Chronic complications of spinal cord injury and disease

Authors: Gary M Abrams, MD Marc Wakasa, MD

Section Editor Michael J Aminoff, MD, DSc
Deputy Editor: Janet L Wilterdink, MD

Contributor Disclosures All topics are updated as new evidence becomes available and
our peer review process is complete.

Literature review current through: Aug 2017. | This topic last updated: Jul 15, 2014.

INTRODUCTION — Spinal cord injury (SCI) is a common event; in the United States,

the incidence of traumatic SCI is about 40 per million persons per year, with
approximately 250,000 living survivors of traumatic SCI in July 2005 [1]. The
prevalence of nontraumatic SCI is unknown, but it is estimated that it is three to four
times greater than traumatic SCI [2]. SCI produces a wide variety of changes in
systemic physiology that can lead to a number of complications, which rival the
neurologic deficits in their impact on function and quality of life.

Medical complications after SCI are both common and severe. In the Model Spinal
Cord Injury Systems Database, rehospitalizations occurred in 55 percent of patients in
the first year after SCI and continued at a stable rate of about 37 percent per year over
the next 20 years [3]. Genitourinary and respiratory complications and pressure ulcers
were the most common reasons for hospitalization. Increased patient age and severity of
the spinal cord lesion also impacted on the risk of complications requiring
hospitalization.

This topic reviews the management of common complications of chronic SCI, whether
due to trauma or other conditions. Acute manifestations and complications of SCI are
presented separately. (See "Acute traumatic spinal cord injury" and "Disorders affecting
the spinal cord".)

LIFE EXPECTANCY — Life expectancy is reduced among survivors of spinal cord

injury (SCI). Mortality rates are highest in the first year. For patients surviving at least
one year after traumatic SCI, life expectancy is approximately 90 percent of normal
[1,4,5]. Higher neurologic level and severity of injury and older age at the time of SCI
negatively impact survival.

The most common causes of death after traumatic SCI are diseases of the respiratory
system followed by cardiovascular events [1,4]. In earlier decades (prior to 1972),
urinary complications were the leading cause of death. The risk of suicide is also
increased among patients with SCI [5]. (See 'Psychiatric complications' below.)

CARDIOVASCULAR COMPLICATIONS

Autonomic dysreflexia — Spinal cord injuries (SCI) above T6 may be complicated by a

phenomenon known as autonomic dysreflexia, a manifestation of the loss of coordinated
autonomic responses to demands on heart rate and vascular tone [6,7]. Uninhibited or
exaggerated sympathetic responses to noxious stimuli below the level of the injury lead
to diffuse vasoconstriction and hypertension. A compensatory parasympathetic response
produces bradycardia and vasodilation above the level of the lesion, but this is not
sufficient to reduce elevated blood pressure. SCI lesions lower than T6 do not produce
this complication, because intact splanchnic innervation allows for compensatory
dilatation of the splanchnic vascular bed.

The estimated frequency of this complication is quite variable, ranging from 20 to 70

percent of patients with SCI lesions above T6 [6,7]. Autonomic dysreflexia is unusual
within the first month of SCI but usually appears within the first year [8,9].

Typical stimuli include bladder distention, bowel impaction, pressure sores, bone
fracture, or occult visceral disturbances [6,7]. Sexual activity can be a trigger.
Autonomic dysreflexia can also complicate medical procedures, as well as labor and
delivery. (See "Neurologic disorders complicating pregnancy", section on 'Spinal cord
injury'.)

Common clinical manifestations are headache, diaphoresis, and increased blood

pressure [8]. Flushing, piloerection, blurred vision, nasal obstruction, anxiety, and
nausea may also occur. Bradycardia is common; however, some patients have
tachycardia instead. The severity of attacks ranges from asymptomatic hypertension to
hypertensive crisis complicated by profound bradycardia and cardiac arrest or
intracranial hemorrhage and seizures. The severity of the SCI influences both the
frequency and severity of attacks.

Management of acute attacks includes [6,8]:

●Measuring and monitoring blood pressure.

●Immediately sitting the patient upright to orthostatically lower blood pressure.

●Removal of tight-fitting garments.

●Searching for and correcting noxious inciting stimuli. Bladder distension and fecal
impaction are the most common precipitants. Bladder catheterization and evaluation for
urinary tract infection should be undertaken; indwelling catheters should be checked for
obstruction, and a rectal examination should be performed.

●Prompt reduction of blood pressure with a rapid-onset/short-duration agent, depending

on the severity of attack and response to above measures. Medications often used in this
setting include nitrates (1 inch, 2 percent nitropaste), nifedipine (10 mg PO or SL),
sublingual captopril (25 mg), intravenous hydralazine (10 mg), and intravenous
labetalol (10 mg). Nitrates should be avoided in patients who may be using sildenafil for
erectile dysfunction.

Recognition and avoidance of inciting stimuli are important in preventing attacks.

Nifedipine, prazosin, and terazosin have been reported to prevent an attack when
administered prophylactically [6,7,10-12].

Coronary artery disease — With improved long-term survival, coronary artery disease

(CAD) has become an increasingly important complication in SCI [4]. CAD risk
factors, such as adverse lipid profile (low levels of high-density lipoproteins, elevated
low-density lipoprotein cholesterol) and abnormal glucose metabolism (impaired
glucose tolerance, insulin resistance, and diabetes) are more prevalent in chronic SCI
patients than the able-bodied population [13]. Factors that contribute to the development
of these disorders include decreased muscle mass, increased fat, and inactivity [14].
Studies suggest that the prevalence of CAD is 3 to 10 times higher in SCI patients
compared with the general population [13]. In addition, a nation-wide cohort study in
Taiwan found that SCI was associated with an increased risk of stroke (HR = 2.9) [15].

CAD mortality also appears to be higher among SCI patients [4]. One contributing
factor may be that SCI lesions above the T5 level may lead to atypical presentations for
cardiac ischemia; manifestations may include autonomic dysreflexia or changes in
spasticity rather than typical chest pain.

Risk factor management and treatment for CAD are similar to that of able-bodied
individuals. (See "Overview of established risk factors for cardiovascular disease".)

Exercise options for SCI patients include hand-crank ergometry, hand cycling,
swimming, and functional electrical stimulation of muscles [16]. Body weight-
supported treadmill training has been reported to improve glucose regulation in
incomplete SCI [17]. However, diminished sympathetic responses, reduced cardiac
output, impaired ventilation, and decreased muscle mass lead to reduced exercise
capacity in chronic SCI [13]. Physiologic responses to exercise, including increased
heart rate, increased cardiac contractility, and vasoregulation, are also impaired with
higher-level SCI.

Others — The autonomic nervous system dysfunction that results from SCI disrupts
normal cardiovascular homeostasis. With SCI above the T6 level, baseline blood
pressure is usually reduced, and baseline heart rate may be as low as 50 to 60 beats per
minute [13,18]. This is generally not a clinical problem, but may contribute to
hemodynamic instability and exercise intolerance.

Orthostatic hypotension due to peripheral vasodilatation is more common in the first

several months of SCI and tends to dissipate with the development of muscle tone in the
lower extremities [8]. However, it may also occur in chronic SCI, especially with
excessive bed rest and diminished fluid intake. Gradual position changes, compression
stockings, and abdominal binders decrease venous pooling and may improve orthostatic
tolerance. Occasionally, increased salt intake, alpha adrenergic agonists (midodrine), or
mineralocorticoid agents (fludrocortisone) may be required. (See "Treatment of
orthostatic and postprandial hypotension".)

Acute cervical SCI is associated with a risk of cardiac arrhythmia due to excess vagal
tone, as well as complicating hypoxia, hypotension, and fluid and electrolyte
imbalances. Arrhythmias are much less frequent in chronic SCI. However, patients with
complete cervical SCI appear to have an ongoing risk of cardiopulmonary arrest
[19,20].

PULMONARY COMPLICATIONS — Cervical and high thoracic spinal cord injury

(SCI) affect respiratory muscles. The severity of ventilatory failure and requirement for
assisted ventilation depends on the level and severity of the SCI. Lesser degrees of
ventilatory failure may produce dyspnea and exercise intolerance. (See "Respiratory
physiologic changes following spinal cord injury" and "Respiratory complications in the
adult patient with chronic spinal cord injury", section on 'Respiratory insufficiency'.)

Because of impaired cough and difficulty mobilizing lung secretions, patients after SCI
are also at increased risk for pneumonia. Although the incidence of pneumonia is
highest in the first year following SCI, these patients remain at increased risk over their
lifetime [21]. Older patients are at higher risk than younger patients. Efforts to prevent
pneumonia include chest physiotherapy and vaccination. (See "Respiratory
complications in the adult patient with chronic spinal cord injury", section on
'Pulmonary infection'.)

Deep venous thrombosis and pulmonary embolism remain common early complications
of SCI despite advances in awareness and treatment. Prophylactic use of low-molecular-
weight heparin is the treatment of choice for most patients with SCI. While there are no
good clinical trial data to guide duration of treatment, we suggest that it should be
continued in paralyzed patients for at least three months after SCI, after which the risk
appears to approximate that of the general population [22]. Specific regimens are
discussed separately. (See "Prevention of venous thromboembolic disease in surgical
patients".)

