The American Academy of Neurology (AAN)-European Federation of Neurological Societies (EFNS) guidelines for the management of trigeminal neuralgia.
The American Academy of Neurology (AAN) and the European Federation of Neurological Societies (EFNS) have organized an expert group to develop guidelines for the management of trigeminal neuralgia, as there are still unresolved issues regarding the diagnosis, pharmacological and surgical management of trigeminal neuralgia. After a systematic review of the literature, the group made a number of recommendations based on evidence-based medical evidence. In patients with trigeminal neuralgia, MRI may be considered to examine the patient for structural changes. Trigeminal sensory loss, bilateral involvement, and abnormal trigeminal reflexes are useful in interpreting symptomatic trigeminal neuralgia, whereas young age of onset, pain localization to the first branch of the trigeminal nerve, poor treatment outcome, and abnormal trigeminal evoked potentials are not useful in differentiating primary trigeminal neuralgia from symptomatic trigeminal neuralgia. Carbamazepine (better evidence-based) or oxcarbazepine (better tolerability) should be the first-line medication for trigeminal neuralgia. In patients with trigeminal neuralgia who have failed to respond to pharmacologic therapy, surgical treatment can be considered as early as possible, using percutaneous hemimelia, gamma knife, and microvascular decompression. Microvascular decompression provides longer-lasting pain relief than some other surgical treatment techniques. In patients with trigeminal neuralgia with multiple sclerosis, the choice between surgical and pharmacologic treatment is inconclusive.
The American Academy of Neurology (AAN) and the European Federation of Neurological Societies (EFNS) have decided to establish scientifically sound, clinically relevant guidelines for the diagnosis, pharmacological and surgical management of trigeminal neuralgia to assist neurologists and non-neurologists in the management of trigeminal neuralgia (TN: trigeminal neuralgia).
The International Association for the Study of Pain (IASP): defines TN as a brief, recurrent episode of severe pain within the distribution of the facial trigeminal nerve that occurs suddenly and can be pins and needles, which is usually unilateral and often affects one or more branches of the nerve. the annual incidence of TN is 4-5/100,000 and is the most common form of neuralgia. In the latest version of the International Headache Society’s classification of headaches, a distinction is made between symptomatic trigeminal neuralgia (STN: symptomatic TN) and primary trigeminal neuralgia (CTN: classical TN): CTN includes all TN without a clear cause, such as idiopathic TN and TN due to vascular compression of the fifth pair of cranial nerves, while STN refers to TN secondary to tumors, malignant nerve sheath tumors, and abnormalities of the skull base. The STN refers to TN secondary to tumor, malignant nerve sheath tumor, abnormal skull base structure, etc. . It must be emphasized that the classification of typical and atypical symptoms is based on the patient’s syndrome rather than the etiology, which will not be discussed further in this guideline.
The first problem clinicians face in treating TN patients is to accurately distinguish whether they are CTN or STN. Therefore, the following questions are answered in the disease diagnosis section of this guideline: 1.
1. to what extent can routine neuroimaging (MRI, CT) confirm the etiology of TN (excluding vascular compression)?
2. What clinical features or laboratory parameters can confirm the diagnosis of a patient with STN?
3. In CTN patients, can high-resolution MRI accurately identify the presence of neurovascular compression?
The first line of treatment for TN is medication, which in most cases can be administered immediately and is usually effective if there is no other specific reason for it, and the introduction of phenytoin sodium in the 1940s and carbamazepine in the 1960s dramatically changed the treatment of TN. Prior to that, the only treatment for TN was surgery. The pharmacological aspects of this guideline answer the following questions.
4. which drugs are effective for patients with CTN?
What drugs are effective for patients with STN?
Is there clinical evidence that intravenous administration is effective in cases of acute exacerbation of TN? When drug therapy fails due to poor pain relief or intolerable side effects, the next option to consider is surgical treatment. Therefore, the timing of surgery and the choice of surgical method become another problem for the patient. The best way to classify surgical interventions is by the target site of the surgical treatment: trigeminal peripheral surgery, where the target site is the end of the trigeminal ganglion to the semilunar ganglion; percutaneous semilunar ganglionectomy, where the target site is the ganglion itself; gamma knife radiation, where the target site is the trigeminal nerve root; and posterior cranial fossa vascular decompression.
7. Under what circumstances does the patient need surgical treatment?
8. Which surgical approach provides the longest pain relief with the fewest complications and the greatest improvement in quality of life?
9. Which surgical approach is suitable for TN patients with multiple sclerosis?
Results
Question 1: To what extent can neuroimaging (CT, MRI) usually confirm the etiology (excluding vascular compression) in TN patients without non-trigeminal positive signs and symptoms?
Conclusion: In TN patients without non-trigeminal positive signs and symptoms, routine neuroimaging may help to confirm the etiology in 15% of patients. (confirmed by four level III studies)
Question 2: For TN patients, what clinical symptoms and laboratory tests can confirm the diagnosis of a patient with STN?
The AAN and EFNS use a very similar approach to evidence-based classification. The two societies differ slightly in their treatment recommendation levels, although they are largely eclectic. Both the American and European authors agreed with the panel’s classification of the studies covered by this guideline, but were unable to harmonize the two societies’ treatment recommendations with those of Class III studies, in which patients with trigeminal first branch involvement and treatment failure did not have a significantly increased risk of STN. The earlier the age of onset, the more likely the diagnosis of STN. However, the age ranges of CTN and STN patients in these studies overlapped considerably, so that although early age of onset increased the likelihood of STN, age of onset was not clinically relevant as a predictor of STN because the accuracy of diagnosis was too low. Sensory deficits and bilateral involvement of the trigeminal innervation area are more common in patients with SIN. However, in many patients with normal sensation and unilateral trigeminal involvement, the presence of a clear etiology of TN was detected.
CONCLUSION: In patients with TN, trigeminal first branch involvement and failure to respond to treatment may not be associated with an increased risk of a diagnosis of STN. Younger age of onset and the presence of abnormal trigeminal nerve evoked potentials are likely to be STN. however, there is a large range of overlap between STN and CTN on these predictable indicators, with little clinical significance. Trigeminal sensory deficit or bilateral trigeminal neuropathy increases the likelihood of a diagnosis of STN, but the absence of these features does not exclude the possibility of STN. It may be more valuable in differentiating CTN from STN because of the high specificity (94%) and sensitivity (87%) of the abnormal trigeminal reflex).
Question 3: In patients with CTN, can high-resolution MRI diagnose patients with problems related to neurovascular compression?
The combined data showed a significant correlation between vascular compression confirmed by MRI and TN onset (P<0.0001< span="">). However, sensitivity and specificity varied considerably (sensitivity 52%-100%, specificity 29%-93%), and the correlation between the presence of vascular compression and TN onset was not significant. Due to the inconsistent results, it is difficult to find sufficient evidence to support or oppose the value of MRI examination in confirming the correlation between vascular compression CTN onset, and it is also quite certain that the most reliable examination technique. However, given the significance of the combined data, we recommend that patients undergo a high-resolution MRI examination before performing vascular decompression procedures.
Recommendations for diagnosis.
Patients with TN without non-trigeminal positive symptoms should be considered for routine imaging to confirm the diagnosis of STN. early age of onset, involvement of the first branch of the trigeminal nerve, poor treatment outcome and abnormal trigeminal evoked potentials should not be considered significant for the diagnosis of STN (level B). Trigeminal nerve sensory loss or bilateral involvement can help distinguish between STN and CTN; however, if the patient does not have these features, they are of little significance for differentiating STN from CTN (Grade B). Trigeminal reflex examination in a qualified electrophysiology laboratory can help distinguish between STN and CTN (Grade B). There is insufficient evidence to support or refute the use of MRI to identify which CTN patients may be effective with vascular decompression.
2. Drug therapy
Question 4: Which drugs are effective overall in patients with CTN?
