264 J Contemp Med Sci | Vol. 7, No. 5, September–October 2021: 264–271 Review Clinical Complications Associated with Spinal Cord Injury: A Narrative Review Ibrahim Mohammed1, Sahar Ijaz2, Morteza Gholaminejhad3, Gholamreza Hassanzadeh3,4* 1Department of Histopathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University Sokoto, Nigeria. 2Department of Anatomy and Histology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 3Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4Department of Neuroscience and Addiction studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. *Correspondence to: Gholamreza Hassanzadeh, (E-mail: hassanzadeh@tums.ac.ir). (Submitted: 12 August 2021 – Revised version received: 27 August 2021 – Accepted: 09 September 2021 – Published online: 26 October 2021) Introduction Spinal cord injury (SCI) is a clinical problem associated with remarkable financial as well as the emotional burden on indi- vidual patient, families, and society as well. Approximately, there is incidence of SCI of about 10–80 cases per million pop- ulations in the world.1-3 Most of the SCI result of tetraplegia (51.57%), followed by paraplegia with (45.9%). SCI due to motor vehicle accident account in almost one-half of the inju- ries worldwide, followed by SCI due to falls, SCI due to violence (like gunshot), and SCI due to sports activities.4 Alcoholism is one of the factors contributing to SCI with 25% new cases of SCI,3 as underlying spine disorder like cervical spondylosis, osteoporosis, atlantoaxial instability, and spinal arthropathies can lead to SCI, too.2,5 The extent of SCI depend on the severity of the initial injury, as well the financial burden depends also between individual patients, with the estimated cost of 500,000 to 2 million US dollars on individual patient’s lifetime.2 Epide- miological studies revealed that the incidence of traumatic SCI in the US is between 27 to 83 per million, in Europe approxi- mately about 10–30 new cases per million.6 In developed areas such as Western Europe (16/million), Australia (15/million) and North America (39/million). Falls on level ground are the most common cause of SCI in older countries such as Western Europe (37%) and Japan (42%). Violence is one of the common causes of SCI in developing regions such as North Africa/ Middle East (24%), Sub-Saharan Africa (38%) and Latin America (22%).7,8 A research conducted in 2008 in Tehran based on population, reported that the prevalence of SCI was 4.4 per 10,000 populations.9 Rahimi Movaghar et al. (2013), reported the incidence of SCI in developing countries has a rate of 25.5 per million per year, which ranged from 2.1 to 130.7 per million per year.10 Also, men are more prone to SCI in the world than women, although there are differences in the data based on the countries.7 Mechanism of SCI categorized into primary and secondary injury, with former resulting from pathologic flexion, compression, rotation, contusion, exten- sion, shearing, fracture-dislocation, ligamentous tears or dis- ruption as well as herniation of intervertebral disk. The primary mechanical injury that happened at the time of injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, inflammation, mitochondrial dysfunction, and delayed apoptotic cell death.11-16 A report from Gholaminejhad et al. (2017), revealed that the stress oxidative level will increase as one of the com- plications of SCI, finally may result to neurons disruption in animal model.17 There are series of complication occurred as a result of SCI starting from primary injury to secondary injury, most often if care is not taken primary injury leads to the sec- ondary injury that increases damage to previously injured spinal cord, it has shown that overexpression of cytokines that are important mediator for inflammation following SCI.18,19 SCI can initiate biochemical and molecular events like inflam- mation which one of the key factor in neurodegeneration development.20 In this paper, the various clinical complica- tions due to SCI were discussed. This narrative review adds to the knowledge of how spinal cord injury occurs, the various complications resulted by spinal cord injury, through the knowledge of different complications immediate attention will be giving to spinal cord injury patients at the early stage. Scopus search, Google Scholar search, PubMed search are the search engines used to get the information for this review. Abstract Spinal cord injury (SCI) is a neuro-destruction occurred from a complete or incomplete, traumatic or non-traumatic that results