 30 Hz with a biphasic rectangular pulse duration of 450 μs with a 50 μs inter-pulse interval [12]. The goal was to complete four sets of ten repetitions per leg. Beginning with the right leg, the current was gradually increased to achieve a full knee extension. The leg remained extended for 3–5 s to evoke maximum tension in the activated motor units. The current was then gradually decreased to move the leg to its starting position. Each leg was allowed 3–5 s of resting period between each repetition and ~2–3 min between sets. The first two training sessions were performed without ankle weights to ensure that the participant can extend his leg against gravity. The ankle weights were gradually increased once participant achieved full knee extension without muscle fatigue [12].

After each set of ten repetitions per leg, BP was measured to ensure that the participant would not develop AD. If BP exceeded 130/80 mm Hg, a training session was ceased, and BP was monitored every 2 min until BP dropped below 130/80 mmHg in order to resume the training session. This BP cutoff or sudden rise in BP >20 mm Hg points above the resting values was previously suggested as index of AD [8].

Passive movement protocol (participant B)

Passive training was performed by research staff starting with the right leg. The leg was stabilized proximal to the knee joint with one hand, and the leg was then cupped proximal to the ankle with the other hand to passively achieve full knee extension from sitting position (90° knee flexion). Once a full knee extension was achieved, the leg was held up for 5 s before bringing it back to the starting position. A resting period of 3–5 s was allowed between each repetition. The goal of the training was to complete four sets of ten repetitions per leg.

FES-LEC protocol (both participants)

A recent video publication provide full details on the FES-LEC protocol [12]. Briefly, two adhesive electrodes were applied bilaterally to the knee extensors as described in NMES-RT protocol section. Two electrodes were also applied to knee flexors (distal electrode was placed 2–3 cm above the popliteal fossa and the proximal electrode was placed 20 cm above the popliteal fossa) bilaterally. Two electrodes were applied to gluteus maximus (both electrodes were placed parallel to each other on the bulk of the muscle belly, separated by two fingers width) bilaterally.

While seated in a power wheelchair, the participant was positioned and centered in front of the FES bike. Stimulator cables were connected to each of the 12 electrodes. Participant’s feet were then placed gently inside the bike pedals and secured with a crossed elastic Velcro strap. The lower leg was secured to the bike by an elastic strap wrapped in a fabric covering. Participant’s wheelchair was then secured to the FES bike by hooking two extendable hooks located at the base of the bike to the most stable structure of the power wheelchair. Then the research staff passively moved the legs to ensure no hyperextension or compression of the legs against the bike; if needed, the height of the bike could be adjusted.

The training protocol was as follows: 3 min of warm up while the stimulation was off, 10 min of three exercise stages while the stimulation was on, with an adjustable resistance starting at 1.04 Nm (stage 1), 1.58 Nm (stage 2), and 2.12 Nm (stage 3), 2 min of resting phase with the simulation off between each exercise stage, and 3 min of cool down while the stimulation was off. The duration of the exercise training session was 40 min.

The stimulator frequency was set to 33.3 Hz with a pulse duration of 350 μs and current amplitudes of 140 mA, 100 mA, and 100 mA for the knee extensors, knee flexors, and gluteus muscle groups, respectively. The target speed for the participant was set up at 45 revolutions per minute with a motor torque at 10 Nm. The goal for the participant was to cycle against resistance without the motor support of the bike. The motor support was only permissible to assist the participant if they fatigued during the training session as well as during the warm up phase, the first 2 min of the active phase, 2 min resting phase between each exercise stage, and 3 min of cool down.

Blood pressure measurement

These participants had an SCI at the C6 level and, therefore, were at risk of developing AD [13], therefore, BPs were measured every 2–5 min during the training session. If BP exceeded 130/80 mm Hg, a training session was ceased, and BP was monitored every 2 min until it dropped below 130/80 mmHg in order to resume the training session. The brachial BP was measured using Connex® Vital Signs Monitor (WelchAllyn). The cuff was adequately secured above the cubital fossa of participant’s right arm, allowing 1 inch between the bottom of the cuff and the crease of the elbow. Participants were asked to relax their muscles and sit upright with their upper arm positioned so that it is leveled with their heart. The BP was measured before the training session (resting BP), and during the NMES-RT and FEC-LEC session (exercising BP). Acute response of either NMES-RT or FES-LEC was defined as the average in SBP or DBP over the first three sessions [14].

Mean NMES-RT SBP (SBP_NMES-RT) and DBP (DBP_NMES-RT) for participant A were calculated as an average of SBP and DBP measurements during a NMES-RT training session. Similarly, mean FES-LEC SBP (SBP_FEC-LEC) and DBP (DBP_FEC-LEC) for both the participants were calculated as an average of SBP and DBP during a FEC-LEC training session. The difference between exercise and resting BP during each session of NMES-RT (participant A only) and FES-LEC (both the participants) was calculated as:

$$\mathrm{\Delta }{\mathrm{S}BP}_{\mathrm{N}MES-\mathrm{R}T}=\mathrm{a}verage\left({\mathrm{S}BP}_{\mathrm{N}MES-\mathrm{R}T}\right)-\mathrm{r}esting\mathrm{S}BP$$ 1

$$\mathrm{\Delta }{\mathrm{D}BP}_{\mathrm{N}MES-\mathrm{R}T}=\mathrm{a}verage\left({\mathrm{D}BP}_{\mathrm{N}MES-\mathrm{R}T}\right)-\mathrm{r}esting\mathrm{D}BP$$ 2

$$\mathrm{\Delta }{\mathrm{S}BP}_{\mathrm{F}ES-\mathrm{L}EC}=\mathrm{a}verage\left({\mathrm{S}BP}_{\mathrm{F}ES-\mathrm{L}EC}\right)-\mathrm{r}esting\mathrm{S}BP$$ 3

$$\mathrm{\Delta }{\mathrm{D}BP}_{\mathrm{F}ES-\mathrm{L}EC}=\mathrm{a}verage\left({\mathrm{D}BP}_{\mathrm{F}ES-\mathrm{L}EC}\right)-\mathrm{r}esting\mathrm{D}BP$$ 4

Subcutaneous fat thickness measurement

Using a Harpenden skinfold caliper (Baty International), skinfold thickness was measured in triplicate at the level of the abdomen (horizontal fold), supra-iliac (oblique fold parallel to the iliac crest), and midthigh (vertical fold). Skinfold thickness was measured to account for gender distribution in adipose tissue between participant A and B [15]. Measurements were reported to the nearest mm and repeated until the three measurements were within 2 mm of one another. Measurements were captured according to the American College of Sports Medicine guidelines for exercise testing and prescription [16].

Outcomes

For participant A, the parameters of FES-LEC were changed for the knee extensors (140 mA to 100 mA), flexors (120 mA to 80 mA), and hip extensors (100 mA to 40 mA) during week 1, due to discomfort, and then remained unchanged for the duration of the study. For participant B, the stimulation parameters of the FES-LEC were kept unchanged for the entire 12 weeks. Participant A was symptomatic, and he complained from pounding headache, blurred vision, and noise in his ears. Contrary, participant B was asymptomatic, and she never reported any major signs or symptoms during FES-LEC. Table 2 presents the SBP, DBP, and mean arterial pressure (MAP) data for participant A during 12 weeks of NMES-RT and 12 weeks of FES-LEC. For participant A, the difference between mean NMES-RT (exercising BP) and resting BP during each session over the entire 12 weeks (24 sessions) is presented in Fig. 1. A line of best fit for ΔSBP_NMES-RT and ΔDBP_NMES-RT demonstrates that this difference decreased over 24 sessions. Over 24 sessions of NMES-RT, this difference decreased from 27.4 mm Hg to −8.8 mm Hg (ΔSBP_NMES-RT) and 6.4 mm Hg to −3.4 mm Hg (ΔDBP_NMES-RT).