Phenytoin sodium was the first effective drug used to treat CTN, but randomized controlled studies are lacking.
Carbamazepine is very effective in achieving effective pain relief for NNT (number needed to treat); carbamazepine is effective in reducing the frequency and intensity of paroxysmal pain episodes. It is equally effective for spontaneous and triggered TN. Older generation seizure medications such as carbamazepine are poorly tolerated and their use is complicated by pharmacokinetic factors and frequent serious adverse events, making it particularly important to balance drug efficacy and adverse events in older patients with TN.
Oxcarbazepine (OXC) is often used as the drug of choice for the treatment of TN. Oxcarbazepine is definitely more effective than carbamazepine in the treatment of epilepsy because it is well tolerated and has fewer drug interactions (Class I). Oxcarbazepine and carbamazepine were equally effective in reducing the number of seizures and reducing pain (>50% reduction in the number of seizures in 88% of patients).
CONCLUSION: Carbamazepine was effective for pain relief in patients with TN (multiple level I and II studies). Oxcarbazepine (one meta-analysis and one level II study). Likely effective, baclofen, raphenazine, and pimozide may be effective for pain relief in patients with TN (one Level II study), and ophthalmic local anesthesia was not effective for the treatment of TN (one Level I study). There was insufficient evidence to support or refute the analgesic effects of clonazepam, gammapentin, tizanidine hydrochloride, topical chili and valproate for TN.
Considering the relatively limited mechanism of action of existing drugs for TN, combination therapy is necessary, however, there is no literature comparing the advantages and disadvantages of monotherapy and combination therapy.
Question 5: Which drugs are effective in patients with STN?
Answer: There is insufficient evidence to support or refute the efficacy of gabapentin, lamotrigine, topiramate, and colloidal bismuth subcitrate in the treatment of STN (Level IV study).
Question 6: Is there clinical evidence that intravenous administration is effective in the setting of acute exacerbations of TN?
Answer: There is insufficient evidence to support or refute the efficacy of intravenous administration of fosphenytoin or other drugs for acute treatment of IN pain (Level IV study).
Medication recommendations.
The efficacy of carbamazepine in the treatment of TN is definite (Level A). Oxcarbazepine is likely to be effective in the treatment of CTN (Grade B). Gabapentin, lamotrigine, and pimozide may be considered for the control of CTN pain (Grade C). Topical tropicamide closure for CTN is likely to be ineffective for pain control (Grade B).
Evidence-based evidence applied to clinical practice: consistent with the most recent guidelines for EFNS, there are 2 first-line therapeutic agents for CTN, carbamazepine (200-1200 mg/day) and oxcarbazepine (600-1800 mg/day). Although the efficacy of carbamazepine is superior to that of oxcarbazepine, the latter has somewhat fewer safety concerns. If any of the above sodium channel blockers are ineffective, surgical consultation should be scheduled as the next step. In cases where surgical intervention is not possible, such as when the patient is too frail, there is insufficient evidence to recommend what to do next, and limited evidence supports adjunctive treatment with lamotrigine or switching to baclofen (pimozide is no longer used). The efficacy of other drugs commonly used to treat neuropathic pain; gabapentin, pregabalin, 5-hydroxytryptamine noradrenaline reuptake inhibitors and tricyclic antidepressants for TN is unclear.
Because the natural recovery of typical CTN is almost impossible and alternates between partial remission, complete remission and relapse, patients should be encouraged to adjust the drug dose according to the frequency of episodes.
3. Surgical treatment
Our literature search on surgery revealed three Level I prospective randomized controlled studies, one Level II prospective cohort study and many Level III studies that were performed for independent efficacy assessment (clearly stated), with the majority of evidence-based evidence being Level IV.
Question 7: Under what circumstances do patients need to undergo surgical treatment?
For patients with IN who have failed to respond to pharmacologic treatment, might it be preferable to have the least amount of pain with the least amount of complications and to maximize the patient’s quality of life?
