Antiepileptic drugs in the management of cluster headache and trigeminal neuralgia

Cluster headache and trigeminal neuralgia are relatively rare but debilitating neurologic conditions. Although they are clinically and diagnostically distinct from migraine, many of the same pharmacologic agents are used in their management. For many patients, the attacks are so frequent and severe that abortive therapy is often ineffective; therefore, chronic preventive therapy is necessary for adequate pain control. Cluster headache and trigeminal neuralgia have several distinguishing clinical features. Cluster headache is predominantly a male disorder; trigeminal neuralgia is more prevalent in women. Individuals with cluster headaches often develop their first attack before age 25; most patients with trigeminal neuralgia are between age 50 and 70. Cluster headaches are strongly associated with tobacco smoking and triggered by alcohol consumption; trigeminal neuralgia can be triggered by such stimuli as shaving and toothbrushing. Although the pain in both disorders is excruciating, cluster headache pain is episodic and unilateral, typically surrounds the eye, and lasts 15 to 180 minutes; the pain of trigeminal neuralgia lasts just seconds and is usually limited to the tissues overlying the maxillary and mandibular divisions of the trigeminal nerve. Cluster headache is unique because of its associated autonomic symptoms. Although the pathophysiology of cluster headache and trigeminal neuralgia are not completely understood, both appear to have central primary processes, and these findings have prompted investigations of the effectiveness of the newer antiepileptic drugs for cluster headache prevention and for the treatment of trigeminal neuralgia. The traditional antiepileptic drugs phenytoin and carbamazepine have been used for the treatment of trigeminal neuralgia for a number of years, and while they are effective, they can sometimes cause central nervous system effects such as drowsiness, ataxia, somnolence, and diplopia. Reports of studies in small numbers of patients or individual case studies indicate that the newer antiepileptic drugs are effective in providing pain relief for trigeminal neuralgia and cluster headache sufferers, with fewer central nervous system side effects. Divalproex has been shown to provide effective pain control and to reduce cluster headache frequency by more than half in episodic and chronic cluster headache sufferers. Topiramate demonstrated efficacy in a study of 15 patients, with a mean time to induction of cluster headache remission of 1.4 weeks (range, 1 day to 3 weeks). In the treatment of trigeminal neuralgia, gabapentin has been shown to be effective in an open-label study. When added to an existing but ineffective regimen of carbamazepine or phenytoin, lamotrigine provided improved pain relief; it also may work as monotherapy. Topiramate provided a sustained analgesic effect when administered to patients with trigeminal neuralgia. The newer antiepileptic drugs show considerable promise in the management of cluster headache and trigeminal neuralgia.     

岩静脉显微解剖在三叉神经痛显微血管减压术中的应用

【目的】研究岩静脉显微解剖在三叉神经痛显微血管减压术中的应用。【方法】回顾分析本院547例三叉神经痛的患者经三叉神经显微血管减压术治疗的临床资料。【结果】547例中127例患者术中行岩静脉处理,其中5例死亡,1例术后出现小脑及脑干梗死。未处理岩静脉的420例患者中,无死亡病例。【结论】岩静脉压迫三叉神经是导致三叉神经痛的原因之一,在显微血管减压治疗三叉神经痛的手术中,岩静脉的保护与合理处理是降低死亡的重要原因,对于岩静脉的处理应该慎重。     

Therapy and prophylaxis of facial neuralgias and other forms of facial pain syndromes -- revised recommendations of the German Society of Migraine and Headache

Trigeminal neuralgia and postherpetic neuralgia are the most relevant neuralgiform facial pain syndromes. Trigeminal neuralgia is characterized by lancinating intensive pain attacks of very short duration, triggered by external cues,whereas postherpetic neuralgia consists predominantly of long-lasting burning pain. