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Neurophysiol C/in (1990) 20, 399 423 © Elsevier, Paris

R e v i e w article

Ablative neurosurgical procedures for the treatment of chronic pain M Sindou, D Jeanmonod, pt°Mertens /

Departentent de neurochirurgie, tt6pital Neurologique et Neurochirurgical Pierre Wertheimer, Universit6 de Lyon, UFR Grange Blanche, 59 bd Pinel, 69003 Lyon, France (Received 21 June 1990; accepted 1 September 1990)

Summary - This article is devoted to ablative neurosurgical procedures used for the treatment of chronic pain. The authors detail only tOose procedures that are currently p e r f o r m e d . T h e procedures are classified as those directed to the peripheral nerves, spinal roots and cranial nerves; the dorsal root entry zone; the ascending extra-lemniscal pathways. The authors have analyzed the results of their own series and those published in the literature. They concentrate on the rationale and neurophysiological effects of the operations.

ablative procedures/ cancerous pain / chronic pain / DREZ-lesions / neurosurgery

R6sum6 - Techniques neurochirurgicales ablatives pour le traitement de la douleur chronique. Cet art# tie est consacr~ aux principales techniques neuroehirurgicales ablatives utilisdes p a r les auteurs p o u r le lraitement de la douleur chronique. Les interventions d~crites ont ~td classdes en trois rubriques: 1) eelles dirigPes sur les nerfs p~riph&iques, les racines spinales et les nerfs craniens sensitifs; 2) celles dont la cible est la jonction radiculo-m6dullaire post&ieure, c'est-~-dire la Dorsal Root Entry Zone (ie D R E Z ) ; 3) celles interrompant les voies extralemniscales. Pour cet article de synthbse, les auteurs oat analysd leurs propres r~sultats et ceux de la litt&ature. L "accent est mis sur les bases anatomo-physiologiques des interventions et sur leurs effets neurophysiologiques.

techniques ablatives / douleur canc~reuse / douleur chronique / I~sions DREZ / neurochirurgie

Introduction In the last two decades, neurostimulation (see references in Sedan and Lazorthes, 1978; Meyerson, 1983; Young et al, 1985) and intrathecal morphine therapy have assumed an important place in the neurosurgical treatment of chronic pain."Our clinical experience suggests that transcutaneous and dorsal column stimulation are only effective in deafferentation syndromes with a sufficient integrity of the correspond-

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ing lemniscal pathways (Sindou and Keravel, 1980, 1981 ; Keravel and Sindou, 1983). Intrathecal morphinotherapy is preferred in neoplasms with short life expectancy. Therefore ablative procedures are still useful for some types of chronic pain. In this article, the authors will not discuss all aspects of the neurosurgical armamentarium. Extensive studies have already been undertaken (White and Sweet, 1969; Gybels and Sweet, 1989). The authors will concentrate on the rationale and neurophysiological effects of the most currently used ablative neurosurgical procedures.

Ablative procedures directed to the peripheral nerve, spinal root and cranial nerve

Ablative procedures on the peripheral nervous pathways - whatever their technical modalities: surgical, chemical or thermal - display few indications for the treatment of chronic pain, with the exception of trigeminal neuralgia. In the majority of patients with so-called nociceptive pain (ie, due to an excess of noxious stimuli coming from the periphery), a total denervation of the painful territory would require interruption of too large a number of nerves or roots, because of extensive overlapping in their peripheral fields. When algias are topographi, call well-defined and very limited, ablative procedures can be useful. In a study analyzing 585 patients who underwent dorsal rhizotomy for pain caused by cancer, Sindou et af (1976) reported a 47% rate of pain relief with an average mortality of 5 %. For pain due to peripheral nerve injuries, post-thoracotomy intercostal neuralgias, occipital neuralgias, herpes zoster, interruption of the peripheral pathways according to most authors (Sindou and Goutelle, 1983) rarely gave long-lasting relief. Ablative procedures can however be used to eliminate the hyperpathic component of pain, not the spontaneous one(s). However, as pointed out by Tasker in a critical review o f the surgical approaches to the primary afferents and the spinal cord (1985): " t o treat deafferentation syndromes, it may be unwise to attack the accompanying hyperpathia by further denervation, for fear of further aggravation of the p a i n " . When resistant to antiepileptic medications, trigeminal neuralgia can be treated conservatively by microvascular decompression o f the trigeminal root entry zone at the pons (Sindou et al, 1990). We prefer this technique, provided the patient is able to tolerate general anesthesia. If the surgeon is not in favour of this method, the disease can be satisfactorily treated b y interruption o f the trigeminal afferent pathways (fig 1) (see references in Sind0u et al, 1987). Among the ablative techniques available, the most selective one is open microsurgical juxtapontine section of the pars major. The other destructive techniques are percutaneous and use as the lesionmaker : RF thermocoagulation, a chemical neurolytic agent such as alcohol, phenol or more recently glycerol, or a temporarily inflated balloon. Whatever the percutaneous method used, the long-term efficacy is proportional to the degree of sensory loss in the operated territory; none is able to selectively interrupt the nociceptive fibers. Radiofrequency (RF) thermocoagulation of the sensory cranial nerves (Kirschner

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I942; Sweet and Wepsic, 1974) as well as of the spinal nerve trunks, ganglia and rootlets (Uematsu et al, 1974) was based on animal experiments showing that a graded thermal lesion instantaneously blocked the action potentials of the delta and C-fibers (Letcher and Goldring, 1968; Frigyesi et al, 1975). In fact the destruction of fibers at temperatures ordinarily used for trigeminal neuralgia (60-80°C) is not so selective. Electrical sensitometry o f the face shows that the thresholds for tact and nociception are equally affected (I4ariz and Laitinen, 1986). Repetitive studies of the corneal, blink and masseter reflexes show a severe impairment to all types of afferences, with slow recovery if any (Cruccu et al, 1987). This lack of selectivity can be.understood if the pathological changes are considered, provoked by thermolesions in the dog. Two weeks after GasSerian thermocoagulation, massive necrosis of the ganglion cells occur s, End a scar tissue invasion not limited to selected fibers (Kanpotat and Onol, 1980)". Anatomical examinations per-