URINARY COMPLICATIONS — Spinal cord injury (SCI) produces bladder

dysfunction, often referred to as the neurogenic bladder. Other complications can result
from this, including infections, vesicoureteral reflux, renal failure, and renal calculi.

Urologic evaluation with regular follow-up is recommended for all patients after SCI;
even ambulatory patients with SCI may have bladder dysfunction that can lead to
complications [23]. Complications such as vesicoureteral reflux, renal failure, and
nephrolithiasis may not produce symptoms, and if untreated, can have serious
consequences. The frequency and specific testing involved (serum creatinine,
cystoscopy, urodynamic studies, renal ultrasound) are not well defined but depend in
part on the nature of the patient's urologic problems and other risk factors [24,25].

Bladder dysfunction — SCI disrupts the two major functions of the bladder, storage and
emptying of urine. Bladder control is a complex activity requiring the coordinated
function of the cerebral cortex, pontine and sacral micturition centers, and peripheral
nervous system [26]. (See "Anatomy and localization of spinal cord disorders", section
on 'Autonomic fibers'.) In SCI, the sensation for bladder fullness as well as motor
control of bladder and sphincter function are impaired. Depending on the acuity, level,
and completeness of the spinal cord lesion, a number of problems can result:

●Bladder or detrusor hyperactivity produces reflexive bladder emptying. Patients may

be troubled by bladder spasms as well as urgency and frequency, often with
incontinence. Over time, this can lead to decreased capacity of the bladder.

●Sphincter hyperactivity can impair complete emptying of the bladder.

●Detrusor sphincter dyssynergia, a combination of detrusor and sphincter hyperactivity,

can lead to bladder contractions against a closed sphincter, leading to elevated bladder
pressures and vesicoureteral reflux.
●Bladder flaccidity is produced in lower motor neuron injuries affecting the cauda
equina or conus medullaris as well as with acute upper motor neuron injuries (spinal
shock). This leads to chronic urinary retention with overflow incontinence and
incomplete emptying.

Most patients with incomplete SCI and all patients with complete SCI, regardless of the
level of the lesion, require assistance with bladder function [21]. Although there are no
clinical trials that guide the long-term management of bladder dysfunction in SCI,
accumulated clinical experience has led to some management strategies [27,28]. The
efficacy of these approaches may be manifest by the declining incidence of urinary
tract-related morbidity and mortality in SCI patients [4,21].

The goal of a SCI bladder program is to preserve renal function while eliminating urine
at regular and socially acceptable times, avoiding high bladder pressures, retention,
incontinence, and infection. This should begin as early as possible after SCI, with
removal of the indwelling Foley catheter.

Clean technique intermittent catheterization (CIC) has a lower infection rate compared
with the use of indwelling catheters [21]. CIC is performed at regular intervals, usually
every four hours. A bladder volume of less than 500 cc of urine is targeted in order to
avoid bladder distention, excessive intravesicular pressure, and reflux, as well as to
reduce the incidence of infections. The timing of CIC and the amount of fluid intake is
adjusted to reach this goal. A fluid intake restriction of two liters a day is common for
patients with SCI. If present, a sensation of fullness and attempt at voluntary voiding is
encouraged prior to CIC, since some incompletely injured persons will regain normal
voiding function.

Intermittent urinary incontinence is expected. Condom catheters (for men) and adult
diapers are important short-term interventions. After ruling out an infection and
adjusting the frequency of CIC and fluid intake, medications are considered.
Urodynamic studies should be considered to assess physiology and guide
pharmacologic intervention [24]:

●Anticholinergic medications (eg, oxybutynin, tolterodine) decrease bladder tone,

suppress bladder contractions, and may reduce urinary frequency and incontinence.
Tricyclic antidepressants such as imipramine have the added side effect of increasing
urethral resistance tone.

●Alpha adrenergic medications (ephedrine and phenylpropanolamine) can increase

bladder storage in patients with pathologic relaxation of the sphincter.

●Cholinergic medications (bethanechol) may help complete bladder emptying in those

with hypotonic bladders.

●Alpha-blockers (eg, prazosin, terazosin) help sphincter relaxation, lowering bladder

pressures during contraction. These can be prescribed for treatment of detrusor sphincter
dyssynergia, but may aggravate hypotension.

Most patients are managed with a combination of CIC and oral anticholinergic
medications [29].
For patients unable to perform CIC and without available caregivers, a chronic
indwelling catheter may be necessary. This is associated with an increased risk of
urinary tract infection (UTI) compared with CIC [30]. The indwelling catheter is
changed every month to minimize infections. Oxybutynin chloride (5 mg bid) can
decrease catheter-induced bladder spasms. With indwelling catheters, there is an
increased risk of prostatitis, epididymitis, and urethral stricture. Suprapubic tube
placement can help minimize the risks of infection and stricture. A cystoscopy every
two years is recommended to monitor for the increased incidence of bladder cancer and
stone development [24].

Studies of detrusor injections of botulinum toxin A in patients with detrusor

hyperactivity suggest that this treatment is safe and highly effective in controlling
symptoms and improving quality of life [29,31-34]. However, the optimal dose has not
been determined and long-term efficacy is unknown. There have been no comparative
studies with anticholinergic agents [35]. The use of botulinum toxin for the treatment of
non-neurogenic lower urinary tract dysfunction is discussed separately. (See "Use of
botulinum toxin for treatment of non-neurogenic lower urinary tract conditions".)

Studies of implanted sacral nerve modulators show promise as a treatment for urinary
incontinence following SCI [36,37].

For patients with unsatisfactory response to medical and catheter management, other
treatments, bladder augmentation, urinary diversion, sphincterotomy, urethral stent, and
electrical implantation devices can be considered in selected cases [2,24].

Urinary tract infection — Urinary tract infections (UTI) are common in SCI, with an
incidence of 2.5 episodes per patient per year [38]. The urinary tract is the most frequent
source of septicemia in SCI patients and has a high mortality rate (15 percent) [38,39].
UTI is more common in women than men. Low-frequency and high-volume
catheterization increase the risk of UTI, as do indwelling catheters and assisted (as
opposed to self) intermittent catheterization [30,40,41].

Symptomatic UTI, as manifest by fever, autonomic dysreflexia, increased spasticity,

foul-smelling urine, incontinence, frequency, or dysuria, warrants prompt antibiotic
treatment to avoid septicemia and other complications. (See "Acute uncomplicated
cystitis and pyelonephritis in women" and "Acute uncomplicated cystitis and
pyelonephritis in men" and "Acute complicated cystitis and pyelonephritis".)

Asymptomatic UTIs are not generally treated; nor is there a role for routine use of
prophylactic antibiotics to prevent UTI in SCI patients, despite the fact that
asymptomatic bacteriuria is common after SCI and is associated with a higher risk of
symptomatic UTI [40]. A meta-analysis of published literature found that antibiotic
prophylaxis in patients with SCI reduced asymptomatic bacteriuria but not symptomatic
infections, and was associated with a twofold increase in the risk of drug-resistant
bacteria [42]. However, some individuals with recurrent UTI may benefit from
prophylactic antibiotic treatment, depending on the frequency and clinical severity of
the infections. In particular, the combination of frequent UTI and vesicoureteral reflux
is associated with a high risk of renal failure. (See "Recurrent urinary tract infection in
women".)
Other methods of reducing the incidence of UTI are under investigation and include
colonization of the urinary tract with inert bacterial strains [43]. Cranberry juice is
believed to reduce bacterial adherence to the uroepithelium and thereby prevent UTI
[44]. However, its efficacy is unproven, and the associated fluid and caloric intake may
be problematic in individuals with SCI. In two small clinical trials, a cranberry
supplement was found ineffective in reducing bacteriuria, pyuria, or UTI in patients
with SCI [45,46].

Urinary calculi — Calculi in the kidney, ureter, or bladder are increased after SCI,
especially in patients who have recurrent UTIs, indwelling catheters, and
immobilization hypercalciuria [21]. (See 'Bone metabolism' below.) Because of altered
bladder sensation, there may not be pain to alert the clinician to ureteral obstruction.
Other clinical symptoms such as increased limb spasticity and episodes of autonomic
dysreflexia should suggest this as a possible diagnosis (see 'Autonomic dysreflexia'
above).

The diagnosis and treatment of urinary calculi is discussed separately. (See "Diagnosis
and acute management of suspected nephrolithiasis in adults" and "Options in the
management of renal and ureteral stones in adults".)

Vesicoureteral reflux — Impaired function of the vesicoureteral insertion may result

from high bladder pressures and recurrent UTI. The estimated incidence of this
complication in SCI patients is as high as 25 percent [47,48]. Because persistent reflux
is associated with a higher risk of pyelonephritis and renal dysfunction, it represents a
treatment imperative. If reflux persists despite the use of anticholinergic drugs and
increased frequency of catheterization, placement of an indwelling catheter or a surgical
procedure may be necessary. The use of oxybutynin may reduce phasic increases in
bladder pressure caused by bladder spasms with an indwelling catheter [49].

Renal insufficiency — The cumulative incidence of renal insufficiency increases with

time since SCI and is as high as 25 percent at 20 years [21,50,51]. Indwelling urethral
catheters, vesicoureteral reflux, and advanced age are associated with the development
of renal failure.

