Morphologic Effects of Glycerol

Glycerol is a trivalent alcohol normally present in human tissue, where it forms the skeleton of the triglycerides, among other functions.^17,18 Glycerol readily penetrates cell membranes and seems to possess distinct cryoprotective properties beneficial to cells. Its toxicity is low, and comparatively high doses must be injected systemically or intrathecally to induce toxic effects.^19,20 Glycerol’s neurolytic action is thought to be due to its hypertonicity, a condition known to injure nerve fibers, especially thin, unmyelinated, and myelinated fibers.²¹ Although the myelin sheath of the coarse fibers gives some transitory protection from this effect, length of exposure, neuron type, and the presence of previous demyelination may be important determinants of the vulnerability of individual fibers. For example, with longer exposures, Robertson²² and Pal and colleagues²³ observed that myelinated fibers were particularly vulnerable, and the degree of damage positively correlated with fiber diameter.

Studies on isolated animal nerve fibers show morphologic changes after exposure to glycerol. These consist of disruption of the tight junction between the Schwann cells and the axolemma, without damage to the axon proper.²⁴ Bathing the fibers in glycerol initially causes the axons to shrink, with a return to basal volume after equilibration of the substance over the cell membranes. With transfer to iso-osmotic conditions, the fibers swell markedly before returning to their normal volume. Thus, marked structural changes are observed with glycerol administration, but the conduction properties of the treated nerve axons remain intact.²⁴

After intraneural and perineural injection of glycerol, Håkanson²⁵ and Rengachary and associates²⁶ observed axolysis with marked myelin sheath swelling. The coarse myelinated fibers sustained the most severe damage, whereas the small-diameter myelinated and unmyelinated fibers are relatively well preserved.²³ In contrast, Bremerich and Reisert²⁷ found only slight histomorphologic changes after glycerol injection in the region of the foramen ovale in the rat in their long-term (180 days) comparative study of axonal damage after injection of glycerol, phenol-glycerol, and saline. A more recent study in dogs submitted to glycerol injection in a single trigeminal ganglion²⁸ demonstrated axonolysis both in myelinated as well as in nonmyelinated fibers.

The damage following glycerol injection into a cavity with isotonic body fluid is probably considerably less severe than perineural deposition. However, Lunsford and associates⁹ observed extensive areas of myelin degradation and axonal swelling in cats subjected to retrogasserian glycerol injections 4 to 6 weeks earlier.

The site of glycerol effects has been specifically studied by Stajcic,²⁹ who injected ³H-labeled glycerol into peripheral branches of the maxillary nerve and in the infraorbital canal of rats. The amount of radioactivity detected in the nerve distal to the foramen rotundum, as well as in the ipsilateral and contralateral gasserian ganglion, was less than 0.1% in all specimens. The author concluded that a retrograde transport mechanism behind the effect is improbable and that the beneficial effect of glycerol occurs at the site of injection.

There is as yet no publication of an autopsy series of patients with TN treated by retrogasserian glycerol rhizolysis. Sweet¹¹ provides an anecdotal description of a patient undergoing a retrogasserian glycerol injection of the extreme volume of 1.5 ml, with subsequent development of anesthesia dolorosa. At a posterior fossa craniotomy “many months” later, the trigeminal rootlets were found to be markedly atrophic.

Neurophysiologic Changes after Glycerol Application

It is likely that the change in osmolarity causes the damage to nerve axons, and the morphologic changes seem to be minimized by a gradual alteration in the osmolarity (e.g., by slowly instilling and removing glycerol from the compartment housing the axons). The functional consequences of glycerol application to normal and damaged nervous tissue are known only fragmentarily, but there are a few observations that might apply to the clinical use of the substance.

Burchiel and Russel³⁰ studied the effect of glycerol on normal and damaged nerves in a rat neuroma model. The neuromas, produced by sectioning of the saphenous nerve, were mechanosensitive and discharged both spontaneously and in response to light manipulation. These researchers found evidence supporting the view that glycerol exerts its major action on the large-diameter fibers. Exposure of the injured nerve to glycerol induced a short episode of increased spontaneous firing in the nerve, a response shown to originate from the myelinated fibers.

The observation by Rappaport and associates³¹ that glycerol injected into neuromas was more effective than alcohol in decreasing autotomy in rats suggests that autotomy may be related to unpleasant “tic-like” paresthesias. The therapeutic mechanism, according to these investigators, could be suppression of ectopic impulse barrage from the neuroma.

Sweet and co-workers³² found that glycerol injected into the trigeminal cistern of patients abolished the late components (corresponding to A-delta and C fibers) of trigeminal root potentials recorded with electric stimulation of the surface of the cheek. These recordings were made only minutes after the injection, and therefore do not permit conclusions concerning long-term effects.

Hellstrand and colleagues (unpublished data; see Håkanson²⁵) studied the effects of glycerol both on isolated frog nerve and on trigeminal root fibers after cisternal injection in the cat. They observed a severe reduction of the evoked potentials with glycerol but a nearly total restoration after rinsing the compartment with saline. This recoverability probably has a bearing on clinical effects and must be taken into account when interpreting the short-term observations of Sweet and associates³² referred to previously. Based on knowledge that glycerol requires at least 30 minutes to equilibrate across a membrane of a living cell and according to the aforementioned experimental observations, evacuation of the glycerol from the cistern after a short time (e.g., 5 to 20 minutes^10,33,34) might induce more severe damage, especially to fine fiber systems, than a slow unloading by diffusion into the subarachnoid space.

Longer-term observations of trigeminal evoked potentials have been reported by Bennett and Lunsford,³⁵ who investigated patients before and 6 weeks after trigeminal glycerol rhizolysis. They confirmed the earlier findings of Bennett and Jannetta³⁶ that thresholds were elevated and evoked potentials had a markedly increased latency on the affected side compared with the healthy one. An additional, unexpected finding was that these aberrations were “normalized” after glycerol rhizolysis. Because partially demyelinated fibers are known to conduct with a slower velocity and at a lower rate,^37,38 they interpreted this finding to indicate that glycerol selectively attacked partially damaged trigeminal axons and, after their elimination, the evoked trigeminal potentials appeared “normalized.”

Further long-term observations were supplied by Lunsford and colleagues,⁹ who noted the most marked changes in trigeminal evoked potentials in cats in the large-diameter myelinated fibers, with additional changes noted as late as 6 weeks after the injection.

Quantitative sensory testing using von Frey hairs, mechanical pulses, and the Marstock technique³⁹ also corroborates the notion that glycerol acts mainly on the large myelinated fiber spectrum.⁴⁰ Eide and Stubhaug⁴¹ examined thresholds for tactile and temperature stimuli in patients with TN before and after glycerol rhizolysis. They found evidence that pain relief after glycerol treatment involved normalization of previously abnormal temporal summation phenomena with little accompanying sensory loss. Kumar and associates⁴² found postinjection quantitative abnormalities of the blink reflex that correlated with sensory impairment.

Thus experimental and clinical observations indicate that the effects of glycerol may be due to its hyperosmolarity and that the rate of alteration of osmolarity is critical for the effect. Furthermore, there are indications that the major part of the effect is exerted through actions on large myelinated fibers, notably those with previous damage to the myelin sheath, thereby possibly affecting the “trigger mechanism” for pain paroxysm. Glycerol has also been reported to downregulate central neuronal hyperexcitability, often without signs of significant additional nerve damage.⁴¹

Preoperative Evaluation

The preoperative evaluation should be focused on the presence of typical signs of TN, previous treatments, the pharmaceutical regimen, the presence of sensory deficits, constant pain components, and ipsilateral hearing loss. Because we recommend the use of contrast medium injection in all cases, intolerance to iodine and previous adverse reactions to contrast medium should be determined. A magnetic resonance imaging study (MRI) with a sequence optimized for the detection of possible neurovascular conflicts, or at least a computed tomography scan with and without contrast injection, should be performed before surgery. The surgeon must evaluate the patient before the procedure to individualize premedication and describe the details of the procedure to the patient to ensure good cooperation during its performance. Most patients tolerate the procedure well in local anesthesia with adequate premedication and with only slight sedation (see Technique section), but very anxious patients may require general anesthesia.

Anesthesia and Sedation

Until the late 1990s, retrogasserian glycerol rhizolysis was performed in a radiographic suite with the patient awake and premedicated approximately 45 minutes before the start of the session with 5 to 10 mg of subcutaneous morphine hydrochloride-scopolamine and 2.5 mg of intramuscular droperidol. The doses were adjusted according to the age and condition of the patient. In some cases, 0.5 mg of atropine was given intravenously immediately before the procedure to prevent bradycardia during needle insertion. An intravenous line with slow infusion of Ringer’s solution is maintained during and for some hours after the session.

Our current protocol involves sedation with intravenous propofol using a syringe pump. No intubation is required and oxygen is supplied via a nasal catheter. In anxious cases a low oral dose of benzodiazepine is given 1 hour preoperatively. The legs are wrapped or compression stockings applied to counteract blood pressure decrease in the semisitting position. General anesthesia and endotracheal intubation are used only in particularly anxious patients. If used, it is important that the anesthesia be terminated with the patient in the sitting position with his head flexed according to the surgeon’s instructions.

The skin at the point of needle insertion and the underlying soft tissue are infiltrated with local lidocaine 0.5%.

Positioning

Since the mid-1990s, a modified dentist’s operating chair has been used in the surgical theater in conjunction with a standard C-arm fluoroscopic image intensifier with image-storing capacity, which provides sufficient picture quality for the clinical procedure.

In most cases, fluoroscopy with lateral projection is used when the cistern is punctured. Further guidance is obtained by switching to the anteroposterior projection. In difficult cases in which entering the proper part of the oval foramen is a problem, the patient’s head may be extended and rotated 15 to 20 degrees from the affected side, and the fluoroscopy arm tilted to give an axial-oblique projection of the skull base including the foramen ovale. With some older equipment, it might be difficult to readily identify the proper foramen on the fluoroscopy monitor. If one needle has already penetrated the foramen, the identification should be easy, and a new needle can readily be inserted in the desired (often medial) part of the foramen.

Trigeminal Cisternography

The technique we use is essentially the same as that described by Håkanson,⁴⁸ although estimation of the cisternal volume is of less importance for deciding what volume of glycerol to inject. The contrast medium must be water soluble, with high radiographic attenuation and low toxicity, and must have a higher specific gravity than CSF. The contrast medium used since 1986 is iohexol (300 mg iodine/ml).⁴⁹ Approximately 0.3 to 0.6 ml is injected with the patient sitting with his or her head slightly flexed to retain as much of the medium in the cistern as possible. If intermittent fluoroscopy is used during injection, the position of the needle tip may be estimated immediately, but it should always be confirmed by radiography in both the lateral and anteroposterior projections. The typical appearance of the trigeminal cistern is illustrated in Fig. 123-3. Ideally, the sensory root filaments (and sometimes the motor portion) should be visualized by lateral cisternography, leaving no doubt about the intracisternal position of the tip. The typical 45-degree medial tilt of the cistern should be seen from the anteroposterior view (Fig. 123-3B). The appearance of the cistern may vary considerably between patients, and it is essential that the surgeon be familiar with this anatomy. Furthermore, there is a subdural-extracisternal compartment in Meckel’s cave that may be injected with contrast medium (Fig. 123-4). This usually happens when contrast medium is injected without prior spontaneous CSF drainage, or if the needle is dislodged from the intracisternal position during injection.

FIGURE 123-3 The typical appearance of the trigeminal cistern filled with contrast medium in the lateral (A) and anteroposterior projections (B). Note the root fibers (A) that give the cistern its striped texture. In the lateral projection (C), there is also sparing of contrast, which indicates the position of the trigeminal motor root (arrow).

