Human Leukocyte Antigen Probable Site on Genome for Ossification of the Posterior Longitudinal Ligament

Multiple studies increasingly document a genetic correlation between OPLL, diffuse idiopathic skeletal hyperostosis (DISH), and ossification of other ligaments, ossification of the yellow ligament (OYL), and ossification of the anterior longitudinal ligament (OALL). In an evaluation of 91 sibling pairs of patients with OPLL (in 53 Japanese families), the genetic locus for OPLL was found near the human leukocyte antigen (HLA) site on chromosome 6-p. In patients with DISH, 50% have concurrent OPLL and test positive for HLA. Stetler and colleagues found multiple genes contributing to the different inheritance patterns of OPLL involved in the production of collagen, nucleotide pyrophosphatase, transforming growth factors, vitamin D receptors, cytokines, growth factors (e.g., bone morphogenetic proteins), proteins, and interleukins.

Autosomal Dominant Inheritance

An autosomal dominant mode of inheritance is supported by genetic and epidemiologic data from patients with OPLL. OPLL is found in 26.15% of parents and 28.89% of siblings of patients with OPLL, a finding that supports a likely autosomal dominant transmission. This hypothesis is further supported by the 53% expression rate of OPLL observed in patients with two concurrent HLA strands compared with 24% in those with one strand. Autosomal recessive transmission was suggested when 56% of patient’s siblings with both HLA haplotypes were symptomatic with OPLL, whereas those with only one HLA haplotype were not. Two additional unique genetic factors were identified in 18 patients with OPLL compared with 51 age-matched controls: BamHI 10/10 kb and HindIII 19/19 kb genotypes.

Other Factors (Hormones, Proteins) That Contribute to Ossification of the Posterior Longitudinal Ligament

Genetically modulated hormone/proteins also appear to contribute to the expression of OPLL. Increased concentrations of growth hormone (GH) receptors and activins enhanced OPLL’s expression/progression. Elevated concentrations of bone morphogenetic proteins (BMPRs) resulted in increased osteogenesis in originally nonossified ligaments of OPLL patients (347 families, 1030 relatives). In a more recent study, BMP-2 additionally positively correlated with the extent of OPLL progression. Insulin was also correlated with the onset/progression of OPLL in non-insulin-dependent diabetics via direct and indirect stimulation of BMP-2 within the ligament. Fibronectin, a glycoprotein that plays a role in the development of bony tissues, was also found to be significantly elevated in patients with OPLL or OYL.

Posterior Longitudinal Ligament

The posterior longitudinal ligament (PLL), composed of collagen fibers with elastin densely concentrated at its center, originates at the base of the clivus and extends to the sacrum. It is attached to each disc annulus where it is widest, and it is narrowest at each midvertebral level; it is 1 to 2 mm thick centrally, thinning out laterally.

Hypertrophied and Ossified Posterior Longitudinal Ligament

Hypertrophy of the PLL is first attributed to fibroblastic hyperplasia followed by increased collagen deposition. The subsequent formation of ossification centers, attributed to progressive mineralization and cartilaginous ingrowth, eventually coalesce, leading to OPLL characterized by mature haversian canals actively engaged in bone marrow production. OPLL enlarges an average of 0.4 mm per year in its anterior-posterior dimension, whereas longitudinal expansion occurs at a rate of 0.67 mm per year.

In Vitro Characteristics of Cultured Posterior Longitudinal Ligament in Patients with Ossification of the Posterior Longitudinal Ligament

In patients with OPLL, the PLL is osteogenic. Immunohistochemical evaluation of PLL cells for patients undergoing anterior cervical decompression for cervical disease revealed “up-regulation of proliferating cell nuclear antigen” in patients with OPLL. This finding of increased osteogenicity of the PLL was also confirmed in myelopathic North American patients with OPLL. Collecting supernatants of PLL obtained intraoperatively from patients with OPLL compared with non-OPLL control patients (with spondylosis) revealed increased osteocalcin synthesis in the OPLL patients. The quantity of osteocalcin induced was determined by incubating these PLL cells with 1.25(OH) ₂ and vitamin D ₃ at 10E-8M for 72 hours in a serum-free medium. Those with OPLL grew to confluence, whereas those with spondylosis alone did not respond to vitamin D3 priming.