SEXUAL DYSFUNCTION — Consequences of spinal cord injury (SCI) on sexual

function include decreased libido, impotence, and infertility [52].

●Male impotence occurs in 75 percent of patients with SCI [24]. Patients with complete
as opposed to incomplete injuries have the greatest incidence and severity of this
complication. There are a variety of treatment options for erectile dysfunction, including
medications, assistive devices, and surgically implanted prostheses. Sildenafil,
vardenafil, and tadalafil have documented efficacy in SCI, but are contraindicated (as
are other phosphodiesterase-5 inhibitors) if there is comorbid coronary artery disease
[53-58]. (See "Treatment of male sexual dysfunction".)

●The prevalence of male infertility in SCI is high as a consequence of erectile

dysfunction, ejaculatory dysfunction, and/or poor sperm quality [25,52]. In general,
male reproduction after SCI requires artificial insemination. (See "Evaluation of male
infertility" and "Treatment of male infertility".)
●Sexual responses in women may also be impaired after SCI, but ovulation and fertility
are generally unaffected [24,52]. The lower pregnancy rates among women with SCI as
compared with the general population are felt to reflect personal choice. Pregnancy in
women with SCI is generally categorized as high risk because of a high rate of
complications including infections and autonomic dysreflexia. This is discussed
separately. (See "Neurologic disorders complicating pregnancy", section on 'Spinal cord
injury'.)

GASTROINTESTINAL COMPLICATIONS — Bowel dysfunction is common and

disabling after spinal cord injury (SCI) and significantly affects functional and quality
of life outcomes [59-61]. A multi-dimensional program is frequently necessary to obtain
the best results [62].

Two patterns of bowel dysfunction may occur [63]. With injuries above the conus
medullaris, neural connections between the spinal cord and bowel are maintained,
resulting in hyperreflexic pelvic muscle contraction and inability to voluntarily relax the
external anal sphincter. This causes constipation and fecal retention. A lower motor
neuron or areflexic bowel occurs with injuries below the conus medullaris, leading to
slower transit, decreased sphincter tone, and constipation with frequent incontinence.

Because few studies have evaluated the management of this problem, recommendations
are based on clinical experience and expert opinion [63,64]. With a goal of predictable
and timely bowel evacuation that avoids fecal incontinence and impaction, a consistent,
structured regimen is integrated into the patient's lifestyle as early as possible after SCI,
using their preinjury bowel pattern as a guide [8,52]. A typical routine may begin at a
regular time point each day (eg, 30 minutes after a meal) with insertion of a chemical
stimulant rectal suppository. After several minutes, digital stimulation with slow, gentle
rotation of the finger for 15 to 60 seconds is repeated every 5 to 10 minutes, until stool
evacuation is complete. Abdominal massage, deep breathing, Valsalva maneuver, and
forward-leaning position may assist evacuation [62].

Oral bowel medications (stool softener, docusate sodium; bowel stimulants, senna and
bisacodyl; bulking agents, psyllium) are often used during the initial phase of
establishing a regular bowel pattern, and are then slowly eliminated [63]. Chronic use of
stimulant laxatives is associated with a number of side effects. (See "Management of
chronic constipation in adults", section on 'Other laxatives'.)

A regular diet is an important feature of the bowel program and should include adequate
fiber intake (30 g) and relatively lower amounts of dairy products and fat content [8,63].
Targets for fluid intake are often dictated by the patient's bladder status, but if possible,
should be high enough to produce 2 to 3 liters of urinary output each day.

If constipation or impaction develops, a trial of enemas, laxatives, or bulk-forming

agents may be considered [63]. Abdominal x-rays should be considered to screen for
evidence of obstruction. Diseases not related to the SCI, particularly colorectal cancer,
should be excluded. Prokinetic medications (eg, cisapride, metoclopramide) are
reserved for persistent, severe constipation that is unresponsive to modifications of the
bowel program [62]. Some patients with severe bowel dysfunction require a colostomy.
Uncontrolled observational studies suggest that regular transanal irrigation can reduce
constipation and fecal incontinence and improve quality of life in some patients with
chronic bowel dysfunction following SCI [65-67]. A new therapeutic technology, sacral
electrical stimulation, is under investigation and appears promising [62]. Details
regarding the treatment of constipation are discussed separately. (See "Management of
chronic constipation in adults".)

Hemorrhoids can be increased by the interventions (suppositories, enemas, digital

stimulation) commonly used in bowel programs for SCI. Treatment includes stool
softeners, minimizing trauma, topical anti-inflammatory creams, and suppositories.
Hemorrhoids causing persistent bleeding, pain, or autonomic dysreflexia warrant
surgical consultation. (See "Home and office treatment of symptomatic hemorrhoids".)

Serious abdominal complications (cholecystitis, upper gastrointestinal bleeding,

pancreatitis, or appendicitis) account for 10 percent of deaths following SCI, with the
most significant risks during the first few months after injury [18,68]. There is an
increased prevalence of gallstones in patients with chronic SCI, perhaps in relationship
to denervation [69]. Sensory deficits resulting from SCI contribute to a delay in
diagnosis and increased mortality associated with these complications. Vague or
nonspecific symptoms such as nausea, anorexia, or autonomic dysreflexia should raise
concern for occult abdominal processes [18].

The superior mesenteric artery syndrome is an unusual complication of SCI, usually in

patients with cervical cord injuries [70,71]. Weight loss leads to loss of the mesenteric
fat pad and compression of the duodenum by the superior mesenteric artery, leading to
symptoms of small bowel obstruction. (See "Superior mesenteric artery syndrome".)

BONE METABOLISM

Osteoporosis — After spinal cord injury (SCI), osteoporosis affects bones below the
level of the injury and increases the risk of lower extremity fractures. In one series of 41
men, after a median of 15 years after SCI, 61 percent had osteoporosis and 34 percent
had had a fracture [72].

The pathogenesis of osteoporosis is unknown; neural factors as well as disuse are

believed to play a role [73]. Biomarkers of bone resorption are increased, beginning as
early as the first week after injury, while markers of bone formation are normal or only
minimally elevated [73,74]. Some studies suggest that about two years after SCI, a new
steady state level between bone resorption and formation is reestablished [73]. Older
age, higher spinal level of injury, lesser degrees of spasticity, and longer chronicity of
the injury have been inconsistently associated with higher degrees of observed bone loss
[21,73-77]. Rates of osteoporosis among men and premenopausal women with SCI are
similar; too few postmenopausal women with SCI have been included in studies to
know whether this population is at additional risk [25].

Occasionally, symptomatic hypercalcemia and hypercalciuria complicate early

resorption of bone mass within the first few months of SCI [8]. Manifestations can
include nausea, vomiting, anorexia, lethargy, and polyuria. There is an increased risk of
nephrolithiasis [74]. Treatment is graded to severity of symptoms. Intravenous
pamidronate has been used for acute immobilization hypercalcemia after SCI [78,79].
(See "Clinical manifestations of hypercalcemia" and "Treatment of hypercalcemia".)
Over time, patients with SCI develop a specific pattern of bone abnormalities, with
marked loss of bone density in the proximal tibia and femur, and relatively less bone
loss in the spine [75,80]. The impact of weight-bearing on the spine during sitting and
wheelchair use may contribute to this discrepancy [74]. Patients with quadriparesis may
also experience bone loss in the distal forearm [77].

In small observational and open-label, randomized studies, treatment with

bisphosphonates such as tiludronate, etidronate, pamidronate, and alendronate has been
shown to attenuate bone loss in patients with SCI [81-84]. In one small, double-blind,
randomized trial (31 patients), alendronate (70 mg weekly) was also shown to prevent
bone loss at the hip when administered within 10 days of acute SCI [85]. Functional
electrical stimulation has shown minimal and largely unsustained benefits in improving
bone density [74,86-88].

Heterotopic ossification — Heterotopic ossification refers to the deposition of bone

within the soft tissue around peripheral joints. This occurs in up to half of SCI patients,
beginning at a mean of 12 weeks after injury [89]. Although heterotopic ossification is
common after SCI, only 10 to 20 percent of patients have clinical symptoms, with
decreased range of motion and inflammatory symptoms in the affected joints. The large
joints below the level of injury are typically affected, most commonly the hip. The
pathogenesis of this phenomenon is incompletely understood, but it is believed to
originate from osteoprogenitor stem cells lying dormant within the affected soft tissues.
With the proper stimulus (as with hip surgery, spinal cord injury, and stroke), these stem
cells may differentiate into osteoblasts that form osteoid and eventually bone.
Heterotopic ossification in the setting of total hip arthroplasty is discussed separately. In
one case-control study of SCI patients, heterotopic ossification was more common in
patients with complete spinal cord lesions, more rostral injuries, and also in those with
associated thoracic trauma [90]. (See "Complications of total hip arthroplasty", section
on 'Heterotopic ossification'.)

Deep venous thrombosis, cellulitis, infection, hematoma, and tumor should be

considered as alternative diagnoses for localized pain in SCI patients. Because
calcification may not appear for weeks after clinical presentation, plain radiographs are
of limited use in the early diagnosis. An elevated serum alkaline phosphatase level can
help differentiate early heterotopic ossification from other conditions, but is not a
specific finding [91]. The triple phase bone scan is the most reliable test for diagnosis.