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Fig.1. Functional a n a t o m y of the trige'minal nerve. The sites of the most currently used procedures for trigeminal neuralgia are shown (Sindou et al, 1987). Long arrow : percutaneous procedures at the Gasserian ganglion (GG) or the root (R) level, through the f o r a m e n ovale : chemical neurolyses (with alcohol, phenol, glycerol), RF - thermocoagulation, balloon compression; short arrow : microsurgical juxta-pontine rhizotomy (ie selective section of the pars major (pro), which contains the pain fibers of'the=three territories of the trigeminal nerve); double arrow: tractotomy of the descending bulbar trigeminal tract or nucleotom y of the spinal trigeminal nucleus.

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formed at intervals up to 6 weeks after RF lesions of the peripheral nerves (made for 2 min at 45, 55, 75 and 85°C) show that ha all lesions, all sizes and types of fiber are affected and that after the 85°C lesion, there is a subtotal loss of myelinated fibers with an extensive myelin breakdown, together with a loss of unmyelinated axons (Smith et al, 1981). The preservation of function in large myelinated fibers, seen in acute experiments (Letcher and Goldring, 1968; Frigyesi et al, 1975) is probably related to a sparing of some of them because of their distance from the lesion site, and not predominantly because they are selectively protected as firstly hypothesized. The use of phenol as a selective neurolytic agent of the C-fibers for intrathecal injections was introduced instead of alcohol because of its high hyperbaric property and low diffusibility (Maher, 1957). In addition, when dissolved in a liposoluble iodine contrast medium, phenol is radiopaque and consequently easier to control. According to Nathan et al (1965) phenol exerts two types of action: an acute blockade of nervous conduction of the anesthetic type, as demonstrated in animals (Iggo and Walsh, 1960) and confirmed in humans v/a intraoperative recordings (Mark et al, 1962) and chronic damage affecting all sizes of fibers. Thus, its chronic effect should not be attributed to selective involvement of the C-fibers, but would be manifested when a "critical" number of fibers of every type are destroyed. This hypothesis is corroborated by postmortem histological studies (Stewart and Lourie, 1963; Smith, 1964) which show that the degenerative lesions involve not only the small caliber fibers, but also the large myelinated ones (both of the dorsal and ventral roots), and in addition some fibers of the cord ascending tracts. These findings are in accordance with the fact that - besides their effective results on nociceptive pain (Papo and Visca, 1976) - phenol neurolyses are not infrequently responsible for disabling dysesthesias and hypoesthesia, persistent motor weakness and hypotonia, and sphincteric disturbances. Relief of trigeminal neuralgia as a result of an injection of glycerol (a hypertonic substance with high viscosity), into the trigeminal cistern is not fully understood. Hakanson (1981) speculated that glycerol, by interacting both with the lipids and proteins of the nervous membrane, might reduce the afferent inflow of normal fibers that trigger pain and/or might selectively destroy the abnormal fibers that show patchy demyelination (Kerr, 1967) and would be responsible for impulse generation (Burchiel, 1980). Intraoperative recordings of the trigeminal root during glycerol neurolyses in man (Sweet et al, 1981) demonstrate a selective loss of A-delta and C waves with preservation of the early A waves. In animal models of injured peripheral nerves developing abnormal impulse generation, topical application of graded concentrations of glycerol (from 25 to 100O7o) first provokes a selective blockade of spontaneous action potential flring and C-fiber conduction, followed by a blockade of A-fiber conduction (Burchiel and Russel, 1985). Histological examinations (Rengachary et al, 1983 ; Lunsford et al, 1985 ; Vallat et al, 1988) have shown that glycerol produces myelin disintegration and axonolysis regardless of fiber size, and that the degree of damage is greatest at the periphery

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of the nerve. These nonselective anatomical alterations, which contrast with the electrophysiological data, but only apparently because the latter were recorded in acute conditions, are actually in accordance with clinical assessments. In fact, electrical sensitometry shows an elevation (in the order of 50°70) o f the thresholds, both for tactile and pain perception (Bergenheim et al, 1988) although patients rarely complain of numbness a n d / o r dysesthesias after surgery (Young, 1988).

Ablative procedures directed to the dorsal root entry zone

In the 1960's, extensive anatomical and physiological y o r k on the dorsal horn, particularly as expressed in the popular Gate Control Theory (Melzach and Wall, 1965), drew clinicians' attention to this site as the first level of modulation for pain sensation. This work convinced the first authors to consider the dorsal root entry zone (DREZ) as a possible target for pain surgery and to undertake anatomical studies and preliminary surgical trials in man in order to determine whether a destructive procedure at this level was feasible (Sindou, 1972). Rationale

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The DREZ is an anatomical entity which includes the central portion of the dorsal roots, Lissauer's tract and laminae 1-5 of the dorsal horn where the afferent fibers articulate with the cells from which the ascending extra-lemniscal pathw~tys originate (Sindou, 1972; Sindou et al, 1974; Mansuy and Sindou, 1978). The dorsal rootlets Each dorsal root divides into 4-10 rootlets, of 0.25-1.50 mm diameter each. Corresponding to two embryologically different elements, each rootlet is formed from a peripheral and central segment. The junction of the two portions named Tarlov's pial ring is, on average, 1 mm from the penetration of the rootlet into the dorsolateral sulcus of the spinal cord (fig 2). As e/ach rootlet has the same proportion of large to small diameter fibers as the root, each rootlet can be considered an anatomicalfunctional entity (Sindou et al, 1976; Sindou and Goutelle, 1983), ie a root in miniature. In the peripheral segment of the rootlet, the fibers have no particular organization with regard to size. However, on entering the spinal cord, most of the smalldiameter fibers (considered nociceptive) are regrouped laterally before penetrating Lissauer's tract, while the large fibers run centrally (with respect to the myotatic fibers which penetrate the grey matter) and medially (with respect to the lemniscal fibers which reach the dorsal column), as shown in figure 2. This lateral regrouping of the small fibers should allow them to be preferentially interrupted without disturbing most of the large fibers.

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Some authors have questioned whether all nociceptive fibers .reach the spinal cord through the dorsal roots. Anatomical and electrophysiological studies in animals showed that about 30°7o of the fibers in the yentral roots were afferent C-axons, originating from the dorsal root ganglion cells and projecting into the dorsal horn (Willis, 1985). These findings, challenging Bell and Magendie's law, have recently been clarified. The majority (but not all) of the ventral root afferents would actually not enter the cord through the lamina cribrosa of the ventral root, but instead make a U-turn to reach the dorsal horn viz the dorsal root (Willis, 1985). Lissauer's tract

The tract of Lissauer (TL), which is situated dorso-laterally to the dorsal horn, is composed of 1), a medial part which the small afferents enter and where they trifurcate to reach the dorsal horn, either directly or through a two metamere ascending pathway, 2), a lateral part through which a large number of longitudinal endogenous proprio-spinal fibers ~interconnect different levels of the substantia gelatinosa (SG).

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Fig 2. A. Dorsal rootlets. Organization of fibers at the dorsal root entry:zone (DREZ) in man. Each rootlet 1 m m in diameter) Consists of a peripheral and a central segment, the juncti6n of which constitutes the pial ring (AP). Peripherally, the fibers have no organization. In the neighbourhood of the pial ring, the small fibers are situated under the rootlet surface, predominantly on its lateral side. In the central segment, they regroup laterally to enter the tract of Lis'sauer (TL). The large fibers are located centrally for the myotatic fibers and~medially for the lemniscal o n e s . . T h e blaok triangle indicates the proposed extent of the surgical lesion, ie, the lateral and central bundles formed by the nociceptive and myotatic fibers, as well as the (excitatory) internal part of the T L a n d the apex of the dorsal horn.

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According to Denny-Brown et al (1973), the TL plays an important role in the intersegmental modulation of the nociceptive afferents, as its medial part would transmit the excitatory effects of each dorsal root to the adjacent segments and its lateral part would convey the inhibitory influences of the SG into the neighboring metameres. Thus, selective destruction of the medial part of the TL could cause a reduction in the regional excitability of the nociceptive afferents. The dorsal horn

Most of the fine nociceptive afferents which enter the cord through the TL medial part perpetrate into the dorsal horn crossing the dorsal aspect of th(e/SG, while the recurrent collaterals of the large lemniscal fibers (Ra~on y Cajal, ~901) approach the dorsal horn through the ventral aspect of the S~G (Szentagothai]~1964). As the dendrites of some of the spino-reticulo-thalamic (SRT) cells make synaptic articulations with the primary afferents inside the SG layers, SG is most appropriate to exert a strong segmental modulating effect on the nociceptive input (Wall, 1964).

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Fig 2. B. Posterior rootlet projections to the spinal cord. The small fibers terminate on the spino-reticulothalamic (SRT) cells, which they activate, and through interneuronal pathways on the anterior horn. The short recurrent collaterals of the large fibers (of cutaneous or proprioceptive origin) terminate on the SRT cells, which they inhibit. The large arrowhead shows the selective microsurgical lesion in the DREZ, which makes a 45 ° angle and extends 2 m m into the rootlet-spinal cord junction. M = media, L =,lateral part of the D R E Z ; GB = Goll and Burdach dorsal columns; Prop, Cut, Myot = proprioceptive, cutaneous, myotatic, afferent fibers ; SG = substantia gelatinosa; I, II, III, IV, V = lamination of Rexed ; ~, ?,-- alpha, g a m m a , motoneurons.

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When the large lemniscal afferents within peripheral nerves or dorsal roots are altered, there is a reduction in the inhibitory control that they exert on dorsal horn mechanisms. This situation results in excessive firing of the dorsal horn neurons. This phenomenon, thought to be at the origiri o f deafferentation pain, has been identified in some human cases by electrophysiological recordings (Loeser et al, 1968; Jeanmonod et al, 1989; Sindou and Jeanmonod, 1990) and reproduced in animal experiments (Loeser et al, 1967 ; Albe-Fessard and Lombard, 1983). Destruction of these hyperactive neurons might suppress the nociceptive impulses generated in the SRT pathways.

The dorso-lateralfuniculus The dorso-lateral funiculus contains descending inhibitory projections to the dorsal horn from the cortex, hypothalamus, periaqueductal grey, nucleus raphe magnus (Besson and Le Bars, 1979) and nucleus reticularis para-gigantocellularis (Hammond, 1986). Its destruction has been associated with hyperalgesia (Vierck et al, 1986).

Methods

Several attempts at lesioning the DREZ for treating pain have been made over the past two decades, using microsurgical techniques (Sindou, 1972), RF-coagulation (Nashold et al, 1976; Nashold and Ostdahl, 1979) and Laser (Levy et al, 1983; Powers et al, 1984).

Microsurgical-DREZ-tomy

(MDT)

The selective posterior rhizotomy in the DREZ method [or microsurgical-DREZ-tomy (MDT)] has been described in detail (Sindou et al, 1986; Sindou and Jeanmonod, 1989). MDT consists of microsurgical incision and bipolar coagulation performed ventro-laterally at the entrance to the rootlets into the dorso-lateral sulcus, along all spinal cord segments which have been selected for operation. The lesion, which penetrates the lateral part of the DREZ and the medial part of LT, extends down to the apex of the dorsal horn. The latter is recognized by its brown-grey color. The lesions are 2 mm deep and made at a 45 o angle (fig 2). The procedure is presumed to destroy the nociceptive afferents, ie, the thin fibers grouped in the lateral bundle of the dorsal rootlets when entering the DREZ, and also the excitatory medial part of the LT; the upper layers of the dorsal horn are also destroyed if microbipolar coagulations are made inside the grey matter of the dorsal horn apex. MDT is intended to preserve, at least partially, the inhibitory structures of the DREZ, ie, the lemniscal fibers reaching the dorsal column, their recurrent collaterals to the dorsal horn and the SG proprio-spinal interconnecting fibers running through the lateral part of the LT. The method has been conceived with a view to preventing complete abolition of tactile and proprioceptive sensations and avoiding deafferentation phenomena.