FIGURE 123-4 Schematic picture of the different compartments in Meckel’s cave. The arachnoid is drawn with a wavy line. Note the sites (^∗) where extracisternal deposits of contrast medium and glycerol may be performed.

(From Pauser G, Gerstenbrand F, Gross D, eds. Gesichtsschmerz, Schmerzstudien Z. New York: Verlag; 1979, with permission.)

Specific Difficulties

Spontaneous CSF drainage from the needle does not guarantee an intracisternal tip location. In fact, if the cannula is placed a few millimeters too lateral, the tip may be located in the subtemporal subarachnoid space, and a flow of CSF will still be produced. Subsequent cisternography solves this problem. Figure 123-5A shows the proximity of the cisternal and subtemporal subarachnoid compartments in the anteroposterior projection. Figure 123-5B and C illustrate a pure subtemporal contrast injection. Our strategy in this case is to leave the first needle in place and to introduce a second needle using the first one for guidance (Fig. 123-6A and B). It cannot be overemphasized that spontaneous CSF drainage is required before contrast injection. If, in such a case, the contrast medium is injected without fulfilling this requirement, the glycerol may be deposited in the extra-arachnoid, subdural compartment as shown above (see Fig. 123-4).

FIGURE 123-5 The anteroposterior roentgenogram (A), with both the trigeminal cistern and the subtemporal space injected with contrast medium, illustrates the proximity of these two compartments. Medially, the contrast-filled cistern (arrow) is seen barely pierced in its lateral margin by one of the needles. Injection of contrast medium through the lateral needle yielded a filling of the subtemporal space (arrow) instead. The lateral roentgenogram (B), shows a pure subtemporal contrast injection. C, Subtemporal outflow of contrast medium in the anteroposterior projection is shown. No contrast filling of the cistern was obtained, although exit of cerebrospinal fluid from the needle was noted.

FIGURE 123-6 The schematic figure (A) illustrates that because the foramen ovale is a fulcrum point, the needle entry site determines the intracranial destination of the needle tip. A too lateral puncture site produces a medial tip position. An entry that is too medial results in placement of the needle lateral to the trigeminal cistern (c). A puncture site that is too lateral produces a medial tip position (a). The adequate entry is shown by the track (b). (From Jho HD, Lunsford LD. Percutaneous retrogasserian glycerol rhizotomy. Neurosurg Clin North Am. 1997;8:63-74, with permission.) B, The anteroposterior roentgenogram demonstrates the penetration of the foramen with three needles. Contrast injection via the most medial, only, produces cistern filling.

Another problem may arise if the patient’s head is not adequately tilted forward during the injection, because the contrast medium then flows out the porus trigemini and escapes to the posterior fossa, with insufficient cisternal filling to confirm the correct position of the needle tip (Fig. 123-7). This situation may also result in an underestimation of the cisternal volume.

FIGURE 123-7 During contrast injection, the patient’s head should be tilted forward to prevent immediate contrast flow to the posterior fossa. In this case, the positioning of the head was not adequate, and some contrast escaped to the posterior fossa, which is the reason why the filling of the cistern was only partial.

Contrast Evacuation

When the intracisternal position of the tip has been confirmed, the syringe is gently removed from the cannula and the contrast medium permitted to flow out of it in a drop-by-drop fashion. We usually evacuate the cistern by tilting the patient to the supine position. If it is difficult to evacuate all contrast medium from the bottom of the cistern to permit the glycerol to reach the lowest root fibers (see later), the patient can be placed in the Trendelenburg position for a few minutes, a maneuver that permits the contrast medium to drain to the posterior fossa. Furthermore, the cistern may be flushed with 2 to 3 ml of sterile saline until the control radiograph indicates that the cistern is properly rinsed from contrast. Some of the less satisfactory results are probably due to failure to empty the cistern properly.^12,44 An extracisternal needle-tip position precludes a subsequent glycerol injection and must lead to repositioning or abortion of the procedure.

Glycerol Injection

Glycerol injection should always be performed with the patient in the sitting position to minimize extracisternal spillover. The glycerol should be anhydrous (greater than 99.5%) and sterile, and should be injected slowly from a 1-ml syringe. In general, 0.18 to 0.30 ml is sufficient, and the usual dose ranges from 0.18 to 0.28 ml (present average, 0.25 ml). When the neuralgia encompasses all three branches with multiple trigger points, a somewhat larger volume is used. Injection exceeding 0.35 ml is discouraged because of the risk for postoperative sensory deficits. Furthermore, inability to demonstrate an adequate an adequate intracisternal needle-tip position precludes glycerol injection.

Branch Selectivity

If it is desired to inject glycerol selectively into one or more trigeminal branches, one of the following four maneuvers can be used.

First, the volume of glycerol can be varied to fill more or less of the cistern. When the trigeminal cistern has been entirely emptied after contrast injection, the amount of glycerol injected partly determines which branches will be influenced. With the head of the patient only slightly flexed, a small volume of glycerol (i.e., 0.15 to 0.2 ml) is deposited at the bottom of the cistern and mainly affects the fibers of the third and second branches. Increasing the amount of glycerol causes additional rhizolysis in the two upper portions.

Second, contrast medium may be left at the bottom of the cistern to protect the third branch. Both contrast agents have a specific gravity exceeding that of pure glycerol (with 300 mg iodine/ml, iohexol = 1.345 g/l; compared with glycerol = 1.242 g/l and CSF = 1.007 g/l). This implies that these substances, when deposited in the same compartment, replace the original CSF contents and are layered with the contrast medium at the bottom and the glycerol on top of that.

With the head slightly flexed and a little contrast medium remaining at the bottom of the cistern, thus protecting the fibers of the third branch, glycerol may be gently injected to form a layer floating on the contrast medium. Rhizolysis will then engage mainly the upper two branches.

When treating a patient with third branch neuralgia, no contrast medium should be allowed to remain in the cistern for the glycerol injection.

Third, the position of the needle tip is partly indicative of which branch will be most affected. The tip of the cannula should preferentially be positioned in the part of the cistern traversed by the root fibers to be treated. This means that for treatment of third branch neuralgia, the optimal position is in the lower part of the cistern, whereas a first- or second-branch neuralgia is best treated using a tip site in the upper portion. This seems especially important at repeat treatments when some degree of intracisternal fibrosis may be present (see below).

During or immediately after injection of glycerol, the patient experiences short bouts (usually <60 seconds) of strong paresthesias, or sometimes even pain in one or more of the divisions of the trigeminal nerve. This is an indication that the substance has been deposited inside the cistern and is affecting the closest root fibers. Proper placement of the needle seems especially important for reinjections when adhesions inside the cistern may be present that partially prevent the glycerol from settling to the bottom. However, needle-tip positions close to the exit of the nerve to the posterior fossa is discouraged due to the risk of corneal problem with this position.

Finally, the position of the patient’s head during and after the injection also produces some selectivity. The patient should be sitting in the upright position during the injection. For first branch neuralgia, the head should be maximally flexed (i.e., approximately 40 degrees) and should be kept in approximately that position for 1 hour after the injection. For second branch treatment, flexion should be approximately 25 degrees, and for the third branch, the head should be slightly tilted laterally toward the affected side, but kept upright in the anteroposterior plane.⁵

The selectivity obtained by varying the head position has been studied by Bergenheim and colleagues,^50,51 who found a highly selective effect of this maneuver with regard to the ophthalmic branch, but less selectivity for the two lower branches.

Immediately before glycerol injection, the free flow of CSF from the needle should be checked to ascertain a persisting intracisternal tip position. Dislocation is not unusual, especially if the full length of the needle has to be used and the patient moves her cheek.

In certain cases, a longer needle has to be used to reach the cistern proper. Often, thin needles (outer diameter 0.7 mm) of adequate length are not readily available in the hospital and have to be ordered separately. We discourage the use of thicker needles because it makes the procedure more painful, theoretically causes more mechanical damage to the ganglion, and makes the estimation of injected volume of glycerol more difficult. However, a 0.9 mm × 120 mm needle is much easier to guide properly and 0.9-mm needles can be used if penetration problems are encountered.