Early administration of NSAIDs (indomethacin 75 mg daily for three weeks or

rofecoxib 25 mg daily for four weeks) after SCI appears to reduce the incidence of
heterotopic calcification according to a 2010 systematic review that included two
randomized trials [92-94]. Further research is required to identify which patients will
benefit from this intervention. Warfarin and pulse low-intensity electromagnetic field
therapy may also be useful in the prevention of heterotopic ossification, but a clinical
role for these modalities for this indication is not yet established.

The initial treatments of heterotopic ossification are passive range-of-motion exercise,

with the goal of maintaining joint mobility, and nonsteroidal anti-inflammatory drugs
(NSAIDS). Bisphosphonates may also be useful [92]. According to uncontrolled case
series, etidronate (given intravenous for three days, followed by six months of oral
therapy) reduced swelling and retarded or halted progression of heterotopic ossification,
particularly if it was administered early, when bone scans were positive, but radiographs
remained normal [92,95-97]. Radiotherapy also appeared to limit progression in one
case series of 52 patients with heterotopic ossification after SCI [92,98]. For refractory
cases, surgery is a treatment option to allow functional range of movement; however,
the majority of patients experience recurrence after surgery [99]. A small retrospective
study found that intravenous pamidronate (a bisphosphonate) prevented recurrent
heterotopic ossification in patients undergoing excision surgery [89]. Reports of early
resection in combination with drug and radiation treatment also appear promising
[100,101].

MUSCULOSKELETAL COMPLICATIONS — After spinal cord injury (SCI), muscle

contractures can result from reorganization of the collagen tissue matrix that occurs
when the muscle lies in the shortened position for an extended period of time. Both
immobility and spasticity contribute to this occurrence [102]. Preventive management is
extremely important and should begin immediately after a SCI and continue for long-
term care:

●Positioning. While in bed, the patient should be positioned, using pillows to minimize
flexion at the hip and knee, and adduction and internal rotation at the shoulder.
Wheelchair positioning should maintain normal lumbar lordosis. Frequent repositioning
prevents skin breakdown as well as contractures; these complications often co-exist
[102].

●Range-of-motion exercise. Paretic extremity joints should be exercised 5 to 20 minutes

daily. The intensity of exercises needed to prevent deformity varies among individuals,
but the goal is maintenance of full range. Any limitation warrants investigation for
heterotopic ossification, fracture, hematoma, infection, or thrombosis.

●Splinting. Upper extremity flexion contractures and ankle plantar-flexion contractures

can be prevented with resting night splints or bivalve (removable) casting. The fitting
and timing of splints must be adjusted based on skin and pain tolerance.

The goal of these interventions is to induce prolonged muscle stretching of vulnerable

muscles; however, their efficacy in preventing contractures has not been documented
[103]. Established contractures may require surgical treatment.

Certain contractures can facilitate function. Patients with SCI at C6 level may gain
improved functional hand tenodesis with finger flexion contractures that enhance
prehension with wrist extension. A slight elbow flexion contracture can improve the
mechanical advantage of a weakened biceps muscle.

Repetitive over-use injuries in the upper extremities are common in SCI patients, related
to transfers and wheelchair use. Rotator cuff and other tendon injuries, carpal tunnel
syndrome, bursitis, and osteoarthritis are common sequelae [104-106]. The shoulders
are most often affected (75 percent), followed by wrists, hands, and elbows (53, 43, and
35 percent, respectively). Specific exercise programs to minimize injuries and preserve
joint function can be helpful, as can the use of power wheelchairs and ergonomic
assessments [107]. (See "Overview of joint protection".)
PRESSURE ULCERS — Pressure ulcers result from tissue damage due to unrelieved
pressure that typically occurs over bony prominences. Shear, friction, poor nutrition,
and changes in skin physiology below the level of the lesion also contribute to the
development of pressure ulcers [21]. Prevalence rates for pressure ulcers in chronic
spinal cord injury (SCI) are difficult to obtain, but have been estimated at approximately
30 percent at 20 years following SCI [21,108]. Both the level and severity of SCI
impact significantly on the risk of developing a pressure ulcer.

Multiple pressure ulcers occur in more than one-third of patients [20]. The most
common locations of pressure ulcers in the SCI patient are [21]:

●Ischium – 31 percent

●Trochanter - 26 percent

●Sacrum - 18 percent

●Heel - 5 percent

●Malleolus - 4 percent

●Feet - 2 percent

Preventative strategies include:

●Examining skin over areas most vulnerable to ulcer formation daily

●Avoiding immobility and excess moisture in susceptible regions

●Use of pressure-relieving wheelchairs, cushions, and other devices

●Maintenance of adequate nutritional intake and weight

Comprehensive treatment includes assessment of health status and status of the ulcer.
An ulcer treatment plan consists of cleansing, debridement, nutritional support, and
management of tissue loads. The prevention and treatment of pressure ulcers are
discussed in detail separately. (See "Prevention of pressure-induced skin and soft tissue
injury" and "Clinical staging and management of pressure-induced skin and soft tissue
injury".)

SPASTICITY — Spasticity is believed to result from disruption of descending

inhibitory modulation of the alpha motor neurons, producing hyperexcitability, which is
manifest as increased muscle tone and spasms [109,110]. Negative effects of spasticity
include pain, decreased mobility, contractures, and muscle spasms, all of which can
interfere with sleep and activities of daily living. At the same time, spasticity has some
positive aspects: increased tone can facilitate some functional activities, including
standing and transfers. Increased muscle tone may also promote venous return,
minimizing deep venous thrombosis and orthostatic hypotension.
Abolishing spasticity is difficult and not necessarily desirable [110]. Treatment should
be directed at minimizing spasticity as it relates to functional impairment and should
follow a graded approach, starting with the least invasive approach. Nonpharmacologic
treatments include physical therapy. Regular stretching and use of braces can help
maintain range of movement and prevent contractures [110]. (See 'Musculoskeletal
complications' above.)

Oral medications — Though often prescribed for spasticity, the evidence of efficacy for
commonly used oral medications is not substantial, side effects are often dose limiting,
and the relative benefit of these treatments has not been established [111]. With all
medications, slow dose escalation may mitigate against adverse side effects, which
include sedation, dry mouth, dizziness, and weakness. Dosing guidelines and adverse
effects of these medications are summarized in the Table (table 1).

●Baclofen, a GABA-B agonist, is the most commonly used oral medication for
spasticity, despite the paucity of evidence-based support for its efficacy [111-113].
Although adverse effects of sedation and weakness can be dose-limiting, baclofen is
safe for long-term use, without evidence of tolerance [110]. Abrupt discontinuation of
baclofen is advised against because of potential withdrawal symptoms. (See
"Neuroleptic malignant syndrome", section on 'Other drug-related syndromes'.)

●Tizanidine, a centrally acting alpha-2 adrenergic agonist, was compared with placebo
in one of the largest studies of spasticity treatment in spinal cord injury (SCI) patients
[114]. Among the 78 of 124 randomized patients who completed the study, tizanidine
produced a significant reduction in spasticity, but had no effect on activities of daily
living and other functional assessments. Sedation was the most common limiting side
effect [115].

●Diazepam, a GABA-A agonist, is the most commonly used benzodiazepine for

spasticity, often in conjunction with baclofen or tizanidine [109,116]. Sedation,
confusion, hypotension, and gastrointestinal symptoms can be dose-limiting. Diazepam
or clonazepam may be particularly useful in controlling nighttime spasms.

●Dantrolene sodium differs from other medications discussed in that it acts

peripherally, inhibiting calcium release from sarcoplasmic reticulum of the muscle
[110]. More than the other agents used, it produces weakness of both affected and
unaffected muscles [113]. Its potential for hepatotoxicity requires liver function test
monitoring every three to six months [109].

●Less commonly used oral medications used for spasticity include clonidine,
gabapentin, cannabinoids, and cyproheptadine (table 1) [109,110,117-119].

Intrathecal baclofen — Baclofen is centrally acting, but crosses the blood brain barrier
ineffectively, limiting its bioavailability when taken orally. Intrathecal baclofen allows
for four-times the amount of baclofen to be delivered to the spinal cord with 1 percent
of the oral dose [18,110]. Treatment is administered by a surgically implanted,
computer-programmed infusion pump with a catheter extending into the intrathecal
space. In general, patients undergo a trial of intrathecal baclofen infusions prior to pump
implantation. Although systemic side effects of baclofen are generally avoided with this
approach, complications of intrathecal baclofen therapy can include spinal fluid leaks,
hemorrhage, infection, catheter dislodgement, and pump failure.

Two double-blind crossover studies compared intrathecal baclofen infusion with saline
placebo in patients after SCI [120,121]. Patients treated with intrathecal baclofen had
both reduced spasticity and improved disability. This approach may also reduce pain
associated with spasticity [122].

Injection techniques — Chemodenervation provides a localized treatment of spasticity

within a muscle or muscle group. Although systemic side effects associated with
medications are avoided, the large number of muscles involved in SCI limit the use of
this approach for these patients. However, in some patients, targeted relief of spasticity
in certain muscle groups can improve ambulation and other specific functions. Agents
include botulinum toxin, phenol, and alcohol.

