Intrathecal baclofen therapy for spasticity in a person with spinal cord injury and end-stage renal disease dependent on hemodialysis: a case report

Abstract

Introduction

Spasticity is one of the most common secondary complications following a spinal cord injury (SCI), which can significantly debilitate a patient irrespective of the severity of the injury. Intrathecal baclofen therapy can effectively reduce global spasticity in bilateral lower extremities at lower doses and allows precise dose titration to manage spasticity optimally. In complex patients with spasticity and multiple medical comorbidities, multidisciplinary teamwork is required to assess ITB safety and deliver timely intervention to prevent secondary complications of spasticity and improve quality of life.

Case presentation

A 61-year-old African American male with multiple comorbidities, including end-stage renal disease (ESRD) requiring dialysis sustained non-traumatic SCI due to epidural abscess resulting in paraplegia and severe debilitating spasticity. Spasticity gradually worsened and interfered with his ability to achieve independence with functional activities appropriate for his neurological level of injury. A multidisciplinary team approach in this complex case resulted in a successful ITB trial and subsequent ITB implantation, resulting in reduced spasticity and improved quality of life. To our knowledge, this is the first case report of the administration of intrathecal baclofen pump therapy in a person with SCI and end-stage renal disease (ESRD) dependent on hemodialysis.

Discussion

ITB therapy can be safely delivered in a person with SCI and multiple medical comorbidities, including ESRD, dependent on hemodialysis to manage spasticity. However, a careful evaluation and discussion among the multidisciplinary team managing the patient’s morbidities and patient is required to assess the risks and benefits of ITB therapy to allow the patient to make an informed decision.

Introduction

Spasticity is one of the most common secondary complications following a spinal cord injury (SCI), which can significantly debilitate a patient irrespective of the severity of the injury. Spasticity has been reported in up to 87% of people with SCI [1–5], and spasticity interferes with function in 41% of people with SCI [2]. Untreated problematic spasticity after SCI can result in multiple complications, including the development of joint contractures/deformities, pain, inability to participate in therapy, poor hygiene, seating and postural problems, skin breakdown, decreased function, poor sleep, and poor quality of life [1, 3, 4, 6, 7]. Despite access to new therapies in addition to oral medications in the last two decades, such as botulinum toxin injections, chemical neurolysis, intrathecal Baclofen (ITB) therapy, and improved orthotics, patients often do not receive the proper treatment at the right time resulting in poor outcomes. Among these interventions, intrathecal baclofen pump therapy is recommended for severe global spasticity, especially effecting the bilateral lower extremities. With ITB therapy, spasticity can be managed with lower dose than oral Baclofen therapy, which also minimizes the side effects of Baclofen. Besides, infusion therapy allows precise titration of the dosing. Despite these benefits, the need for surgery to implant the pump and the fear of potential complications with the implant limit the acceptance of this therapy among physicians and patients. Additional barriers to ITB therapy include but are not limited to lack of knowledge and misconception on the appropriate timing of offering this therapy, lack of inter and multidisciplinary teamwork, and lack of resources for continuity of care. These barriers double in patients with multiple comorbidities, where decision-making involves input from numerous specialties, requiring care coordination and additional resources.

We present a complex case of an adult with non-traumatic SCI and multiple comorbidities, including end-stage renal disease (ESRD) dependent on hemodialysis, h/o epidural abscess, congestive heart failure, and deep venous thrombosis requiring anticoagulation who developed severe spasticity and had successful ITB pump implantation with the input from a multidisciplinary team.

To our knowledge and on literature search, this is the first case of successful ITB therapy in a person with ESRD dependent on dialysis for the management of severe spasticity.

Case presentation

Patient information & clinical findings

A 61 years old African American male with morbid obesity, end-stage renal disease (ESRD) on hemodialysis, diastolic congestive heart failure (CHF), hypertension, and hyperlipidemia presented to an acute care hospital with chest pain and generalized weakness. The patient was diagnosed with non-ST elevation myocardial infarction and sepsis and treated with intravenous antibiotics. Once the patient was medically stabilized, he was noted to have weakness and loss of sensation in bilateral lower extremities. Magnetic resonance imaging of the thoracic spine revealed an epidural abscess compressing the spinal cord at the T1–T3 level. The patient was transferred to a tertiary care center for further management, where he had a T1- T3 laminectomy and evacuation of epidural abscess by a neurosurgeon. The infectious disease consultant started him on long-term antibiotic therapy to treat epidural abscess. His hospital course was further complicated by right internal jugular vein thrombosis, warranting anticoagulation therapy with Coumadin. On postoperative day 14, the patient was transferred to an acute inpatient rehabilitation hospital for comprehensive rehabilitation therapy due to a non-traumatic spinal cord injury from an epidural abscess resulting in paraplegia and functional decline. Please see Table 1 for a detailed timeline of the events.

