Pain is one of the most common symptoms experienced by cancer patients and probably the one that maximally influences the quality of life. More than 75% of patients with advanced disease complain of severe pain.¹ The majority of these patients can benefit from treatment with oral opioids,¹ probably because of the nociceptive nature of pain in such cases. Other options are rehabilitation techniques, transcutaneous electrical nerve stimulation (TENS), acupuncture, and physical therapies.²^–⁵ For medically intractable pain from malignant disease, intrathecal administration of drugs can be taken into account, but considering the possible development of addiction and tolerance, which can turn into serious impairment of the overall quality of life,⁶ these patients may be considered for neuroablative procedures.^7,⁸

Chronic benign pain, on the other hand, can result from a multitude of causes and, despite the individual predominance of nociceptive or neuropathic features, in the majority of cases it is a combination of both, with the significant addition of psychopathological features. For these reasons, chronic pain from nonmalignant disease remains the major challenge to pain doctors and still today there is great uncertainty as to the proper surgical and nonsurgical treatment.^9,¹⁰

Nonmalignant and predominantly nociceptive pain results by definition from non-neural tissue damage (trauma, inflammation, degenerative disease, etc.); conversely, neuropathic pain results from neural tissue damage. In both cases psychological and psychosocial factors, typically coexisting with painful symptoms, make the eventual pre- and postoperative clinical assessment particularly difficult.

For many years, surgical therapy for pain has relied on ablative or “lesional” procedures, consisting of disruption or interruption of anatomical structures and pathways involved in the transmission of painful sensations. However, the rates of complications, pain recurrence, and the development of deafferentation pain due to such procedures were noted to be rather high; over time, these techniques benefited by several improvements, thanks to the introduction of microsurgery and to a more extensive knowledge of the anatomical functional correlations between pain modulative systems.

Although the patients’ selection criteria for ablative procedures have become increasingly selective (also with the aid of thermocoagulation and of CO₂ laser), the development of neuromodulation procedures (by means of electrical stimulation or of intrathecal administration of drugs) has led to a decrease in the indications for such surgery.⁶

The recent advancements in the electrophysiological field along with the development of neuronal and axonal network modeling have made possible the explorative instrumental armamentarium now available for functional neurosurgeons, and a large surgical experience has been gained with patients suffering from refractory pain.

Lesional Surgery

Lesional procedures for the treatment of refractory pain have their own rationale in the causative role of a given nuclear or axonal structure in the generation of altered nociceptive information. After the identification of the putative structure responsible for the transmission of established painful symptoms, this structure is ablated or “lesioned” by means of different techniques. It is important to consider neuromodulative procedures before proceeding to ablative techniques, and of course the indication for such surgery strictly depends on the prognosis quoad vitam of the individual patient, the previous pharmacological or surgical attempts already administered, the overall medical condition, and the patient’s choice. Before considering a patient for an ablative procedure, conservative nonsurgical therapy (or neuromodulation procedures) must have been attempted, maximized, and failed.¹¹

Peripheral Neurectomy

Known from the sixteenth century, thanks to Ambroise Paré, neurectomy consists of the resection of a portion or the whole of one or more peripheral nerves. It is an easy and simple procedure, performed under local anesthesia, but its long-term failure rate makes its indications in chronic pain management very limited today.¹² In fact, adjacent intact sensory nerves can reinnervate the anesthetic region, thus causing pain recurrence; a new pain sensation due to the denervation hypersensitivity and painful postoperative neuromas may develop, too.^12,¹³

Neurectomy is indicated in those cases in which pain is limited to the nervous distribution of a specific nerve; such cases are rare and it is thus preferable (given the innervation’s juxtaposition of different dermatomes) to perform peripheral neurotomies in steps. Painful neuromas following peripheral nerve injuries may benefit from neuroma excision and neurectomy, if conservative nonsurgical treatment has not succeeded.^13,¹⁴ Proximal neurectomy in amputee patients with painful stump neuromas can be of benefit, but nonspecific stump pains or phantom limb pains do not respond to nerve resection.^12,¹⁵ Chest wall cancer pain and postherpetic neuralgia also do not benefit from neurectomy.

In some rare cases it is possible to perform a trial infiltration of long-acting anesthetic, eventually followed by neurolysis with percutaneous thermocoagulation or with injection of neurodestructive agents, such as phenol or alcohol;¹⁶ potential action sites are the posterior ramus of the second cervical nerve in the case of occipital neuralgia and the posterior rami of the spinal intercostal nerves in the case of drug-refractory intercostal neuralgia.

Dorsal Rhizotomy and Dorsal Root Ganglionectomy

Dorsal rhizotomy implies the sectioning of the dorsal nerve roots. Extradural, percutaneous, and radiofrequency methods have been described as well as partial rhizotomy.¹⁷^–²⁰ The procedure was indicated especially in the thoracic and sacral regions for malignant pain,²¹ but because of the high rate of pain recurrence^22,²³ and development of dysesthesic or deafferentation pain²⁴ the procedure has been all but abandoned these days.

