FormalPara Key Points

  • Percutaneous procedures are safe and effective in treating drug-refractory trigeminal neuralgia (TGN)

  • Percutaneous retrogasserian glycerol rhizolysis (PRGR) is cost-effective, easy to perform with an image intensifier, and provides immediate pain relief for a variable time-period

  • Complications during and after PRGR are comparable to other percutaneous techniques

Introduction

A plethora of percutaneous procedures are available for the management of trigeminal neuralgia (TGN). Percutaneous procedures are useful in patients with drug-refractory TGN, who either refuse surgery, or in those with significant medical risks to undergo invasive surgical procedures. Percutaneous retrogasserian glycerol rhizolysis (PRGR) is one of the most popular methods of treatment for TGN. PRGR is carried out by injecting anhydrous glycerol into the Meckel’s cave and its safety has been established by several studies [1,2,3,4]. The major advantages of PRGR are: (1) long-term pain relief following single injection, (2) significant reduction in postoperative facial deafferentation compared to thermal rhizotomy, and (3) simple to perform with an image intensifier. Precise anatomic placement of anhydrous glycerol is achieved with the help of intraoperative trigeminal water-soluble contrast cisternography prior to drug injection [5,6,7,8].

Indications

PRGR may be the first-line treatment in the following patients:

  • Patients with idiopathic TGN

  • Patients with significant medical comorbidities where surgical procedures such as microvascular decompression (MVD) would be very risky

PRGR is used as the second-line treatment in the following patients:

  • Patients who have not responded adequately to gamma knife radiosurgery (GKRS)

  • TGN secondary to multiple sclerosis (MS)

  • Failure of surgical procedure such as MVD

Pre-procedural Preparation

Pre-procedural examination is important to find out associated co-morbid illnesses in the patient. Routine blood examinations carried out to rule out bleeding diathesis. Anticoagulant medications must be discontinued 5–7 days prior to the procedure. PRGR may be carried out under local anesthesia (LA) or monitored anesthesia care (MAC), with or without sedation. Many pain physicians prescribe atropine or glycopyrrolate to prevent bradycardia during needle progression through the foramen ovale (FO) [3, 6, 7]. Transient cardiac arrest has been reported during placement of the needle through the FO [9]. Patients who are on anti-hypertensive drugs and beta blockers are advised to continue their medications on the day of procedure with a sip of water.

Procedure

PRGR can be carried out either inside the operating room (OR) or in the radiology suite. Proper imaging is important to delineate the anatomical landmarks during the procedure. Some pain physicians take the help of computed tomographic (CT) guidance or even, ultrasound, to localize the target. Single plane flat panel detector angiography system has also been described to delineate the exact position of the trigeminal ganglion [10]. Despite availability of sophisticated imaging modalities, fluoroscopic image intensifier system is popular because it is widely available and easy to operate.

Drugs and Equipment (Fig. 1)

  • Fluoroscopic imaging machine to identify FO and place the needle

  • Disposable syringes (2 mL/5 mL)

  • Local anesthetic agent (Lidocaine 2%)

  • 26 G hypodermic needle

  • 20/22 G spinal needle

  • Freshly prepared anhydrous glycerol

  • Tuberculin syringe to administer anhydrous glycerol

Fig. 1
figure 1

Drug and equipment for retrogasserian glycerol rhizolysis; (1) 5 mL syringe, (2) spinal needle, (3) Tuberculin syringe, and (4) freshly prepared anhydrous glycerol

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Technique

The procedure is performed under strict aseptic measures. The patient is placed supine with the head resting on a two-inch pillow or a head-ring, with slight extension at the atlanto-occipital joint. An intravenous (IV) cannula is secured. Continuous monitoring of electrocardiogram (ECG), heart rate, oxygen saturation and non-invasive blood pressure is obtained. Oxygen is supplemented through nasal cannula at a flow of 2–3 L/min. The image intensifier is placed to obtain a sub-mental view, and then tilted obliquely towards the affected side, until the foramen ovale (FO) is visualized, medially in relation to the mandibular process, and laterally in relation to the maxilla. The C-arm position is then adjusted in such a way that the FO is seen as an oval-shaped opening (Fig. 2a). Skin of the affected side of face is prepared with antiseptic solutions. Classic Hartel’s technique is most commonly used to access the trigeminal cistern or the retrogasserian region via FO [3,4,5,6]. The tip of a spinal needle (22 G) may be used as metal marker and placed on the middle of the FO with the help of fluoroscopy. A skin wheal is raised 2.5–3 cm lateral to the angle of mouth with a 26 G hypodermic needle, after local infiltration with 2% lidocaine. The needle is advanced through the skin wheal into the subcutaneous tissue pointing the tip of the needle towards the midpoint of the zygomatic process; 3–5 mL of 2% lidocaine is injected for adequate local anesthesia along the needle tract. Under continuous fluoroscopic guidance, the spinal needle is gradually inserted by placing a finger in the same side of the mouth to prevent inadvertent insertion into the oral cavity. The needle is directed in such a way that the tip points towards the mid-pupillary plane and the hub of the needle remains in the mid-zygomatic plane. The most painful part of the procedure is when the needle enters the FO. This may induce hypertension and at times, severe bradycardia. Close observation of hemodynamic parameters at this stage is important. Cardiac arrest has been reported during needle placement through the FO, presumably due to stimulation of trigemino-cardiac reflex. In such circumstances, the needle should be promptly withdrawn to restore cardiac activity [9]. After placement of the needle in a tunnel view (Fig. 2b), lateral view of the skull is obtained to find out the depth of the needle penetration (Fig. 2c). The tip of the needle should not cross beyond the level of the clivus.

