Myelopathy, used interchangeably with spinal myelopathy, refers to any neurologic deficit related to the spinal cord [1, 2]. Spinal myelopathies are characterized by severe spinal cord compression occurring within the spinal column [3]. They can be further divided into two groups based on their etiology: inflammatory myelopathies, which include transverse myelitis, multiple sclerosis (MS), and viral myelitis, and non-inflammatory myelopathies, which include traumatic spinal cord injuries, tumors/epidural abscesses, and degenerative conditions such as cervical spondylotic myelopathy (CSM), among others [4]. Spinal myelopathies are becoming increasingly common in aging populations worldwide, with CSM alone accounting for the hospitalization of 15,000–20,000 patients per year in the United States [5]. Common clinical manifestations of spinal myelopathy include pain, extremity numbness, weakness, gait instability, paresthesia, dysesthesia, and, in severe cases, loss of bladder function [6–10]. With this wide range of clinical presentations, diagnosing spinal myelopathies can be challenging. A systematic approach incorporating a detailed physical examination, laboratory testing, advanced neuroimaging, and cerebrospinal fluid analysis is thus paramount to timely diagnosis and intervention [4, 6, 11].

Traditionally, spinal cord injury (SCI) and myelopathy have been described in association with motor and sensory deficits. An often overlooked and severe complication of myelopathy, however, lies in its ability to disrupt autonomic regulation, specifically control over the gastrointestinal (GI) tract. Acutely, spinal myelopathies have been associated with constipation and abdominal bloating [12, 13]. More chronic issues include abdominal pain, gastroparesis, and fecal incontinence as a result of neurogenic bowel [14–16]. Both contribute to poor quality of life among patient populations and are a large cause of hospitalization among people with SCI [16, 17]. The autonomic nervous system (ANS) is a branch of the peripheral nervous system that regulates various involuntary physiological processes, helping to maintain homeostasis [16, 18, 19]. It can be further divided into three divisions, all of which play essential roles in maintaining GI function: the sympathetic nervous system responsible for inhibiting GI activity (“fight or flight”), the parasympathetic nervous system responsible for stimulating GI activity (“rest and digest”), and the enteric nervous system (ENS) responsible for mediating digestive motor functions such as peristalsis and intestinal epithelial barrier functions including regulating gastric secretions [19–21]. All three divisions work in concert with the spinal cord via afferent and efferent nerve fibers, emphasizing the impact spinal myelopathies may have on enteric function.

The impact of spinal cord myelopathy on GI function continues to be poorly understood [17]. This review aims to summarize existing literature on how spinal cord damage may induce enteric dysfunction, incorporating discussion of relevant anatomy and paths of innervation. It focuses on the etiology of various spinal cord injuries, namely cervical myelopathy, thoracic myelopathy, lumbar/sacral myelopathy, and traumatic spinal cord injuries, as well as the associated symptoms that arise from these conditions.

Proper discussion of the effects of spinal myelopathy in enteric dysfunction necessitates reference to the role of spinal innervation in the maintenance of digestion. The GI tract heavily relies on the nervous system to facilitate proper digestion and absorption of food. It primarily receives innervation from the ANS and sensory divisions of the peripheral nervous system (Figure 1). The ANS consists of the sympathetic, parasympathetic, and enteric divisions, each playing an important role in GI function [22]. With regards to the extent of innervation of the GI tract, the ENS is the most prominent of the nervous system divisions, consisting of over 100 million neurons in humans [23]. The ENS has earned the name of the “second brain” on account of its autonomy and similarities to the brain [24]. A number of researchers have achieved full or partial separation of the ENS from the central nervous system (CNS) while still maintaining bowel function in mammals [25, 26]. However, pathologies, such as Hirschsprung disease and Chagas disease, which lead to impaired or missing portions of the ENS, can almost entirely halt proper GI functioning and be fatal [27]. Despite the autonomy of the ENS, spinal nerves still play an important role in providing feedback to the CNS and regulating digestion and defecation.