Performed first in 1966 by Scoville,²⁵ based on the discovery that a certain number of axons in the ventral root were unmyelinated afferent fibers from the dorsal root ganglion,²⁶^–²⁸ dorsal root ganglionectomy showed some long-term pain relief in the treatment of chest wall pain, known as the postthoracotomy syndrome.¹¹ Some authors suggest it for sciatica, too, but there is some controversy about this indication.

Dorsal Root Entry Zone Lesions

The dorsal root entry zone (DREZ) is an anatomical entity that includes the central portion of dorsal root, the tract of Lissauer (TL), and layers I to V of the dorsal horn, where the afferent fibers synapse with the origins of the sensory pathways.²⁹ The TL plays an important role in the intersegmental modulation of the nociceptive afferents. It is located dorsolaterally to the dorsal horn and it is divided in two parts: (1) the medial part receives nociceptive afferents directed to the dorsal horn and transmits the excitatory effects of each dorsal root to the adjacent segment;^30,³¹ (2) the lateral part receives longitudinal endogenous propriospinal fibers interconnecting different levels of substantia gelatinosa (SG) and thus conveying the inhibitory influence of the SG into the neighboring metameres.³¹ The SG, through synaptic connections with the dendrites of some neurons of the spinoreticulothalamic (STR) tract, exerts a strong modulating effect on the nociceptive input (Fig. 49.1A). When the large lemniscal afferents in peripheral nerves or dorsal roots are altered, there is reduction of the inhibitory control of the dorsal horn, hence resulting in excessive firing of the dorsal horn neurons and causing deafferentation pain.³²^–³⁵

FIGURE 49.1 A, Transverse hemisection of the spinal cord at the lower cervical level with myelin stained by luxol-fuchsin showing the myelinated rootlet afferents that reach the dorsal column (DC). Small arrow: Pial ring of the dorsal rootlets. Large arrow: Microsurgical DREZotomy target. B, Scheme of DREZ area and DREZotomy target. The pial ring (AP), located about 1 mm before the penetration of the rootlet into the dorsolateral sulcus, is considered the point of transition from the peripheral to the central segment of the rootlet. Peripherally, the fibers are mixed together, but at the level of the AP, the fine nociceptive fibers run more laterally on the rootlet surface. In the central segment, they group in the ventrolateral portion of the DREZ to enter the dorsal horn (DH) through the tract of Lissauer (TL). The lemniscal fibers (Lem) run dorsomedially in the deeper part of the rootlet, and the myotatic fibers (myot) run in the middle of the DREZ. The black triangle indicates the proposed extent of the surgical lesion. C, Intraoperative view during microDREZotomy. While the sucker is elevating the dorsal rootlet, the dissector is pointing at the DREZotomy target. DREZ, dorsal root entry zone.

(A modified from Fig. 56.1 in Burchiel KJ, editor. Surgical Management of Pain. New York: Thieme; 2002.)

Following avulsion injuries of the brachial or lumbosacral plexus between 20% and 90% of patients may develop severe deafferentation pain either immediately after injury or delayed until up to 3 months.

The first DREZ open surgery procedure was performed by Sindou in 1972 on a patient with chronic pain due to Pancoast syndrome.³⁶ Soon after him, in 1974, Nashold started using radiofrequency thermocoagulation.^37,³⁸ Later, DREZ procedures were performed with laser^39,⁴⁰ and with the use of ultrasound probes.^41,⁴²

The procedure known as microsurgical DREZotomy (MDT) was again accomplished by Sindou ²⁹ and involves several segments of the lateral portion of the dorsal horn (where C fibers predominate), meaning the destruction of the LT and laminae I to V of Rexed (Fig. 49.1B and C). By sparing the medial portion of the dorsal horn where large A fibers enter, Sindou tried to avoid complete abolition of tactile and proprioceptive sensation, preserving antinociception and preventing deafferentation.⁴³ Intraoperative sensory evoked potentials (SEPs) during MDT are recommended for identification of the spinal cord segments and can also be helpful in monitoring the surgical procedure itself.⁴⁴^–⁴⁶ Sindou developed special microelectrodes for intraoperative microelectrophysiology studies and performed microdialysis studies in the dorsal horn as well.^47,⁴⁸

MDT has several indications. Some cancer pain patients may benefit from MDT. Good candidates are patients with long life expectancy, sufficient general conditions to undergo surgery and general anesthesia, and topographically delimited pain due to well-localized tumors. MDT from C7 to T2 can be performed for Pancoast syndrome.⁴⁹ Malignancies with circumscribed invasion of the thorax, of the abdomen wall, of the perineal floor, or lumbosacral roots or plexus are other indications for MDT. For more extensive cancer, intrathecal opioids or high cervical anterolateral cordotomy is preferable.²⁹

Patients with chronic deafferentation pain from plexus avulsion are tremendously difficult to manage for pain doctors. Even if in some cases initial conservative therapy may be of some help, standard analgesics and narcotics are usually ineffective and medical management is limited to antidepressant, sedative, and anticonvulsant medications combined with psychological support.⁵⁰ DREZ lesion surgery that is not limited to the avulsed segments but is extended to the adjacent roots is instead recommended for plexus avulsion pain. The results are extremely good, with more than 85% of patients reporting good to excellent pain control after brachial avulsion,^6,^36,⁵¹^–⁵⁴ although pain relief is fairly lower for conus medullaris root avulsion.⁵⁵ Mortality rate is low,^6,⁵¹ and morbidity consists of transient sensory deficit and mild weakness.⁶ DREZ lesion surgery for lumbosacral avulsion carries less than 10% risks of bladder and sexual dysfunction.⁵⁵

Pain following spinal cord injuries (SCIs) can have a multitude of causes, and hence rigorous patient assessment is mandatory. MDT is indicated for burning pain with radicular distribution at the level of the lesion or for patients complaining mainly of allodynia and electric shock–like border-zone pain. Conversely, pain in the totally or almost totally anesthetic area below the lesion, especially in the perineosacral region, is not favorably influenced by MDT.²⁹ These patients should be referred to rehabilitation services.

Neurostimulation techniques are the first treatment option for relief of pain due to peripheral nerve injuries and to limb amputation; if these methods fail, DREZ lesion surgery can be considered for both. In peripheral nerve injuries, DREZ surgery may be particularly useful when the predominant component of pain is paroxysmal (electrical shooting pain), associated with allodynia, hyperalgesia, or both.²⁹ After limb amputation two types of pain may develop and may coexist: pain in the phantom limb and pain in the stump. The former may be reduced by DREZotomy, while the latter is inconstantly influenced.²⁹

Finally, MDT can be performed also for severe occipital neuralgia, unbearable laterocervical pain, and postherpetic pain, but the procedure has been performed only in small subgroups of patients and has had a high recurrence rate.^56,⁵⁷ Based on the fact that muscle tone was decreased in the operated areas after MDT,^36,⁵⁸ Sindou applied it also for treatment of harmful spasticity with reasonably good results.^59,⁶⁰^–⁶²

In 1978 Nashold described nucleus caudalis tractotomy/nucleotomy, also known as caudalis DREZotomy, in which DREZ lesion surgery is extended to the trigeminothalamic system for treatment of facial deafferentation pain such as trigeminal postherpetic neuralgia and facial anesthesia dolorosa.^10,⁶³ The results are not as good as those for the other major indications of DREZotomy, but almost 50% of patients may obtain pain relief, and it should be considered that these patients are typically not responding to standard narcotic therapies. For patients without prominent allodynia or hyperpathia, on the other hand, neurostimulation procedures are preferred.⁶

Provided that rigorous selection criteria are applied, DREZ surgery can achieve very good pain control in some intractable painful syndromes. Sindou proposed a schematic decision-making process for neuropathic pain.⁵⁶ Accurate DREZ surgery requires good knowledge of the radicular innervation and of the surgical anatomy of the spinal cord and roots.⁵⁶

Sympathectomy

Sympathectomy means the interruption of the paravertebral sympathetic ganglion chain at a chosen level. Used since the end of the nineteenth century for several diseases,⁶⁴ it is still indicated for the treatment of a wide group of conditions sympathetically maintained and in some cases of vascular diseases.⁶⁵^–⁶⁷

The term causalgia (“burning pain”) was first introduced by Mitchell in 1864 to describe a syndrome characterized by burning pain following a partial peripheral nerve injury caused by a high-velocity missile. Its classic triad includes burning pain (associated with allodynia and hyperpathia), autonomic dysfunction, and trophic changes.⁶⁸ The severe form is known as major causalgia and implies always a high-velocity missile injury, and minor causalgia is reserved for less severe forms including also some described after nonpenetrating trauma.⁶⁹ The median and sciatic nerves and the brachial plexus are most commonly affected.

Reflex sympathetic dystrophy (RDS)⁷⁰ consists of many pain syndromes that result from a variety of causes that may or may not include direct nerve trauma. The autonomic nervous system was thought to be implicated, although the “reflexive nature” is still to be demonstrated and the distrophic features are not always present. Sudek’s atrophy and Raynaud’s syndrome have been attributed to sympathetically mediated disorders, too.

In order to reduce confusion the term complex regional pain syndrome (CPRS) was coined to describe a symptom complex and not a particular syndrome or a medical entity.⁷¹ The expression sympathetic maintained or mediated pain embraces a spectrum of conditions in which the main symptom, pain, may be associated with vasospasticity and dystrophic features and can be relieved by interrupting the sympathetic outflow to a body region.^66,⁷²^–⁷⁴

Upper extremity and upper thoracic sympathectomy implies dividing the chain below the first thoracic ganglion and resecting the T2 ganglion either with open surgery or endoscopically ^75,⁷⁶ or percutaneously by chemical, electrical, or radiofrequency techniques.^77,⁷⁸

Lumbar sympathectomy requires the removal of the L2 and L3 sympathetic ganglia (occasionally L1 and T12 to reach the thigh) usually through a retroperitoneal approach.