Finally, as already mentioned above, when the tip of the needle is placed posteriorly in the cistern close to its clival passage, the injection might cause pain projected to the eye, which is why such a position should be avoided. It is also possible that some corneal complications are related to injections in this area.

Permanent Marking of the Cistern

A permanent marking of the cistern is recommended and can easily be achieved with a mix of glycerol and sterile radiopaque tantalum dust (Merck, Haar, Germany; grain size less than 0.042 mm). Approximately 0.5 g of tantalum is mixed with 2 ml of glycerol and the suspension is then used for injection to outline the bottom of the cistern (Fig. 123-8). This is of considerable help as a guide if reinjections are needed. With certain requirements fulfilled, permanent marking may replace the need for renewed cisternography. The tantalum marking is clearly visible on radiography years after the injection. There are no indications that the metal dust causes inadvertent effects or otherwise influences the results of the treatment.

FIGURE 123-8 The trigeminal cistern on the patient’s left side is permanently marked by tantalum dust, which lines the arachnoid of the bottom and walls of the cistern (anteroposterior view). The right cistern has been punctured and injected with contrast medium. After marking of the cistern with tantalum, the puncture and glycerol injection may be carried out without the intervening cisternography.

Special Considerations for Repeated Injection

Incomplete pain relief after the initial injection seems in most cases to be the result of technical problems during the procedure. Reinjections should not be performed within 3 to 4 weeks after the initial trial to allow late responders to emerge. Before reinjection, facial sensibility should be carefully examined, and if sensory impairment is found, the reinjection should be performed with a minimal amount of glycerol. Alternatively, a nondestructive procedure should be considered in these patients.

When trigeminal cisternography is performed after one or more intracisternal glycerol injections, a less satisfactory outlining of the cistern sometimes is obtained, probably due to adhesions within the cistern induced by the glycerol or contrast medium.⁵² The situation seems to be the same regardless of whether tantalum has been added. Figure 123-9 illustrates the appearance of a cistern before the first treatment (A) and at the repeat injection (B).

FIGURE 123-9 When a case has been submitted to one or more previous cisternographies and glycerol injections (or other destructive procedures directed onto the Meckelian cave) and suffers from a recurrence of the neuralgia, a new cisternography may show irregularities in the cistern likely due to fibrosis. In A the first procedure is illustrated, while B shows the cisternography preceding the second treatment.

If the cistern has been properly marked by tantalum dust during the initial injection and the marking is clearly visible during fluoroscopy, reinjection may be very simple and fast. When the position of the tip of the cannula is within the cistern according to radiography in the lateral and at least two anteroposterior projections at different angles, spontaneous drainage of CSF through the needle confirms an intracisternal tip position. However, if there is no exit of CSF through the cannula, cisternography with positive contrast should always be performed.

Because of the cisternal adhesions, images on repeat cisternography may differ from the initial cisternography films. This also points to the advantage of placing the needle tip in the part of the cistern housing the root fibers to be treated because the glycerol might become trapped by fibrotic strands, preventing it from reaching the bottom of the cistern.

In contrast to our experience and the observations of Rappaport and Gomori⁵² and Lunsford⁵³ noted no abnormalities of the cistern in patients undergoing repeated glycerol injections.

Postoperative Management

After injection, the patient should remain seated upright in bed with his head in the selected position for an hour. There is no convincing evidence that extending the time of controlled head positioning increases the therapeutic effect. However, there are indications that shortening the period of fiber exposure to glycerol by actively evacuating it from the cistern may cause more extensive and less well-controlled rhizolysis.^10,50 Sweet^10,34 reported that if first-branch sensory loss appears, leaving the glycerol in the cistern for 12 minutes or more may result in persistent corneal anesthesia. Hence, he recommended evacuation of the glycerol from the cistern within 10 minutes after the onset of first branch analgesia. This procedure and the amount of glycerol used are not recommended by us.