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Other methods RF-electrocoagulation In 1974, Nashold et al developed a technically original method using an RF electrode to destroy hyperactive neurons in the SG layers (1976) and later on, the entire DREZ region (Nashold and Ostdahl, 1979). In their modified technique (Nashold, 1981), the lesion is made with a 0.5 mm insulated stainless-steel electrode, with a tapered uninsulated 2 mm tip, introduced into the dorso-lateral sulcus at a distance of 1-3 mm and angled at 25 ° in the lateral medial direction. A series of RF coagulations were made under the microscope at a current of 35-40 mA (not over 75°C) for 10-15 s. The RF lesions are spaced at 2-3 mm intervals along the longitudinal extent of the dorso-lateral sulcus. The lesion observed under magnification is seen as a circular whitened area which extends 1-2 mm beyond~the tip of the electrode. ¢! Laser-beam Levy et al (1983) and Powers et al (1984) advocated a CO 2 and an argon laser, respectively, as the lesion maker. According to Levy et al's description, the pulse duration of the CO 2 laser is 0.1 s and the power is adjusted to about 20 W, so that one or two single pulses create a 2 mm depression at a 45 ° angle in the DREZ. The lesions are probed with a micro-instrument marked at 1 mm increments to ensure that the depth of the lesions (1-2 mm) is adequate.

Results

Results o f DREZ-lesions with M D T O u r first a t t e m p t at s u r g e r y in the D R E Z was in M a r c h 1972 f o r p a i n due to the P a n c o a s t - T o b i a s s y n d r o m e . Several other patients with cancer were o p e r a t e d on s o o n after. A s the first results in m a l i g n a n t p a i n were e n c o u r a g i n g , we decided, in the s a m e year, to a t t e m p t t h e p r o c e d u r e in p a t i e n t s with c h r o n i c n o n - c a n c e r o u s algias, n a m e l y : p a i n f u l p a r a p l e g i a , a m p u t a t i o n s t u m p , a n d brachi~al plexus i n j u r y ( p e r f o r m ing m i c r o c o a g u l a t i o n s o f the d o r s a l h o r n aigex with the s h a r p b i p o l a r forceps at the avulsed r o o t levels a n d selective v e n t r o - l a t e r a l D R E Z lesions in the r e m a i n i n g r o o tlets).

Cancer pain In cancer algias, a n effective result was o b t a i n e d in 87.5070 a n d 78.5070 o f the 38 a n d 32 p a t i e n t s o p e r a t e d on, respectively at the cervical (or c e r v i c o - t h o r a c i c ) a n d at the l u m b a r a n d / o r sacral levels. These patients h a d t o p o g r a p h i c a l l y limited algias due to w e l l - f o c a l i z e d lesions. T h e i r survival t i m e r a n g e d f r o m o n e m o n t h to 4 years ; 13 m o n t h s o n average. S u r g e r y was c o m p l i c a t e d with w o u n d i n f e c t i o n in 2 cases a n d was c o n s i d e r e d as h a v i n g p r e c i p i t a t e d d e a t h in 2 cases.

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Neurogenic pain In the group of 87 patients with pure neurogenic pain, followed-up over a period of 1 to 16 years, 87°70 of patients benefited from surgery. Long lasting, good results (ie, more than 75°70 relief) were achieved in painful states due to: spinal cord lesions in which pain had a "radiculo-metameric" distribution corresponding to or situated just below the level of the lesion; brachial plexus injuries, and to a lesser degree post-radiation plexopathies ; peripheral nerve injuries - especially causalgic syndromes and following amputation; and - less frequently - in herpetic neuralgias. In the latter etiologies, relief was more pronounced when the predominant component o f pain was of the paroxysmal type (ie, electrical shooting crises) a n d / o r corresponding to a superficial-provoked hyperalgesia (or allodynia). In this group of pure neurogenic pain, there were no vital or significant neurological complications, as far as the dorsal column and the pyramidal tract were concerned.

Painful hyperspasticity As it was noticed that muscular tone diminished in the operated territories after MDT performed for treatment of pain, the procedure was applied, as early as 1973, for harmful spasticity (Sindou et al, 1986; Sindou and Jeanmonod, 1990). The antispastic effects can be explained by the fact that MDT : interrupts the afferent components of the myotatic mono- and the polysynaptic reflexes, which have been cut off from their suprasegmental inhibitory control by pathological conditions; deprives the somatosensory relays of the dorsal horn of most of their excitatory inputs; while preserving their inhibitory segmental (ie lemniscal), intersegmental (ie lateral part of Lissauer's tract) and supra-segmental influences. On the basis of the above, MDT was applied, as early as 1973, for the treatment of harmful spasticity in the lower limb(s) of paraplegics or in the upper limb(s) of hemiplegic patients. For paraplegia, the L2-$5 segments are approached through a T1 l-L2 laminectomy, while for the hemiplegic upper limb, a C4-C7 hemilaminectomy with conservation of the spinous processes is sufficient to reach the C5-T1 segments. MDT was applied in 73 bedridden-paraplegic patients with harmful spasticity in flexion, of whom 47 had additional pain. Spasticity and spasms decreased significantly or were suppressed in 85°70 of cases. When present, pain was relieved without loss of sensation in 91 °70. MDT was also applied in 25 hemiplegic patients with hyperspasticity in the upper limb. The excess of spasticity diminished in all but 2 cases. Of the 17 patients with pain, 15 were improved. In both groups, follow-up ranged from 2 to 17 years (6 on average). Complications. Whatever the indications may be, the neurological post-operative deficits and the side-effects caused by MDT were minimal. There was no pyramidal or dorsal column deficit post-operatively, except in one case with an incomplete Brown-Sequard syndrome. When there was no marked pre-operative sensory deficit,

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the procedure allowed tactile and proprioceptive ~sensory capacities of a significant degree to be retained, avoidingcomplete functional sensory loss in the operated area. Results o f D R E Z - l e s i o n s with R F or laser

The data published in the literature essentially concern neurogenic pain. A review has been made in the Proceedings of the Vth World Congress on Pain (Sindou and Daher, 1988). The results were considered to be good when at least 50% pain relief was obtained. In brachial (150 cases) and lumbosacral plexus (11 cases) injuries, good results averaged 75% and 82% respectively. In spinal cord (92 cases) and cauda equina (6 cases) injuries, good pain relief was achieved in 47% and 83%, respectively. Better relief was obtained when pain was of a dermatomal type and situated at the junction between sensory loss and normal sensation. Diffuse pain and predominantly midline perineo-sacral pain did not respond as well or not at all in some cases (Nashold and Bultit, 1981 ; Friedman and Nashold, 1986). In patients with amputations (40 cases), the phantom component was frequently relieved, but stump pain was often unaffected (Proc 1st World Congr DREZ, 1984; Saris et al, 1985). In post-herpetic neuralgia (25 cases), good results averaged 60°/0 and surgery was more effective in alleviating the superficial burning pain and hyperesthesia than in relieving the deep ache (Friedman et al, 1984). The most frequent complications encountered in the literature included ipsilateral cortico-spinal tract and dorsal column deficits below the level of DREZ surgery. The complications rate ranged from 5 to 71% of the cases for the RF series and from 0 to 15% for the Laser series (Sindou and Daher, 1988).

Discussion

The question as to what the most efficient and iess dangerous technical procedure is as regards the DREZ target is still under discussion. The lack of information, with the exception of one autopsy study published in the proceedings of the First World Conference on DREZ (1984), concerning the characteristics of the anatomical lesions produced by the various techniques directed at the DREZ target led several authors to undertake animal experiments. Powers et al (1984) found that the argon laser produced precise and well-defined lesions in the DREZ, while Walker et al (1984) reported on the danger of creating extensive damage and syrinx cavities with the laser. Levy et al (1985) compared experimental lesions made with the CO 2 laser and RF and concluded that the laser lesions were more circumscribed and less variable. In a well-documented study evaluating the effects in dog spinal cord o f DREZ lesions with RF and CO 2 or Yag laser, Young et al (in preparation) found that the size and extent of the lesion related primarily to the magnitude of power used to

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make the lesion. They showed that, provided the procedure are performed with proper parameters, the lesions could be successfully localized to the DREZ, including the layers I-VI of the dorsal horn, and spare the dorsal columns and the cortico-spinal tract, using any of the three techniques. The main difference was that with laser, the lesion was shaped like the letter " V " , with the maximum width at the surface, while with RF it tended to be more spherical. In both methods, in chronic animals, the same glial reactions were observed. At present, only one experimental study compared RF and Laser lesion makers with the microsurgical procedure (MDT). The lesions produced by the latter were significantly less extended than with the other procedures (Broseta et al, in preparation). Postmortem anatomical and histological examinations in 4 patients having received the MDT anteriorly have shown a total destruction of the lateral bundle of fibers in the DREZ and the medial part of Lissauer's tract and a partial destruction of the superficial half of the dorsal horn (laminae I to III); a partial preservation of the large diameter primary afferent fibers and a total preservation of the dorsolateral funiculus as well as of the deep laminae of the dorsal horn (laminae IV to VI) (Sindou and Jeanmonod, 1990.) These anatomical findings are consistent with the clinical findings. Not only did MDT have a much lower rate of pyramidal and/or dorsal column deficits, but it was also able to spare some sensory functions in the operated areas, which is important in patients who retain motor and sensory capacities in their painful limbs. All the authors using RF or laser noted that all sensation was lost in the cutaneous distribution of the nerve roots where the DREZ operation was performed. On the contrary, pre- and post-operative standardized somatosensory examinations of the patients who underwent MDT revealed that the MDT produces an analgesia or marked hypoalgesia with only a moderate tactile hypoesthesia and a discreet proprioceptive and discriminative loss in the metameres innervated by the operated cord segments. Intraoperative electrophysiological recordings (Jeanmonod et al, 1989; Sindou and Jeanmonod, 1990) studying the effects of MDT on the Evoked Electro Spino Gram (EESG) (fig 3) have shown good correlations between the marked hypoalgesia, with only a moderate decrease of tactile sensation on the operated segments ; the intraoperative preservation with some loss of amplitude of the presynaptic compound action potentials (N11 and N21) and the marked diminution of the post-synaptic dorsal horn (N13/N24 waves) ; the postoperative maintenance of the cortical N20 wave; and the histological demonstration of a partial lesioning of the large diameter afferents. The disappearance of the late EESG post-synaptic dorsal horn components related to the activation of the fine afferent fibers correlates well with the total destruction of the lateral part of the DREZ and the medial part of Lissauer's tract. With regard to the mechanism of action of MDT on deafferentation pain, it could well be specifically related to the suppression of the dorsai horn hyperactive units described by Jeanmonod et al (1989). It is hypothesized that pain relief could be obtained, but not exclusively, thanks to a destruction of the faulty hyperactive cells,

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but also through a selective and massive interruption of the excitatory peripheral inputs with a concomitant preservation of the inhibitory ones, ie a kind of "retuning" of the dorsal horn. Whatever the technical modality used for DREZ procedures, there is still a need for further experimental work and larger clinical series to clarify the anatomical effects in the DREZ and to understand why certain painful states do not respond. Inappropriate levels or an insufficient amount of DREZ lesioning may explain failures, but more complex neurophysiological phenomena, such as those pointed out by AlbeFessard and Lombard (1983) may also explain such failures. In recent animal experiments to evaluate the origin of deafferentation pain, they demonstrated that after dorsal root section, abnormal spiking appeared not only in the dorsal horn, but also secondarily in more central structures such as thalamic nuclei and somesthetic / cortex, through a kind of progressive kindling process. Thus, chronic pain may be an evolving disease extending to affect neural structures more and more centrally.