Peripheral trigeminal nerve procedures: These involve blocking or destroying the portion of the trigeminal nerve distal to the semilunar ganglion. Two small-sample randomized controlled studies comparing streptomycin combined with lidocaine therapy to lidocaine monotherapy for TN (Level I studies) showed no pain relief with either therapy. Other trigeminal peripheral branch disruptions (including cryotherapy, neurectomy, alcohol injection, phenol injection, peripheral acupuncture, and radiofrequency thermocoagulation) have been reported in series of case studies, but independent efficacy assessments are lacking (Level IV studies). These studies showed pain recurrence after 1 year in 50% of patients and a low mortality rate for peripheral nerve surgery. There are no data from studies on patient quality of life.
Percutaneous semilunar nerve surgery: These procedures involve transcatheter cannulation of the foramen ovale followed by skillful focal destruction of the semilunar nerve or semilunar nerve root by various methods, including thermal (radiofrequency thermocoagulation), chemical (glycerol injection), and mechanical (compression of the vessel with a balloon in a Meckel’s chamber). Although thousands of patients have undergone/are undergoing percutaneous procedures, we found only a few case reports of series without controls. Two thermocoagulation reports, one glycerol injection and one balloon compression technique, were reported using independent efficacy assessment (Level III study). 90% of patients received pain relief after surgical treatment. Treatment failure was still mainly due to technical reasons. The rate of pain relief at 1 year after surgery was 68%-85%, decreasing to 54%-64% at 3 years after surgery. Five years after thermocoagulation, pain relief was achieved in approximately 50% of patients. About half of the patients undergoing percutaneous surgery developed sensory loss (Figure 2), 6% developed sensory dullness, and the incidence of painful numbness was about 4%. About 12% of patients complained of various discomforts after surgery: burning, heaviness, pain and numbness. Postoperatively, patients develop corneal numbness, the incidence of keratitis is 4%, the risk of other cranial nerves is low, and the main perioperative complication is meningitis, mainly aseptic meningitis (0.2%). Temporary masticatory difficulties occur in up to 50% of patients undergoing transballoon compression surgery, but are rarely chronic. The mortality rate of percutaneous hemimelia surgery is extremely low.
Gamma Knife: This is the only non-creative treatment, primarily a radiotherapy approach to the trigeminal nerve root in the posterior cranial fossa. A class I randomized double-blind controlled study comparing two different gamma knife procedures showed no difference. In addition, we identified three case series reported with independent efficacy assessment and long-term follow-up (Level III). Pain relief without medication was 69% one year after Gamma Knife. it decreased to 52% after 3 years. Pain relief after gamma knife surgery was delayed by a mean of 1 month. Complications of sensory deficit averaged only 6% in the Class III study. In the large sample of Class IV studies 9%-37% of patients had facial numbness (although it was able to improve with time) and 6%-13% had sensory loss and sensory abnormalities (however painful numbness was not present). No complications outside the trigeminal innervation area were reported, and patients’ quality of life improved, with 88% of patients satisfied with the results of treatment.
Microvascular decompression (MVD): This is the predominant neurosurgical procedure. It requires craniotomy to reach the posterior cranial fossa of the trigeminal nerve, identify the vessels compressing the nerve and surgically release this compression. We retrieved five studies with independent efficacy assessment (Level III studies) in which 90% of the patients experienced pain relief. Pain relief was still achieved in more than 80% of patients one year after surgery, 75% three years after surgery, and 73% five years after surgery. The average mortality rate for this procedure is 0.2%, although in some reports it can be as high as 0.5%, with the vast majority of the literature reporting a very low risk of postoperative mortality. There is a 4% chance of postoperative complications, including cerebrospinal fluid leaks, infarcts, and hematomas, with aseptic meningitis being the most common postoperative complication. Diplopia due to injury to the 4th or 6th cranial nerve pair is transient, palsy due to injury to the 4th or 6th cranial nerve pair is almost never present, and sensory loss occurs in approximately 7% of patients. A long-term complication is ipsilateral hearing loss, with an incidence of up to 10%, depending on its assessment criteria (objective audiometric techniques or subjective patient reports) (Figure 2).
