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The goal of surgical treatment of tic douloureux, even in elderly and medically infirm patients, remains the production of pain relief without significant facial sensory loss and without undue surgical risk. Percutaneous transovale trigeminal rhizotomy by injection of glycerol into the retrogasserian cistern of Meckel's cave is a useful alternative treatment for tic douloureux. The major advantages of glycerol rhizotomy include (1) significant reduction in postoperative facial deafferentation and its sequelae when compared to differential thermal rhizotomy performed by graded radio-frequency­induced lesions; (2) simplification of technique by elimination of intraoperative sensory testing and sophisticated lesion generators; and (3) precise anatomic placement of glycerol on the basis of the results of intraoperative trigeminal water-soluble-contrast cisternography. The effects and mechanism of relief after glycerol injection have been studied in detail.


Jefferson used glycerol as an agent to convey phenol, a potent neurolytic alcohol, into the trigeminal cistern for chemical ablation of the trigeminal ganglion and nerve.  The discovery that glycerol alone is effective in the treatment of tic douloureux resulted from a serendipitous observation by Hkanson. During the preparation of several patients for stereotactic irradiation of the trigeminal ganglion using the multisource cobalt 60 unit ("Gamma knife"), Hkanson introduced glycerine mixed with tantalum dust into the trigeminal cistern to provide a permanent radiographic target. Surprisingly, relief of trigeminal neuralgia occurred in the interval between the radiologic localization of the target and the production of the stereotactic lesion. Hkanson subsequently demonstrated the proper technique for roentgenographic definition of the trigeminal cistern with the water-soluble contrast agent metrizamide. The development of the technique of percutaneous retrogasserian glycerol rhizotomy and the results after treatment of 100 patients have been reported. After a follow-up of between I and 6 years, Hkanson indicated that 96 percent of patients were rendered pain­free after an initial injection, although pain recurred in 31 percent. After the reinjection of 16 patients, a total of 77 percent of patients were pain-free, and an additional 19 percent had only residual mild symptoms controlled with medication.


The procedure is performed with the patient awake after light premedication with 50 to 100 mg of intramuscular hydroxyzine hydrochloride. Addition of an anticholinergic agent (atropine sulphate 0.4 mg) has reduced vasovagal symptoms during the procedure, Intravenous fentanyl (1 to 2 ml) and medazolam is given in the operating room prior to the insertion of the needle and again just prior to glycerol injection. Short-acting intravenous barbiturate (methohexital sodium) administration is often valuable during needle placement or injection. The procedure is done with the patient supine on an electrically controlled operating room table with the suboccipital region of the patient supported by a cerebellar headrest. A C-arm fluoroscopic image intensifier equipped with image storage capacity (video disc recorder) is positioned in the anteroposterior (AP) skull projection. Only AP and lateral projections are used, since neck hyperextension for submentovertex views is often difficult for elderly patients and since the foramen ovale is usually identified in the AP projection.

Most patients are taken to surgery after admission to the hospital on the day of the scheduled procedure. After local 1% lidocaine infiltration of the skin, the spinal needle is inserted through the cheek 2.5 cm lateral to the corner of the mouth and directed toward a point 2,5 cm anterior to the external auditory canal (patient superior-inferior and anterior-posterior coordinates) and toward the medial aspect of the ipsilateral orbit (patient left-right coordinate). Deep injection of 1ml of lidocaine just exterior to the foramen ovale allows relatively painless transovale penetration, After fluoroscopy confirms the appropriate location of the needle, the stylet is removed to observe CSF flow. When a standard spinal needle is properly placed, the hub frequently rests against the skin of the cheek. Free CSF flow is highly desirable, although demonstration of CSF does not exclude the possibility of subtemporal needle placement. When glycerol injection is attempted after prior destructive procedures of the trigeminal nerve, CSF flow may vary from only several drops to brisk flow.