Table 1.

Timeline of the events.

Timeline	Location	Event
Day 0–Day 10	Admitted to acute care hospital	Presented with BLE weakness and chest pain Diagnosis: NSTEMI, bacteremia, weakness in legs
Day 10–Day 15	Transferred to quaternary care acute care hospital for spine decompression	Surgery: T1-T2 laminectomy and evacuation of epidural abscess Complication: Deep vein thrombosis
Day 30–Day 63	Inpatient rehabilitation facility	Transferred from acute care hospital to inpatient rehabilitation facility
Day 169	Outpatient clinic	Evaluation by the SCI team, and he was referred for spasticity evaluation
Day 193	Outpatient clinic	Evaluation in spasticity clinic
Day 254	Outpatient clinic	ITB trial
Day 288	Acute care hospital	ITB implantation
Day 319	Outpatient clinic	Post-ITB implantation clinic follow-up for ITB adjustment
Day 403	Outpatient clinic	The optimal ITB dose achieved (274 mcg/day)
Day 513–Day 527	Inpatient rehabilitation facility	Phase 2 IRF admission
6 years post-SCI	Outpatient clinic	Last clinic follow-up

BLE Bilateral lower extremity, NSTEMI Non-ST elevation myocardial infarction, ITB Intrathecal Baclofen, SCI Spinal cord injury, IRF Inpatient rehabilitation facility.

On admission to an inpatient rehabilitation facility (IRF), the patient was noted to have a sensory level of T6, complete loss of motor function in bilateral lower extremities from L2-S1 and absent voluntary anal contraction but preserved deep anal pressure (see details in Table 2). He had severe spasticity in the bilateral lower extremities with modified Ashworth scale (MAS) [8, 9] ranging from 2-3 in most lower extremity muscle groups and Penn spasm frequency scale [9] of 4 (ten or more spasms per hour). The patient was dependent on activities of daily living (ADLs), transfers, and wheelchair mobility at the time of admission. Before this event, he was independent with ADLs and transfers and could ambulate independently without an assistive device.

Table 2.

Relevant neurological exam at the time of 1st admission to an inpatient rehabilitation facility.

	Light touch			Pinprick			Motor hypertonia
Right lower extremity	Intact from C2 to S4-S5			Intact C2- T6, impaired at T7 & T8, and absent from T9-S3			MAS 1+ to 2 in HA, HF, and KF muscle groups
Left lower extremity	Intact from C2 to S4-S5			Intact C2- T6, impaired at T7 & T8, and absent from T9-S3			MAS 2 to 3 in HA, HF, and KF muscle groups
Motor level	C5	C6	C7	C8	T1	L2	L3	L4	L5	S1
RLE motor score	5	5	5	5	5	0	0	0	0	0
LLE motor score	5	5	5	5	5	0	0	0	0	0
Deep anal pressure	Present
Voluntary anal contraction	Absent

HA Hip adductors, KF knee flexors, HF hip flexors, UE upper extremity, LE Lower extremity, MAS Modified Ashworth score, UE Upper extremity, LE Lower extremity.

Therapeutic interventions & Challenges with spasticity management

1. Phase 1- Inpatient acute rehabilitation facility: During his first inpatient rehabilitation stay, the patient developed drowsiness at a low dose of Baclofen 5 mg at bedtime due to ESRD. Spasticity was interfering with his ability to participate in therapy, but we had limited options. Botulinum toxin injections were unavailable during inpatient stays due to high costs and internal hospital policy during IRF stays. Due to recent DVT warranting anticoagulation, epidural abscess requiring IV antibiotics, and need for dialysis, the patient was deemed a poor candidate for intrathecal baclofen trial and implant.

   He received phenol neurolysis to obturator motor branches to address spasticity in hip adductors and femoral motor branches to iliacus and sartorius to address spasticity in hip flexors, resulting in some relief, but it was not optimal. During the inpatient IRF stay, the patient’s progress with transfers and ADLs remained poor due to severe spasticity. He was subsequently discharged to a skilled nursing facility after 33 days of acute IRF stay due to a lack of progress.

2. Outpatient follow-up: Evaluation and management of spasticity: The patient’s spasticity progressively worsened. He was evaluated in the spasticity clinic approximately five months after discharge from the IRF.