Early Ossification of the Posterior Longitudinal Ligament

OPLL represents a continuum of maturation that starts with hypertrophy of the PLL and ends with frank ossification. Early OPLL usually originates opposite multiple interspaces in patients in their mid-40s and is often misdiagnosed as multiple disc herniations. However, unlike disc herniations, it begins with a retrovertebral extension that can be seen on enhanced Magnetic Resonance Imaging (MRI) studies performed with Gadolinium-Diethylenetriamine Pentaacetic acid (GD-DTPA) and as punctate CT-documented ossification. Too often, patients undergo multilevel anterior discectomy and fusion procedures where the PLL is ignored, leading to many retained disc fragments and, in early OPLL, leaving patients with continued symptomatology.

Classical Ossification of the Posterior Longitudinal Ligament

There are four types of mature/classical OPLL ( Figs. 101-5 through 101-7 ). The segmental variant (39%), located behind the vertebral bodies, does not cross the intervening disc spaces. The continuous type (27%) extends from vertebra to vertebra, traversing the disc spaces. The mixed form (29%) simultaneously includes both continuous and segmental elements with “skip” areas, whereas the “other” form (5%) is localized to the disc spaces with limited degrees of rostral and caudal retrovertebral extension.

This axial noncontrast CT study demonstrates the classical double-layer sign characterized by a hyperdense line of OPLL directly behind the vertebra, followed by a hypodense mass representing the penetrated dura, followed by an intradural hyperdense mass of OPLL. Note in this case that the intradural ossified OPLL lesion is massive.

The single-layer sign is characterized by a large typically irregular central hyperdense mass contiguous with the dorsal aspect of the cervical vertebral body. However, as in this case, when the mass extends laterally but is not directly contiguous with the dorsal vertebral body it forms a positive “C” sign. This reflects “imbrication” (infolding/redundancy) of the lateral dura and indicates a greater risk for CSF fistula formation.

This midline sagittal 2D CT study demonstrates the multiple forms of OPLL. Behind the C4 vertebral body you can see the segmental variant, whereas below this from C5 to C6, C7, and even crossing the C7-T1 interspace, you can visualize continuous OPLL. Note, however, that at the C5-6 level you have the double-layer sign wherein ventrally you have ossified OPLL followed by a hypodense region (incorporation of the dura) followed by intradural OPLL.

Myelopathy Scales

Two major myelopathy scales are used worldwide: the Nurick scale and the Japanese Orthopaedic Association scale.

Associated Conditions

Patients with OPLL are frequently diabetic or have coexisting hypoparathyroidism, acromegaly, vitamin D–resistant rickets, spondyloepiphyseal dysplasia, DISH, ankylosing spondylitis, OYL, OALL, and myotonic muscular dystrophy.

Radiographs

Based on lateral 6-foot plain x-rays, the normal anteroposterior (AP) dimension of the cervical spinal canal should measure 17 mm from C3-7. Absolute stenosis was defined as a canal measuring 10 m or less, whereas relative stenosis was defined by a canal of 10 to 13 mm. OPLL’s occupancy ratio is defined by dividing the thickness of the measured ossified lesion by the anterior/posterior developmental canal diameter; if the ratio is greater than 40%, the risk of myelopathy increases.

Computer-assisted measurements based on plain x-rays may be utilized to follow the postoperative progression of OPLL. In a multicenter study, lateral x-rays were taken immediately and 1 and 2 years following posterior decompressions (131 patients). Over 2 years, there was a 56.5% rate of progression, occurring more often in younger patients with the mixed and continuous forms of OPLL.

Magnetic Resonance Imaging

T1- and T2-weighted MRI studies, in particular and MRI examinations, performed with and without contrast (gadolinium-DTPA), demonstrate the spinal column, spinal cord, nerve roots, intrinsic cord disease, and extrinsic cord compression from the occiput through the cervicothoracic junction in the transaxial, coronal, and sagittal planes. Hypertrophied PLL on MRI often appears opposite multiple disc spaces with retrovertebral extension that enhances with gadolinium-DTPA. Classical OPLL is identified on 50% of T1-weighted MRI studies by a hyperintense signal reflecting the presence of fat within mature haversian canals actively engaged in bone marrow production. Additionally, utilizing MRI along with CT studies, Yang and colleagues documented that 26 of 142 patients with cervical OPLL (15 segmental-type, 9 mixed-type, 2 continuous-type) also had herniated discs.

