Introduction

The number one overall complaint from patients in an outpatient clinical setting is pain. At times, the diagnosis and treatment of a given pain syndrome can be challenging. Patients present to pain clinics for a multitude of different reasons. In any physical examination involving a chronic pain patient, a thorough sensory neurological examination is important. Clinicians need to understand the evolution of nerve testing and to be able to differentiate the small-pain-fibers method of testing from previous techniques. In the 1940s, a logical approach to the sensory examination was identified with defined surface areas highly correlated with specific anatomic dermatomes. These dermatomes are associated with specific nerve roots and are very useful for the clinician attempting to ascertain the source of a pain generator. The concept of current perception threshold was later developed to measure the level of sensory deficit. There was significant variability associated with this diagnostic technique, which involved changing skin resistance. These limitations led to further evolution and development of sensory conduction testing which will be discussed in this chapter.

Sensory Nerve Conduction Threshold Testing

A sensory nerve conduction threshold test (sNCT) is a psychophysical assessment of both central and peripheral nerve functions. It measures the detection threshold of specifically calibrated sensory stimuli. Normal sensory nerve action potentials indicate that the cells of the dorsal root ganglion and the large myelinated axons are healthy and intact. If a patient has numbness, the abnormal process lies proximal to the dorsal root ganglion, or the patient has common small fiber or nociceptive neuropathy. Sensory nerve conduction testing can localize the anatomic basis of the disease and may become abnormal earlier in the course of a disease state as compared with motor nerve conduction testing. This procedure is intended to evaluate and quantify function in both large- and small-caliber fibers for the purpose of detecting neurologic disease. Sensory perception and threshold detection are dependent on the integrity of both the peripheral sensory apparatus and peripheral-central sensory pathways. In theory, an abnormality detected by this procedure may signal dysfunction anywhere in the sensory pathway including the receptors, the sensory tracts, and the primary sensory cortex up to the association cortex. This procedure is distinct from an assessment of nerve conduction velocity, amplitude, and latency. It is also different from short-latency somatosensory-evoked potentials. This instrument provides testing which is voltage mediated, and results are independent of changes in skin resistance. Essentially, voltage-actuated sensory nerve conduction has resulted in the development of a different type of instrument to quantitate sensory function.

Sensory nerve conduction studies are performed by electrical stimulation of a peripheral nerve and are recorded from a purely sensory portion of the nerve, and the recording electrode is the more proximal of the two. Sensory latencies are on the scale of milliseconds. Sensory amplitudes are much smaller than the motor amplitudes, usually in the microvolt (μV) range. The sensory nerve conduction velocity is calculated based upon the latency and the distance between the stimulating and recording electrode.

Sensory nerve conduction information can lead to a diagnosis other than peripheral neuropathy to explain the process that is occurring. It is limited in that it is not precise as to the site of deficit. sNCT testing is applicable and useful in many different clinical environments but may particularly be useful in the realm of spinal cord stimulation. The sNCT test measures painless current perception thresholds (CPTs) and atraumatic pain tolerance thresholds (PTTs) . Spinal cord stimulation modulates segmental large afferent fiber input, and sNCT testing reflects increases in both large and small fiber CPTs when functioning correctly. Monitoring spinal cord stimulator functionality via this method can confirm a sensory (suprasegmental) modulating effect on nociceptive fiber activity.

Additionally, despite the widespread application of sNCT testing and possible aid in assessing neuropathy, in 2004 the Center for Medicaid Services concluded the use of any type of sNCT device to diagnose sensory neuropathies or radiculopathies in Medicare beneficiaries is not reasonable and necessary. This has created a need to have more precise and cost-effective methods to define the specific pathological etiology.

The Small-Pain-Fibers Method

In 1998, the small-pain-fibers method was approved by the FDA. The pain-fiber nerve conduction threshold (pf-NCT) method uses an electrical stimulus with a neuroselective frequency to determine the minimum voltage causing conduction. Rather than comparing the data with population averages on a bell-shaped curve which has about 65% sensitivity, the patient is his control (e.g., a nerve on the left hand is measured against a nerve on the right hand). In a 3-year Louisiana State University School of Medicine Pain Center study, it was found that the nerve requiring the greatest voltage to cause conduction of the A-delta (fast pain) fibers identified nerve root pathology with 95% sensitivity. The test is painless and rapidly performed. A new version uses a potentiometer to objectively measure the amplitude of the action potential applied at a distant site along the nerve being tested. The previous version required the reporting of a sensation when the nerve fired, which introduces potentially confounding variables. This test does not require the patient to report a sensation though one may be experienced nor does it require myelin loss to detect function change (such as nerve conduction velocity testing), so velocity is not measured.

Devices used for pf-NCT such as the PAIN-NCS and Axon-II consist of a potentiometer (detector) placed near the spine, a ground sponge placed on the back, and a test probe (stimulator) placed near peripheral nerves being tested. An electrical stimulus of set frequency is applied with increasing amplitude until the potentiometer detects electrical nerve conduction. One such device that uses this technology is the neural scan. The neural scan has been shown to be an effective diagnostic device designed to identify selective nerve pathology by measuring the amplitude of localized sensory nerves, not only nerve functionality. A sNCT testing device only identifies a dysfunction somewhere in a sensory pathway, making the small-pain-fibers technology valuable regarding accuracy and precision of spinal cord pathology. A small-pain-fibers device assesses nerve pathology by measuring nerve response at differing points along a sensory nerve. It does not rely on the integrity of the overall central sensory pathways to the cortex rather specific and individual sensory nerves. Small-pain-fibers technology performs pain fiber nerve conduction studies by measuring the amplitude of the stimulus and the amplitude of the action potential.

In summary, the small-pain-fibers method of testing for spinal cord pathology is relatively new and largely unknown in the medical community. Future studies are warranted to better understand this technology and its role in identifying spinal cord pathology.

Altered Intraepidermal Nerve Fiber Density in Suspected Small Fiber Neuropathy

Determining intraepidermal nerve fiber (IENF) density is a useful clinical tool in the diagnosis of small fiber neuropathies (SFNs). SFNs involve C-fibers and Aδ-fibers conveying nociceptive and thermal stimuli and often present clinically as a burning sensation with diffuse pain. Despite the pain of SFNs, routine examination and electrodiagnostic studies do not determine the underlying pathology and often show no abnormalities in these conditions. IENF imaging is especially useful in patients with peripheral neuropathy and normal electrodiagnostic studies. IENF density is significantly reduced in patients with SFNs.

Analysis of skin biopsies using immunohistochemistry or indirect immunofluorescence can dependably identify IENFs. In several systemic illnesses, including diseases associated with mutations in genes encoding ion channels, immune-mediated SFNs, and neurodegenerative disorders, visualization of degenerated IENFs reveals the underlying pathology of the perceived pain. SFNs are most often seen in diabetes mellitus type II but have also been implicated in other diseases and idiopathic peripheral pain. Recent studies have established reference ranges for comparison, making these imaging methods clinically useful.

Methods of Intraoperative Neurophysiological Monitoring

With the increasing number and wide variety of spinal surgeries, iatrogenic neurologic injury is a rare but increasingly real complication. To reduce perioperative neurologic deficits, intraoperative neuromonitoring techniques (IONM) have been developed with notable technologic advancements over the last four decades. There are two main methods for IONM, specifically combined somatosensory-evoked potentials (SSEPs) and motor-evoked potentials (MEPs) . MEPs have been shown to have better sensitivity and specificity for new spinal cord deficits. Because of this increased accuracy, utilization of MEPs has become more commonplace in spine procedures over the last few decades relative to somatosensory-evoked potentials. Several specific newer methods of motor-evoked potential monitoring include transcranial motor-evoked potentials (tcMEPs), descending neurogenic-evoked potentials (dNEPs), and spontaneous electromyography. These newer methods utilize the same basic principles and offer alternative monitoring techniques when conventional techniques are unavailable or too difficult to employ.

In tcMEPs, the motor cortex is stimulated transcranially via electrodes placed on the scalp that act on the motor cortex with a pulse train of high-voltage, short-duration signal. Recording of peripheral muscles responses allows for testing of the entire motor pathway. This is favorable in events such as anterior spinal artery syndrome, where SSEP responses would fail to identify changes in spinal cord function because the dorsal columns would remain intact.

dNEPs record motor-evoked potentials from peripheral nerves or muscles via either direct or indirect stimulation of the spinal cord. An indirect stimulus is provided via the placement of needles into consecutive spinous processes. Direct stimulation is achieved by insertion of an epidural catheter onto the dura through a laminotomy defect within operative spinal levels. The sciatic nerve at the popliteal fossa is a common anatomical landmark for recording responses distally. dNEPs can help localize the area of spinal cord deficit by systematically stimulating at multiple points along the spinal column, allowing for precise mapping of the injury level.

Spontaneous electromyography detects the spontaneous electrical activity of muscles. Bipolar needles are used either intramuscularly or subdermally to detect neurotonic discharges from muscles during spine surgery. Proper needle placement is essential for an accurate EMG recording, with the electrodes being placed into the “belly” of each recorded muscle. Baseline EMG values are recorded before surgical start, and continuous recordings are made throughout the case. Unlike other modalities, spontaneous electromyography can provide real-time information about intrinsic nerve root function.

Historically, the ability to reliably monitor sensory afferents during cerebellopontine angle surgery has been difficult. However, in 2018 a new method utilizing the blink reflex was proposed by Simioni et al. The blink reflex can monitor the integrity of the sensory component of the trigeminal nerve, corresponding brainstem connections, and the facial nerve. More studies need to be performed, but the blink reflex has the potential to be a promising adjunct for neurophysiological monitoring in the future.

A case report from May 2018 showed how these methods of intraoperative neuromonitoring can be employed in a practical and clinically relevant manner. The case report addresses two cases of surgical correction of secondary scoliosis and describes monitoring spinal cord segments cranial and caudal to the level of an acute spinal cord injury using epidural electrodes. In both cases there was an intraoperative spinal cord injury during the instrumentation, which was detected by loss of the tcMEPs caudal to the intercostal thoracic muscles and loss of the lower limb somatosensory-evoked potentials (SSEPs) . The level of spinal cord damage was identified and confirmed by combined use of spinal cord recorded SSEPs and D waves. Two epidural recording electrodes were placed, one cranial and one caudal to the level of the lesion. In both cases, the spinal cord SSEPs were absent above the lesion but present below. D waves were present above the lesion and absent below. In these cases, during the remainder of the surgery, the authors used epidural SSEPs for monitoring of spinal cord function caudal to the lesion and D wave for the levels cranial to the lesion. They also performed the spinal cord-to-spinal cord-evoked potentials (stimulating proximally and recording distally to the lesion using the epidural electrodes), demonstrating a reproducible potential, which remained stable throughout the remainder of the surgery. They concluded spinal cord monitoring using epidural electrodes in patients with acute intraoperative spinal cord lesions facilitates identification and confirmation of the level of spinal cord injury, allows the surgeon to continue with the instrumentation in those cases when necessary, and can help establish a postoperative prognosis.

In summary, this chapter describes new horizons for diagnosing neuropathies and neurophysiological monitoring. These newer methods have the potential to increase accuracy, allowing practitioners to make more informed clinical decisions and to improve patient outcomes. Clinicians should be cognizant of the different approaches for the evaluation of neurologic injuries.