in degeneration, structural, biochemical, and physiological changes of tissue. SCI is a clinical problem associated with impairments in different aspects of the patient’s life. The pathophysiology of SCI involves a primary phase that directly disrupts axons, cell membranes, and blood vessels. This primary phase is followed by a secondary phase involving vascular dysfunction, ischemia, excitotoxicity, oxidative stress, inflammation, and cell death. If this second phase isn’t managed, it will result in many pathological processes that will cause several clinical complications. The aim of rehabilitation and other treatments is to enhance the functional level and to reduce secondary morbidity as well as improve the quality of health of the patient. SCI results in different complications in different organs of the individual. Early diagnosis, treatment, and prevention of complications in SCI patients are very important for limiting these complications. This review was carried out in order review the data about clinical complications associated with SCI, including multiple organ dysfunction, systemic inflammation, immune suppression, neurogenic shock, autonomic dysreflexia, orthostatic hypotension, temperature regulation, sweat secretion, respiratory complications and dysphagia, thromboembolism, urinary system, reproductive system, skeletal muscle, bone, liver, spleen and gastrointestinal tract. The purpose of this narrative review is to provide knowledge on the SCI complications, sign and symptoms, risk factors prevention and treatment of complications caused by SCI. Keywords: Spinal cord injury, Inflammation, Oxidative stress, Clinical complications ISSN 2413-0516 265J Contemp Med Sci | Vol. 7, No. 5, September–October 2021: 264–271 I. Mohammed et al. Review Clinical Complications of Spinal Cord Injury Multiple Organ Dysfunctions Apart from impairments to sensation and voluntary move- ment, SCI interrupts the autonomic nervous system and leads to dysfunction or failure in multiple organs due to a vital role of the spinal cord in coordinating bodily functions.21 Short term as well as long complications due to SCI may happen in the nervous system (like neurogenic pain and depression), in lungs (pulmonary edema and respiratory failure), in cardio- vascular system (like autonomic dysreflexia and orthostatic hypotension), in spleen (like splenic atrophy and leukopenia), in urinary tract (neurogenic bladder, urinary tract infection as well as kidney damage), in skeletal muscle (muscle spasticity and atrophy), in soft tissue as well as bone (osteoporosis and heterotopic ossification), in skin (pressure sores), there are also sexual dysfunction, hepatic pathology, neurogenic bowel dysfunction, syringomyelia as well as high susceptibility to infection. Some SCI complications if care is not taken can easily cause the death of the patient, such as liver, kidney as well as lungs damage (Figure 1).21-24 Multiple organ dysfunc- tions due to SCI are complex regulation by various compo- nents. Cranial nerves that originate from brainstem (pons and medulla) regulate the functions of multiple organs, the brain- stem reflexes were found to be changed in SCI patients.25 This shows a complex relationship between multiple organ dys- function, SCI and altered brainstem activity. This suggests that a good care should be given to the brainstem’s role in multiple organ dysfunctions due to SCI.25 Systemic Inflammation The local inflammatory microenvironment around the injured spinal cord is the aggregation of degenerating neurons, damaged myelin sheath, damaged endothelial cells as well as activated glial and infiltrating cells, this microenvironment yields different kind of pro-inflammatory mediators.26,27 Apart from this intraspinal inflammation, SCI may results in sys- temic inflammatory response syndrome (SIRS), this is a life-threatening situation that can affect other organs, such as liver, kidney, and lung.28 Previous research revealed that there is a functional relationship between systemic inflammation and pathogenesis of post injury complications: patients with SIRS-positive have more injury severity with more chances of complications compared to SIRS-negative patients.29 There are some other different factors like dysregulation of the neuroen- docrine system and altered neuroimmune regulation, known as major key factors in determinants of the onset as well as the development of post-SCI systemic inflammation. For example, SCI induces the hypothalamic-pituitary-adrenal axis, results in increased macrophage migration