Open surgical sympathectomy carries high success rates, up to 100%, and low complication rates, between 2.5% and 5%.^6,^51,^68,⁷⁹ Pain recurrence is possible, but its rates vary considerably, ranging between 0% and 33% in many series reported.^64,^67,^68,⁸⁰ Conversely, it is well recognized that best results are obtained early in the course of the disease before the development of trophic changes,^64,^66,^73,⁷⁴ and therefore, rigorous early assessment by a pain specialist is needed.¹⁰

Sympathetically maintained pain is one of the few pain syndromes in which the first treatment option may include an ablative procedure rather than conservative therapy.

Cordotomy Procedures

Anterolateral Cordotomy

Anterolateral cordotomy (AC) for the management of pain related to malignancies or chronic pain has been commonly used in the past. Now it is performed much less frequently than it was several decades ago owing to the better results in pain control achieved with the pharmacological approach and the development of neuromodulation devices. However, AC remains a valuable technique for some patients, and it should be part of the armamentarium of any surgeon who is caring for patients with intractable pain.

The basis for AC resides in the neuroanatomy of the ascending pathways transmitting nociceptive information. A detailed description of this anatomy is not the aim of this chapter, and the reader can find more extensive information in other publications.^81,⁸² Both clinical and experimental observation in the last century provided evidence that the anterolateral quadrant of the spinal cord contained mainly contralateral ascending nociceptive pathways.⁸³^–⁸⁹ This fnding suggested the use of AC for the control of pain. The pathways reaching suprasegmental levels throughout the anterolateral quadrant of the spinal cord are the spinothalamic tract (STT), the spinoreticular tract (SRT), the ventral spinocerebellar pathway, the spino-olivar pathway, and the propriospinal pathways.^90,⁹¹ The STT and SRT are the tracts mainly involved in pain transmission. The SRT, also termed paleospinothalamic tract, provides indirect connection between the spinal cord and the thalamus,⁹² and the STT, also termed the neospinothalamic tract, provides a more direct monosynaptic connection mainly to the lateral thalamus.⁸³ The primary terminations of the SRT are the intralaminar nuclei of the thalamus,⁹³ thus being primarily related to the aversive and alerting aspect of pain. The STT participates in both the sensory discrimination aspects of pain projecting to the lateral thalamus and in the aversive aspects of pain projecting to the intralaminar thalamus, thus representing the main target of AC. Unfortunately, the STT is not a discrete, separate bundle of fibers, but is diffusely intermixed with other ascending and descending systems (this being responsible for many of the unwanted side effects and complications that can accompany AC). The general organization of the anterolateral quadrant (AQ) ascending sensory system is that lower spinal dermatomes are represented more dorsally and laterally, whereas the higher dermatomes are represented more anteriorly and medially.^90,^94,⁹⁵ The descending spinoreticular pathways are also located in the AQ of the spinal cord, and they mediate myriad automatic functions.

The ideal candidates for AC are cancer patients with unilateral, localized pain. Even unilateral upper body pain, such as that experienced by patients with lung carcinoma, mesothelioma, or Pancoast tumor, can be treated by a cervical percutaneous approach.^96,⁹⁷ Bilateral cordotomy can be proposed only for cases with bilateral pain in abdominal, pelvic, or lower extremity regions, and pain in the upper trunk or extremity is considered a contraindication because of the high risk of respiratory complications.^96,⁹⁷ Nonmalignant pain can be treated even if it is probably preferable to use a morphine pump.

Spinothalamic cordotomy aims to interrupt the spinothalamic tract ascending contralaterally to the painful side. The technique of AC has evolved over the past decades in attempts to make the procedure safer and more effective. AC can be performed as an open or percutaneous procedure.

Open Cordotomy

The open approach is done only at high thoracic levels, with the patient in general anesthesia, and with less possibility to control the functional effect of the section of the AQ. This procedure is appropriate only for patients with pain that is lower than the midthoracic level. In addition, there is a discomfort for the patient related to the healing of the thoracic wound. The advantage is related to the ability to destroy the AQ more completely and to avoid the respiratory complications that can attend high cervical cordotomy.

The procedure is performed with the patient in the prone position. Neurophysiological monitoring can be done with electromyography (EMG) activity recorded in the lower extremities during spinal cord stimulation prior to the section.⁹⁸ Removal of the spinous processes and the lamina bilaterally at T2-T3 more widely to the side of the AC is performed. The dura is opened under microscopic view. The arachnoid over the lateral spinal cord and associated nerves are dissected carefully in order to identify the dentate ligament, which is divided. The cord is then rotated gently in order to visualize the ventral roots. Using microtechnique, the pia over the AQ is opened at an avascular area from the level of the dentate ligament posteriorly to the level of the ventral roots anteriorly. At this point a cordotomy electrode can be inserted into the white matter of the AQ. Neurophysiological monitoring can be performed to identify the corticospinal tract. Higher frequency of stimulation can be used to activate ascending fibers if the wakeup test is performed, as advocated by some authors.⁹⁸ The transverse diameter of the spinal cord is measured, and a right angle probe with blunt extremity that will reach the midline is used to make the incision. The probe is swept anteriorly and a large anterolateral quadrant lesion is completed. The dura is therefore closed in a watertight fashion and the remainder of the wound is closed in a standard fashion.

Percutaneous Cordotomy

Percutaneous AC is superior to conventional open methods. It is performed with the patient under local anesthesia, requires no incision, and allows excellent functional monitoring prior to completion. In addition, with the patient awake in response to neuromodulation, the functional characteristics of the region of the spinal cord to be sectioned can be studied in more detail. It is also more likely to provide pain relief for symptoms above T5 than the open cordotomy. This technique has been pioneered by Mullan and associates,⁹⁹ and later modified by the use of radiofrequency, image guidance, and functional mapping.¹⁰⁰^–¹⁰²

Contrast material should be administered in the subarachnoid space. This could be done preoperatively (20-30 minutes before) by a lumbar puncture (in this case the patient should be maintained in the Trendelenburg position before the procedure) or at the beginning of the procedure by needle insertion at the C1-C2 level. The patient is placed in a supine position in the computed tomography (CT) unit with the head slightly flexed. Under local anesthesia and intravenous sedation if needed, the needle is advanced from the lateral neck into the C1-C2 intradural space. Lateral fluoroscopy allows identification of the appropriate site to start the needle trajectory toward the spinal canal and the final position of the needle (Fig. 49.2A). Once the dura is penetrated, cerebrospinal fluid (CSF) flow will be evident after stylette removal. At this point, an axial scanogram by CT allows the measurement of the spinal cord and is used to better understand intradural needle positioning. The tip diameter of the needle should be guided anterior to the dentate ligament and posterior to the anterior cord (1 mm anterior for lumbar fibers and 2-3 mm anterior for thoracic and cervical fibers). The needle in its ideal position is nearly perpendicular to the spinal cord (Fig. 49.2B). Once the position of the needle is satisfactory, the electrode is passed through the spinal needle into the spinal canal and the spinal cord. Penetration of the pia results in a brief increase in local pain. Correct positioning of the electrode can be performed by CT scan (Fig. 49.2C and D). Now electrical stimulation is performed to adjust the electrode position. Stimulation at low frequency (2-5 Hz) is used to evoke motor responses. Sensory stimulation is done with higher frequency (100 Hz). Placement of the electrode in the STT and SRT area is confirmed by the occurrence of contralateral sensory phenomena, usually a feeling of warmth or cold; with higher stimulus strength, a painful sensation can be evoked.¹⁰³ When adequate electrode positioning has been performed, the initial lesion is made by using an electrode with a 2-mm exposed tip applying 30 to 40 mA for 30 to 60 seconds.¹⁰¹ After this lesion, the patient is examined to evaluate the area of analgesia obtained. Further lesions can be performed in cases of incomplete results in the target area by increasing the time of passing current or advancing the electrode tip in small increments of 0.5, 1 mm. If the procedure is performed satisfactorily, an ipsilateral Horner’s syndrome usually occurs.

FIGURE 49.2 A, Schematic representation of cordotomy procedure. Insertion of the needle into the C1-C2 level in the supine position (B), position of the needle at the right C1-C2 space in the axial computed tomography (CT) image (C), and final position of the electrode in the axial CT scan (D). Schematic representation shows the final electrode position in the target at the level of the cervical spinal cord and the close anatomical structures.

(Modified from Burchiel KJ, editor. Surgical Management of Pain. New York: Thieme; 2002, Figs. 59.1A (part A), 59.3B (part B), 59.3C (part C), and 59.1C (part D).)

The results of the cordotomy are variable and mainly related to the investigator who is doing the reporting and the criteria used for determining success.

The more recent literature is almost exclusively related to percutaneous procedures. The results are better for pain related to malignancies. In experienced hands, the initial pain control is achieved in 90% of patients. However, the level of analgesia falls with time, reaching 40% of patients at 2 years.¹⁰⁴

The complications resulting from AC are related to the damage of the STT and SRT and of all the other adjacent tracts (Fig. 49.2D). Damage to STT and SRT can lead to painful dysesthesias. Damage to nearby structures can result in (a) respiratory failure and death, (b) bowel, bladder, and sexual disfunction, (c) hypotension, (d) ipsilateral weakness, (e) mirror pain, or (f) ataxia. In cervical cordotomies, respiratory dysfunction can be the principal complication. This is particularly true for patients with preexistent respiratory disorders and in cases of bilateral cordotomies. In this last situation, respiratory functions should therefore be carefully observed in the postoperative period. In the past, with the use of open cordotomy, higher rates of complications were observed. Two reasons can be recognized as the cause of complications: (1) needle mislocalization, which is more difficult with the use of CT-guided AC; and (2) involuntary enlargement of the sectioned area, which is less frequent with the use of recently developed electrodes and small thermic lesions. Therefore, percutaneous AC offers a reduction in the percentage of complications.

Percutaneous CT-guided anterolateral cordotomy is an effective method to control pain in cancer patients. It can be used in association with other less invasive methods, such as morphine pumps and neurostimulation, to offer these patients a higher quality of life.

Cingulotomy

Cingulotomy has been successfully used to treat intractable cancer pain.¹⁰⁵^–¹⁰⁸ The cingulate cortex is a key component of the limbic system, and its anterior cingulate gyrus plays an important role in the integration of nociceptive, motor, affective, and memory functions.¹⁰⁹ Experimental studies on animals and also functional studies in human volunteers demonstrated a role of cingulate gyrus in control of contralateral nociceptive information.¹¹⁰^–¹¹⁵

Cingulotomy can be considered as an option for patients with intractable cancer pain after failure of antineoplastic and pharmacological treatments and when conservative anesthetic procedures are not available.

Proper pre- and postoperative neuropsychological evaluation should be performed in every case. Magnetic resonance imaging (MRI)-guided stereotactic bilateral cingulotomy is performed.

Results of bilateral cingulotomy are variable. It can assure an improvement of pain control in selected cases.¹¹⁶ However, even after MRI-guided localization of the cingulate cortex, complications related to behavioral changes or cognitive deficit can occur.¹¹⁶

MRI-guided stereotactic cingulotomy, although valuable in selected cases, probably should be reserved for complex and refractory pain problems.

Mesencephalotomy

After the first attempts by Walker ¹¹⁷ and Drake and McKenzie,¹¹⁸ the procedure was modified by the application of stereotactic technique¹¹⁹ and avoidance of the medial lemniscus. With these changes, it was possible to reduce the incidence of severe dysesthesia and to reduce the mortality rate.

The first attempts in open surgery were to perform a section of the lateral spinothalamic pathways, but these resulted in unacceptable risks. Stereotactic procedures were therefore applied to interrupt nociceptive pathways with more precision. Looking for an ideal target for pain control, Shieff and Nashold ^120,¹²¹ elucidated that the procedures worked better and with fewer side effects when the lesion involved the multisynaptic reticulospinal pathways, sparing the spinothalamic tract, which was the original target.

The primary indication for mesencephalotomy is management of cancer pain involving the head, neck, or upper extremities when all other treatments have failed. The most important consideration is patient selection; in fact, this invasive approach can be considered only after an extensive clinical evaluation with a good correlation between the site of cancer involvement and the generation of pain. It can be of particular help when patients report the generation of intense psychological suffering.

Stereotactic procedure is performed to complete the sectioning, following target selection.

Gybels and Sweet ¹²² reported pain relief in 86% of patients, usually lasting for the remaining part of the patient’s life. Mortality rates ranged from 1.8% to 8%, although it can be difficult to attribute deaths to the procedure itself and not to the disease. Oculomotor dysfunction is a relatively frequent complication. Dysesthesia can occur in 15% to 21% of cases.

Mesencephalotomy can be a valuable option for the management of cancer pain in selected cases.

Percutaneous Techniques for Trigeminal (and Glossopharyngeal) Neuralgia

The first clear description of trigeminal neuralgia (TN) was given in 1671.¹²³ John Fothergill,¹²⁴ in a paper published in 1773, described the typical features of TN, including its paroxysmal nature and association with triggering factors such as eating, speaking, or touching the face. In 1756, the French surgeon Nicholas André coined the term tic douloureux to describe at least three patients with TN treated by neurectomy.¹²⁵^–¹²⁸

The clinical features of the so-called classic idiopathic TN have been well documented and are now universally recognized. One of the pillars in our understanding of this syndrome is the classification that Eller and colleagues proposed in 2005.¹²⁹ These authors classified TN on the basis of two broad categories: the patient’s history and seven specific diagnostic criteria. Following Eller’s classification, TN type 1 identifies the classic idiopathic form, also known as the typical form of TN, and from now on we will refer to TN as this entity. TN is a chronic pain syndrome whose patients suffer from idiopathic episodes of spontaneous facial pain. This pain, which is experienced in one or more divisions of the trigeminal nerve, expresses itself as paroxysms of brief and excruciatingly intense bouts of stabbing, electrical shocks. These paroxysms of TN can arise spontaneously or in response to gentle tactile stimulation of a trigger point on the face or in the oral cavity. They may also be triggered by such natural activities as chewing, speaking, swallowing, touching the face, or brushing the teeth. TN pain is almost always experienced unilaterally, although there have been some relatively rare reports describing bilateral signs and symptoms.¹²⁹ TN type 1 pain typically occurs after conspicuously obvious pain-free intervals that can last for weeks, months, and years. The neurological examination is almost always normal, although cases have been reported in which a slight degree of sensory loss has been described.¹³⁰ The diagnosis of TN is always based on the patient’s clinical history. In terms of its pathophysiology, the features of classic TN are currently thought to be related to a compression of the trigeminal nerve root, usually by a blood vessel, at or near the root entry zone of the trigeminal nerve.¹³¹^–¹³⁴

The incidence of TN is about 2.3 to 4.5 per 100,000 new cases per year.¹³⁵ Age at onset is variable, but the incidence increases in the fifth and sixth decades of life.