The patient is placed in the semi sitting position with the neck slightly flexed, A 1-ml syringe is used to inject 0.1 to 0,5 ml of sterile nonionic water soluble iodine contrast medium under fluoroscopy. The roentgenographic appearance of the trigeminal cistern is variable, but often an ovoid filling defect can be noted on the lateral projection. The retrogasserian fibers are identified on AP and lateral fluoroscopy. Subdural injection requires repositioning of the needle or replacement with a second needle. When the needle is advanced too far, contrast material can exit immediately through the trigeminal porus into the posterior fossa and can layer out along the petrous ridge. It may also be injected into the cavernous sinus. Layering out of the contrast agent beneath the temporal lobe can be demonstrated when the needle is placed in a too lateral position, or occasionally after a prior subtemporal operation has distorted the normal cistern anatomy. Inability to successfully demonstrate the trigeminal cistern precludes further attempts at glycerol injection, unless the needle can be redirected to obtain more typical cisternal findings. The cistern size is estimated by recording the volume of the contrast material just before it escapes from Meckel's cave into the posterior fossa. In 90 percent of patients, the total cistern volume has been less than 0.34 ml, and no cistern larger than 0.6 ml has been seen. The contrast material is evacuated by allowing it to flow from the needle. In order to completely evacuate the cistern, it is often necessary to place the patient in the Trendelenburg position with the neck extended, to allow residual minute amounts of the contrast agent to escape into the posterior fossa. After this manoeuvre, the patient is returned to the semisitting position. Sterile undiluted 99.9% anhydrous glycerol is mixed with small amounts of sterile radiopaque tantalum dust. The glycerol­tantalum combination is injected slowly into the cistern. The radiopacity of the combination allows further intraoperative confirmation of proper placement of the glycerol. If the pain recurs, a permanent marker of the trigeminal cistern has been established to facilitate further treatment.

The volume of glycerol injected depends on the affected divisions of the nerve and the volume of the cistern. Mandibular and maxillary division pain have been treated satisfactorily with 0.15 to 0.3 ml. Ophthalmic division fibers have been treated selectively by allowing a small residual amount of contrast material to layer out on the floor of the cistern. Glycerol could then be "floated" on top of the metrizamide, an agent heavier in concentration than glycerol, which is in turn heavier than the CSF. After removal of the needle, the patient is transferred in a sitting position with neck continually flexed to a hospital bed and remains sitting for 2 h. Thereafter, the patient resumes normal activity. Patients are discharged on the first postoperative day. Prior medications are tapered off gradually on an outpatient basis over 5 to 10 days. Trigeminal sensation is tested at 24 h and 6 weeks after injection.

Patient Data

All patients are usually refractory to or intolerant of medical therapies such as carbamazepine, baclofen, phenytoin, and clonazepam, used alone or in combination. Fifty-eight percent has right-sided pain and 42 percent has left-sided pain; 8 percent has bilateral symptoms. The ophthalmic division usually affected in 25 percent of patients, the maxillary division in 43 percent, and the mandibular division in 60 percent. Many patients has more than one division affected. Prior surgical management was performed in 41 percent, all of whom had inadequate pain control before glycerol rhizotomy.

Microvascular decompression is usually reserved for those patients who are less than 65 years old and who are in general good health. Glycerol rhizotomy is performed as the initial surgery in patients with multiple sclerosis or for those whose concomitant medical illnesses make them poor candidates for general anesthesia and craniotomy.


Immediate pain relief after the first glycerol rhizotomy usually obtained in 90 percent; 10 percent has initial technical failures due to an inability to define the trigeminal nerve fibers during contrast cisternography, due to subtemporal or subdural glycerol injection, or due to insufficient glycerol injection for the size of the cistern or the divisions affected by pain. 71 percent having one procedure, 21 percent- two, 7 percent- three, and 1 percent undergoing four glycerol rhizotomies. Long-term pain relief after one or more glycerol procedures is found in 55 percent of patients and 22 percent having pain control with medication, repeat rhizotomy. or other surgical procedures 23 percent have inadequate pain relief.


According to Lunsford L.D in early operative complications, one patient died (0.2 percent) in the recovery room immediately after undergoing glycerol rhizotomy. The patient complained of immediate chest pain after injection and was noted to develop electrocardiographic changes compatible with an acute myocardial infarction. Twenty minutes later she died from cardiac arrest. Postoperative headache was noted in 15 percent. nausea or vomiting in 8 percent, vasovagal symptoms (bradycardia and hypotension reversible with atropine sulphate ) in 15 percent. and hypertension (to levels of 180 to 220 systolic) in up to 20 percent. The frequency of such symptoms reinforced the value of performing glycerol rhizotomy in the controlled environment of a properly equipped neurosurgical operating room with an anesthesiologist present at all times.

During the first 3 days after rhizotomy. aseptic meningitis could be confirmed by cerebrospinal fluid analysis in 0.6 percent. Tantalum powder could be the cause since switching to sterilization of the tantalum powder with steam rather than ethylene oxide. Water soluble non ionic iodine contrast agents (300 mg iodine per ml) still in use for intraoperative contrast cisternography. The risk of development of postoperative herpes simplex perioralis was noted in 37 percent:  the onset of cold sores 2 to 5 days after glycerol rhizotomy. Perioperative administration of acyclovir ointment to the lip region in those patients who reported a history of cold sores during the preoperative screening examination must be considered.

