Restoring initial steps by intermittent theta burst stimulation in complete spinal cord injury patient: a case report

Abstract

Introduction

Spinal cord injury (SCI) causes damage to neurons and results in motor and sensory dysfunction. Intermittent theta burst stimulation (iTBS) has been used to induce neuronal and synaptic plasticity by applying a magnetic field in the brain. The plasticity induced in the cortex has an imperative role in the recovery of motor and sensory functioning. However, the effect of iTBS in complete SCI patients is still elusive.

Case presentation

We report here the case of a 27-year-old female who sustained an L1 complete spinal cord injury (SCI) with an ASIA score of A. The patient lost all the sensory and motor functions below the level of injury. Intermittent theta burst stimulation (iTBS) was administered at 80% of the resting motor threshold over the M1 motor cortex, along with intensive rehabilitation training to promote sensorimotor function.

Discussion

There was a partial recovery in functional, electrophysiological, and neurological parameters. The case report also demonstrates the safety and efficacy of iTBS in complete SCI patients. No adverse event has been observed in the patient during intervention sessions.

Introduction

Fall from height is one of the leading causes of spinal cord injury (SCI) worldwide. 30% - 40% of cases of fall from height account for SCI [1–4]. The damage to the spinal cord can cause temporary or permanent changes in sensation, movement, strength, and body functions below the injury site [5, 6]. SCI has devastating repercussions and the treatment mainly includes surgery to stabilize the spine and drugs to reduce symptoms [7]. Rehabilitation and assistive devices allow many people with spinal cord injuries to lead somewhat productive lives.

Intermittent theta burst stimulation (iTBS) has emerged as a newer paradigm of TMS in recent years to improve the motor and sensory functions of patients with SCI [9–11]. iTBS can induce plasticity and modulate local cortical neuronal excitability. We hypothesize that combined approach of iTBS and rehabilitation might accelerate motor and sensory function recovery in complete SCI patients by facilitating upper as well as lower motor neuron excitability and induce synaptic plasticity [8]. Therefore, this case report aims to provide an initial valuation of the feasibility and efficacy of therapeutic iTBS combined with rehabilitation in a paraplegic complete SCI patient.

Case representation

A 27-year-old female with no history of dizziness falls from a height of 12–14 feet (1^st Floor) while having her evening coffee. The chief complaint following injury was pain, lack of mobility and sensation in the lower limbs. The patient has no history of stroke or trauma.

Clinical findings

A contrast-enhanced computed tomography (CECT) of the torso revealed a burst fracture of the L1 vertebra with a retro-pulsed fragment causing spinal cord compression (Fig. 1). The patient becomes paraplegic due to trauma with an ASIA score of A. The power in lower limb key muscles (Hip, Knee, Ankle, and EHL) was 0 out of 5. The sensory level was preserved at L1.

Fig. 1.

A pre-operative computed tomography shows a burst fracture of the first lumbar vertebra.

The Glasgow Coma Score of the patient was GCS 15: E4 V5 M6. There was no bony injury or obvious intracranial and epidural hematoma. A computed tomography (CT) scan revealed no bony lesions, dislocation, or canal compromise.

Timeline

Historical and current information organized as a timeline.

Diagnostic assessment

On day 7 post-injury, she underwent surgery. A burst fracture of L1 with a retropulsion bone fragment caused anterior cord compression and pushed the conus posteriorly. The spinal column was initially stabilized with 2 levels up and 2 levels down transpedicular screws. Subsequently, L1 laminectomy was done to prevent conus injury during transpedicular reduction of retropulsion L1 vertebral body fracture segment. The patient was reviewed in OPD after 2 weeks (14 days) of surgery for suture removal. The ASIA score was similar to pre-operative.

The ASIA score, Spinal cord independence measure (SCIM), Walking Index for SCI (WISCI), and Visual Analog Scale (VAS) were assessed.

Ag/AgCl electrodes were attached at the Abductor pollicis brevis (APB) muscle to record motor threshold (MT), motor evoked potential (MEP), and cortical silent period (cSP), in response to the single magnetic pulse applied over the scalp 5 cm lateral and 2 cm anterior from the contralateral primary motor cortex (Cz).

The parameters were recorded at pre-intervention, post-intervention, and at follow-up periods of 1 month and 2 month.

Therapeutic intervention

The study protocol was approved by the ethics committee of All India Institute of Medical Sciences, New Delhi (Ethical no: IECPG-551/28.07.2022 and CTRI no: CTRI/2022/11/047038). Further, the study was carried out in compliance with the 1964 Helsinki Declaration and its later amendments. Informed written consent was obtained from the patient before the conduct of the study.