Ossified OPLL, appearing hypointense on MRI studies, may lead to an underestimation of the true extent of the OPLL and should be combined with CT-based studies to accurately document the true extent of cord compression. In a multicenter study, 156 OPLL patients from 16 institutions were followed an average of 10.3 years with plain x-rays, MRI, and CT studies. Of interest, all 39 patients with OPLL occupying greater than 60% of the AP diameter of the spinal canal were myelopathic, whereas only 49% with OPLL occupying less than 60% of the spinal canal were myelopathic.

Intrinsic cord swelling/edema, myelomalacia, and gliosis produce hyperintense signals on T2-weighted MRI images and are considered poorer prognostic signs for patients with cervical spondylotic myelopathy (CSM) compared with OPLL patients. Despite the 43% incidence of increased preoperative cord signals on MRI studies that failed to resolve postoperatively, OPLL patients exhibited better outcomes compared with those with CSM. Dynamic MRI studies may also prove useful in demonstrating “dynamic” compression preoperatively and residual cord compromise postoperatively.

Preoperative Magnetic Resonance Angiography

Measurement of the interpedicular distance on preoperative CT scans typically dictates the medial/lateral dimension of the surgical trough to be created, which may vary from an average of 14 mm in the Japanese population to 18 to 20 mm in North Americans. Preoperative magnetic resonance angiography (MRA) studies may help determine whether a vertebral artery follows an unusually tortuous course, thus altering the size/laterality of a ventral decompression trough.

Vertebral Angiography for Vascular Injuries

The management of vertebral artery injuries is controversial. Direct surgical repair of an injured vessel is often difficult, and many prefer “endovascular” procedures. Injuries less than 6 hours old may be managed with stents, whereas those longer than 6 hours old may warrant endovascular trapping/coiling techniques. Both endovascular techniques avoid delayed reopening of the vessel, avoid pseudoaneurysm formation, and limit the risk for cephalad clot propagation and cranial embolization.

Computerized Axial Tomography

Noncontrast CT, intravenous-enhanced contrast CT, two-dimensional (2D) and three-dimensional (3D) reconstructed CT, and myelo-CT studies directly demonstrate punctate ossification characteristic of early OPLL or frank ossification typical of classical OPLL (see Figs. 101-5 through 101-7 ). CT studies also demonstrate degenerative changes adjacent to levels of prior surgery. Two-dimensional and 3D noncontrast CT reconstructed images provide a sagittal overview of the extent of cord compression without incurring the risk associated with myelo-CT studies. In particular, younger patients with OPLL normal-sized spinal cords are at greater risk for acute deterioration following myelography compared to older individuals with OPLL and significant underlying cord atrophy.

Computed Tomography Signs of Dural Penetrance

Bone-window CT examinations document two major signs of dural penetrance: the double-layer and single-layer CT signs (see Figs. 101-5 through 101-7 ). The double-layer sign is characterized by a hyperdense line of OPLL directly behind the vertebra, followed by a hypodense mass representing penetrated dura, and, finally, an intradural hyperdense mass of OPLL (see Fig. 101-5 ). The single-layer sign is represented by a large central mass of OPLL. However, when the single mass is lateralized, the resulting positive “C” sign reflects an “imbrication” of the lateral dura and a greater likelihood for cerebrospinal fluid (CSF) fistula formation (see Fig. 101-6 ).

The double-layer sign is most highly correlated with absent dura, with CSF fistulas occurring between 52.6% and 84% of the time, whereas the single-layer signs (“C” sign) produce CSF fistulas in 13.6% to 25% of cases. In one series, 10 of 12 OPLL patients with CT-documented double-layer signs developed dural defects at surgery, whereas only 1 of 9 patients showing the single-layer sign developed a CSF leak intraoperatively. From a series of 197 Korean patients undergoing anterior resection of OPLL, signs of dural penetration were observed in 30.5% of patients; 52.6% (20 of 38 patients) showed a double-layer sign (nonsegmental OPLL), and 13.6% (2 of 33) showed single-layer signs. For those with double-layer signs, the thicker the central mass of OPLL, the greater the incidence of intraoperative CSF fistula. When intraoperative fistulas arise, they should be treated with complex dural/wound repairs utilizing 7-0 GOR-TEX sutures and microdural staples (if edges can be everted), bovine pericardial grafts (when indicated), fibrin sealant, microfibrillar collagen, and often wound-peritoneal/lumboperitoneal shunts.

Cerebrospinal Fluid Fistulas Rare without Single- or Double-Layer Signs

The majority of patients with OPLL who exhibit neither the single- or double-layer signs, should not develop intraoperative CSF fistulas if careful dissection is carried out under an operating microscope. When Epstein performed multilevel simultaneous anterior corpectomies with posterior fusions in 54 OPLL patients, only one demonstrated the double-layer CT sign, and one demonstrated the single-layer sign. For 85 similar patients, 3 CSF fistulas resulted: 1 double-layer CT sign and two single-layer CT signs.

Myelo–Computed Tomography Studies

Myelo-CT studies are now rarely performed, as MRI/CT studies combined are extremely accurate and avoid myelography’s inherent risks of precipitating neurologic deterioration. Dorsally and dorsolaterally, myelo-CT studies (dynamic, static) demonstrate shingling of the lamina, OYL, OPLL, spondylosis, and disc pathology contributing to significant cord compression/stenosis. Postoperatively, myelo-CT studies also confirm whether the posterior decompression has been adequate or if further possible anterior surgery is warranted. Following open-door laminoplasty performed in OPLL patients, there was less dorsal shift of the cord but greater cord expansion, the latter factor positively correlating with outcome.

Documentation of Fusion Following Multilevel Anterior Cervical Surgery

Fusion criteria, documented on static and 2D CT studies performed immediately postoperatively and repeated at 3, 6, and 12 months postoperatively included (1) the presence of bony trabeculation, (2) lack of bony lucency at the fibula strut allograft/vertebral body interface, and (3) ingrowth of bone centrally into the fibula. Dynamic radiographs additionally revealed (1) less than 3.5 mm of translation, (2) less than 5 degrees of angulation, and (3) less than 1 mm of motion demonstrated between the tips of adjacent spinous processes. An additional criterion for fusion following multilevel anterior corpectomy/fusion (ACF) performed with fibula strut allograft consists of cephalad or caudad bony ingrowth from the vertebral end plate into the central canal. Eighteen patients with OPLL had average 2.9 level ACF performed with fresh frozen fibula strut allografts, accompanied by C2-T1 posterior wiring and fusion (PWF). CT documentation of bony ingrowth and other signs of fusion were observed in 17 (94%) of 18 patients (ingrowth documented utilizing 500 to 900 Hounsfield units). Bony ingrowth doubled from 3 to 6 months postoperatively, increasing both rostrally (1.5 mm to 3.5 mm) and caudally (2.1 mm to 4.6 mm).

Documentation of Posterior Fusion

When posterior fusions are performed, whether utilizing wiring techniques (facet wiring, rod-eyelet-cable fusion constructs), lateral mass screws, or pedicle screws, dynamic x-ray criteria enumerated previously should be met, whereas 2D coronal and sagittal CT-based studies should demonstrate (1) continuity between the bone graft and underlying laminae (2) and continuity of bone graft and fusion across facet joints.

Diffuse Idiopathic Skeletal Hyperostosis

Diffuse idiopathic skeletal hyperostosis (DISH), an ossifying diathesis involving extensive ossification of the anterolateral aspect of contiguous vertebral bodies, is readily demonstrated on preoperative CT examinations. It typically occurs (15% to 30%) in adults over 65 years of age, is often asymptomatic , and is far more prevalent than OALL among North Americans. OPLL contributes to the diffuse ligamentous ossification seen in up to 50% of patients with DISH, but it should only be resected either anteriorly or posteriorly in symptomatic patients. As DISH often becomes massive before producing dysphagia, other etiologies of dysphagia must be sought before the surgical resection of DISH, which may result in several months of dysphagia.

Ossification of the Anterior Longitudinal Ligament

Ossification of the anterior longitudinal ligament (OALL) is defined by initial hypertrophy of the anterior longitudinal ligament, followed by progressive cartilaginous infiltration, and, ultimately, frank ossification. On T1-weighted MRI studies, although the ossified OALL mass appears hypointense, the fat reflecting active bone marrow production occurring within mature haversian canals is hyperintense. On CT examinations, ventral OALL may become massive but rarely produces dysphagia, and it should therefore only be resected once other etiologies for these symptoms have been eliminated.

Conservative Treatment of Ossification of the Posterior Longitudinal Ligament

Although conservative management of patients with OPLL may include the use of oral nonsteroidal or steroidal agents and conservative rehabilitation therapy, epidural steroid injections should be avoided due to markedly altered pathology of the spinal canal that may include obliteration of an epidural space. Bracing is discouraged, as these devices frequently exacerbate rather than relieve symptoms and may inadvertently place the neck in hyperextension or hyperflexion.