Spinal myelopathies can substantially alter GI function through disruption of spinal neural pathways that control autonomic and somatic nervous system function on the GI tract. While the ENS can maintain autonomous control over GI motility through intrinsic reflex arcs, disruption of extrinsic neural input can have pathological effects by way of impaired attenuation of ENS activity through myenteric and submucosal ganglia connections and impaired control of extrinsically innervated smooth muscle.

As has been discussed, innervation is integral to the function of digestion and mobility through the GI tract. Therefore, damage to the spinal cord disrupts the autonomic innervation of the GI tract and can lead to chronic GI problems [47]. This section will explore the etiologies of spinal myelopathies, paying attention to the different spinal regions, and how these may cause varying degrees of impact on GI function (Figure 2).

As discussed, spinal myelopathies often present with enteric disturbances leading to significant clinical implications [87]. This section describes the spectrum of clinical presentations for enteric dysfunction associated with spinal myelopathies, highlighting their impact on patient outcomes and quality of life.

GI complications such as constipation, diarrhea, abdominal bloating, pain, dyspepsia, gastroparesis, and fecal incontinence are prevalent among patients with spinal myelopathies [56, 87] (Figure 3). Manifestations of GI complications are often linked to impaired autonomic regulation, which in turn adversely impacts GI motility [56]. This is particularly relevant to spinal myelopathies as GI issues can lead to malnutrition, anemia, and vitamin B12 deficiency, all of which have the potential to further exacerbate spinal cord dysfunction and negatively impact any potential myelopathy-related surgical recovery [56]. Case studies highlight the interplay between GI and neurological symptoms. A case study has described a patient with acute transverse myelitis following Campylobacter jejuni infection who initially presented with diarrhea but subsequently developed bowel dysfunction, lower limb weakness, and sensory disturbances, indicative of spinal cord involvement [88]. It must be emphasized that this case report identifies the significance of considering a potential neurological sequel in patients with acute GI symptoms who present with new-onset neurological symptoms. Early diagnosis and treatment continue to be crucial to improving patient outcomes and minimizing long-term neurological injury [88].

Mechanisms underlying these GI disturbances are complex and multifaceted. In a review of GI motility disorders in neurologic disease, Camilleri [87] (2021) emphasizes that disruptions in the ENS can lead to motor, sensory, storage, and excretory disruptions, manifesting as complex GI symptoms. Some of the symptoms listed include dysphagia, intestinal pseudo-obstruction, gastroparesis, diarrhea, and fecal incontinence. Furthermore, Camilleri [87] emphasizes that interplay between the central and ENS s is crucial in understanding these manifestations. Consequently, effective management of gut neuromuscular disorders involves not only addressing the underlying neurologic condition but also prioritizing the restoration of hydration and nutritional status [87].

The diagnosis of spinal myelopathy is reached through a combination of clinical assessment, imaging, and functional tests. While the etiologies of myelopathies are myriad, the consequences of a compromised spinal cord present similar signs and symptoms. Thus, a thorough history and physical examination remain fundamental in identifying spinal cord dysfunction. Jiang and colleagues [94] (2024), highlights that the most sensitive indicator of degenerative cervical myelopathy, the most prevalent form of myelopathy, is the presence of hyperreflexia and Tromner signs, whereas Babinski, Tromner, clonus, and inverted supinator signs are considered the most specific. Complementary imaging modalities, particularly MRI, play a critical role in diagnosing myelopathies. Uda and colleagues [95] (2013) measured a level of sensitivity of 100% and a specificity of 75% in diagnosing cervical spine myelopathy using a mean diffusivity (MD) z score of 1.40 at the most compressed level of the spine [95].