4 weeks after surgery, iTBS was administered at the primary motor cortex (vertex) corresponding to the leg area in motor homunculus using a figure of 8-coil (Neurosoft - Neuro-MS 5 (Neurosoft Ltd®, Ivanovo, Russia). The center of contact between the two circles of the coils was placed vertically over the determined stimulation site, aiming to predominantly stimulate bilateral leg motor areas. The iTBS consisted of 20 trains having 10 bursts in each train and 3 pulses in each burst. The burst is applied in pulses of three, delivered at a frequency of 50 Hz and an inter-burst interval of 200 msec (5 Hz). This resulted in 2 s of stimulation with an inter-train interval of 8 s for 3 min 9 s, yielding 600 stimuli per session. A total of 10 sessions (2 per day at an interval of 2 hours for 5 consecutive days), yielded a total sum of 6000 stimuli per complete treatment.

Rehabilitation

The rehabilitation regime was initiated after surgical intervention once the patient became hemodynamically stable. A thorough physiotherapy assessment is done before the exercise regime begins. The range of motion exercises (ROM) were suggested to patients which includes both passive or active assisted ROM exercises of the lower limb (LL). Bed mobility (supine to side, side to prone, prone to supine, and vice-versa in a log rolling fashion) with 7 repetitions (reps.) of 2 sets twice a day were given. The patient was also advised for graded sitting using Thoraco-Lumbar Spinal Orthosis 3 rep., 3 times/day. To prevent bed soreness a pneumatic air bed was prescribed along with regular skin inspection. After suture removal, upper limb (UL) strength training in the form of progressive resisted exercise (PRE) started with external weight (dumbbell, and weight cuff) with 2 sets of 10 reps., twice a day.

Once the patient was able to perform comfortably all the previous exercises, in addition, she was also advised to perform bridging, kneeling, and wheelchair training (moving in different directions, overcoming hurdles, transferring from wheelchair to bed, ground, commode, and vice versa). After 1^st follow-up, gradually advanced balance training was performed with a gym ball. The patient also performed quadruped exercises, half-kneeling, crossed leg, and single limb bridging with support. HKAFO (Hip Knee Ankle Foot Orthosis) was prescribed to aid in physiological standing initially for 7-10 minutes, gradually extending to 30 minutes in due course of time. The patient was graduated with an axillary crutch for 4-point swing-to-gait training for at least 3 minutes for another 15 days. At 2^nd follow-up, the patient progressed to KAFO (Knee Ankle Foot Orthosis) with a walker for at least 5-10 minutes for gait training with emphasis on heel strike, push-off, ground clearance, and adequate hip, knee, and ankle flexion.

Outcomes and follow-up

The AIS is a standardized test that includes anorectal, sensory, and myotomal components. The term “sensory function” describes the transient sensations that are distributed throughout the dermatomal segments, such as light touch and pinprick. Key muscle functions distributed in myotomal segments are primarily evaluated by motor scores [12]. There were no sensory and motor functions preserved at S₄-S₅ segments, hence the injury was of complete type. The sensory score has improved at post-intervention, first and second follow-up in comparison to baseline. Lower extremities motor score improved gradually from baseline (Rt= 29; Lt=29), to post-intervention (Rt= 31; Lt=31), first (Rt= 31; Lt=31) and second follow-up (Rt= 35; Lt=34). The neurological level of injury also improved at the second follow-up (L2) as compared to the baseline (L1) (Table 1).

Table 1.

Neurological status measures.

Neurological status	Baseline		Post-therapy		1 month		2 month
	L	R	L	R	L	R	L	R
Neurological levels Sensory
	L1	L1	L2	L2	L2	L2	L3	L3
Motor	L1	L1	L2	L2	L2	L2	L2	L3
LEMS	4	4	6	6	6	6	9	10
Total motor score (UEMS + LEMS)	29	29	31	31	31	31	34	35
Total sensory score (LT + PP)	86	86	88	88	88	88	92	94
Neurological levels of injury (NLI)	L1		L2		L2		L2
Complete or Incomplete	C		C		C		C
ASIA impairment scale	A		A		A		A

After completion of 10 sessions of intervention, the motor threshold dropped from 40% to 15%. At the second follow-up, the recorded threshold intensity decreased further from the baseline and post-intervention. The first follow-up data was not considered for analysis as 2 days before the appointment, the patient complained of irritation and sourness from spilled tea. The latency of the MEP remained unchanged, but the cortical silent period showed a significant decline in comparison to the baseline (Table 2).