The development of trigeminal sensory loss in  patients after one or more glycerol rhizotomies and at the time of follow-up. 49 percent have no demonstrable sensory loss (light touch or pain). 32 percent will have mild sensory loss. 13 percent- moderate sensory loss, and 6 percent- severe loss. Deafferentation pain characterized as annoying paresthesia or dysesthesia were seen in 1.2% of patients. No patient in Lunsford series, developed anesthesia dolorosa.

Predictors of Success

The best results are obtained when patients undergo glycerol rhizotomy as the first surgical procedure. and thus do not represent failures of prior surgical management. During the glycerol procedure itself, several features can be identified that are highly associated with an early successful outcome (i.e.. complete pain relief within 7 to 10 days): easy penetration of the needle through the foramen ovale, return of cerebrospinal fluid, normal appearance of the trigeminal postganglionic fibers on anteroposterior and lateral radiographic contrast cisternography, easy evacuation of the contrast agent, ipsilateral ophthalmic or maxillary pain with injection of the glycerol, systemic physiologic signs such as bradycardia/ hypotension or hypertension, ipsilateral axoaxonic reflexes such as a facial skin blush, and normal appearance of the trigeminal cistern at the conclusion of the glycerol/tantalum instillation. If all these factors were present intraoperatively. 99 percent of the patients can have pain relief within 5 days, regardless of prior procedures or etiology of the pain.


Predictors of Failure

Percutaneous retrogasserian glycerol rhizotomy should be considered only for those patients with typical trigeminal neuralgia. Atypical facial pain, the success rate for such patients must be extremely small. In addition. the potentially neuroablative effects of glycerol increase the risk of adverse and usually untreatable deafferentation sequelae in these patients. The most likely associated intraoperative sign associated with failure of glycerol rhizotomy is an abnormal trigeminal cistern. Failure to identify the cistern during contrast injection is almost always associated with incomplete pain relief. Subdural or infra­temporal contrast injection requires repositioning of the needle into the actual trigeminal cistern; the cistern may lie only 1 to 2 mm away from the subarachnoid space underneath the temporal lobe.

Failure to calculate the volume of the cistern accurately, thereby leading to insufficient glycerol injection for the volume or the trigeminal divisions affected, will lead to incomplete relief. Escape of the glycerol into the posterior fossa, a result that develops occasionally during transfer of the patient to the stretcher at the conclusion of the procedure, leads to failure. The patient must have the glycerol injected in the semi-sitting position with the neck flexed; he or she must remain in this position for approximately 2 h in order to ensure the appropriate response.

Deafferentation sequelae are relatively rare after glycerol rhizotomy. Trigeminal sensory loss increased with repeated procedures. After the first procedure, approximately 20 percent of patients had detectable sensory loss, almost always mild. With each successive procedure the risk of sensory loss doubled, probably related to the increasing number of trigeminal fibers damaged by the neurolytic effect of glycerol.

Patients with multiple sclerosis has the same chance of initial success as do patients with trigeminal neuralgia due to other causes; however, the chance of relapse seemed greater. Recurrence of trigeminal pain in multiple sclerosis patients may reflect the ongoing demyelinating process that may affect them. Glycerol rhizotomy was reported in one patient with an arteriovenous malformation of the cerebellopontine angle; this patient remained pain-free for 11 years and in two of four patients with meningiomas of Meckel's cave that caused their trigeminal neuralgia; in both patients the cistern was identified and was normal despite the contiguity of the tumor.

Trigeminal Evoked Potential (TEP) Recordings

Pre- and postoperative trigeminal evoked potentials (TEPs) obtained after gum stimulation have remained normal after successful surgery in 10%. 90% has abnormal ipsilateral TEPs, recorded 6 weeks to 6 months after surgery. No patient have deterioration or improvement in the TEP recordings after then.

Experimental Studies

The mechanism of pain relief and the effect of injection of glycerol into the trigeminal nerve are under evaluation. Both neurolytic and osmotic effects have been proposed. Extraneural application of glycerol to the sciatic nerve of rats, as well as injection of glycerol into the rat sciatic nerve, results in extensive myelin disintegration and axonal swelling and degeneration. Hkanson contends that small myelinated and unmyelinated fibers appear to be less vulnerable than large fibers to glycerol, and that this feature may be essential in the mechanism of pain relief after trigeminal glycerol injection. In other studies of the effects of gasserian and retrogasserian injection of glycerol in cats. TEPs were recorded before, immediately after. and at 4 to 6 weeks after the retrogasserian injection of minute amounts of anhydrous glycerol (0.05 ml) and were compared with TEPs from the contralateral trigeminal nerve which served as a control in each cat (after an injection of 0.05 ml of normal saline. Histologic studies of the trigeminal ganglion and nerve were performed. In 10 cats 4 to 6 weeks after injection, no consistent reduction in the TEPs was noted on the injected side on follow-up, although the histologic studies disclosed extensive areas of myelin degeneration and axonal swelling in the nerves injected with glycerol. It seems likely that glycerol injection results in destruction of the trigeminal nerve similar to that produced by thermal rhizotomy but perhaps of lesser degree.