Fig. 2
figure 2

Submental view shows oval-shaped foramen ovale (black arrow) (a), spinal needle insertion in a tunnel view (white arrow) (b) followed by confirmation of the position of needle tip with lateral view (black arrow) (c)

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Once the needle is in the trigeminal cistern, stylet is removed and egress of CSF is observed. If no flow is observed, the needle may be advanced further at 1 mm increments, under continuous fluoroscopic guidance, until the trigeminal cistern is entered. At times, CSF may not egress due to clogging of the needle tip with tissue, debris or blood. Some practitioners may inject a small volume of 2% lidocaine (0.25 mL) into the hub of the needle, which helps to clear the needle lumen allowing free flow of CSF. Sometimes, the egress of CSF is not observed, but the patient develops hypoesthesia on the injected side, which is a confirmatory sign of correct needle placement in the trigeminal cistern. Although CSF flow is desirable, its absence does not preclude identification of the trigeminal cistern [1, 3, 11].

Rhizolysis of Individual Divisions: Placement of the needle on the lateral and middle parts of FO blocks the mandibular division [6, 7]. If the needle is advanced through the middle part of FO and placed a little beyond the mid portion of the clivus and the foramen, it blocks the maxillary division [6, 7]. To block the ophthalmic division, the needle is placed towards the medial aspect of FO, such that the tip remains just below the clivus [6, 7].

Preparation of Anhydrous Glycerol: Glycerol commonly available in the pharmacy is not anhydrous. To make it anhydrous, glycerol is heated at 180 °C for 45–60 min in a Bunsen burner (Fig. 3) [2]. Anhydrous glycerol can also be prepared heating the glycerol inside an electric oven at 180 °C for 1 h [2].

Fig. 3
figure 3

Preparation of anhydrous glycerol using burner along with a thermometer to measure the temperature continuously

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Administration of Glycerol: Once the tip of the needle is in the trigeminal cistern, 0.3–0.4 mL of Iohexol (Omnipaque) contrast medium is injected to obtain cisternography. Delineation of the trigeminal cistern in the shape of a pear, or a sphere, helps in further confirmation of the trigeminal ganglion [12]. The dye is aspirated and the patient is allowed to sit. Freshly prepared anhydrous glycerol 0.25–0.4 mL is taken in a tuberculin syringe and injected slowly depending on the capacity of the cisternal space (maximum capacity is 0.4–0.45 ml). There may be some discomfort in the peri-orbital region of the injected side or flushing on the injected side [3, 6, 7]. After injection of glycerol, the patient is asked to sit with the head slightly flexed for 1–2 h to prevent escape of glycerol into the posterior fossa; it allows better contact of injected glycerol with the structures in the retrogasserian area [3, 5, 8].

Mechanism of Action of Anhydrous Glycerol: Both neurolytic and osmotic effects of glycerol have been proposed [2, 5]. Glycerol is a weak alcohol, which selectively causes neuroablation of large myelinated fibres that are already damaged by the pathologic processes of TGN [13, 14]. Hakanson contended that small myelinated and unmyelinated fibres appear to be less vulnerable to the effects anhydrous glycerol than large fibres [1]. Another proposed mechanism of action is that anhydrous glycerol insulates the pathological site on the axon, and because it has a high dielectric constant (45.5 at 25 °C), it makes the nerve a poor conductor. This causes presynaptic inhibition and delays impulse propagation through the nerve [15].

Complications

  • Immediate

    • Injection site hematoma

    • Inadvertent entry of needle into the oral cavity

    • Vasovagal attack, severe bradycardia and transient cardiac arrest

    • Hypertensive episodes

    • Excruciating pain while entering the foramen ovale

  • Late Complications

    • Mild hypoesthesia on the injected side

    • Dysesthesia, anesthesia dolorosa

    • Corneal hypoesthesia

    • Activation of dormant Herpes simplex virus in the Gasserian ganglion

    • Motor paresis of mandibular nerve

    • Rarely, aseptic meningitis

Outcome

Udupi and colleagues retrospectively compared PRGR and radiofrequency thermocoagulation (RFT) in 79 patients with TGN [16]. It was observed that more patients in RFT group had excellent pain relief compared to PRGR group (84% vs. 58%). However, the mean duration of excellent pain relief in both groups were similar, and more patients in the RFT group had recurrence of pain compared to PRGR group (51% vs. 39%) [16]. Noorani and colleagues carried out a retrospective study comparing three percutaneous procedures—PRGR, RFT and percutaneous balloon compression (PBC) for TGN [17]. They found that PBC provided longer duration of pain relief, but with a slightly higher rate of transient side-effects [17]. In another study, the effectiveness of PRGR was assessed prospectively by studying the blink reflex, which involves the fifth and seventh cranial nerves, before and after PRGR. The authors found better function on the contralateral side following pain relief after glycerol rhizotomy [18]. In a recently published retrospective cohort study, both PBC and PRGR were found to be effective as primary surgical treatment methods in TGN, however, the side-effects were less common with PBC technique [19]. In a prospective comparative study of 45 patients undergoing either PBC or PRGR, recurrence as well as complications were significantly higher in PBC procedures compared to PRGR [20]. The authors of another prospective study of 93 patients, who were treated with PRGR, concluded that it is a simple, minimally-invasive and cost-effective method of treating drug-refractory TGN [21]. This study found immediate post-procedure pain relief in 97% patients, long-term pain control in nearly 90% patients, and only 10% recurrence rate at 18 months [21].

Conclusion

PRGR provides immediate and long-lasting pain relief in patients with drug-refractory TGN. It is a minimally-invasive, safe, relatively simple, and cost-effective procedure, with very few side effects or complications. Most of the side-effects can be prevented by proper identification of anatomic structures under continuous fluoroscopic guidance.