Postoperative pain recurrence: Postoperative pain recurrence, especially localized burning sensation, is common, occurring in up to 50% of cases 5 years after surgery. Several studies elucidate the management of patients with pain recurrence, but their quality of life decreases and there is a lack of independent observer studies.
CONCLUSION: Percutaneous hemimelia, gamma knife, and microvascular decompression are all likely to be effective in the treatment of TN (multiple Level III studies). Compared with other surgical approaches, microvascular decompression may provide the longest duration of pain relief (multiple III studies). Peripheral therapeutic compression may take the longest to relieve pain (2 Level I studies of combined lidocaine-streptomycin or lidocaine monotherapy), or there is insufficient evidence (IV studies of all other peripheral procedures).
Question 9: Which surgical approach is indicated for patients with TN with multiple sclerosis?
Evidence-based evidence: Clinical studies on surgical treatment of TN patients with multiple sclerosis have only a few case reports, and the available studies tend to conclude that such patients are not as effective when treated surgically. Most investigators recommend the use of percutaneous hemimelia unless TN is confirmed by MRI to be caused by vascular compression of the trigeminal nerve. There are case reports of poorer outcomes with microvascular decompression in patients with TN with multiple sclerosis compared with those without multiple sclerosis.
CONCLUSION: There is insufficient evidence to support or oppose the effectiveness of surgical treatment in patients with multiple sclerosis. Because of the uncertainty of the effectiveness of surgical treatment, we suggest that the effectiveness of drug therapy needs to be carefully evaluated in such patients. Neurosurgical treatment should be considered only in the presence of drug resistance.
Recommendations for surgical treatment.
Early surgical treatment is recommended for patients with drug-refractory TN (grade C). Percutaneous surgical hemimelia, gamma knife, and microvascular decompression can be considered (Grade C); compared with other surgical methods, microvascular decompression may provide longer-term pain relief (Grade C); although there is insufficient evidence to support or oppose surgical treatment in patients with multiple sclerosis, we recommend that such patients should always maximize the effect of medication before surgical intervention. treatment (a valuable recommendation for clinical practice).
Conclusions and recommendations for future research
Regarding the diagnosis: the presence of trigeminal sensory deficit, bilateral trigeminal nerve involvement or abnormal trigeminal reflexes are suggestive of STN; whereas an earlier age of onset, involvement of the first branch of the trigeminal nerve, poor treatment outcome and abnormal trigeminal evoked potentials are often not useful indicators for the diagnosis of STN. We recommend the use of carbamazepine or oxcarbazepine as the preferred drug regimen for CTN, with baclofen and lamotrigine as second-line treatment agents. Although there is no strong evidence to support surgical treatment of TN, the outcomes of thousands of surgically treated patients suggest that surgical treatment of TN is effective and safe. A direct comparison of the advantages and disadvantages of various surgical procedures through evidence-based medical evidence is currently difficult. To briefly distinguish between the various surgical modalities, it can be broadly concluded that: percutaneous hemimelia is safer for elderly patients, but often causes facial numbness; microvascular decompression provides the longest pain relief, but is more likely to cause major neurological complications; and gamma knife is the safest non-invasive surgical method, but pain relief is delayed by one month.
To improve the treatment of TN, many future clinical studies are needed: population-based studies of TN patients to determine the actual prevalence of STN in patients without non-trigeminal positive signs and symptoms of TN; more prospective cohort studies of TN patients to determine the clinical features or electrophysiological characteristics of STN patients; cohort studies of patients scheduled for microvascular decompression A randomized controlled study (RCTS) of adequate sensitivity comparing other novel agents with carbamazepine, primarily comparing all outcomes related to treatment tolerability, safety, and impact on patient quality of life; direct studies of drug resistance and timing of referral to surgical treatment; a randomized controlled study of patients with STN studies; randomized controlled studies comparing the efficacy of various surgical treatments; and long-term cohort studies of how long drug therapy has failed.