inhibitory factor pro- cessing via pituitary gland.30 Macrophage migration inhibitory factor is one of the key factors in systemic inflammation, revealing that SCI-elicited neuroendocrine changes lead to the advancement of systemic inflammation. Chronic activation of microglia, the neuroimmune cells of the central nervous system, happens in the hippocampus and cerebral cortex fol- lowing SCI; this is showing that neuroimmune dysregulation played an important function in systemic inflammation after SCI.31 A research conducted by Zandedel et al., (2016) reported that stromal cell-derived factor-1 alpha (SDF-1α) or CXCL12 is the main principal cytokine with numerous functions in the brain at fetal development as well as adult period. The inflam- matory response occurred due to SCI requires the processing of interleukin-1beta (IL-1β) as well as IL-18 mediated by caspase-1 in which an intracellular multiprotein complex con- trol it (inflammasome).32 Fig. 1 Clinical complications of spinal cord injury. After spinal cord injury, several clinical complications occur in the short term or the long term. Some of these clinical complications include disorders in the reproductive system, respiratory system, digestive system, urinary system, sweat secretion, skeletal muscles, liver, spleen, bones and systemic inflammation that afflict a person with physical, psychological, social and economic problems. 266 J Contemp Med Sci | Vol. 7, No. 5, September–October 2021: 264–271 Clinical Complications of Spinal Cord Injury Review I. Mohammed et al. Immune Suppression Complications occur on the immune system as result of SCI known as SCI-induced immune depression syndrome (SCI-IDS), due to dysregulation of the sympathetic nervous system as well as immune organ dysfunction.33 SCI can result in sympathetic nervous system malfunction instantly through prominent projections of the thoracolumbar spinal cord to sympathetic ganglion or directly through damaging supraspinal control by the hypothalamic-pituitary-adrenal axis. SCI-IDS, revealed by the loss of splenocytes as well as leukopenia, is a presumed self-defense mechanism that decreases potential autoimmunity to self-antigens released by damaged in the CNS.34 Report from different sources has shown that SCI-IDS worsens neurological environments and damages the functional recovery of SCI patients. Riegger et al., (2009) revealed that a remarkable decrease in the amount of circulating cells associated with innate and adaptive immunity in the acute phase after SCI on rat model.35 Similar reports were also made in a pilot research that involves 16 patients with SCI and 10 healthy individuals as control: decreased monocytes, T lymphocytes, and B-lymphocytes, but granulo- cytes were not seen in the blood circulation within 24 hours following SCI.36 SCI-IDS has a vital clinical relevance, as SCI patients show a higher susceptibility to different infections (like wound infections and pneumonia)37 as well as poor func- tional recovery.38 Autonomic dysreflexia, as well as the expan- sion of myeloid-derived suppressor cells after SCI, has a mutual relationship with SCI-IDS.39 Neurogenic Shock At the level of cervical vertebra of SCI in human, the common features of neurogenic shock are severe hypotension as well as continuance bradycardia.40 In a study conducted by Glenn and Bergman (1997) revealed that chronic hypotension was seen 31 tetraplegic subjects examined with chronic SCI, most of the subjects need pressure therapy so that the arterial blood pres- sure will be maintained.41 Apart from pronounced hypoten- sion, the majority of the patients with SCI experience chronic abnormalities in heart rate. Bradycardia was seen in 64–77% of patients with cervical SCI at the acute post-injury level and was so chronic and frequent at the first 5 weeks after the injury.42 Furthermore, when the injury is at the level of mid-thoracic spinal cord, leaving cardiac sympathetic neurons under brainstem control, the severity of bradycardia problem is very less. Furlan et al. (2003) revealed that the hypotension and bradycardia seen at the beginning following the injury persisted in the individuals with more chronic injury of the descending cardiovascular autonomic cascades.43 Apart from neurogenic shock, SCI as well associated with “spinal shock”.44,45 These are two different complications of SCI, neu- rogenic shock is identified by changes happening in blood pressure control after SCI, while spinal shock is identified by a marked decrease or abolition of motor, sensory or reflex activ- ities of the cord