Patients with OPLL, whether under or over 65 years of age, with progressive myelopathy, with or without evidence of cord edema and minimal to no significant medical risk factors are considered good surgical candidates. For those with marked radiographic evidence of cord compromise, operative intervention should be performed prior to the anticipated 10% incidence of even minor cervical trauma that can precipitate severe or permanent myelopathic progression.

In patients with OPLL over 70 years of age with severe myelopathy and significant medical comorbidities, surgery is considered high risk at best. For patients undergoing either multilevel anterior or posterior surgery for myelopathy/OPLL, poor prognostic factors include age over 70, severe myelopathy, cardiovascular, or peripheral vascular disease, and a recent trauma history. In two of Epstein’s initial 44 patients undergoing multilevel circumferential surgery for OPLL, two patients expired from acute or 3-week delayed myocardial infarction. Such older patients with significant major comorbidities, or fixed deficits, should alternatively be managed at comprehensive pain management centers.

Role of Prophylactic Surgery for Ossification of the Posterior Longitudinal Ligament

Younger asymptomatic patients, those under 65 years of age, may be considered candidates for prophylactic decompression if severe cervical OPLL is radiographically or physiologically documented. This population, with a longer life expectancy, is at greater risk for inadvertent trauma and resultant irretrievable myelopathy. T2-weighted MRI studies demonstrating high cord signals, reflecting cord edema or myelomalacia, may indicate the need for surgery. Similarly, abnormal somatosensory evoked potential responses may indicate subclinical dorsal cord compromise and the need to consider operative intervention. Surgery, performed prior to the onset or progression of a neurologic deficit, correlated with better outcomes in 87% of patients in the series by Saunders.

Anesthetic Protocol for Ossification of the Posterior Longitudinal Ligament Patients Undergoing Circumferential Cervical Surgery

Patients undergoing multilevel anterior corpectomy with fusion, posterior stabilization, and halo application for complex OPLL are managed with a strict anesthetic protocol to avoid emergent hypoxia, reintubation, tracheostomy, and death. Awake fiberoptic intubation and positioning are performed first under continuous intraoperative somatosensory evoked potential (SSEP) monitoring. More recently, when Kill and colleagues compared the value of the GlideScope (GlideScope, Verathon Inc., Bothell, WA) versus conventional laryngoscope (MacIntosh) in patients with “unsecured cervical spines,” they found the GlideScope successfully reduced motion during intubation and would likely limit secondary damage during emergency intubation for patients with traumatic spinal injuries.

Eliminating cervical motion utilizing either technique limits inadvertent hyperextension/hyperflexion injury to the cord. Postoperatively, patients are kept prophylactically intubated the first postoperative night to limit acute respiratory distress due to tracheal swelling and to avoid emergent reintubation. The next day, patients must meet the following parameters prior to extubation: (1) direct fiberoptic assessment of the trachea/vocal cords for swelling, (2) letting down the endotracheal cuff looking for an air leak/verbalization, (3) reviewing the patient’s postoperative CT scan for soft tissue swelling/air around the cuff, and (4) evaluating the patient’s medical risk factors. For 58 patients undergoing average three level ACF with average 6.5 level PWF, spanning 10 hours and requiring usually 2.6 units of blood transfusion, fiber-optic extubation was successfully performed the first postoperative day in 40 patients.

For another 15 patients with major risk factors, extubation was delayed between 2 and 7 postoperative days, and 3 patients required elective tracheostomy (day 7). Six major risk factors correlated with delayed extubation or tracheostomy included (in descending order) (1) surgical time over 10 hours (12 patients), (2) obesity greater than 220 pounds (12 patients), (3) transfusions of over 4 units of blood (10 patients), (4) secondary anterior cervical surgery (9 patients), (5) anterior surgery including the C2 level (7 patients), (6) four-level ACF (5 patients), and (7) asthma (5 patients). Minor risk factors additionally included advanced age (> 65 years old), severe preoperative neurologic deficits (Nurick grades IV and V for moderate/severe myelopathy), and an intraoperative CSF fistula. Utilizing this protocol, only 1 patient with three major risk factors (prior C4-7 ACF 3 years earlier, asthma, and 14-hour surgery) required emergent reintubation.