Table 2.

Electrophysiological parameters assessments.

Electrophysiological parameters	Baseline	Post-therapy	2 month
Motor Threshold (MT)	40	15	10
Latency	14	15.15	13.1
Cortical silent period (CSP)	304	56.05	176

All three domains of SCIM (self-care, respiratory and sphincter management, and mobility), walking index, and visual analog scale showed improvement at the end of TMS intervention and remained consistent for up to 2 months (Table 3).

Table 3.

Functional outcome measures.

SCI outcomes		Baseline	Post-therapy	1 month	2 month
Spinal cord injury independence measure (SCIM)	Total score (0–100)	18	26	37	58
	Self-Care (0–20)	1	5	6	13
	Respiratory and sphincter Management (0–40)	15	15	18	26
	Mobility indoors and outdoors (0–40)	2	6	13	19
Walking Index for SCI (WISCI) (0–20)		0	0	6	9
Visual Analog Scale (0-10)		6	4	6	1

No adverse events related to iTBS (Headache, nausea, and tremors) were reported during the intervention period and follow-up assessments.

Discussion

Complete SCI patients received a 5-day iTBS intervention at 80% of the resting motor threshold and rehabilitative training throughout the intervention and till the last follow-up. This combined approach led to significant, consistent improvement in all neurological and functional parameters. The main limitation of this case report is to generalize the validity of the intervention.

iTBS has been suggested to have a neurostimulatory effect when applied to the primary motor cortex (M1) and facilitates cortical excitability that typically lasts for 20–30 min [13, 14]. It increases cortical excitability by inducing long-term potentiating (LTP) - like effects [11, 15]. The neural effects of iTBS are usually studied using motor thresholds (MTs) and motor evoked potentials (MEPs), which are muscle responses induced by a single pulse of TMS [16, 17].

Changes in MEP amplitude, latency, threshold, and cortical silent period are used to infer corticospinal transmission, pyramidal tract excitability, and cortico-spinal integrity after SCI [18]. The decreased motor threshold after the intervention was suggestive of the increased corticospinal excitability [19]. Additionally, we observed a decreased cortical silent period after the intervention which was sustained for 2 months. This reduced silent period, is probably due to the decreased activity of the GABAergic inhibitory interneurons that modulate the cortical motor neuronal output [20–22].

The change in the motor score for the lower extremities contributed to the locomotor improvement, which increased gradually from the baseline till the last follow-up. After 5 days of iTBS intervention, the completely paraplegic patient was able to sit by herself. During the first follow-up, the patient had gained strength in key muscles and thereby could perform basic mobility activities. By the time of the second visit, the patient could get up and walk around, up to a distance of 10 meters, with a walker and HKFO. During the first and second follow-ups, following the intervention, the sensory score also increased in comparison to the baseline.

Spinal cord independence measure is used to make functional assessment of SCI patients in 3 domains: self-care, respiration and sphincter control, and mobility. Results showed an increase in self-care and mobility scores after the intervention and throughout follow-up. Mao et al. [23] gave iTBS along with nerve root stimulation in incomplete SCI patients and also found an increased SCIM score after the intervention [23].

This case report suggests that iTBS along with rehabilitation training could be a promising tool in sensorimotor recovery in complete SCI patients. As iTBS uses a shorter stimulation period as compared to conventional rTMS, it is more comfortable for patients and thus may be a good alternative to rTMS in clinical practice.

Patient perspective

The patient does not register any complaints such as headache, dizziness, nausea, or seizure during and after intervention.

13. The patient has given an informed and written consent.

Author contributions

DP: Conceptualization, Data curation, Investigation, Writing—original draft. RB: Data curation, Methodology. KF: Patient recruitment and screening, Investigation, Writing—review & editing. DG: Patient recruitment and screening, Methodology, Writing—review & editing. BG: Investigation, Patient recruitment and screening. NK: Supervision, Lab facility. GHT: Supervision, Rehabilitation training. KPK: Writing—review & editing, supervision. SJ: Lab facility, Supervision, Writing—original draft.

Funding

This work was supported by the Department of Biotechnology (DBT) Ministry of Science and Technology, Government of India in 2019 (BT_2052).

Data availability

The data generated or analyzed during this study can be found within the published article and additional data will be available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Supplementary information

The online version contains supplementary material available at 10.1038/s41394-024-00669-8.