under the level of injury.45 Clinically, spinal shock period takes about 1 day to 2 weeks in human, with mean period of 4 and 6 weeks after the injury. Traditionally the ideas of the medical course of the recovery of spinal shock were associated with the appearance of some groups of reflexes. For instance, most clinicians assumed that spinal shock had ended when the emergence of initial reflexes, like the bulbocavernosus reflex, happened at the beginning after SCI, some assumed with the recovery of deep tendon reflexes at two weeks after the injury, while other groups of clinicians categorized the end of spinal shock as the time after 2 months they recovered bladder voiding reflexes.45 Autonomic Dysreflexia Patients with cervical or high thoracic SCI experience life-long abnormalities of blood pressure control.46,47 Most often, the resting arterial blood vessels pressure in these patients is lower when compared with normal individuals, usually associated with disabling event of orthostatic hypotension. Nevertheless, clinical complications of autonomic dysreflexia, associated with high hypertension together with a pounding headache, sometimes accompanied by slow heart rate as well as upper body flushing, in which systolic blood pressure may rise up to 300 mmHg. Untreated autonomic dysreflexia may results in serious complication such as retinal detachment, intracranial hemorrhage, seizures and death.48 Majority of non-noxious and noxious stimuli like bowel and bladder distension, pres- sure sores and spasticity may stimulate the sudden high rate in arterial blood pressure of autonomic dysreflexia.47 These car- diovascular complications are associated with autonomic instability, due to the changes happening within the spinal autonomic circuits in stages of SCI in acute and chronic stages.46,47 The damaging of the descending vasomotor path- ways leads to the loss of excitatory supraspinal input to the sympathetic preganglionic neurons and is assumed to be the main factor responsible for the lack of sympathetic tone as well as continuance arterial hypotension observed following SCI.43 Orthostatic Hypotension Low arterial blood pressure is another complication occurred due to SCI both acute and chronic. a study reported that there was an inverse linear relationship between the degree of resting blood pressure as well as SCI.46,49 The lower resting blood pres- sure is assumed to be secondary to the decrease in sympathetic nervous activity below the degree of the injured spinal cord. Apart from low blood pressure, patients with SCI experience other complication of the drop in blood pressure in the upright posture (orthostatic hypotension), most especially in the acute phase of the injury.49 The symptoms of orthostatic hypoten- sion in with SCI patients’ are the same as those individuals without SCI experiencing orthostatic hypotension, and all are related to cerebral hypoperfusion.50 The common symptoms usually seen are light-headedness, dyspnea, fatigue or weak- ness, dizziness, blurred vision and restlessness.51 A study by Illman et al., (2000) reported that 41.1% of patients with SCI that developed orthostatic hypotension were seen asympto- matic regardless of significant falls in blood pressure, it was also documented that orthostatic hypotension is a common complication among patients with SCI.52 Orthostatic hypoten- sion due to SCI seems to be associated with excessive pooling of blood in the viscera as well as dependent extremities, prob- ably caused by low level or absence of efferent sympathetic preganglionic neurons below the injured area.49 This is pos- sibly to be compounded by the loss of lower limbs muscle function that identified to be essential in counteracting venous pooling in the upright level. The remaining excessive venous pooling in the lower limbs and decreased blood ratio within 267J Contemp Med Sci | Vol. 7, No. 5, September–October 2021: 264–271 I. Mohammed et al. Review Clinical Complications of Spinal Cord Injury the intrathoracic veins results in a decreased pressure in the veins that drain through the atria of the heart.53 These will leads to reduce in ventricular end-diastolic filling pressure and stroke volume,54 resulting in the low in heart output as well as arterial pressure. Tachycardia may happen due to the decrease cardiac parasympathetic (vagal) activity, reflexly produced by unloading the arterial baroreceptors, but this activity most usually is too small to compensate for the reduced stroke volume as well as blood pressure remains low. Temperature Regulation In the