Evaluation

On evaluation in clinic (Table 3), he was noted to have a modified Ashworth score (MAS) of 4 in bilateral lower extremity hip flexors, knee flexors, and hip adductors, suggesting severe spasticity. He was unable to get out of bed to a chair due to severe spasticity, and his hips and knees stayed flexed and adducted when he was supine on the bed. Severe hip adductor spasticity was interfering with perineal hygiene and lower body dressing. He suffered from impaired sleep and pain due to poor posture on the bed from severe spasticity. The patient continued to require total assistance for transfers, bed mobility, lower body dressing, and bathing. He was bed-bound. Though he had no neurological deficits in the upper extremity, he was not able to progress in therapy with activities of daily living and transfers due to difficulty managing his legs due to spasticity, poor endurance from multiple comorbidities, and obesity.

Table 3.

Pre and post-ITB trial exam.

	Pre-ITB trial		Post ITB trial
Penn spasm frequency	4		4
Penn spasms severity	3		1
Wong-baker pain scale	9		0
Modified Ashworth Score (MAS)	RLE	LLE	RLE	LLE
Hip flexors	4	4	2	2
Hip adductors	4	4	2	3
Knee flexors	4	4	1	0
Ankle Plantar Flexors	2	1+	0	0
Joint range of motion
Hip Extension	Lacks 45° from neutral	Lacks 45° from neutral	Lacks 26° from neutral	Lacks 22° from neutral
Knee Extension	Lacks 90° of full extension	Lacks 90° of full extension	Lacks 45° of full extension	Lacks 70° of full extension

ITB Intrathecal Baclofen, RLE Right lower extremity, LLE Left lower extremity.

*MAS scores in available range.

Management

After weighing the risks and benefits and with a plan to seek input from other physicians managing his comorbidities, an ITB trial was recommended to manage severe spasticity in bilateral lower extremities. However, medical clearance was sought from the primary care physician, nephrologist, and infectious disease (ID) specialists, given the presence of multiple medical comorbidities and the lack of data on the safety of intrathecal baclofen pump therapy in people who have end-stage renal disease and are on dialysis. He had completed antibiotics for the treatment of an epidural abscess at that point; however, input from an infectious disease physician was warranted due to the known risk of infection with implants. He was still on Coumadin for DVT treatment and needed clearance from his primary care physician to hold anticoagulation for the ITB trial and implantation due to the risk of DVT and bleeding. All the physicians discussed potential risks of infection, DVT off anticoagulation, and possible adverse events such as overdosing with ITB in the setting of ESRD. The multidisciplinary physician team and the patient agreed that given the significantly poor quality of life without optimal spasticity management, the likely benefits of therapy outweigh the potential risks. His spasticity provider/physician coordinated input from a multidisciplinary team (Table 4), ITB trial, and ITB implantation with a neurosurgeon. The patient had an ITB trial with a 50-mcg dose, significantly reducing spasticity in major BLE muscle groups in the available joint range (Table 3). The post-trial assessment indicated a limited hip extension and knee extension range, suggesting the development of contractures in BLE hip flexors and knee flexors due to the shortening of respective tendons secondary to spasticity (details in Table 3. The ITB pump was implanted 34 days after a positive ITB trial. His ITB dose was titrated over 3.5 months to 274 mcg/day, and he reported adequate spasticity control at this dose with MAS scores ranging between 0-1 in various muscle groups in the available range in lower extremities, suggesting a reduction in spasticity. During this time, the patient received therapy at the nursing home to maintain joint range of motion.

Table 4.

Multidisciplinary team and contribution.

Team members	Contribution
Spinal cord injury Physician	•Identified spasticity as a problem and barrier to improving function and quality of life •A referral was placed for evaluation and management of spasticity
SCI Physician with Spasticity expertise	•Identified barriers to delivering optimal therapies to control spasticity •Formulated a plan to address these barriers •Coordinated care among multiple physicians and therapy teams to address these barriers
Primary Care Physician	•Provided medical clearance for ITB therapy after thoroughly evaluating risks and benefits
Infectious disease Specialist	•Evaluated risk of recurrent infection given h/o epidural abscess and need for chronic dialysis and discussed these risks to allow the patient to make an informed decision.
Nephrologist	•Evaluated the risk of potential side effects or overdosing with an intrathecal baclofen pump in a patient with end-stage renal disease requiring chronic hemodialysis
Neurosurgeon	•Performed ITB implantation after approvals from the above physicians
Rehabilitation team-Nurses, Physical therapists, occupational therapists	•Once spasticity was optimally controlled, the team worked with the patient on improving independence with activities of daily living, transfers, wheelchair mobility, bowel management, and skin management.

ITB Intrathecal baclofen.