The latency for relief from neuralgia varies. Approximately half of the patients report that their paroxysms disappear immediately after the glycerol injection. In the remaining group, there may be occasional spells during the first postoperative day and sometimes for periods of up to 5 days, after which the neuralgia fades away. Even longer latencies of up to 3 weeks have been reported.⁵³ In younger patients, the procedure may be performed on an outpatient basis. In elderly or weak patients or following general anesthesia, an overnight hospital stay is usually required.

Facial sensibility should be examined on the first postoperative day and after 3 months. Patients are encouraged to report fevers, ulcers in the vicinity of the mouth, rash, eye problems, or any adverse effects that might be due to the treatment. A telephone report to the surgeon about the treatment effects is due 10 days after surgery.

The pharmaceutical regimen for the neuralgia is usually tapered off during 7 to 10 days or even during longer periods after a successful injection. If high doses of carbamazepine have been used, we usually decrease the daily intake by 100 mg every third day. If several drugs are used, the patient is provided with a schema for gradual decrease of pharmacotherapy after discharge from the hospital.

Evaluation of Different Series

A major problem in the evaluation of results from different series is the variation in technique. Different methods have been used by different authors to determine an intracisternal needle position before glycerol injection. Strategies vary from that recommended—use of cisternography,^6,7,53,54 drop-by-drop incremental glycerol injection, and intraoperative recording of sensory response^5,8,55—to the use of electric stimulation in the same way as is done in selective thermocoagulation.^32,33

In some series, cisternography has not been used^8,55,56; in others only in conjunction with treatment of first branch neuralgia; and in some only when there is no spontaneous CSF outflow through the cannula.⁵⁷ The extent to which cisternography is used in the series reviewed is shown in Table 123-1. In our experience, there is a relationship among the quality of the cisternography, adequacy of needle placement, and treatment outcome.

A very important factor is the amount of glycerol used. Sometimes the range of volumes is not explicit, and in several series it far exceeds the original recommendations.^8,12,58,59 This has to be taken into account when interpreting the data (ranges of volumes of glycerol used are given later; see Table 123-3).

A third factor of major importance for the outcome is whether the patient has been subjected to some other destructive procedure before (or after) the glycerol rhizolysis and if information about this is given in the reports. This is of critical importance with regard to the estimation of sensory disturbances after the procedure, and it also has an impact on deciding the volume of glycerol to use in a specific case.

In some series, patients with diagnoses other than classic TN are included. It is often impossible to determine this from the reports. This is of course most important when judging the outcome, because the results, as described later, in other facial pain conditions often are inferior to those in classic tic.

Short- and Long-Term Results

The outcomes in 22 major series with long-term follow-up periods encompassing more than 2700 patients are given in Table 123-1. Cisternography was used routinely for all patients in only 16 of the series.^{7,12,44,47,53,54,57–67}

The percentage of patients experiencing relief from paroxysmal facial pain within 2 weeks varies in the different series from 67% to 97%. There is no clear association between the mere use of cisternography and success rate for either immediate or long-term outcomes. This finding may seem remarkable in light of the experiences of the current authors’ but it may also point to large differences in the accuracy of the cisternographic procedure.

The follow-up periods in these series range from a few months to more than 10 years. The recurrence rates are difficult to estimate correctly because of the differences in techniques of reporting, statistics, and so forth. Kaplan-Meier analysis has been used by several researchers,^44,55,57,59 facilitating the interpretation of recurrences.

The recurrence rate in relation to length of follow-up is reviewed in Table 123-2. Within roughly 2 years of treatment, between 2% and 50% of patients with a successful initial outcome experience recurrent pain. This large variation obviously casts doubt on both the technical performance of the procedure and the follow-up methodology. It is difficult to evaluate how many of the patients have been reinjected, and if these cases are included in the final results.