ability to control temperature by SCI patients is among the clinical complications caused by SCI, most usually occurred with patients affected by cervical as well as thoracic SCI. This is occurred due to decreases sensory input to thermo-regulating centers as well as loss of sympathetic control of temperature and sweet regulation lower than the affected area.55 There are a lot of thermoregulation complications caused by SCI. Some SCI patients were found to have poikilothermia, in the ability to maintain a normal temperature notwithstanding of the ambient temperature. SCI above T8 is usually related to actu- ating temperature, hyperthermia as well as hypothermia.56 Sweat Secretion The innervations of sweat glands are mostly by the upper region of the body from T1-T5 spinal cord segments, at the lower part innervated by T6-L2 spinal cord segments. Hypo- thalamus and amygdala are the regions where supraspinal control of sweat excretion occurred.55 As results of SCI changes in sweat secretion will occur, the absence of sweating (anhi- drosis), excessive sweating (hyperhidrosis), and diminished sweating (hypohidrosis) may all occur following SCI.55 Exces- sive sweating is a typical complication seen in SCI patients.57 In most of the patients, episodic hyperhidrosis is mostly related to other autonomic dysfunctions like autonomic dysre- flexia as well as orthostatic hypotension, or with post-trau- matic syringomyelia. The typical symptoms seen are minimal or abolished sweating below the injury and profuse sweating above the injured area. This is occurred due to the compensa- tory high in secretion of sweat above the level of the injured area because of the loss of sympathetic stimulation below the injured area, which leads to decrease in production of sweat.58 There is also the possibility of sweat production exclusively below the level of the injured area. This kind of sweating is known as reflex sweating and is mostly a symptom of massive autonomic response that happened specifically with cervical and high thoracic SCI.58 Respiratory Complications SCI at the cervical region has major complications on the pul- monary system, as well respiratory difficulties are among the most complications and can lead to frequent death, both in the acute and chronic level of SCI.59 Results from the previous research revealed that 67% of acute SCI individuals have severe respiratory problems at the first day of the injury; ate- lectasis 36.4%, pneumonia 31.4% as well as respiratory failure 22.6%.60 It was also revealed that in the acute phase 84% of SCI patients with injuries above C4, 6% with injuries from C5-C8 would develop respiratory complications.61 Regular monitoring of respiration on SCI patients with such injuries is advisable. There is possibility of 56% of SCI patients with injuries at the level of T1–T12 to develop severe respiratory problems.62 30–50% reduction of vital capacity is observed in the first week of injury in injured patients at the level of C5–C6. Vital capacity, as well as arterial blood gases, should be meas- ured regularly until the patient is normal.63 Thromboembolism SCI patients have a higher risk of coagulation complications as well as venous stasis due to physical inactivity, altered hemo- stasis with decreased fibrinolytic activity and high factor VIII activity.64 The patients also are at high risk of thromboembo- lism.65 At the first year of injury, the chances of deep vein thrombosis, as well as pulmonary embolism, are assumed to be 15% and 5% respectively.66 The chances are higher at 2–3 weeks of the injury, at 3 months following the injury it will be at a small peak.67 At the chronic stage, the incidence of throm- boembolism is less than 2%.64 Urinary System Patients with SCI have high risk of developing urinary tract complications as well as renal damage, in which both can result in fatal.68 Apart from the direct loss of neuronal input following the injury, inflammation has been involved in the pathogenesis of urinary tract malfunction in patients with SCI. The inflammation that is possibly occurred due to SCI is the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), infiltration of immune cells, upregulation of inducible nitric oxide synthase, myeloperoxidase as well as cyclooxygenase-2, then activation of NF-κB.68,69 SCI caused complication in bladder, interrupts control of the bladder.70 As a result of SCI immediately after the injury, the bladder as well as sphincter is frequently hypotonic. At the chronic stage the bladder dysfunction is categorized as either upper or lower motor