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Fig 3. Evoked electro-spino-gram (EESG). Whilst treating patients with microsurgical DREZ-tomy (MDT), we have studied spinal cord surface evoked potentials, ie EESG. The active EESG electrode was a silver ball placed on the surface of the dorsal column, at the.cervical (C7) or, the lumbo-sacral (L5-S1) level, medially to the dorsal root entry zone (DREZ), ipsil'ateral to the peripheral stimulation applied in the median or the tibial nerve, respectively. The goal was to analyze the effects of M D T on the EESG components. The figure shows EESG at the cervical (Ce) level (left) before (A) and after (B) M D T , and at the lumbo-sacral (LS) level (right), also before (C) and after (D) M D T . The initial positive event P9 (for cervical) (P17 for lumbo-sacral) corresponds to the far-field c o m p o u n d potential originating in the proximal part of the brachial (lumbo-sacral) plexus. The small and sharp negative peaks N11 correspond to nearfield pre-synaptic successive axonal events, probably generated in the proximal portion of the dorsal root, the dorsal funiculus a n d the large-diameter afferent collaterals to the dorsal horn. After M D T , all these pre-synaptic potentials remain unchanged. The large slow negative wave N13 (N24) corresponds to the post-synaptic activation of the dorsal horn by group I and II peripheral afferent fibers of the median (tibial) nerve. They are diminished after M D T (in the order of 2/3 rds). The later negative slow wave N2 (just visible in the cervical recording) corresponds to a post-synaptic dorsal horn activity consecutive with the activation of group II and III afferent fibers. N2 is suppressed after MDT. The vertical bars are 10 ~V, the horizontal ones 10 ms.

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Ablative procedures directed to the ascending extra-lemniscal pathways Extra-lemniscal pathways convey nociceptive input from layers I, IV to VII, and X, up to the reticular formation, thalamus, and also hypothalamus and telencephalon (Willis, 1985 ; Burstein et al, 1988). They can be interrupted by sectioning them in their contralateral ascending trajectory either by anterolateral cordotomy or mesencephalic tractotomy, and also in the midline using commissural myelotomy or extralemniscal central myelotomy.

Antero-lateral cordotomy Spiller's anatomo-clinical findings and Schuller's experimental work in the monkey first demonstrated the role of the antero-lateral columns in conveying pain sensation. On the basis of this work, the first antero-lateral cordotomies (ALC) were carried out in 1911 by Martin at the cervico-thoracic level (Spiller and Martin, 1912) and in 1927 by Foerster at the high cervical level. Both authors used a similar open postero-lateral approach. Later on, Collis (1963) and Cloward (1964) described the anterior cervical approach. In 1963, Mullan et al pioneered the percutaneous method, first using a radioactive strontium needle inserted postero-laterally and then a unipolar electrode (Mullan et al, 1965). In 1965, Rosomoff et al described an RF technique with an electrode introduced through the CI-C2 interlaminar space. In 1966, Linet al proposed an anterior percutaneous approach at the lower cervical levels, in order to avoid damage to the descending respiratory pathways. Crue et al (1968) and Hitchcock (1969) introduced a percutaneous posterior approach between the base of the skull and C1. Since these early studies, several important technicaland electrophysiological refinements have made ALC an increasingly popular procedure, especially for pain due to cancer. Rationale

ALC aims to interrupt the spino-reticulo-thalamic ascending system, contralaterally to the painful side, since at least 80% of fibers in this system cross the midline obliquely over 2 to 5 segments before entering the antero-lateral columns. The antero-lateral tract consists of two anatomically different pathways (Bowsher, 1957): the neo-spino-thalamic tract, which relays with the lemniscal pathways to the VPL thalamic nucleus and probably plays a major role in the topographical localization of painful stimuli, and the paleo-spino-reticulo-thalamic tract, probably related to stimulus intensity and responsible for emotional reactions to pain, thanks to its diffuse central projections, particularly the limbic system. In the antero-lateral column, the fibers of the spino-thalamic tract have a relative somatotopic arrangement, with the sacral fibers being dorso-lateral, while the cervical ones are situated more deeply and ventrally (Walker, 1940).

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Such a localization explains why ALC must be performed as posteriorly as possible for treatment of pain below the waist, whereas for pain in the upper part of the body, ALC must be performed more anteriorly. Of prime importance, when ALC is performed at high cervical levels (C1-C2), is the location of the descending respiratory pathways which lie just lateral to the ventral horn and are likely to be sectioned at the same time as the deeper nociceptive fibers. The descending autonomic pathways for vasomotor and genito-urinary control are situated in the intermedio-lateral columns at the equator of the cord, intermingled with the lumbo-sacral nociceptive fibers in the spino-thalamic tract. Bilateral interruption of these descending autonomic pathways may lead to transient or even permanent disturbances in blood pressure or sphincter control. Methods

"

Open A L C may be carried out using various procedures. The traditional posterior approach allows the procedure to be performed at any level o f the cervical or thoracic spinal cord. Thanks

!

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Fig 4. Antero-lateral cordotomy. Lower left : Iopographic organization of the spino-reticulo-thalamic tract (adapted from Walker, 1940): sacral (S), lumber (L), thoracic (T), cervical (C). Lower right: functional organization of the extralemniscal pathways (adapted from Bowsher, 1957). Most of the nociceptive pathways run through the paleo-reticulo-thalamic tract (PSRT) which lies deeply under the neo-spino-thalamic tract (NST). Upper left : for the open antero-lateral cordotomy, the pia mater of the antero-lateral quadrant is incised with a micro-bistoury, from the pial insertion of the dentate ligament to the emergence of the ventral rootlets. Upper right : the deep part of the quadrant is then interrupted with a sr~ooth hook, in order to avoid injury to the anterior spinal artery (ASA). P : pyramidal tract; RS : reticulo-spinal motor phrenic fibers (above C4).