Table 2.

SBP, DBP, and MAP data for participant A during NMES-RT and FES-LEC.

	Session number	Resting SBP	Exercising SBP	Resting DBP	Exercising DBP	Resting MAP	Exercising MAP
NMES-RT	1	144	171	91	97	109	122
	2	133	155	85	96	101	116
	3	144	162	88	99	107	120
	4	165	163	90	91	115	115
	5	130	156	77	94	95	115
	6	130	155	83	94	99	114
	7	111	145	71	88	84	107
	8	108	141	70	84	83	103
	9	116	146	72	93	87	111
	10	–	–	–	–	–	–
	11	138	140	86	86	103	104
	12	146	177	100	110	115	132
	13	134	136	88	86	103	102
	14	135	139	87	86	103	103
	15	119	124	77	76	91	92
	16	137	152	73	90	94	111
	17	124	123	75	79	91	93
	18	120	140	72	83	88	102
	19	–	–	–	–	–	–
	20	–	–	–	–	–	–
	21	132	119	80	76	97	90
	22	134	148	86	93	102	111
	23	148	143	94	89	112	107
	24	133	124	80	77	98	92
FES-LEC	1	120	204	78	97	92	133
	2	120	181	84	108	96	132
	3	130	177	87	108	101	131
	4	136	184	82	102	100	129
	5	137	189	91	110	106	136
	6	138	186	94	113	109	138
	7	109	115	71	72	84	86
	8	–	–	–	–	–	–
	9	112	157	72	94	85	115
	10	154	197	82	109	106	138
	11	144	181	91	107	109	132
	12	131	140	67	86	88	104
	13	151	160	90	96	110	118
	14	127	130	87	80	100	97
	15	145	168	97	100	113	123
	16	112	117	62	69	79	85
	17	–	–	–	–	–	–
	18	129	154	80	85	96	108
	19	91	126	58	74	69	91
	20	138	141	90	83	106	103
	21	–	–	–	–	–	–
	22	125	144	84	82	98	103
	23	124	166	82	89	96	115
	24	130	143	101	82	111	102

Mean arterial BP was calculated using the following equation: MAP = (SBP + 2*DBP)/3).

– indicates missed session.

Fig. 1. Difference between mean NMES-RT and resting BP during each session for participant A over 24 sessions.

(Top): Systolic BP, (Bottom): Diastolic BP. Mean NMES-RT BP for each session was computed as average BP during four sets of exercise.

Table 3 presents SBP, DBP, and MAP data for participant B during 12 weeks of passive movement and 12 weeks of FES-LEC. Fig. 2 shows the difference between mean FES-LEC (exercising BP) and resting BP during each session over 24 sessions for both the participants. This difference for ΔSBP_FES-LEC and ΔDBP_FES-LEC decreased over 24 sessions as demonstrated by a line of best fit. There is an indication that this difference decreased at faster rates for participant A (ΔSBP_FES-LEC: −1.98 mm Hg/session and ΔDBP_FES-LEC: −1.16 mm Hg/session) than participant B (ΔSBP_FES-LEC: −1.41 mm Hg/session and ΔDBP_FES-LEC: −0.86 mm Hg/session). Importantly, this difference in SBP and DBP for participant A was smaller than participant B over 24 sessions. Lastly, this difference averaged over 24 sessions was smaller for participant A (ΔSBP_FES-LEC: 31.25 mm Hg and ΔDBP_FES-LEC: 10.44 mm Hg) as compared with participant B (ΔSBP_FES-LEC: 58.62 mm Hg and ΔDBP_FES-LEC: 35.07 mm Hg). This may be attributable to the NMES-RT that preceded FES-LEC for participant A.

Table 3.

SBP, DBP, and MAP data for participant B during passive movement and FES-LEC.