neuron syndrome.70 Upper motor neuron syndrome known as reflex bladder result in cortical inhibition of sacral reflex arcs because of disturbance of descending spinal tracts, results in detrusor hyperactivity mostly together with detrusor sphincter dyssynergia.71 Suppression of the stretch reflex by the pontine storage center is eliminated. A minor quantity of stretch will provide a contraction of the bladder wall; the external urethral sphincter has no voluntary control, leading in recurrent and spontaneous voiding.71 Lower motor neuron syndrome occurred due to injury to the sacral region S2–S4, which is part of the autonomic nervous system leading in diminished motor stimulation of the bladder and decreased or lack of contractility of the detrusor and eventually an enlarged bladder.72 Reproductive System Impaired fertility is among the major complications occurred in men with SCI that result in erectile as well as ejaculation malfunctions. Semen analysis of SCI patients are always poor, there is much evidence from previous research reported that a low sperm viability, motility, leukocytospermia, and high sperm DNA fragmentation are common among men with SCI.73,74 Most of the male SCI patients suffer a lot from infertility. Nucleotide-binding oligomerization domain-like receptors 268 J Contemp Med Sci | Vol. 7, No. 5, September–October 2021: 264–271 Clinical Complications of Spinal Cord Injury Review I. Mohammed et al. NOD-like receptors (NLRs) are the receptors that conjoin with the inflammasome complex. Results from different studies revealed that inflammasomes are one of the key factors for secreting cytokines in semen. Reactive oxygen species (ROS) is one of the agents responsible to initiate inflam- masome activation. Genital infections as a result of SCI can bring about ROS generation.75 Only a few studies revealed tes- ticular tissue become involved post-SCI. Impaired spermato- genesis, apoptosis, vast germ cell, inflammatory cytokines elevation, and blood-testis barriers disruption, as well as leu- kocytes influx, has been shown as abnormal changes in the testis of SCI patients, result to the inflammatory event and unstable niche in this tissue.76 A study conducted by Nikmehr et al., (2017), examined sperm parameters of SCI using rats’ model at acute as well as chronic phases. The result shows a fall in sperm count by half after one day and a third after three days post SCI. The severe decrease in sperm count was very significant in the acute phase, sperm motility was also decreased following SCI on acute as well as chronic phases compared to the control group.73 SCI, a neurogenic impair- ment, resulted to infertility by disturbing the plasma testos- terone balance which is very difficult to be restored by exogenous testosterone administration. SCI results in some alteration in oxidative markers, with the reduced free radical scavenging activities of GPx and SOD,77 as well as, increased MDA concentration and NLRP3 expression after SCI.75 Skeletal Muscle SCI makes paralysis and atrophy on the skeletal muscle, espe- cially the muscles controlled by the spinal cord below the level of the injury.78 Physiological examinations have shown many alterations in the properties of paralyzed muscles from patients with SCI, such as reduced mass area, high susceptibility to fatigue, decreased muscle cross-sectional area as well as the increased proportion of fast glycolytic muscular fibers.79 Mus- cular inflammation can be seen in the acute phase of SCI prior to muscular atrophy.80 In long period SCI, muscle atrophy is related with the remarkable elevation of inflammatory media- tors (such as IL-1β, IL-6, and TNF-α) as well as activation of NF-κB signaling,81 which is the main agent that regulates the inflammatory state in muscle atrophy.82 Bone Osteoporosis, which is defined as the loss of bone mineral density (BMD), is formed as a result of SCI.83 The distal femur, proximal tibia as well as distal boney sites at sub-lesional area are the major susceptible to BMD loss.84 The low level of BMD is increasing following SCI; as well the possibility of patients’ fracture is high,85 there are other various factors that contribute the pathogenesis of osteoporosis as a result of SCI. Apart from the deficiency in neuronal control, hormonal regulation as well as vascular function,86 the inflammatory microenvironment in bone brings about osteoclast differentiation as well as bone loss.87 Liver From the previous report, it was revealed that there are hepatic complications due to SCI.88 There are many reports that show