Percutaneous retrogasserian glycerol rhizotomy (PRGR) is a safe and effective alternative to other surgical treatments of trigeminal neuralgia. When compared with differential thermal rhizotomy by radio-frequency-induced lesions, PRGR is simpler to perform. is less painful, can be done with the patient under light premedication and local anesthesia, and does not require sophisticated lesion generators or intraoperative patient sensory testing. Successful penetration of the foramen ovale, proper intracisternal needle placement verified by contrast cisternography. and selective treatment of both upper and lower division trigeminal pain are possible with the glycerol technique. The incidence of postoperative facial sensory loss is significantly less than that associated with thermal or other chemical rhizotomies. Patients with tic douloureux associated with multiple sclerosis as well as with other causes also respond to PRGR in most cases.

Hkanson's carefully performed assessment of 100 patients treated with this technique demonstrated that up to 96 percent of patients could be rendered pain-free after one injection. although 31 percent relapsed when followed between 1 and 6 years. The vast majority of the relapsed patients developed recurrent pain in his series within 2 years after injection. After 16 patients were reinjected, 77 percent remained completely pain-free and 19 percent had only residual mild symptoms controlled with drug therapy. Ninety-six percent of patients were thought to have satisfactory relief.

Glycerol is a weak neurolytic alcohol that is a normal constituent of human plasma. In sufficient strength (99.9% anhydrous form). it seems to have a selective neuroablative effect on the large myelinated fibers that are already damaged by the pathologic process that initiates trigeminal neuralgia. It is not surprising therefore that it seems to have equally satisfactory results in patients who have demyelinating disease and those that are suspected of having vascular cross­compression as an etiology. Repeated procedures with glycerol lead to further nerve fiber damage that is manifested by the development of cumulative sensory loss.

Trigeminal neuralgia is often a dynamic process: some patients seem to have long-term remission of their pain with a single procedure, while others will require a variety of medical and surgical therapies in order to remain comfortable for long periods. Spontaneous remission of the pain is not infrequent. although over the years the duration of the remissions usually lessens and the severity of the pain during exacerbations often worsens. No set pain­free interval seems to guarantee lasting pain relief. It happens that recurrent pain develop more than 10 years after an initially successful glycerol rhizotomy. Since glycerol rhizotomy is a symptomatic therapy designed to eliminate the fibers implicated in the mechanism. but does not eliminate the etiologic causes. it is not surprising that pain relapses occur.

The vast majority of symptomatic trigeminal neuralgia patients either can be rendered pain-free or can become satisfactorily controlled with tolerable medications after glycerol rhizotomy. Refractory pain can be treated by repeating the procedure as needed. The permanent marker of the trigeminal cistern supplied by tantalum powder permits easy identification of the cistern during repeat procedures. Cerebrospinal fluid can be identified in 90 percent of patients undergoing the first procedure: if a third procedure is eventually required. approximately 50 percent of patients have good CSF flow after intracisternal needle placement. Repeat glycerol rhizotomy can still be successful if the cistern is identified during contrast injection. We have found a few patients with typical trigeminal neuralgia who seem very refractory to a wide variety of medical and surgical options. Glycerol rhizotomy can be successful in such patients provided that the cistern is still normal. For those patients who fail glycerol rhizotomy. selective nerve section, microvascular decompression, balloon inflation. and radiosurgical ablation can be considered. At present, PRGR should be considered in older or medically infirm patients who require a simple and relatively rapid treatment. in those patients whose postoperative facial deafferentation is to be minimized. and in patients with upper division trigeminal pain. for whom thermal rhizotomy may carry distinct risks of injury to corneal sensation.

Failure of glycerol rhizotomy is frequently due to technical features, including (1) prior surgical procedures that obliterate the trigeminal cistern: (2) subdural injection or infratemporal placement of the needle: (3) insufficient volume of glycerol injected to affect the desired trigeminal divisions. The long-term effects of intracisternal injection of glycerine mixed with tantalum dust are now known: no significant sequelae have been noted. Postoperative skull films continue to demonstrate the retrogasserian fibers impregnated with tantalum dust long after treatment. Although the symptoms of tic douloureux can be relieved in most patients by trigeminal glycerol injection. experimental studies indicate that the effect is probably dependent on demyelination within the trigeminal nerve. However. the absence of significant postoperative facial sensory loss in patients suggests that tic douloureux can be treated effectively by a "minimal" lesion produced by glycerol.


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