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to microtechniques, the approach can be made very small through a single interlaminar opening (fig 4). For bilateral ALC, one or two spinal segments should intervene between the bilateral lesions in order to minimize the risk of spinal cord ischemia. Although the anterior cervical approach viz discectomy affords direct visualization of the anterior cord and spinal artery, this method is rarely used because of a number of other disadvantages. The procedure is restricted to the lower cervical levels ; it does not provide sufficient landmarks to avoid the cortico-spinal tract and is performed through a narrow opening which makes dural closure difficult. The most common method for percutaneous ALC consists of introducing, under local anesthesia and X-ray control, an RF electrode through the C1-C2 interlaminar space (Rosomoff et al, 1965) into the antero-lateral column. Radio-opaque contrast medium is used to identify the dentate ligaments and the anterior margin of the cord (Onofrio, 1971). Since 1988, Kanpolat et al (1989), have been using CT-guidance for positioning the electrode. The correct placement of the electrode is confirmed with impedance monitoring (Gildenberg et al, 1969) and electrical stimulation testing (Taren et al, 1969; Tasker, 1973).

Results

The following summary of results has been taken from an analysis of 171 personal cases and a review of 37 series of the literature, altogether totalling 5 770 cases (Sindou and Daher, 1988). Pain relief was evaluated independently in cancerous and noncancerous patients. In the cancer group (2 022 cases), A L C was able to provide effective pain relief during the survival period in a significant number of patients, ie in 75% at 6 months and 40% after one year. Long-term results in non-cancerous painful states could be evaluated in only 455 patients. Lasting good results were achieved in 47% of patients, whereas early pain relief was noted in 68.2%. The more favorable results were obtained in pain related to lower spinal cord or cauda equina injuries and in painful amputation stumps or phantom limbs. Complications related to the procedure were difficult to differentiate from those related to the evolution of the underlying disease, as most patients had advanced cancers and were in poor medical condition. This qualification holds particularly true for mortality, which averaged 5.1% for open and 3% for percutaneous ALC. Percentages of motor complications (most often mild weakness) were significantly different according to whether the procedure was unilateral ( 0 - 1 5 % ) or bilateral ( 1 2 - 3 9 % ) . These complications attained the degree of complete paraplegia in only a small percentage of cases (in the order of 0.8%). Permanent urinary disturbances were frequent (40%), but only after bilateral procedures. This also holds true with regard to rectal and sexual ffinctions. Orthostatic hypotension was frequently seen after bilateral ALC, but remained permanent in only 5% of patients. Horner's syndrome was frequently observed immediately after all types of cervical cordotomy, but in most cases it disappeared by the time of longer-term follow-up.

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Respiratory failure after unilateral high cervical ALC was observed in 3% of patients. It was especially severe when phrenic paralysis or a pulmonary pathology was present on the painful side prior to ALC. The high frequency of sleep-apnea observed after bilateral high cervical ALC led most authors to stop performing ALC bilaterally above C4. Dysesthesias usually appeared several months post-operatively. In White and Sweet's series (1969), they were present in 16.2% of their 80 non-cancerous patients but were severe in only 5%. The potential for distressing dysesthesias after ALC has led most surgeons to be very cautious in recommending ALC for pain due to noncancerous diseases.

Discussion

Apart from cases with rapid extension of the carcinoma, initial failures and recurrences of pain cannot always be attributed to clear anatomical causes. In some instances, insufficient interruption of fibers could be demonstrated when complete pain relief was obtained with an additional section of the entire antero-lateral quadrant carried out at the same site. An inadequate height level can be demonstrated by achieving effective analgesia in redoing the procedure at a higher site. Unilateral ALC can be insufficient, especially in pelvic malignancies ; as a matter of fact, it is not infrequent for a pain, ipsilateral to the procedure to appear post-operatively (39~0 o,f cases). Such pain can be hypothesized as being pre-existent and hidden by predominant algias on one side and can be relieved by bilateral ALC. When no obvious anatomical factor can be found, explanations may lie in the possible development of new pain pathways or in the appearance of deafferentation phenomena. Because ALC does not afford very long-lasting pain relief, most authors consider that it is best reserved for pain caused by cancer. As for the choice o f technical approaches, ie, open (easier and more reproducible) or percutaneous (less invasive, in conscious patients), an approximately equal number of surgeons are in favour of each of them.

Mesencephalic tractotomy The first open operations for sectioning the spino-thalamic tract at the mesencephalic level were performed by Dogliotti in 1938 and then by Walker in 1942, and the first ones by stereotactic methods by Spiegel and Wycis in 1948 and then by Mazars et al (1960). This target has the advantage of obtaining a high level o f analgesia including the cephalic extremity, without impairing the reticulo-spinal respiratory fibors. At the present time, the most commonly used method consists of the coagulation of the contralateral spino-thalamic tract just below and posterior to the thalamus

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in the mesencephalon, using a stereotactically-guided electrode introduced through a para-saggital supero-posterior trajectory.(Peragut et al, 1989). On a transverse section of the mesencepha!on, the target is situated 8 mm lateral to the midline, and at 3.5 mm and 1 mm below the level of the posterior commissure and the aqueduct, respectively. At this point, electrical stimulation testing (before performing the coagulation) must produce a contralateral sensation. The best indications are represented by cancers invading the upper thoracic a n d / o r cervico-facial regions. According to the literature, pain relief was obtained in 87% of cases, mortality amounted to 2%, dysesthesias were present in 10%, and oculomotor disturbances occurred in 5o/o on average (up to 60% in certain series). Commissural myelotomy