Botulinum toxin acts at the neuromuscular junction, preventing acetylcholine release.

Treatment effects last a few months, requiring repeated injections. Side effects include
muscle weakness and injection-site reactions, but in general this treatment is safe and
effective [123]. One randomized study compared botulinum toxin injections to
tizanidine for upper limb spasticity following stroke or traumatic brain injury [115].
Botulinum toxin treatments were more effective in reducing tone and were associated
with fewer adverse effects than tizanidine. However, spasticity is not as yet an FDA-
approved indication for botulinum toxin.

The US Food and Drug Administration has issued a warning about the possibility of
life-threatening systemic adverse effects from local botulinum toxin injections. The
warning was based on reports of severe difficulty swallowing or breathing in several
patients and occurred mostly in children with cerebral palsy receiving local injections
for limb spasticity. Some of these complications appear be caused by inadvertent
overdosing, because potency determinations expressed in "units" varied among
botulinum toxin products. In response, the FDA mandated changes in drug names that
were designed to emphasize these differences in drug potency and prevent medication
errors [124]. Providers should be alert for the potential of systemic effects, including
dysphagia, dysphonia, weakness, or dyspnea, occurring up to several weeks after
treatment.

Phenol and ethanol nerve blocks essentially superimpose a lower motor neuron lesion
on the upper motor neuron deficit [109,110]. Weakness, injection site pain, phlebitis,
permanent nerve damage, and sensory dysesthesia can be problematic complications of
this procedure.

Surgery — Surgical destructive procedures, rhizotomy, myelotomy, cordotomy, and

cordectomy are reserved for refractory cases [18]. Orthopedic procedures involving the
muscle or tendon can be used to treat established contractures.

PAIN SYNDROMES — A significant number of patients develop a chronic pain

syndrome several months to years after spinal cord injury (SCI). Reported prevalences
vary considerably. On average, two-thirds of patients suffer chronic pain and about one-
quarter to one-third of patients have severe pain that significantly affects quality of life
[113,125].
Neurogenic pain after SCI can be both spontaneous and stimulus-evoked, is often
poorly localized, and is often described as burning, stabbing, or electrical in quality.
Hyperesthesia is a common component. These qualities can help distinguish neurogenic
from musculoskeletal pain (usually dull, aching, and well-localized) that can result from
a number of complications common to SCI patients. (See 'Musculoskeletal
complications' above.)

Although neurogenic pain appears to be associated with neuronal hyperexcitability,

mechanisms are poorly understood. Two types of neurogenic pain syndromes are
recognized: at-level pain (ie, pain in segments at the level of SCI) and below-level pain.
These are believed to have different neuroanatomic and pathophysiologic bases, with
injury to nerve roots and dorsal gray matter causing at-level pain, and injury to
spinothalamic tracts and/or thalamic deafferentation responsible for below-level pain
[126]. Development of at-level pain should provoke an evaluation for post-traumatic
syringomyelia, with which it is associated. (See 'Syringomyelia' below.)

Medical treatments are often unsatisfactory; antidepressant, antiepileptic, and standard

analgesic medications are tried, often in combination:

●Antiepileptic drugs are believed to improve neuropathic pain by suppressing abnormal

neuronal hyperexcitability. Two randomized studies of pregabalin (150 to 600 mg daily)
in patients with pain after SCI have reported improvements in blinded assessments of
pain scores, as well as in disturbed sleep, anxiety, and depression [127,128].  Other
randomized trials have studied lamotrigine, gabapentin, valproate in SCI; with mixed
evidence of efficacy [129-132].

●Antidepressant medications are also used in a variety of central and peripheral

neuropathic pain syndromes. Randomized trials of trazodone and amitriptyline in SCI
have not demonstrated efficacy [132-134].

●Opiates may provide relief in anecdotal reports, but side effects, tolerance, and
dependence are significant issues [135].

It is reasonable to believe that non-oral routes of administration may provide better

efficacy with fewer side effects; however, evidence supporting these therapies is
somewhat limited in SCI. Therapies have included intrathecal administration of
morphine, clonidine, and baclofen [136,137].

Invasive treatments, including deep brain stimulation, motor cortex stimulation,

cordotomy, and dorsal root entry zone lesions have been tried, again without substantive
evidence of success [113,138]. In the absence of good therapies, it is not unreasonable
to also consider nontraditional treatments such as acupuncture and biofeedback [18].

Details regarding dosing regimens, side effects, and other aspects of chronic pain
management are discussed separately. (See "Overview of the treatment of chronic non-
cancer pain".)

NEUROLOGIC DETERIORATION
Syringomyelia — A delayed progressive intramedullary cystic degeneration
complicates 3 to 4 percent of traumatic spinal cord injury (SCI) as well as other acute
myelopathies. The interval since SCI can vary from several months to many years
[139]. Postulated mechanisms include scarring with obstruction of CSF flow and altered
tissue compliance leading to expansion of the central canal and compression of
surrounding cord tissue [140]. Symptoms are consistent with a progressive myelopathy
and include worsening motor, sensory, bowel, and bladder deficits and pain [139].
Arachnoiditis, cord compression and/or a narrowed spinal canal, and bony deformity,
especially kyphosis, seem to be risk factors for progressive enlargement of the cyst and
neurologic deterioration [141-144].

An asymptomatic syrinx is a common incidental finding on neuroimaging in SCI

patients. This entity usually has a benign prognosis, and likely represents a focal area of
liquefaction necrosis of cord tissue.

Treatment is aimed at reducing expansile intracystic pressure and improving CSF flow
[139]. Surgical approaches include shunt placement, lysis of subarachnoid adhesions,
cyst fenestration, and dural augmentation. Extradural decompression is anecdotally
reported to be helpful when there is significant bone deformity and compression of the
spinal canal with restriction of spinal fluid circulation [145,146]. Unfortunately, long-
term treatment benefits are seen in less than half of patients, and shunt failure is
common [146,147]. Pain may be more responsive to intervention than are motor
symptoms [148,149].

Progressive posttraumatic myelomalacic myelopathy — Also known as the marshy cord

syndrome, progressive posttraumatic myelomalacic myelopathy is a less frequent
complication of SCI and is characterized pathologically by microcysts, reactive gliosis,
and meningeal thickening. Adhesions and cord tethering appear to be causally related;
surgical untethering and duraplasty with expansion of the subarachnoid space can lead
to clinical improvement [139,150].

PSYCHIATRIC COMPLICATIONS — Psychosocial complications associated with

spinal cord injury (SCI) include depression, suicide, drug addiction, and divorce [5,8].

Between 20 to 45 percent of patients are depressed after traumatic SCI [8,151]. This
symptom often emerges early on, within the first month after SCI, and is not closely tied
to the severity of injury. Patients with SCI have a four to five times higher rate of
suicide compared to age-matched population samples [5,152]. Suicide is a leading cause
of death in traumatic SCI patients younger than 55 years; 75 percent of suicides occur
within the first five years of injury [8]. Similar rates of depression and suicide are
observed after transverse myelitis [153].

Because of its high prevalence and serious consequences, patients with SCI should be
regularly screened for symptoms of depression. High levels of pain and lack of social
support identify patients at high risk for depression and suicidality [151].

Depression and anxiety following SCI should be treated; it should not be assumed that
symptoms are a "normal" reaction to the circumstances and do not require treatment [8].
Recommended interventions include psychologic counseling, pharmacologic
intervention, and peer support groups. (See "Unipolar depression in adults: Assessment
and diagnosis" and "Unipolar major depression in adults: Choosing initial treatment".)

THERMOREGULATORY DYSFUNCTION — Disrupted autonomic pathways

following spinal cord injury (SCI) can lead to impaired vasomotor and sudomotor
responses in regions of insensate skin, reduced thermoregulatory effector response for a
given core temperature, and loss of skeletal muscle pump activity from paralyzed limbs
[154]. Consequences can include hyperthermia during exercise or high ambient heat and
hypothermia in lower ambient heat. There can be a blunted fever or a hypothermic
response to infection. Others have noted episodes of hyperthermia or hypothermia in the
absence of infection or environmental temperature change in SCI patients.

FUNCTIONAL DEFICITS — The level and completeness of the spinal cord injury

(SCI) are the principal determinants of the needs, goals, and expectations in functional
abilities. Age, general health, body habitus, concurrent injuries, spinal instrumentation,
intelligence, and motivation also influence recovery [155].

Functional recovery after a SCI begins in the acute care setting as soon as the patient is
medically stable with range-of-motion and resistive exercise, upright positioning, and
transfer work. In the inpatient rehabilitation setting, physical and occupational therapists
experienced in SCI rehabilitation develop individualized programs that emphasize
strengthening, joint protection, and compensatory strategies, combined with creative use
of assistive devices and equipment to maximize function. There are no studies that
suggest one form of therapy is more effective than another; despite evolving
technological advances, the simplest traditional approaches are often the best [156,157].

The general expectations for functional recovery based on motor level are outlined in
the Table (table 2) [158]. These assume an uncomplicated, complete SCI followed by
appropriate rehabilitation interventions in a healthy, motivated individual.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces
are written in plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10 th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on “patient info” and the keyword(s) of
interest.)