Follow-up and outcomes

The patient was readmitted to an IRF once spasticity was optimally controlled to work on independence with activities of daily living, bed mobility, wheelchair mobility, and transfers. After 14 days of IRF stay, he required minimum assistance with bed mobility and moderate assistance for transfer with the sliding board, and he achieved complete independence with power chair mobility. While he achieved complete independence with upper body dressing, feeding, and grooming, he still required moderate assistance with lower body dressing and bathing his lower body at discharge due to body habitus and contractures. However, overall, the patient reported significant improvement in quality of life due to improved pain, sleep, improved mobility, and ability to transfer from bed to chair and use a wheelchair independently, which he was not able to do since his spinal cord injury for 18 months. He was discharged back to a nursing home due to a lack of assistance and the availability of caregivers. The patient was still tolerating ITB therapy at the time of the last follow-up six years post-ITB implantation without any complications related to ITB such as sedation, baclofen overdose, baclofen withdrawal, pump dysfunction, catheter dysfunction, or infection of pump site or any other site.

Discussion

Severe spasticity can be debilitating and often challenging to manage if appropriate interventions are delayed and often leads to poor functional outcomes and quality of life. Medical comorbidities may further contribute to these adverse outcomes. Early spasticity management in these cases allows maximal participation in rehabilitation therapy, preventing many complications associated with immobility and SCI, such as joint contractures, muscle atrophy, deconditioning, deep venous thrombosis, and pressure injuries. Therefore, assessing the risks and benefits in such cases with input from multidisciplinary team members is essential rather than deferring necessary therapy due to fear of potential risks in the presence of comorbidities. While the patient presented in this case report was at higher risk of complications due to implantation/ ITB therapy compared to someone without comorbidities, it is essential to weigh in the risks and morbidities associated with poorly controlled spasticity leading to poor outcomes. The multidisciplinary team should discuss these risks and benefits with the patients and allow them to make an informed decision based on their priorities and preferences, as we did in this case. While everyone on the team was aware that the patient needed intrathecal baclofen therapy, coordinating the care among multiple clinicians in the outpatient setting was daunting due to a lack of knowledge on the safety of intrathecal baclofen therapy in a person with end-stage renal disease and multiple comorbidities. Nevertheless, there was a significant delay in the spasticity referral in this case. The patient missed post-hospital discharge appointments due to acute care hospitalization after discharge from IRF. Additionally, comorbidities requiring input from multiple physicians further delayed the ITB trial and implantation. An early and timely intervention could have prevented joint contractures in this case. In complex cases, the assignment of a patient navigator could prevent such delays.

There are several case reports of oral baclofen toxicity in people with acute and chronic renal failure. However, there is no literature or case reports of ITB therapy in a person with end-stage renal disease who is dependent on dialysis [10–12]. It is essential to understand that baclofen toxicity depends on the dose and severity of renal impairment. In a person with severe renal impairment, even a small dose of 5 mg oral baclofen can result in overdose and side effects [10–12]. Baclofen is a gamma-aminobutyric acid (GABA) receptor agonist. The exact mechanism is unknown, but it is thought to reduce the excitability of pre-synaptic neurons with subsequent reduction in the hyperactivity of muscle reflexes [13, 14]. Baclofen is water-soluble with poor lipid solubility and doesn’t cross the blood-brain barrier easily, resulting in a significantly higher concentration in the plasma than the cerebrospinal fluid [14–16]. An optimal concentration in the CSF is the goal to achieve anti-spasmodic effects. Increasing the oral baclofen dose to achieve higher CSF concentration results in up to 8.5 times higher plasma concentration, leading to side effects, and this can worsen significantly in people with end-stage renal disease as kidneys eliminate the majority of the drug [14–17]. A higher CSF concentration of baclofen can be achieved with a very low baclofen dose without increasing plasma concentration when baclofen is administered intrathecally [16, 18]. However, baclofen levels can fluctuate in people with end-stage renal disease before and after dialysis [17]. Therefore, one should monitor the patient closely during the trial and titrate the ITB dose slowly to achieve adequate spasticity control without resulting in a baclofen overdose. Additionally, it is crucial to note that hemodialysis is an effective treatment for baclofen overdose or toxicity due to the baclofen’s low molecular weight and minimal plasma binding [17, 19, 20].

To our knowledge, there are no previously published case reports or studies that specifically assessed the safety of intrathecal baclofen pump therapy in an adult with SCI and ESRD dependent on dialysis. In our case report, we reported that with multidisciplinary teamwork (Table 4), intrathecal baclofen therapy in an individual with SCI and ESRD dependent on dialysis and other medical comorbidities is safe and feasible. Optimal spasticity control allowed the patient to work with the rehabilitation team and improve independence with bed mobility, transfers, and activities of daily living. Future studies are needed to assess the safety of ITB therapy in individuals with upper motor neuron syndrome with renal impairment.

Author contributions

All contributions were from the single author, Radha Korupolu.

Competing interests

The author declares no competing interests.