Efficacy of Multi-component Therapy for Peripheral Nerve Injury: A Case Report

INTRODUCTION

Despite recent advances in surgical techniques, including nerve grafting and transfer, the outcomes following peripheral nerve injuries (PNI) often remain suboptimal. In particular, patients frequently experience persistent pain, sensory abnormalities, and impaired motor function even after anatomically successful nerve repair. One study found that only 50%–60% of patients achieved functional recovery after median or ulnar nerve repair, whereas the remaining patients experienced ongoing sensory and motor deficits. PNI affects a significant proportion of young adults, with 57% of PNI patients aged between 16 and 35 years. Upper-extremity PNI often leads to prolonged absence from work, because a quarter of these patients are unable to return to their jobs within 1.5 years following surgical intervention.¹⁾ These unsatisfactory results highlight the need for additional therapeutic strategies to augment recovery after peripheral nerve surgery.²⁾

Although surgical repair is often necessary to restore neural continuity, rehabilitation plays a crucial role in promoting functional recovery. Emerging evidence from mammalian animal studies suggests that treatments such as transcutaneous electrical nerve stimulation (TENS), peripheral magnetic stimulation (PMS), exercise therapy, and sensory re-education may promote axonal regeneration and improve clinical outcomes.^{3,4,5,6,7,8,9)} However, there is a lack of knowledge regarding the effects of combined rehabilitation therapy in humans. We report a case with a good prognosis achieved by comprehensive rehabilitation therapy using TENS, PMS, exercise therapy, and sensory re-education.

CASE

A 28-year-old man with no significant medical history presented for outpatient rehabilitation 2 months after a traumatic laceration of the left median nerve. Initial examination revealed complete transection of the median nerve, the superficial and deep flexor tendons of the index and middle fingers, and the flexor carpi ulnaris tendon. The wound extended dorsally through the interosseous space of the ulna, revealing transection of the extensor pollicis longus tendon. Emergency department notes reported that “left forearm wound debridement with exploration and repair of the vessels, nerves, and musculotendons” was performed under brachial plexus anesthesia.

The patient underwent surgical nerve repair at an acute care hospital and was subsequently discharged without formal rehabilitation services. During the initial evaluation at the rehabilitation clinic, the patient reported decreased grip strength, diminished fine motor control, paresthesia, and sensory deficits, accompanied by significant discomfort and hypersensitivity caused by abnormal sensation in the left hand. The patient did not take any medication, and at the initial evaluation, he achieved a perfect score of 126 on the Functional Independence Measure (FIM), indicating complete independence in activities of daily living. The AMADEO^® system task level and the modified 2-minute O’Connor Finger Dexterity Test were employed for evaluation of dexterity and sensorimotor integration. A comprehensive clinical examination was conducted, including nerve conduction studies to assess the integrity and function of the left median nerve, the Manual Muscle Test, grip and pinch strength testing to quantify upper extremity strength, and sensory testing, encompassing two-point discrimination and Semmes-Weinstein monofilament testing, to evaluate the extent and nature of sensory impairment. The results of the diagnostic tests are presented in Fig. 1 and Table 1. Based on these findings, the patient was diagnosed with left median nerve motor and sensory deficits secondary to axonal injury.

Fig. 1.

 Initial assessment of patient. (a) The wound site exhibited signs of inflammation, including heat, swelling, and paresthesia in the palm. (b) Flexion of the first to third fingers was limited, and dysfunction of the abductor pollicis brevis muscle was evident, hindering grip strength in the left hand. (c) Nerve conduction studies revealed no sensory nerve action potential in the left median nerve. Although no motor compound muscle action potential (CMAP) was elicited by stimulation at the wrist, a CMAP (1.7 mV) was detected upon palmar stimulation (50 mA). Nerve conduction of the left ulnar and left radial nerves was within normal limits. Other sensory modalities such as vibration sensation showed a mild decrease only in the index finger during the initial assessment. Temperature and pain sensation were decreased along the median nerve distribution, accompanied by significant discomfort and hypersensitivity because of abnormal sensation.

Table 1.  Results of initial assessment.

Test			Left	Right
ROM (degrees)	Wrist	Extension	70 (70)	-
		Flexion	60 (90)	-
	Thumb	MP joint flexion	74 (60)	-
		IP joint flexion	74 (80)	-
	Index	MP joint flexion	72 (90)	-
		PIP joint flexion	80 (100)	-
		DIP joint flexion	54 (80)	-
	Middle	MP joint flexion	80 (90)	-
		PIP joint flexion	92 (100)	-
		DIP joint flexion	60 (80)	-
TPD (mm)	Thumb		>20	-
	Index		>20	-
	Middle		>20	-
SWMT	Thumb pad		4.17 (≤ 2.83)	-
	Index pad		5.46 (≤ 2.83)	-
	Middle pad		4.74 (≤ 2.83)	-
Strength (kg)	Grip		7.5	45.0
	Lateral pinch		2.7	10.3
	Tip pinch		0.6	3.3
MMT	MP, IP joint flexion	Index–little	3	5
	MP joint extension	Index–middle	2	5
		Ring–little	3	5
	Wrist flexion		4	5
	Wrist extension		5	5

Normal values are shown in parentheses.