First carried out by Armour in 1927, at the suggestion o f Greenfield, and by Leriche in 1928, commissural myelotomy (CM) aims at dividing the nociceptive and thermoreceptive fibers which decussate from both sides o f the body in the anterior white commissure, over the spinal cord segments corresponding to the painful territory. The myelotomy should be extended rostrally, on the assumption that the spinoreticulo-thalamic fibers cross the midline up to two or three segments above the level at which the corresponding dorsal roots enter the cord (Guillaume et al, 1949). CM's main advantage over bilateral anterolateral cordotomy is that a single incision may provide bilateral effects as long as the site of pain is limited. CM has mostly been used at the thoraco-lumbar level for pain in the abdomen, pelvis a n d / o r perineal region; but the procedure has also been attempted at the cervical level for pain in the upper extremities and thorax. Opening of the dorsal fissure and interruption of the commissures may be performed either with a blunt instrument as classically described or with a CO2-1aser (Ascher, 1978; Fink, 1984) or an ultra-sound probe (Richards et al, 1966). The use of microtechniques is of prime importance to avoid damaging the dorsal columns or injuring the anterior spinal artery. In the 17 literature series that we have reviewed and which include 445 cases (Sindou and Daher, 1988) CM was carried out for patients with advanced cancers in 86% and for pain from traumatic, inflammatory or degenerative origin in only 14%. Early pain relief was obtained in 75% of cases, and remained long-lasting, in 50%. The post-operative mortality rate amounted to 6%. Post-operative weakness was present in 12% but in most cases was mild and transient. Permanent sphincter disturbances were reported in 20%. Persistent lemniscal sensory deficits were observed in 10%. Post-operative dysesthesias or radicular-like pain were very frequent in the early postoperative period (more than ~55%) but remained important and long-lasting in only 6.4%. Because of the relatively low rate o f long-lasting effects, CM must be reserved for treatment of pain due to malignancies, especially when pain is strictly located on the midline in the rectal, perineal a n d / o r sacral areas.

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All the authors emphasize the difficulty in understanding the common finding of pain relief in areas not rendered analgesic, in spite of a complete section of all the crossing fibers as well as analgesia extending downwards, far from the spinal cord segments operated on. To explain these effects, CM is hypothesized (Nathan et al, 1986) to give lesions not only in the commissures, but also in the deeper parts of the non-lemniscal system, as well as in the post-synaptic dorsal column afferent system. Extra-lemniscal myelotomy

On these bases, Hitchcock (1970) and Schvarcz (1974) have developed a stereotactic lesioning procedure directed at the center of the spinal ~ord at the cervico-medullary junction, for the treatment of pain throughout the body. An RF-electrode with tip exposure of 1 mm is introduced percutaneously under local anesthesia, through the atlanto-occipital ligament, into the cord, with impedance monitoring. The target is in the midline, 5 mm from the dorsal surface of the cord. The RF-lesion, averaging 3 mm in diameter, is made fractionally at the site at which threshold stimulation evokes a tingling or electrical sensation in both distal lower limbs. A similar CT-guided 16rocedure has been developed by Kanpolat e t al (1988). On the same basis, Gildenberg and Hirshberg (1984) carried out open central myelotomies with mechanical or RF-lesions limited to a single segment at the thoracolumbar junction, for bilateral pelvic pain of cancerous origin. In the 114 cancer patients reported in the literature, the early, good results on pain amounted to 85o70, whilst they remained long-lasting in less than 50% (Sindou and Daher, 1988). In his 14 patients with neurogenic pain (four causalgias, four postherpetic neuralgias, three brachial plexus avulsions and three spinal cord lesions), Schvarcz (1978) reported a 64O/o rate of success with a 6 months to 4 year follow-up. All three results were achieved without mortality and with minimal side-effects, even in the sensory fields.

Conclusion

The large number and variety of surgical pain-relieving procedures impose a difficult choice on the neurosurgeon, but at the same time provide the patients with a better chance to be adequately treated and consequently relieved. In cancer pain, ablative procedures may be indicated, but only if the pain is not too extended and the patient in good general condition and with a not too short lifeexpectancy; otherwise intrathecal morphinotherapy is preferable. As the malignant lesions responsible have usually spread over large areas, invading many somatic and visceral sensory structures, DREZ surgery must be used only for pain due to topographically well-defined neoplasms such as those in the Pancoast-Tobias syndrome. In more wide-spread lesions, myelotomies or antero-lateral cordotomies are prefer-

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able. The most c o m m o n indications for commisural myelotomies are pelvic carcinomas with pain limited to the saddle region. F o r pain below the waist, cordotomies should not be performed below the cervico-thoracic junction and for chest or arm pain not below C2, so as to ensure a sufficiently high level of analgesia. For median bilateral pain, extralemniscal myelotomy may be an alternative to bilateral cordotomy. When non-malignant pain does not respond to neurostimulation methods, which should be attempted first, ablative procedures m a y be useful in some strictly selected cases. As clinical experience has shown that the effects of surgery at the level of the spino-thalamic tract do not usually last for more than one or two years and m a y generate secondary burning and painful dysesthetic manifestations, cordotomies and myelotomies are rarely indicated for treatment of non-malignant pain. The good preliminary results obtained with D R E Z operations in certain types of nonmalignant painful states indicate that they m a y be useful in some topographicallylimited neurogenic pain syndromes, which are resistant to non-narcotic medications and conservative treatments. For trigeminal neuralgia when medical treatment fails, there is the choice between the so-called microvascular decompression in the cerebello-pontine angle and a variety of selective destructive procedures. Whatever the pain syndrome to be treated, when choosing the appropriate procedure, the surgeon must consider, on the one hand, the neurophysiological mechanisms of the pain, and on the other, the effects which will result f r o m the surgical manipulation of the target.

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No 433, Excerpta Medica A~msterdam, 267-270 Bergenheim AT, Brophy BP, Laitinen LV (1988) Sensory disturbances after glycerol rhizotomy. Presented at the 8th meeting of the European Society for Stereotactic

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