	Session number	Resting SBP	Exercising SBP	Resting DBP	Exercising DBP	Resting MAP	Exercising MAP
Passive Mov.	1	88	87	60	61	69	70
	2	67	67	45	51	52	56
	3	105	98	74	72	84	81
	4	83	93	56	63	65	73
	5	80	101	61	72	67	82
	6	106	71	77	55	87	60
	7	77	68	52	49	60	55
	8	64	71	46	56	52	61
	9	109	113	78	80	88	91
	10	85	72	61	52	69	59
	11	110	101	77	75	88	84
	12	97	108	67	75	77	86
	13	86	60	83	61	84	61
	14	106	123	72	81	83	95
	15	119	80	117	83	118	82
	16	130	102	86	70	101	81
	17	109	119	76	83	87	95
	18	114	112	77	82	89	92
	19	109	119	76	83	87	95
	20	–	–	–	–	–	–
	21	97	117	66	78	76	91
	22	101	103	69	71	80	82
	23	81	103	60	70	67	81
	24	61	77	47	56	52	63
FES-LEC	1	80	191	59	121	66	144
	2	96	188	64	119	75	142
	3	112	173	76	115	88	134
	4	–	–	–	–	–	–
	5	105	165	70	112	82	129
	6	66	164	51	96	56	119
	7	68	137	50	86	56	103
	8	78	138	53	92	61	107
	9	104	141	69	96	81	111
	10	93	137	67	93	76	108
	11	137	160	93	112	108	128
	12	83	142	57	93	66	109
	13	103	150	70	103	81	119
	14	103	146	72	103	82	117
	15	97	154	71	101	80	119
	16	74	130	57	90	63	104
	17	72	131	50	86	57	101
	18	77	140	53	92	61	108
	19	97	144	68	101	78	115
	20	91	154	67	94	75	114
	21	104	156	70	104	81	121
	22	–	–	–	–	–	–
	23	85	130	62	90	70	103
	24	105	149	79	99	88	116

Mean arterial BP was calculated using the following equation: MAP = (SBP + 2*DBP)/3).

– indicates missed session.

Fig. 2. (Top) Difference between mean FES-LEC and resting SBP during each session for both the participants over 24 sessions. (Bottom) Difference between mean FES-LEC and resting DBP during each session for both the participants over 24 sessions.

Mean FES-LEC SBP for each session was computed as average SBP during three exercise stages. Mean FES-LEC DBP for each session was computed as average DBP during three exercise stages.

Discussion

Autonomic dysreflexia is a life-threatening event that develops in persons with SCI (T6 or above). Episodes of AD are thought to develop due to noxious sensory input below the level of the lesion or other complications similar to urinary tract infection, bowel problems, and fractures [8, 17, 18]. This disturbance below the level of the lesion may lead to a disruption in BP control that is typically regulated by sympathetic neurons. Due to the disruption of central nervous system (CNS) communications, the spinal cord below the level of the lesion functions independent of supraspinal control [19]. An acute episode of AD has been reported to cause a 15% reduction in the blood flow velocity of the middle cerebral artery in persons with complete SCI [20]. Proposed mechanisms for AD include hyperresponsive peripheral alpha adrenoreceptors, loss of inhibitory inputs to spinal sympathetic neurons, and/or loss of baroreceptor reflex [21, 22].

The two comparative case reports presented demonstrate that “priming” the nervous system with surface NMES for 12 weeks may attenuate the response of the autonomic nervous system, and decrease the likelihood of developing AD in individuals with SCI undergoing FES-based exercise. Previous studies have investigated a variety of pharmacological options for management of AD and the results have been mixed [8, 17, 18, 23, 24]. Matthews et al. [23] investigated the effects of surface anesthesia on the AD response during FES-LEC. The effect of two treatment conditions, topical anesthetic (EMLA, a mixture of lignocaine and prilocainc—Astra Pharma Inc.) and placebo creams in a randomized trial was investigated in seven subjects with an SCI above the T6 level. No difference was found in AD response between the topical anesthetic and placebo conditions. Phillips et al. [18] investigated the effect of a α₁-adrenergin receptor antagonist (prazosin) on AD response during medically supervised penile vibrostimulation in six males with cervical SCI. Beat-by-beat BP and heart rate were recorded throughout penile vibrostimulation during placebo and prazosin-treated conditions. It was demonstrated that increase in SBP was significantly mitigated during vibrostimulation in subjects administered with prazosin as compared with placebo. A potential limitation of using prophylactic pharmaceutical agents are the negative side effects, slow action, cardiovascular effects, and the costs. For example, administering prazosin may cause irregular heartbeat, depression, and swelling of hands and feet.