To evaluate enteric dysfunction secondary to spinal myelopathy, functional assessments such as high-resolution anorectal manometry, colonic transit studies, and standardized disability indices are employed. High-resolution anorectal manometry measures the rectoanal inhibitory reflex in response to rectal distention, providing valuable insights into conditions like fecal incontinence by assessing anal sphincter strength and rectal sensory function [96, 97]. Colonic transit studies, involving the ingestion of radiopaque markers followed by X-rays taken 3–7 days later, enable the assessment of segmental colon function and transit times. As mentioned earlier, the parasympathetic pathways from S2–S4 play a role in reflexes associated with defecation in the distal portion and can extend the colonic transit time creating a possible proxy [38, 41, 43]. While this method is well-established, the standardization of result interpretation remains under investigation [98]. Alternative methods such as wireless motility assays and capsule endoscopies offer similar functional assessment.

Disability indices, including the myelopathy disability index (MDI) and the modified Japanese Orthopaedic Association (mJOA) score, further quantify the functional impact of myelopathies. The MDI is a questionnaire that describes the difficulty of daily tasks that patients experience while minimizing subjective physician bias. Current advancements in the MDI are establishing severity and then correlating it to the likelihood that surgery will be a benefit [99]. mJOA scores are another popular means of assessing myelopathy induced disability. In this variation, the physician answers questions about the patient’s ability to complete daily activities and retain urine [100]. Additionally, emerging research has been trying to understand the connection between neurotransmitter concentrations, such as cholinergic and serotonergic biomarkers, and clinical parameters like colonic transit time, aiming to elucidate the pathophysiological basis of enteric dysfunction in spinal myelopathies [21].

Management strategies for enteric dysfunction range from invasive procedures, such as the implantation of bioelectric stimulation devices, to pharmacological agents and non-pharmacological treatments like diet-specific interventions. As previously mentioned, the cohorts described by Nouri and colleagues [56] (2020) were more likely to experience GI comorbidities (GIC) when female, with worse general and psychiatric health, along with clinical exams and imaging studies suggesting less neurological complication. This indicates the potential to characterize and specifically target those experiencing GIC more effectively. Given their minimal risk, non-pharmacological treatments should be attempted first. While it is difficult to produce diet related interventions which show causal changes in enteric dysfunction from SCI, Hamilton and colleagues [101] (2024) showed in mice models that inulin, a dietary fiber, and short-chain fatty acids (SCFAs) can attenuate enteric dysfunction by promoting ENS resilience. Other studies have gathered information on the immune and motility related benefits of SCFAs [102]. Exercise has also long been prescribed for chronic constipation, and a meta-analysis by Gao and colleagues [103] (2019) showed that those who exercise by means of walking and other aerobic exercises improved their likelihood of recovery by 2.42 times.

Pharmacological approaches have included, osmotic and stimulatory laxatives, prosecretory agents, and 5HT4 agonists to target constipation secondary to upper motor neuron injury [104]. Osmotic laxatives, such as polyethylene glycol, have been shown to improve stool frequency, consistency, and straining compared to placebo in both functional and irritable bowel syndromes (IBS). Aziz and colleagues [104] (2020) noted that while stimulatory laxatives have less data, agents like bisacodyl and sodium picosulfate have demonstrated superiority to placebo and may be considered if osmotic laxatives fail. Prosecretory agents like linaclotide, plecanatide, and lubiprostone enhance enterocyte biology to increase luminal fluid secretion, providing a cellular mechanism to alleviate constipation (Figure 4). Prucalopride, a 5HT4 agonist, has also shown efficacy in improving constipation and abdominal pain in both functional and opioid-induced constipation [104].

Bioelectric neuromodulation is an intervention that has been gaining traction in multiple pathologies that affect colorectal function including spinal trauma, MS and Hirschsprung disease [105]. By modulating CNS-ENS innervation and increasing lower motor neuron activity, sacral nerve stimulation has demonstrated utility in reducing inflammation in IBS, alleviating postoperative ileus via vagal nerve stimulation, and via sacral nerve stimulation, addressing fecal incontinence via anal sphincter contraction. Such an approach represents an exciting area of development with promising applications for upper motor neuron lesions [105]. As a last resort, colostomy is also an option to mitigate quality-of-life impairments and serves as one of few interventions outside of diet for those with lower motor neuron injuries. With indications for reflexive constipation from upper motor neuron injury and are flexible fecal incontinence from lower motor neuron injury. Both colostomy and ileostomy reduce the amount of time needed to manage bowel and overall, patients have reported a desire to be counseled about this treatment earlier. No significant differences have been observed between colostomy and ileostomy in SCI patients [106].