From the time of its first recognition, TN has been treated in a variety of ways.^136,¹³⁷ Today several medical and surgical treatments are available.

Medical treatment is mainly based on the use of an anticonvulsant: carbamazepine, phenytoin, and gabapentin are the most frequently recommended. Centrally acting muscle relaxants, such as baclofen, are also used.

Glossopharyngeal neuralgia (GN) is a spasmodic, lancinating, and paroxysmal pain that starts in the posterior throat or base of the tongue and often radiates down the throat and side of the neck. Often pain is triggered by swallowing or yawning. Typically, cocainization of the area reduces pain and has been proposed to confirm diagnosis.¹³⁸ Seldom, hypotension, syncope, and cardiac irregularities may accompany GN.^139,¹⁴⁰ Isolated GN occurs at a rate of 1 case in every 70 to 100 cases of TN;¹⁴¹ concurrence of TN and GN is also possible.¹⁴²

Percutaneous Injection of Neurodestructive Substances

In 1912 Hartel proposed the procaine injection, and later in 1914 the alcohol injection, of the gasserian ganglion for TN.^143,¹⁴⁴ In 1940 Harris reported a series of 2500 cases treated through this method.¹⁴⁵ However, the high rate of postinjection paresthesia and anesthesia dolorosa and some reported cases of major complications due to the diffusion of alcohol in the posterior fossa, along with a high pain recurrence rate, caused the technique to be abandoned.

Conversely, glycerol injection of the ganglion, first introduced by Hakanson in the 1970s,¹⁴⁶ occasionally is still performed today. The procedure is relatively safe, can be repeated if necessary, and is well tolerated, but it may cause transient sensory loss, corneal anesthesia, and dysesthesia.^147,¹⁴⁸ The main drawback is the rate of pain recurrence, which is reported to be up to 10% in the early postoperative period, up to 50% at 3 years, and 90% at 6 years.^147,^149,¹⁵⁰

Percutaneous Trigeminal Radiofrequency Thermocoagulation

Even though it had been tried since the beginning of the twentieth century,^151,¹⁵² it was not until the mid-1960s, with the modifications of the technique by Sweet, that this procedure became popular. Sweet’s modifications consisted of electrophysiological stimulation for precise localization, reliable radiofrequency current for nerve destruction, intermittent patient sedation with short-acting intravenous drugs allowing intraoperative patient assessment, and temperature monitoring to control precisely the configuration of the site.^94,^153,¹⁵⁴ With these modifications the use of radiofrequency rhizotomy spread widely and it is still commonly used.

The rationale is based on the fact that pain fibers are carried by unmyelinated C-fibers or thinly myelinated Aδ-fibers that are blocked at a lower temperature than those of larger Aα- and β-fibers carrying deep and tactile sensations.¹⁵⁵^–¹⁵⁷ Thus, radiofrequency-induced heat will destroy the former fibers, sparing the latter ones.

The procedure is done in the operating room, even though some authors perform it as outpatient surgery in the radiography suite.

The technique consists of the introduction of a needle under fluoroscopy at the level of the gasserian ganglion through the foramen ovale, entering 2.5 cm lateral to the oral commissure and aiming toward the medial aspect of the pupil (Fig. 49.3A and B). Several methods have been described to place the needle into the foramen ovale;¹⁵⁸^–¹⁶⁰ careful checking under fluoroscopy (Fig. 49.3C) and considerable training and experience are mandatory to avoid internal carotid artery injuries or penetrating the foramina adjacent to the foramen ovale. Once at the target, confirmed by outflow of CSF, the electrode can be inserted.

FIGURE 49.3 A, Schematic representation of the anatomical landmarks for needle insertion in the foramen ovale, following Hartel’s technique. Point 1, medial aspect of the pupil, and point 2, 3 cm anterior to the auditory external meatus, indicate the direction of the foramen; point 3, 3 cm lateral to the oral commissure, defines the point of needle initial penetration. B, Intraoperative picture of the needle insertion toward the patient’s cheek in the right foramen ovale. C, Intraoperative fluoroscopy showing the needle inserted into the left foramen ovale. D, Intraoperative clinical assessment of trigeminal functions after thermocoagulation of left trigeminal nerve.

