Clinical trial NCT06416878: Brief ES for Recovery of Autonomic Function in CES
Official title: Can Brief Perioperative Epidural Electrical Stimulation Improve Recovery of Autonomic Function in Cauda Equina Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cauda Equina Syndrome
Keywords: cauda equina syndrome
electrical stimulation
spinal cord stimulator
recovery of autonomic function
axonal regeneration
Lead sponsor: University of Liverpool
Sponsor class: OTHER
First posted: 2024-05-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Consecutive patients presenting to neurosurgical department with acute cauda equina syndrome with autonomic dysfunction.
Primary purpose: TREATMENT

Brief summary: BESCES is a study that aims to explore the feasibility of intraoperative brief epidural electrical stimulation (ES) for patients undergoing routine decompression for cauda equina syndrome. In consenting patients, brief ES will be applied using a CE-marked SCS trial kit once sufficient decompression is achieved. In participants who do not recover function following decompression, brief post-op ES will be applied to see if can facilitate micturition and/or removal of the catheter.

The study will assess:

The feasibility of intervention. If brief ES can facilitate conduction in residual neurons. If brief ES can facilitate neuronal recovery

Detailed description: Cauda equina syndrome (CES), defined as a compression of nerves controlling bowel, bladder and sexual function due to lumbar disc prolapse has a prevalence of 2 per 100,000 UK population per year. It mostly affects individuals 30-49 years of age. Emergency surgery to decompress the nerves is the mainstay of treatment. Despite adequate decompression, 17% of patients are left incontinent and 50% experience persistent bowel, bladder or sexual dysfunction needing long-term supportive symptomatic management and compromising their social cohesion and economic productivity.

Theoretically, there are two possible ways of improving these functions - improving regeneration of damaged cells and improving conduction in partially damaged/residual cells. The use of perioperative electrical stimulation (ES) has shown significant promise in facilitating recovery in peripheral nerve compression syndromes. Epidural stimulation is routinely used for treating neuropathic pain and there is anecdotal evidence of improved bladder and bowel function in patients with CES who have received epidural spinal cord stimulation for chronic pain.

The overall aim of this feasibility study is to determine if a full definitive RCT is possible. The investigators want to see if it is possible to timely and safely deliver epidural stimulation in patients presenting with bowel, bladder or sexual dysfunction due to cauda equina compression, undergoing emergency lumbar decompression, assess the potential effect size of brief post-decompression ES proximal to the level of compression in facilitating axonal regeneration to support further RCT. The investigators also want to see if brief ES can improve conduction in residual neurons.

40 patients presenting with CES shall be enrolled. At the time of decompression surgery, consenting patients shall receive ES. With standard care, patients who still have symptoms after decompression, remain symptomatic at 1 year. Comparison of functional outcomes post-surgery and at 3, 6 and 12 months will enable assessment of recovery due to axonal regeneration.

Results shall assess the safety and feasibility of doing the study in emergency settings - enrolment and consent issues and assess effect size, this will provide sufficient information and, if successful, will lead to a definitive Randomised Control Trial (RCT).

Eligibility criteria: Inclusion Criteria:

* Age \>18.
* Cauda equina syndrome with bladder, bowel or sexual dysfunction (CES-I or CES-R) secondary to acute lumbar disc prolapse.
* Selected for emergency surgery.

Exclusion Criteria:

* No bladder, bowel or sexual dysfunction (Only bilateral radicular symptoms).
* Previous spinal surgery with risk of adhesions.
* Multilevel degeneration with inadequate safe space to pass epidural electrode.
* Pre-existent bladder, bowel or sexual dysfunction.
* History of peripheral neuropathy.
* Contraindications to neurostimulation (e.g. pacemaker, immune deficiency, uncontrolled diabetes, sepsis, active pressure sore, spinal cord stimulator in situ).
* Intraoperative CSF leak.

Primary outcomes:
measure: Recruitment Rate
timeFrame: 6 months
measure: Pudendal Somatosensory Evoked Potentials (SEP) - amplitude (uV)
timeFrame: Post-operatively and at 3 months.
measure: Pudendal Somatosensory Evoked Potentials (SEP) - latency (ms)
timeFrame: Post-operatively and at 3 months.
measure: Stimulation parameters - Frequency (Hz)
timeFrame: At the time of the surgery and immediately post-op
measure: Stimulation parameters - Amplitude (mA)
timeFrame: At the time of the surgery and immediately post-op
measure: Stimulation parameters - Pulse width (microseconds)
timeFrame: At the time of the surgery and immediately post-op
Secondary outcomes:
measure: Short Form Incontinence Questionnaire (SFIQ)
timeFrame: On admission and at 3, 6 and 12 months.
measure: Arizona Sexual Experiences Scale (ASEX)
timeFrame: On admission and at 3, 6 and 12 months.
measure: Neurogenic Bowel Dysfunction (NBD) Questionnaire
timeFrame: On admission and at 3, 6 and 12 months.
measure: Oswestry Disability Index (ODI)
timeFrame: On admission and at 3, 6 and 12 months.
measure: Rand SF-36 Questionnaire
timeFrame: On admission and at 3, 6 and 12 months.
measure: Post-void bladder scan (PVBS)
timeFrame: At baseline, post-operative (x3) and at 3 months.
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Foundation Trust
state: Merseyside
Study officials:
affiliation: University of Liverpool
name: Andrew Marshall, PhD
role: STUDY_CHAIR
References:
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citation: Rascon-Ramirez FJ. Spinal cord stimulation and cauda equina syndrome: Could it be a valid option? A report of two cases. Neurocirugia (Engl Ed). 2021 Feb 5:S1130-1473(21)00003-8. doi: 10.1016/j.neucir.2020.12.002. Online ahead of print. English, Spanish.
citation: Sayanagi J, Acevedo-Cintron JA, Pan D, Schellhardt L, Hunter DA, Snyder-Warwick AK, Mackinnon SE, Wood MD. Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice. J Bone Joint Surg Am. 2021 Oct 20;103(20):e80. doi: 10.2106/JBJS.20.01965.
citation: Woodfield J, Hoeritzauer I, Jamjoom AAB, Jung J, Lammy S, Pronin S, Hannan CJ, Watts A, Hughes L, Moon RDC, Darwish S, Roy H, Copley PC, Poon MTC, Thorpe P, Srikandarajah N, Grahovac G, Demetriades AK, Eames N, Sell PJ, Statham PFX; UCES Collaborators; British Neurosurgical Trainee Research Collaborative. Presentation, management, and outcomes of cauda equina syndrome up to one year after surgery, using clinician and participant reporting: A multi-centre prospective cohort study. Lancet Reg Health Eur. 2022 Nov 17;24:100545. doi: 10.1016/j.lanepe.2022.100545. eCollection 2023 Jan.