In order to offset the use of more invasive procedures, sacral and pudenal nerve stimulation (PNS) has emerged as a promising treatment option for patients suffering from intractable constipation [107]. The therapeutic effects of PNS are hypothesized to stem from its interactions with the somatic and autonomic pathways in the spinal cord and higher brain centers, offering a potential solution for neurogenic bowel dysfunction [107]. While this approach holds promise, future research is necessary to provide insight into the long-term efficacy and sustainability of PNS outcomes. In addition, mechanistic research investigating the biological mechanisms behind the effects of the PNS on somatic and autonomic pathways is essential. A deeper understanding of these mechanisms may yield improved treatment protocols, better patient selection, and potentially the development of more targeted therapies that enhance the efficacy of PNS while minimizing adverse side effects.

In patients with neurogenic bowel dysfunction who do not respond to conservative bowel management strategies, transanal irrigation (TAI) has become an emerging therapeutic option. The Navina Smart system, an electronic TAI device, has demonstrated improvement. In a prospective study led by Emmanuel et al. [108], patients reported improvements in bowel function, reduced constipation, decreased incontinence, as well as high satisfaction levels, highlighting Navina Smart’s capabilities as a valuable treatment option. Additionally, patient-centered studies focused on customization and optimization of TAI systems could enhance treatment outcomes by addressing individual patient needs and preferences.

Gut microbiota plays a crucial, yet incompletely understood, role in regulating the inflammatory response and affecting neurological recovery after spinal cord trauma. The gut-brain-spinal axis represents the two-way communication between the gut and CNS [109]. Following an injury, the gut-brain axis contributes to the production of pro-inflammatory metabolites, creating a difficult environment for cell survival and the recovery of movement. Consequently, understanding the relationship between pharmacological treatment and microbiome imbalances is crucial to enhancing regeneration, promoting cell survival, and improving behavioral outcomes [109]. Additionally, proper small bowel motility, governed by intrinsic and extrinsic neurons and humoral factors, is essential for nutrient absorption and digestive health. Impairment in the integrity of coordinated movement of the small bowel, known as small bowel dysmotility, can lead to symptoms such as abdominal pain and distention, constipation, and diarrhea. Given the incomplete understanding of the gut-brain-spinal axis and its complex interactions, further research is necessary.

Mesenchymal stem cells (MSCs) have also gathered attention for their applications in regenerative medicine and their ability to support repair and recovery in spinal cord injuries [110]. Despite their promise, MSC therapies still face significant challenges including optimizing delivery methods, ensuring cell survival, and promoting integration with host tissues [111]. Overcoming these barriers is critical to realizing the full therapeutic potential of MSCs. Continued research and innovation in this field are vital for advancing the treatment of spinal cord injuries and enhancing patient outcomes [111].

Spinal myelopathy-related enteric dysfunction caused by spinal cord compression is commonly associated with dysfunction of spinal cord reflex arcs and the ENS. The disruption of such enteric gut-brain-spinal pathways ultimately contributes to a myriad of clinical presentations and reduced quality of life. Symptoms include gastroparesis, dyspepsia, fecal incontinence, abdominal bloating, constipation, abdominal pain, diarrhea, and chronic neurogenic bowel disease. Enteric dysfunction in the setting of SCI is currently diagnosed and treated with a range of management strategies that encompasses non-pharmacological and pharmacological interventions, neuromodulators, and surgical interventions. However, there remains a lack of complete understanding of ENS dysregulation and its clinical relevance regarding assessment, diagnosis, and treatment options. Future research directions concerning nerve stimulation, treatment options, MSCs, the gut microbiome, and biochemical processes in relation to the gut-brain-spinal nerve axis may prove beneficial in improving clinical outcomes and quality of life for those who suffer from SCI related GI enteric dysregulation.