Recently, it has been shown that persons with SCI above or at T6 can be safely treated with NMES to manage variations in BP [25]. Twenty participants with chronic paraplegia were divided into two groups (G1 and G2) and subjected to an upper limb exercise test. The G1 (T2–T6, n = 13) participants were treated with NMES for 2 years or more, at least once a week and G2 (T3–T5, n = 7) participants did not receive NMES training [25]. No differences were noted in BP during upper limb exercise test in any of groups. However, the study did not report changes in either SBP or DBP during NMES training.

Mechanistic explanation of the current findings

In this report, the difference between mean FES-LEC exercise and resting BP during each session was smaller for participant A, who received NMES-RT, as compared with participant B. In addition, this difference also decreased at faster rates for participant A as compared with participant B. Differences in subcutaneous adipose tissue may effect responses to and tolerance of NMES, as demonstrated by reports of gender differences in NMES responses [26] with women having less tolerance to electrical stimulation and lower sensory thresholds. This is attributed to the fact that women had greater subcutaneous adipose tissue underneath the electrodes [27]. Of note, in the current report, participant B has approximately twofold greater thigh skinfold thickness compared with participant A.

The NMES may have resulted in desensitizing the peripheral skin nociceptors thus, attenuating the hyper responsiveness during FES-LEC training. Another possible explanation is potential autonomic modulation by increasing the activity of parasympathetic nervous system over the sympathetic activity during electrical stimulation [28]. Therefore, it is likely to assume that the high intensity current required to evoke leg extension also resulted in co-stimulation of branches of the sacral parasympathetic nervous system, which may neuromodulate the sympathetic nervous system response to noxious stimuli with FES training.

Limitations

There are some limitations of the comparative case reports that need to be addressed in future studies. Firstly, the findings of the current trial should be treated with caution; because of the exploratory nature and the small sample size. The findings may be considered as exploratory pilot work that can be effectively used to calculate effect sizes to adequately power future clinical trials. Pilot studies are of substantial value to gain feasibility, and a preliminary indicator of adverse events. The preliminary findings are promising, and a larger powered randomized placebo-controlled trial may be warranted to test the hypothesis and provide firm scientific conclusions. Secondly, the small sample size does not allow one to assume that NMES-RT is responsible for lower BP during FES-LEC in participant A compared with participant B. However, given the magnitude and trend in BP reduction during FES-LEC for participant A; larger and randomized clinical trials are warranted to clarify the relationship. Importantly, we did not use specific guidelines, such as international standards to document remaining autonomic function after SCI to understand the autonomic status of the participants. Future clinical trials should make use of these guidelines to understand the autonomic status of the participants.

Conclusions

The current findings may indicate important clinical implications for persons with SCI. Persons with mid-thoracic and cervical SCI represent 70% of the entire SCI population. Exercising lower extremity and trunk muscles using electrical stimulation are of paramount importance to persons with SCI; however, individuals who experience recurrent episodes of AD are likely to be excluded from these studies. The current findings provide preliminary evidence of a potential nonpharmacological intervention to manage AD during FES-LEC in persons with SCI. The findings of the current case reports suggest that 12 weeks of NMES-RT that preceded FES-LEC may possibly attenuate the development of AD after SCI. Risk of AD may be dampened overtime with FES-LEC training in persons with SCI.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.