ROM, range of motion; MP, metacarpophalangeal; IP, interphalangeal; PIP, proximal interphalangeal; DIP, distal interphalangeal; TPD, two-point discrimination; SWMT, Semmes-Weinstein monofilament test; MMT, Manual Muscle Test.

A comprehensive outpatient rehabilitation program was initiated (2-h sessions 5 times per week). This program was formulated based on prior research.⁹⁾ We included 60 min of electrical stimulation (20 Hz) in accordance with multiple prior studies that recommend this as the optimal duration for peripheral nerve regeneration.^10,11,12,13) In addition, 60 min of exercise therapy was performed,¹⁴⁾ anticipating a synergistic effect when combined with electrical stimulation, given its established beneficial effects.⁵⁾ The integration of other therapies into the program was determined by considering their potential for combined use with TENS, as well as the clinical necessity of such interventions for the patient. From day 84 of treatment, the patient independently performed 1 h of home exercise, including aerobic exercise, finger dexterity training, and finger muscle strengthening. The patient was an inbound patient who sought medical treatment in Japan. The treatment program was implemented intermittently because visa conditions and personal obligations required the patient to repeatedly return to his home country during his time in Japan. The specifics of this therapeutic rehabilitation program are described in Table 2 and illustrated in Fig. 2. Patient progress is illustrated in Fig. 3, and the results of a final nerve conduction study are detailed in Fig. 4. Synkinesis, dysesthesia, or adverse effects were not observed during the course of recovery. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Table 2.  Comprehensive rehabilitation program.

Task		Device	Time	Settings and methods	Objective
TENS		GD-611, OG Wellness Technologies	60 min	Normal mode, 20 Hz, intensity 15%–35% of maximum stimulator output (below motor contraction) for 1 h, 5 times/week. Electrodes (40 mm diameter) placed efferently proximal and distal to the surgical site of left nerve.	Reinnervate the nerves.
PMS		Pathleader, Institute of Field Generation	10 min	20 Hz, biphasic waveform, on time 2 s, off time 3 s, intensity 80% of maximum stimulator output for 10 min, 5 times/week. Circular coil (70 mm diameter) placed over the left intrinsic muscles.	Prevent disuse atrophy, increase muscle strength, and reinnervation.
ET	Aerobic exercise	VR device (Meta Quest3, Meta) Strengthening machines Ergometer	40 min	Software (PUNCH FIT, The Strippers), 15 min Leg press /extension; 20 times × 3 sets; 10 min Ergometer; 30 W 1 min–85 W 15 min Exercise load was carried out using a Borg scale of 11 to 12 as a guide. TENS was used in combination.	Enhance whole body condition, reinnervation.
	Task-oriented approach	Peg, clothespins, cup, coin	40 min	Tasks to manipulate small objects in the palm of the hand or to manipulate objects with the fingertips on a desk.	Acquisition of dexterity movement.
	Strengthening exercises	Hand grippers, putty, robotic device (Cantley Medical; AMADEO®)		Tasks such as crushing putty by gripping a stick or picking it up with fingertips.	Increase muscle strength.
	ROM exercises			For at least 2 min. The patient was instructed to continue these exercises independently as a home exercise program.	Prevent and improve contractures.
Traditional and activity-based SR		Handy massager, ice pack, hot packs, needles, cloth, sandpaper, robotic device (AMADEO®).	30 min	Input a variety of stimuli to the epidermis in areas where sensory function is impaired. The difficulty level of the AMADEO task was adjusted appropriately with a success rate of 70% as a guideline.	Enhance sensory awareness, finger coordination, and dexterity movement.

TENS, transcutaneous electrical nerve stimulation; PMS, peripheral magnetic stimulation; ET, exercise training; VR, virtual reality; ROM, range of motion; SR, sensory re-education.

Fig. 2.

 Aspects of the comprehensive rehabilitation program. (1a/b) AMADEO^® built-in game challenges: “Elevator”, “Firefighters”, “Labyrinth”, and “Medieval Wizard”. (2) TENS was used in conjunction with other treatment programs. (3) Input vibratory stimulation using a handheld massager. (4) Hot or cold stimulation of the hand by applying hot packs or ice packs. (5) Aerobic exercise with an ergometer for approximately 15 min. (6) Leg press and extension exercises with strengthening machines for 10 min. (7) Playing “PUNCH FIT” for 15 min with Meta Quest3. (8) Task-oriented approach to manipulate objects with the fingertips on a desk, including examples of finger-strengthening exercises. (9a/b) Pathleader placed over the left intrinsic muscles.

Fig. 3.