Somatosensory Evoked Potential and Motor Evoked Potential Monitoring

Continuous intraoperative somatosensory evoked potential (SSEP) monitoring may limit morbidity associated with cervical surgery for OPLL. SSEP monitoring includes the evaluation of median/ulnar and posterior tibial responses. Awake fiberoptic nasotracheal intubation and positioning is performed with the patient awake, under continuous SSEP monitoring. For patients operated on in the supine position, the chin is taped/distracted slightly superiorly. For patients undergoing surgery prone, the three-pin head holder is applied using local anesthesia (1% lidocaine injection), and the patient is positioned awake. To avoid SSEP changes or loss, inhalation anesthetics (Isoflurane, nitrous oxide, etc.) are usually kept at concentrations below 0.4%; an alternative balanced narcotic technique is typically employed.

Significant Changes to the Somatosensory Evoked Potential

SSEP changes are defined by (1) a 50% decline in the amplitude and (2) a 10% decrease in latency. Such changes are initially observed over 50 seconds for the first recording and are reproduced within 100 seconds. Once reproduced and not considered false positives, immediate medical or surgical resuscitative measures may be initiated. Medical measures include inducing hypertension, warming the irrigating fluids, decreasing the concentration of inhalation anesthetic, and increasing oxygen concentration. Surgical resuscitative measures include releasing distraction, removing an oversized graft, and ceasing manipulation. Epstein, Danto, and Nardi demonstrated that no instances of quadriplegia or death were encountered in 100 prospectively SSEP-monitored cervical surgical cases. Eight of 218 previously unmonitored cervical operations resulted in quadriplegia (the prior series included eight surgeons).

Intraoperative Motor Evoked Potentials and Electromyographic Monitoring

Transcranial motor evoked potentials (MEPs) or transcutaneously placed epidural electrodes are typically utilized to monitor anterior cervical cord function. Complications associated with MEP electrode placement are often minimal (seizures, headache, transient motor deficit), and successful monitoring typically correlates with positive outcomes. In a cervical surgical series (1055 patients) combining all three intraoperative monitoring modalities—somatosensory evoked potentials (SEP) (all 1055 patients), MEP (26 patients), and electromyographic (EMG) (427 patients)—34 patients (3.2%) had new postoperative deficits; SSEP sensitivity was 52% (specificity 100%), MEP sensitivity was 96% (specificity 100%), and EMG sensitivity was 46% (specificity 73%). In an editorial, Epstein noted that although MEP could help minimize major motor injuries and more reliably detect impending anterior cord deterioration missed with SEP monitoring alone, MEPs were routinely available but not routinely employed. Furthermore, although most medicolegal cervical suits previously focused on negligent surgery, the lack of informed consent, failure to diagnose/treat, and failure to brace, perhaps the fourth most prominent reason for negative outcomes may be failure to monitor MEP.

Risk Factors

Major risk factors that correlated with new neurologic deficits following cervical surgery including OPLL were (1) multisegmental surgery, (2) severe preoperative neurologic deficits, (3) age over 70, and (4) the use of instrumentation. In many series, 50% of patients with complete intraoperative loss of potentials may show partial deficits, whereas intraoperative recovery of SSEP potentials often correlates with eventual neurologic recovery or no deficit. Of the 34 (3.2%) of 1055 patients in Kelleher’s series who experienced new postoperative deficits following cervical surgery, 6 had sensory/motor concerns, 7 had new sensory deficits, 9 had motor weakness, and 12 had new root injuries; deficits in 21 patients fully resolved (average 3.3 mos), 9 partially resolved, while 4 were permanent.

Value of Somatosensory Evoked Potentials and Transcranial Motor Evoked Potentials Combined: 100% in Cervical Surgery

Patients undergoing OPLL procedures usually require the “balance technique” or total intravenous anesthesia (TIVA), consisting of propofol and alfentanil, without inhalation anesthetics to avoid interfering with intraoperative monitoring parameters. Li and associates discussed the value of intraoperative SEP and transcranial electrical motor evoked potentials (TcMEPs) in 200 spinal operations where TIVA was employed. The relative sensitivities of SEP and TcMEP alerts in detecting impending neurologic damage were, respectively, 37.5% and 62.5%, but combined they were 100%, without false-positive or false-negative alerts. Therefore, TIVA maximized the SSEP and TcMEP evaluations intraoperatively, thus improving the sensitivity and specificity of intraoperative neural monitoring (IONM).