●Basics topics (see "Patient education: Neurogenic bladder in adults (The Basics)" and
"Patient education: Paraplegia and quadriplegia (The Basics)")
SUMMARY AND RECOMMENDATIONS — Medical complications after spinal cord
injury (SCI) are both common and severe, contributing to a high rehospitalization rate
and decreased life expectancy. (See 'Life expectancy' above.)

●Autonomic dysreflexia can complicate SCI above T6. This is an exaggerated

sympathetic response characterized by headache, diaphoresis, and increased blood
pressure that occurs with noxious stimuli such as pain from bladder distension,
constipation, or pressure sores. (See 'Autonomic dysreflexia' above.)

●Patients with SCI also have an increased incidence of CAD. Hemodynamic instability
and cardiac arrhythmias can be problematic in the acute and subacute SCI and are less
frequent problems in chronic SCI. (See 'Cardiovascular complications' above.)

●The severity of ventilatory failure and requirement for assisted ventilation depends on
the level and severity of the SCI. Lesser degrees of ventilatory failure may produce
dyspnea and exercise intolerance. (See "Respiratory physiologic changes following
spinal cord injury" and "Respiratory complications in the adult patient with chronic
spinal cord injury", section on 'Respiratory insufficiency'.)

●An increase risk of pneumonia is highest in the first year following SCI, but patients
remain at increased risk over their lifetime. (See "Respiratory complications in the adult
patient with chronic spinal cord injury", section on 'Pulmonary infection'.)

●Prophylactic use of low-molecular-weight heparin to prevent deep venous thrombosis

and pulmonary embolism should be continued for at least three months after SCI, after
which the risk appears to approximate that of the general population. (See "Prevention
of venous thromboembolic disease in surgical patients".)

●SCI produces bladder dysfunction, often referred to as the neurogenic bladder. Other
complications can result from this, including infections, vesicoureteral reflux, renal
failure, and renal calculi. Clean intermittent catheterization, supplemented by
medications as needed is the usual initial treatment. Some patients require a chronic
indwelling catheter. Botulinum toxin and sacral nerve modulators are being investigated
as alternative treatment options. (See 'Urinary complications' above.)

●Sexual dysfunction after SCI can include decreased libido, impotence, and infertility.
Erectile dysfunction may respond to treatment with a phosphodiesterase-5 inhibitor.
(See 'Sexual dysfunction' above.)

●Bowel dysfunction after SCI usually requires treatment with a bowel evacuation
protocol and a multi-dimensional approach. A regular diet that includes adequate fiber
is an important part of management. (See 'Gastrointestinal complications' above.)

●Osteoporosis affects bones below the level of the SCI and increases the risk of
fracture. The role of bisphosphonates in this setting is under investigation. (See 'Bone
metabolism' above.)

●Positioning and mobilization can help ameliorate contractures and pressure ulcers after
SCI. (See 'Musculoskeletal complications' above and 'Pressure ulcers' above.)
●Spasticity is common after SCI and has positive as well as negative effects. Treatment
is empiric and is aimed at minimizing pain while maximizing function. Options include
oral medication, intrathecal baclofen, botulinum toxin, and nerve blocks. Refractory
spasticity may require surgery. (See 'Spasticity' above.)

●Neurogenic pain after SCI is often refractory but may respond to standard analgesic
therapy, antiepileptic drug therapy, and/or antidepressant therapy. (See 'Pain syndromes'
above.)

●Depression frequently complicates SCI; patients are at high risk for suicidality and
should be monitored. (See 'Psychiatric complications' above.)

●Functional neurologic deficits are determined by the level and completeness of the SCI
and are ameliorated by appropriate rehabilitation interventions. If patients experience
neurologic decline, neuroimaging is indicated to exclude syringomyelia, posttraumatic
myelomalacic myelopathy, or other neurologic pathology. (See 'Functional deficits'
above and 'Neurologic deterioration' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

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Anatomy and localization of spinal cord disorders
Author: Andrew Eisen, MD, FRCPC
Section Editor: Michael J Aminoff, MD, DSc
Deputy Editor: Janet L Wilterdink, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process
is complete.

Literature review current through: Aug 2017. | This topic last updated: Nov 18, 2015.

INTRODUCTION — Because it is the primary pathway of communication between the

brain and peripheral nervous system, diseases that affect the spinal cord are clinically
eloquent. Many of these disease processes have a predilection for targeting specific
areas or tracts within the spinal cord. As a result, knowledge of spinal cord anatomy and
recognition of typical common spinal cord syndromes are useful in the evaluation of a
patient with a myelopathy and can allow for a more directed diagnostic evaluation.

The anatomy of the spinal cord and its vascular supply and clinical features of common
spinal cord syndromes will be reviewed here. Diseases that affect the spinal cord are
discussed separately. (See "Disorders affecting the spinal cord".)

SPINAL CORD ANATOMY — There are 31 spinal cord segments, each with a pair of
ventral (anterior) and dorsal (posterior) spinal nerve roots, which mediate motor and
sensory function, respectively. The ventral and dorsal nerve roots combine on each side
to form the spinal nerves as they exit from the vertebral column through the
neuroforamina (figure 1).

Longitudinal organization — The spinal cord is divided longitudinally into four regions:

the cervical, thoracic, lumbar, and sacral cord. The spinal cord extends from the base of
the skull and terminates near the lower margin of the first lumbar vertebral body (L1).
Below that level, the spinal canal contains the lumbar, sacral, and coccygeal spinal
nerve roots that comprise the cauda equina.

Because the spinal cord is shorter than the vertebral column, vertebral and spinal cord
segmental levels are not necessarily the same. The C1 through C8 spinal cord segments
lie between the C1 through C7 vertebral levels. The T1 through T12 cord segments lie
between T1 through T8. The five lumbar cord segments are situated at the T9 through
T11 vertebral levels, and the S1 through S5 segments lie between T12 to L1. The C1
through C7 nerve roots emerge above their respective vertebrae; the C8 nerve root
emerges between the C7 and T1 vertebral bodies. The remaining nerve roots emerge
below their respective vertebrae (figure 2).

Cervical cord — The first cervical vertebra (the atlas) and the second cervical vertebra
(the axis), upon which the atlas pivots, support the head at the atlanto-occiput junction.
The interface between the first and second vertebra is called the atlanto-axis junction.

Cervical spinal segments innervate the skin and musculature of the upper extremity and
diaphragm (figure 3 and figure 4):

●C3 through C5 innervate the diaphragm, the chief muscle of inspiration, via the
phrenic nerve

●C4 through C7 innervate the shoulder and arm musculature

●C6 through C8 innervate the forearm extensors and flexors

●C8 through T1 innervate the hand musculature

Thoracic cord — The thoracic vertebral segments are defined by those that have an
attached rib. The spinal roots form the intercostal nerves that run along the inferior rib
margin and innervate the associated dermatomes, as well as the intercostal abdominal
wall musculature. These muscles are the main muscles of expiration. The thoracic cord
also contains the sympathetic nerves that innervate the heart and abdominal organs.
Lumbosacral cord — The lumbosacral spinal cord contains the segments that innervate
the muscles and dermatomes of the lower extremity, as well as the buttocks and anal
regions (figure 5 and figure 6). Sacral nerve roots S3 through S5 originate in the narrow
terminal part of the cord, called the conus medullaris.

●L2 and L3 mediate hip flexion

●L3 and L4 mediate knee extension

●L4 and L5 mediate ankle dorsiflexion and hip extension

●L5 and S1 mediate knee flexion

●S1 and S2 mediate ankle plantar flexion

Sacral nerve roots also provide parasympathetic innervation of pelvic and abdominal
organs, while lumbar nerve roots L1 and L2 contain sympathetic innervation of some
pelvic and abdominal organs.

Cauda equina — In adults, the spinal cord ends at the level of the first or second lumbar
vertebral bodies. The filum terminale, a thin connective tissue filament that descends
from the conus medullaris with the spinal nerve roots, is connected to the third, fourth,
and fifth sacral vertebrae; its terminal part is fused to the periosteum at the base of the
coccygeal bone.

Pathology at the T12 and L1 vertebral level affects the lumbar cord. Injuries to L2
frequently damage the conus medullaris. Injuries below L2 usually involve the cauda
equina and represent injuries to spinal roots rather than to the spinal cord (figure 2).

Cross-sectional anatomy — The spinal cord contains the gray matter, the butterfly-
shaped central region, and the surrounding white matter tracts. The spinal cord gray
matter, which contains the neuronal cell bodies, is made up of the dorsal and ventral
horns, each divided into several laminae [1,2].

Dorsal horn — The dorsal horn is the entry point of sensory information into the central
nervous system. It is divided into six layers or laminae that process sensory information.
More than a relay station for the transmission of sensory information, the dorsal horn
also modulates pain transmission through spinal and supraspinal regulatory circuits.
Three major categories of sensory input that are important to the clinical examination of
spinal cord pathology include:

●Afferents from muscle spindles that participate in spinal cord reflexes.