 Clinical course of the patient. Regarding finger dexterity, the AMADEO^® system demonstrated a ceiling effect by day 66. Consequently, the O’Connor Finger Dexterity (OFD) Test was also discontinued, because the patient’s finger dexterity had improved to a level where it no longer posed a functional impediment in daily life. At the final evaluation, abnormalities in proprioception and abnormal sensation had resolved. Residual impairments in temperature and pain sensation were consistent with the degree of impairment indicated by the SWMT. The MMT scores improved to 5 by the final evaluation. ROM, range of motion; IP, interphalangeal; DIP, distal interphalangeal; OT, occupational therapy; PT, physical therapy; TPD, two-point discrimination; SWMT, Semmes-Weinstein monofilament test; TENS, transcutaneous electrical nerve stimulation; PMS, peripheral magnetic stimulation; ET, exercise training; VR, virtual reality; SR, sensory re-education.

Fig. 4.

 The final nerve conduction study showed that sensory nerve action potential (SNAP) of the left median nerve was recorded between the index finger and wrist. Motor compound muscle action potential (CMAP) was recorded in the abductor pollicis brevis muscle. CMAP improved to the normal range in amplitude, nerve conduction velocity (NCV), and distal latency, although SNAP was not recorded.

DISCUSSION

This report details a successful comprehensive rehabilitation program integrating TENS, PMS, exercise therapy, and sensory re-education to address persistent motor and sensory deficits following left median nerve laceration and surgical repair. The patient demonstrated substantial improvements in grip and pinch strengths, fine motor control, and sensory discrimination, ultimately achieving functional hand use.

Several basic research studies have examined the effects of TENS, PMS, exercise therapy, and sensory re-education on PNI, with most studies reporting positive outcomes.^3,4,7,8) However, most studies that validate the efficacy of these treatments are based on animal experiments. Despite the established clinical use of individual components in humans, a combined therapeutic approach for peripheral nerve injury remains to be established. To our knowledge, this is the first report on the effectiveness of comprehensive rehabilitation treatment in humans using multiple components, including stimulation devices.

Several factors may have contributed to the favorable outcomes. First, each component of the program was supported by evidence promoting nerve regeneration and plasticity. TENS, PMS, and exercise have been shown to influence the expression of neurotrophic factors (e.g., brain-derived neurotrophic factor) and Schwann cell activity, which are crucial for nerve repair.^{11,14,15,16,17)} Second, concurrent targeting of the nerve, effector muscles, and cerebral cortex likely maximizes the therapeutic impact. Willand et al.¹⁰⁾ showed that PNI can lead to a 70% reduction in the cross-sectional width of skeletal muscle within 2 months. In the present case, intrinsic muscle weakness was observed in the early stages, suggesting a high risk of atrophy because of denervation. The use of PMS on the palm likely mitigated this risk. Furthermore, the absence of afferent inputs from peripheral nerves to the cerebral cortex can lead to plastic changes in the cortex,¹⁸⁾ which may be associated with poor treatment outcomes in PNI.^19,20) Early sensory re-education is considered crucial for patients, because it enhances neuroplasticity and allows the nervous system to adapt to altered sensory feedback.^8,21) Finally, as suggested by Thompson et al.,⁵⁾ the potential synergistic effects of combining these modalities cannot be ignored.

Although the optimal parameters for multicomponent therapy are still being investigated, existing evidence suggests that 1 h of electrical stimulation at 20 Hz is effective in promoting nerve regeneration.^12,13) The duration of therapy might also play a crucial role, and studies have shown that 1 h of daily electrical stimulation and 1 h of daily exercise therapy 5 days a week can lead to significant improvements in nerve function.^10,14) The treatment protocols were determined based on these findings. Consequently, the appropriate strength of each parameter may have positively influenced clinical outcomes.

In conclusion, this case report demonstrates the effectiveness of a comprehensive rehabilitation program incorporating TENS and PMS with exercise therapy and sensory re-education for promoting functional recovery after PNI. This combined approach facilitated successful restoration of hand function to a practical level without adverse events. By promoting nerve regeneration, this comprehensive rehabilitation program may help restore nerve function and alleviate symptoms of neuropathy. Further studies are warranted to elucidate the underlying mechanisms and optimize rehabilitation protocols for patients with PNI.

This case report has several limitations. First, the findings from this single patient may not be generalizable to all individuals with PNI. Second, the intermittent treatment schedule, necessitated by the patient’s compliance with visa conditions, could have influenced the observed outcomes. Third, during the initial nerve conduction studies, technical difficulties caused by swelling around the wrist stimulation site may have hindered the elicitation of a motor compound muscle action potential upon wrist stimulation. Fourth, further research is needed to determine the optimal electrical stimulation parameters, including site, method, intensity, and dosage. Fifth, although both electrical and magnetic stimulation were utilized, further investigation is warranted to elucidate the distinct mechanisms of action for each modality in PNI. Sixth, regarding exercise therapy, although animal studies suggest the benefits of targeted exercise protocols,^14,16) further human research is required to confirm these findings and optimize exercise prescriptions for PNI. Future studies should address these limitations to refine combined rehabilitation protocols for PNI.