Electrode placement is guided by fluoroscopy: For V3 pain, the electrode tip lies within 5 mm proximal to the clivus profile and is directed caudal. For V2 pain it should placed at the clivus profile, and for V1 pain the electrode tip lies within 5 mm distal to the clivus profile and is directed cephalad. The electrode tip should not be advanced more than 8 mm deep to the clivus profile because it can injure the abducens nerve in Dorello’s canal or penetrate the temporal lobe. Final placement of the electrode tip is determined by the patient’s response to electric stimulation.

With the patient under mild sedation, an average of three lesions at 60 to 70 degrees for 90 seconds are usually done. The goal is analgesia in the primarily affected trigeminal division, hypalgesia in correspondence of trigger points, and mild hypalgesia in the secondarily affected trigeminal divisions. After each lesion, clinical assessment of facial sensitivity, corneal reflex, and strength of the muscles of mastication is mandatory (Fig. 49.3D).

The procedure does not require general anesthesia, can be performed for patients not suitable for open surgery (the elderly, those with comorbid conditions, etc.), and can be repeated if necessary. Immediate pain relief can be obtained in up to 98% of patients,^147,¹⁶¹ but the long-term recurrence rate may be particularly variable: 25% to 37% at 5 years, 25% to 80% after 10 years,^162,¹⁶³ or 27% overall (early and late recurrence) in a study with an average follow-up period of 9 years.¹⁶⁴ Almost all patients develop numbness in the face after the procedure, but in most cases this is tolerable. The mortality rate is extremely low;^147,¹⁶⁵ loss of corneal reflex occurs in 3.5% to 7%; and cheratitis is seen in less than 3%.^147,¹⁴⁸ Dysesthesia develops in 6% to 24% of patients, but anesthesia dolorosa occurs in only 0.2% to 4%, with higher risk in more complete or extensive procedures.^147,^150,^161,¹⁶⁴ Trigeminal motor function may be impaired, but most of the time this effect is transient.¹⁶⁴ When patients are asked to rate the procedure and the outcome, the majority of them are usually satisfied.^162,¹⁶⁴

By the same technique, the glossopharyngeal nerve can be reached percutaneously at the foramen lacerum, allowing a postganglionar sectioning of the fibers.¹⁶⁶

Percutaneous Trigeminal Balloon Compression

The idea of compressing with open surgery the root of the trigeminal nerve to treat TN was first proposed around 1950, but the results were not encouraging.^167,¹⁶⁸ Later, Mullan proposed the gasserian ganglion compression through a percutaneus approach, reporting good results.¹⁶⁹^–¹⁷¹

The procedure is performed in the same way as for radiofrequency thermocoagulation until the ganglion is reached. Then a balloon catheter is inserted. A characteristic pear figure appears under fluoroscopy when the balloon is properly inflated with contrast agent in Meckel’s cave (Fig. 49.4). The goal is to compress the nerve at 1100 mm Hg or 1.3 to 1.5 atm for 1 minute.

FIGURE 49.4 When the balloon is properly inflated with contrast agent in Meckel’s cave, the typical pear-shaped figure appears under fluoroscopy.

Balloon compression is particularly indicated for first trigeminal division pain, because it carries a lower risk of corneal reflex loss and cheratitis compared to radiofrequency thermocoagulation. Nevertheless, during the procedure the patient may develop bradycardia and hypotension ¹⁷² and a pacemaker may be required; the compression is mild and this leads to a higher rate of pain recurrence. The initial rate of pain relief is 92% and the overall recurrence rate is 26%; postoperative numbness and mild to moderate hypesthesia occur in about 50% to 60% of patients; and anesthesia dolorosa and corneal anesthesia are extremely rare, less than 0.1% of cases. On the other hand, masseter weakness can occur in about 10% of patients.¹⁴⁷

Microvascular Decompression for Trigeminal (and Glossopharyngeal) Neuralgia

Dandy ¹⁷³ was the fist to propose that there might be a causal relationship between pain paroxysms and the compression of the trigeminal root. This compression is typically caused by adjacent arterial loops, although on occasion, tumors, arteriovenous malformations, and aneurysms located in this region have been known to cause this kind of compression. Though Dandy was the first to describe the role played by compression in 1929, it was not until the 1950s that any kind of therapeutic relief became obtainable by decompressing the trigeminal nerve in TN patients.^174,¹⁷⁵ The notion that a microvascular compression might be causing TN has gained much support from the work of Jannetta,^134,¹⁷⁶^–¹⁷⁸ who was able not only to find a compressing vascular contact in a high percentage of TN patients but also to demonstrate that prolonged pain relief could be obtained by decompressive surgery, without causing any sensory loss. Patients suffering from typical idiopathic TN usually are found to have a blood vessel that is in close contact with the trigeminal root entry zone (TREZ). This finding is typically made during surgery, during the exploration of the cerebellopontine angle (CPA), or radiologically by MRI^176,¹⁷⁸^–¹⁸⁰ (Fig. 49.5).