●Axons, mostly small and unmyelinated, mediating sensory modalities of pain and
temperature. These can travel up and down a few segments before synapsing with the
second order neurons, which then cross the midline of the cord in the anterior
commissure, just anterior to the central canal, and then enter the contralateral anterior or
lateral spinothalamic tract.
●Axons mediating the sensory modalities of proprioception, vibration, and touch
discrimination. These large myelinated fibers pass through the dorsal horn to enter the
ipsilateral dorsal column.

The anatomy of the sensory system is discussed in more detail separately. (See
"Approach to the patient with sensory loss".)

Ventral horn — The motor nuclei of the spinal cord are contained within the ventral
horn, which also contains interneurons mediating information from other descending
tracts of the pyramidal and extrapyramidal motor systems. These ultimately synapse on
the alpha and gamma motor neurons, which subsequently leave the ventral horn via the
ventral nerve root to terminate at the neuromuscular junction.

White matter tracts — The major white matter tracts of clinical importance in the
assessment of spinal cord disease include:

●The dorsal or posterior columns, the fasciculus gracilis, and the fasciculus cuneatus.
These contain sensory information regarding joint position and vibration. They are
organized anatomically such that cervical sections lie most laterally and sacral segments
most medially (figure 7). These pathways will cross in the medulla; hence, in the spinal
cord, these tracts contain ipsilateral sensory representation.

●The anterior and lateral spinothalamic tracts contain sensory information regarding
pain, temperature, and touch. These axons have crossed in the ventral commissure and
therefore contain contralateral sensory representation. This tract is somatotopically
organized with cervical inputs located most medially and sacral inputs most laterally
(figure 7).

●The corticospinal tracts contain the upper motor neurons that originate in M1 of the
primary motor cortex. These axons synapse either directly or indirectly on the anterior
horn cells, and as such have distinct sites of anatomic origin within M1 [3]. A single
corticomotoneuronal axon synapses with many anterior horn cells of its own motor
neuron pool and also with those of agonists and antagonists, allowing for coordination
of highly skilled movements.

The lateral corticospinal tract contains the majority (80 to 85 percent) of these fibers,
which have previously decussated (crossed) at the cervicomedullary junction and
therefore provide input to the ipsilateral musculature. Fibers are somatotopically
organized within the tract such that fibers destined for upper extremity motor control lie
most medially, while fibers controlling the lower extremity lie more laterally (figure 7).
The anterior corticospinal tract contains undecussated fibers, some of which will
subsequently cross at the spinal level through the anterior commissure.

Other descending tracts include:

●The tectospinal tract originates in the superior colliculus and mediates reflex postural
movements of the head in response to visual and/or acoustic input.

●The rubrospinal pathway originates from the magnocellular subdivision of the red
nucleus, markedly developed in reptiles, birds, and other lower mammals, but is much
less evident in primates, in which there are direct connections with motoneurons
innervating wrist muscles.

●The vestibulospinal tracts arise from the vestibular nuclei and facilitate spinal cord
reflexes and muscle tone to maintain posture.

●Reticulospinal connections are widely assumed to be responsible for coordinated gross

movements primarily of proximal muscles, whereas the corticospinal tract mediates fine
movements, particularly of the hand [4]. However, the reticulospinal system may form a
parallel pathway to distal muscles, alongside the corticospinal tract. As a result,
reticulospinal neurons may influence upper limb muscle activity after damage to the
corticospinal system as may occur in stroke [5,6].

Other ascending tracts include:

●The dorsal and ventral spinocerebellar tracts carry inputs mediating unconscious
proprioception directly to the cerebellum

●The spinoreticular tract carries deep pain input to the reticular formation of the
brainstem

Autonomic fibers — Autonomic fibers of hypothalamic and brainstem origin descend in

the lateral aspect of the spinal cord but not in a well-defined tract. These synapse with
cell bodies in the intermediolateral columns of the central gray matter of the spinal cord.
Sympathetic fibers exit between T1 and L2, and parasympathetic fibers exit between S2
and S4.

The sympathetic neurons lie in the lateral horn of the central gray matter at spinal levels
T1-L3. The preganglionic fibers exit via the ventral root, spinal nerve, and ventral
ramus to reach the paravertebral ganglion. Many will synapse at the paravertebral
ganglion, others pass through it to terminate on postganglionic neurons (eg, coeliac,
superior mesenteric, and inferior mesenteric ganglia) more proximate to their end organ.

Parasympathetic neurons originate in the sacral spinal cord and exit the spinal cord with
other efferents to the ventral ramus. After leaving the ventral ramus, they may
subsequently join with sympathetic nerves to reach the viscera. These preganglionic
fibers then synapse with a diffuse network of terminal ganglion cells that affect organs
in the pelvis.

Autonomic dysfunction is an important determinant of site, extent, and severity of

spinal cord pathology. Many autonomic functions can be affected by spinal cord
pathology, but for clinical evaluation, the most useful symptoms relate to bladder
control.

Autonomic bladder control is primarily parasympathetic, and is unaffected by isolated

injury to the sympathetic fibers. Voluntary bladder control is under somatomotor
control, mediated by motor fibers originating from the anterior horn cells at levels S2-
S4. A spinal cord lesion that interrupts descending motor and autonomic tracts above
the S2 level produces an "automatic bladder" that cannot be emptied voluntarily, but
empties reflexly when expanded to a certain degree, the so-called neurogenic bladder
[7-10]. Loss of descending inhibition of segmental reflex control leads to urinary
urgency and incontinence. Injury to S2-S4 spinal levels interrupts the bladder reflex
circuit; the bladder becomes flaccid, and fills beyond capacity with overflow
incontinence.

Other autonomic functions are disturbed by spinal cord pathology. The effects of spinal
cord injury on the colon and rectum are similar to those on the bladder. Spinal cord
transections interrupt voluntary control of the external sphincter and produce
constipation. Sacral lesions cause a loss of the anal reflex and rectal incontinence.
Impotence can result from spinal cord lesions at any level. Spinal cord injuries can also
affect cardiovascular function, most dramatically with lesions above T6 which can
produce a phenomenon of autonomic dysreflexia. (See "Chronic complications of spinal
cord injury and disease", section on 'Autonomic dysreflexia'.)

Blood supply — A single anterior and two posterior spinal arteries supply the spinal
cord (figure 8). The anterior spinal artery supplies the anterior two-thirds of the cord
[11-15]. The posterior spinal arteries primarily supply the dorsal columns. The anterior
and posterior spinal arteries arise from the vertebral arteries in the neck and descend
from the base of the skull. Various radicular arteries branch off the thoracic and
abdominal aorta to provide additional blood supply to the spinal arteries. The largest
and most consistently present of these radicular branches is the great ventral radicular
artery or the artery of Adamkiewicz, which supplies the anterior spinal artery [16]. This
artery enters the spinal cord anywhere between T5 and L1 (usually between T9 and
T12).

In most people, the anterior spinal artery passes uninterrupted along the entire length of
the spinal cord; in others, it is discontinuous, usually in its midthoracic segment, making
these individuals more susceptible to vascular injury. The primary watershed area of the
spinal cord in most people is in the midthoracic region.

The vascular anatomy of the spinal cord is discussed in detail separately. (See "Spinal
cord infarction: Vascular anatomy and etiologies", section on 'Vascular anatomy'.)

CLINICAL LOCALIZATION — A spinal cord lesion may be suspected when there are
bilateral motor and sensory signs or symptoms that do not involve the head or face.
Motor deficits are manifest by weakness and long tract signs (spasticity, increased
reflexes, Babinski sign) [8,17-19]. When the pathology is localized or segmental, these
findings will be present in muscle groups innervated below that level and will be normal
above. A sensory level, with normal sensation above and reduced or absent below, can
also often be defined and should be specifically sought. Other so-called segmental signs
include lower motor neuron findings (atrophy, flaccid weakness, loss of reflexes) in a
myotomal distribution at the specific level of involvement; however, these are usually
not elicitable in thoracic lesions. (See "The detailed neurologic examination in adults",
section on 'Motor examination' and "The detailed neurologic examination in adults",
section on 'Reflex examination' and "The detailed neurologic examination in adults",
section on 'Sensory examination'.)

As well as longitudinal localization within the spinal cord, it can also be helpful to
distinguish specific areas of functional loss with a spinal cord level (or across spinal
cord levels for nonsegmental pathologies). Some disorders affecting the spinal cord
preferentially affect different structures, and therefore careful testing of all spinal cord
functions, including motor, reflex, and all sensory modalities, and sphincter function is
important for clinical localization.

Several distinct spinal cord syndromes are recognized. These are useful in the clinical
evaluation, as they often correspond to distinct pathologies. These are summarized in
the table and are discussed below (table 1).

Segmental syndrome — Pathologies that affect all functions of the spinal cord at one or
more levels produce a segmental syndrome. Loss of function may be total or
incomplete. A total cord transection syndrome results from the cessation of function in
all ascending and descending spinal cord pathways and results in the loss of all types of
sensation and loss of movement below the level of the lesion. Less profound injuries
produce a similar pattern of deficits, which are less severe: ie, weakness rather than
paralysis and decreased sensation rather than anesthesia.

Acute transection can cause spinal shock, with a flaccid paralysis, urinary retention, and
diminished tendon reflexes. This is usually temporary, and increased tone, spasticity,
and hyperreflexia will usually supervene in days or weeks after the event.