The original Stockholm series of 100 patients was followed between 5 and 10 years (mean, 5 years, 4 months). At the last follow-up, 53% were still pain free after the first injection. Twenty-two patients had at that time been reinjected with glycerol and, in total, 75% of patients from the entire series were pain free, and an additional 23% had only mild pain easily controlled by a pharmaceutical regimen.⁴⁰ The average volume of glycerol injected in this series was 0.21 ml.

The average risk of recurrence within 2 years is approximately 20%, and the rate of late reappearance of symptoms (within 5 to 10 years) approaches 50%. Nevertheless, because injection can be repeated and carries little risk for the patient, most of the patients (more than 75%) may be maintained pain free by a small number of reinjections (Table 123-1). By comparison, Jannetta⁶⁸ found an 80% rate of permanent pain relief in most series of microvascular decompression, 10% with some pain, and a 10% failure rate.

Two reports of major series of patients with TN treated by glycerol rhizolysis have been presented by Spaziante and colleagues⁶⁹ and Lunsford and Duma.⁷⁰ The two series comprise 191 and 480 patients, respectively. The follow-up periods are as long as 10 years. The percentage of patients pain free immediately after treatment was 93% in the series of Spaziante and associates⁶⁹; long-term follow-up showed that 77%⁶⁹ and 75%⁷⁰ of patients were pain free. No patients with anesthesia dolorosa were observed, but mild hypesthesia was found in 46% and 20%, respectively. Both teams of researchers concluded that glycerol rhizolysis is a mildly neurodestructive procedure indicated as the first choice⁶⁹ in elderly patients, those with MS, and in patients in whom other procedures, including microvascular decompression, have been unsuccessful.⁷⁰

A 1997 report of the Pittsburgh series by Jho and Lunsford⁴⁷ showed that of their large group of 523 patients, 90% were immediately pain free and 55% stayed pain free at follow-up (which extended to more than 10 years). The highest figures for patients initially pain free are those of Håkanson⁴ (96%) and Bergenheim and Hariz⁶¹ (97%).

Side Effects and Complications

Glycerol rhizolysis in the hands of an experienced and careful neurosurgeon should not result in serious complications. Only one fatal myocardial infarction has been reported^47,70,71 in the recovery room after the procedure. Despite the fact that glycerol rhizolysis is used in patients of advanced age and sometimes with severe disabilities, the number of severe complications is remarkably low. Other serious complications relate to the attempts to penetrate the foramen ovale with a needle (e.g., intracranial hemorrhage) rather than glycerol instillation per se.¹¹

The most feared consequence of neurolytic procedures, postoperative anesthesia dolorosa, is rarely observed after glycerol rhizolysis. An exception to this is the rather heterogeneous series of 552 cases by Saini,⁵⁶ in which rhizolysis was performed without cisternography or some other technique to confirm the localization of the needle tip before glycerol injection. In this series, the number of patients with anesthesia dolorosa was 26 (5%). Furthermore, 6 patients (3%) had signs of disturbance of third-branch motor function. This malfunction resolved within 3 to 4 months after injection. Transient masseter weakness has also been described by others.^58,59 Otherwise, only single cases with transitory cranial nerve dysfunction after glycerol rhizolysis have been reported. Some of these are reviewed by Sweet.¹¹

A review of 260 consecutive procedures performed in 139 patients between 1986 and 1987 reported a fairly high frequency of perioperative side effects.⁶³ In this series, a variety of intraoperative technical obstacles, severe vasovagal responses, and even cardiac arrest occurred. In total, complications or side effects occurred in 67.3% of procedures. This series evidently encompasses learning curves for several surgeons. Penetration of the foramina of Versalius (0.8%) and spinosum (0.4%) occurred, as did buccal penetration (1.5%). Actually, three patients (1.2%) reported a postoperative ipsilateral decrease of hearing ability. Arterial bleeding occurred in 0.4%, while venous blood from the needle occurred in 3.5%. The side effects and complications are detailed in Tables 123-3 and 123-4.

Infectious Side Effects

Serious infectious complications after retrogasserian glycerol rhizolysis are rare. However, reactivation of latent viral infections of neural tissue (notably herpes simplex type 1) seems more common than expected (see Table 123-4).