liver dysfunction can be related to SCI, as the liver plays a sig- nificant role in the metabolic dysfunction usually seen in patients with SCI. Experimental research using animal model revealed that SCI activates macrophage activation, neutrophil infiltration, expression of pro-inflammatory cytokines as well as chemokines in the liver.89 This inflammation occurs imme- diately following the injury,90 and its severity is related to the level of injury.91 A significant amount of accumulated lipid has been seen in rodent liver after SCI.92 Given the pro- inflammatory as well as cytotoxic effects of myelin-laden macrophage related to the accumulation of lipid in the SCI,93 macrophage-mediated inflammation considerably leads to hepatic dysfunction following SCI. Spleen Spleen is a very vital lymphoid organ functioned for infiltra- tion of monocytes in the injured spinal cord; spleen is inner- vated by the autonomic nervous system and regulated by the high thoracic spinal cord. A research using rat model has shown a significant spleen dysfunction due to SCI at the T3 level. Spleen dysfunction as a result of SCI at T3 level was revealed by splenic atrophy with decrease in size, decrease in the amount of splenic leukocyte and increased splenic norepi- nephrine was seen.94,95 SCI mice induced with viral infection revealed impaired immune responses as well as decreased survival, and these results seen in mice were related with defi- cient CD4+ and CD8+ T cell functions, deficient primary anti- body response as well as suppressed activation of macrophages.96 This indicates that dysfunction of the spleen may possibly result in immune suppression in patients with SCI. Remarkably; post-SCI mRNA levels of pro-inflammatory cytokines IL-17, as well as IL-23, were seen upregulated in tissue spleen of rat model by STAT3 signaling,97 consequently, crosstalk between spleen and SCI could be mediated by neuroinflammation. Gastrointestinal Tract There are many complications occurred due to SCI in the gas- trointestinal tract (GIT), for example, severe constipation, dif- ficulty with evacuation, painful defecation or incontinence, is advisable to restrict and limit the diet and outdoor activities of SCI patients.98 Despite the fact that function of GIT is basically regulated by its own intrinsic nervous system as well as auto- nomic control by the brainstem, SCI may cause the destruc- tion of neuronal control of GIT sensory as well as motor functions, leading to neurogenic bowel dysfunction (NBD). It was estimated that 50% of SCI patients are having moderate to severe NBD,99 it appears that abnormal bowel function has a more negative influence on the quality of life of patients with SCI.100,101 The clinical presentations of NBD with SCI are pro- longed bowel transit time; decrease colonic motility as well as anorectal dysfunction.102 Even though there is inflammation in colonic lesions of patients with SCI,103 the association between systemic inflammation as well as NBD is not well understood. A report from Guo et al., (2016) on rat model of NBD after SCI shows that upregulation of neuronal nitric oxide synthase leads to colonic dysfunction,104 thus creating inflammation as a possible target for reducing post-SCI NBD. Conclusion SCI leads to different complications in various parts of the body, most often, primary injury gives rise to secondary injury 269J Contemp Med Sci | Vol. 7, No. 5, September–October 2021: 264–271 I. Mohammed et al. Review Clinical Complications of Spinal Cord Injury that increases damage to the previously injured spinal cord. Among several processes of secondary injury phase, it seems inflammation is most important because it involves in many pathological problems. Therefore, suppression of inflammation maybe is a good target for degenerative diseases. Also, knowl- edge of possible complications by SCI is very vital because the complications may be life-threatening and may lead to pro- longing rehabilitation for SCI patients, also early detection and treatment of the complications will help in managing the patient. Even though there is no way to reverse damage to the spinal cord. But there are various researches continually working on new treatments, including transplanting stem cells and medications that may promote nerve cell regeneration or improve the function of nerves that remain after SCI. Conflicts of Interest None.  References 1. 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Spinal cord This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly. https://doi.org/10.22317/jcms.v7i5.1106