Transverse injuries above C3 involve cessation of respiration and are often fatal if acute.
Cervical cord lesions that spare the phrenic nerve but impair intercostal nerve function
can produce respiratory insufficiency. Lesions above the L2 cord level will cause
impotence and spastic paralysis of bladder. There is loss of voluntary control of the
bladder, which will empty automatically by reflex action.

Causes of a cord segmental syndrome include acute myelopathies, such as traumatic

injury and spinal cord hemorrhage. Epidural or intramedullary abscess, tumors, and
transverse myelitis may have a more subacute presentation. (See "Disorders affecting
the spinal cord".)

Dorsal (posterior) cord syndrome — Dorsal cord syndrome results from the bilateral
involvement of the dorsal columns, the corticospinal tracts, and descending central
autonomic tracts to bladder control centers in the sacral cord (figure 9). Dorsal column
symptoms include gait ataxia and paresthesias. Corticospinal tract dysfunction produces
weakness that, if acute, is accompanied by muscle flaccidity and hyporeflexia and, if
chronic, by muscle hypertonia and hyperreflexia. Extensor plantar responses and urinary
incontinence may be present.

Causes of a dorsal cord syndrome include multiple sclerosis (more typically the primary
progressive form), tabes dorsalis, Friedreich ataxia, subacute combined degeneration,
vascular malformations, epidural and intradural extramedullary tumors, cervical
spondylotic myelopathy, and atlantoaxial subluxation. (See "Disorders affecting the
spinal cord" and "Cervical spondylotic myelopathy".)

Ventral (anterior) cord syndrome — Ventral cord or anterior spinal artery syndrome

usually includes tracts in the anterior two-thirds of the spinal cord, which include the
corticospinal tracts, the spinothalamic tracts, and descending autonomic tracts to the
sacral centers for bladder control (figure 10). Corticospinal tract involvements produce
weakness and reflex changes. A spinothalamic tract deficit produces the bilateral loss of
pain and temperature sensation. Tactile, position, and vibratory sensation are normal.
Urinary incontinence is usually present.

The causes of a ventral cord syndrome include spinal cord infarction, intervertebral disc
herniation, and radiation myelopathy. (See "Disorders affecting the spinal cord".)

Brown-Sequard (hemi-cord) syndrome — A lateral hemisection syndrome, also known

as the Brown–Sequard syndrome, involves the dorsal column, corticospinal tract, and
spinothalamic tract unilaterally (figure 11). This produces weakness, loss of vibration,
and proprioception ipsilateral to the lesion and loss of pain and temperature on the
opposite side. The unilateral involvement of descending autonomic fibers does not
produce bladder symptoms. While there are many causes of this syndrome, knife or
bullet injuries and demyelination are the most common. Rarer causes include spinal
cord tumors, disc herniation, infarction, and infections. (See "Disorders affecting the
spinal cord".)

Central cord syndromes — The central cord syndrome is characterized by loss of pain

and temperature sensation in the distribution of one or several adjacent dermatomes at
the site of the spinal cord lesion caused by the disruption of crossing spinothalamic
fibers in the ventral commissure (figure 12). Dermatomes above and below the level of
the lesion have normal pain and temperature sensation, creating the so-called
"suspended sensory level." Vibration and proprioception are often spared.

As a central lesion enlarges, it may encroach on the medial aspect or the corticospinal
tracts or on the anterior horn gray matter, producing weakness in the analgesic areas.
Fibers mediating the deep tendon reflexes are interrupted as they pass from the dorsal to
the ventral horn, thus causing tendon reflex loss in the analgesic areas. There are usually
no bladder symptoms.

The classic causes of a central cord syndrome are slow-growing lesions such as
syringomyelia or intramedullary tumor. However, central cord syndrome is most
frequently the result of a hyperextension injury in individuals with long-standing
cervical spondylosis. This form of central cord syndrome is characterized by
disproportionately greater motor impairment in upper compared with lower extremities,
bladder dysfunction, and a variable degree of sensory loss below the level of injury [20-
22]. (See "Cervical spondylotic myelopathy".)

Pure motor syndrome — A pure motor syndrome produces weakness without sensory
loss or bladder involvement. This may involve only the upper motor neurons, producing
hyperreflexia and extensor plantar responses, or only the lower motor neuron bilaterally,
producing muscle atrophy and fasciculations. Other disorders involve both the upper
and lower motor neurons and produce mixed signs.

The causes of a pure motor syndrome include chronic myelopathies such as HTLV-I
myelopathy, hereditary spastic paraplegia, primary lateral sclerosis, amyotrophic lateral
sclerosis, progressive muscular atrophy, post-polio syndrome, and electric shock-
induced myelopathy. (See "Disorders affecting the spinal cord".)

Conus medullaris syndrome — Lesions at vertebral level L2 often affect the conus

medullaris. There is early and prominent sphincter dysfunction with flaccid paralysis of
the bladder and rectum, impotence, and saddle (S3-S5) anesthesia. Leg muscle
weakness may be mild if the lesion is very restricted and spares both the lumbar cord
and the adjacent sacral and lumbar nerve roots.

Causes include disc herniation, spinal fracture, and tumors [7,23].

Cauda equina syndrome — Though not a spinal cord syndrome, cauda equina syndrome
is considered here because its location within the spinal canal subjects it to many of the
same disease processes that cause myelopathy. The syndrome is caused by the loss of
functions of two or more of the 18 nerve roots constituting the cauda equina. Deficits
usually affect both legs but are often asymmetric. Symptoms include [24-26]:

●Low back pain accompanied by pain radiating into one or both legs. Radicular pain
reflects involvement of dorsal nerve roots and may have localizing value [24].

●Weakness of plantar flexion of the feet with loss of ankle jerks occurs with mid cauda
equina lesions, involving S1, S2 roots. Involvement of progressively higher levels leads
to corresponding weakness in other muscles (figure 5).

●Bladder and rectal sphincter paralysis usually reflect involvement of S3-S5 nerve roots
[24,25].

●Sensory loss of all sensory modalities occurs in the dermatomal distribution of the
affected nerve roots (figure 6).

Many etiologies can cause a cauda equina syndrome, including intervertebral disc
herniation, epidural abscess, epidural tumor, intradural extramedullary tumor, lumbar
spine spondylosis, and a number of inflammatory conditions including spinal
arachnoiditis, chronic inflammatory demyelinating polyneuropathy, and sarcoidosis
[23,27-32]. The cauda equina can also be the primary site of involvement in
carcinomatous meningitis and a number of infections (eg, cytomegalovirus, herpes
simplex virus, herpes zoster virus, Epstein Barr virus, Lyme disease, mycoplasma, and
tuberculosis). (See "Lumbar spinal stenosis: Pathophysiology, clinical features, and
diagnosis" and "Clinical features and diagnosis of neoplastic epidural spinal cord
compression, including cauda equina syndrome".)

Lhermitte's sign — This well-described sign describes a sensation of electric shock-like

sensations that run down the back and/or limbs during flexion of the neck. This
generally occurs with pathologies involving the cervical spinal cord, but is not specific
to etiology, occurring in patients with cervical spondylotic myelopathy [33], multiple
sclerosis, radiation myelopathy, and vitamin B12 deficiency, among others. It can also
occur with cervical nerve root pathology.

DIAGNOSIS — The differential diagnosis of myelopathy is wide, but can be

significantly narrowed by the clinical syndrome (table 1). Other features in the
examination and history also limit the differential diagnosis and tailor the diagnostic
work-up. Clinical features of some of the more common causes of myelopathy are
outlined in the Table (table 2). These are discussed in detail separately (see "Disorders
affecting the spinal cord").
For patients with a clinical syndrome that suggests a localized process within the spinal
cord (eg, transection syndrome, central cord syndrome, ventral cord syndrome, etc), an
imaging study, usually magnetic resonance imaging (MRI), of the relevant section of
the spinal cord is usually required [19,34]. Administration of gadolinium contrast is
often helpful. When an infectious or inflammatory disorder is suspected, cerebrospinal
fluid examination may be helpful. The role of positron emission tomography in
evaluating patients with myelopathy is under investigation; it appears to be particularly
sensitive for neoplastic disease [35].

In general, the pace at which spinal cord deficits appear dictate the urgency of the
neurologic evaluation. Even when the deficits are not severe, acute myelopathic signs
need to be evaluated urgently because neurologic deterioration can occur abruptly, and
the clinical deficit at the time of intervention often dictates the chances of recovery.
This is true particularly for compressive etiologies such as spinal cord metastases and
epidural spinal abscess.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces
are written in plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10 th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on “patient info” and the keyword(s) of
interest.)

●Basics topics (see "Patient education: Central spinal cord syndrome (The Basics)" and
"Patient education: Cauda equina syndrome (The Basics)")

SUMMARY — Disorders that affect the spinal cord often target specific structural and
functional anatomic regions, producing distinct clinical syndromes. The spinal cord
syndromes are summarized in the table (table 1). The clinical syndrome along with
other features in the examination and history usually significantly limits the differential
diagnosis and tailors the diagnostic work-up (table 2). (See "Disorders affecting the
spinal cord".)

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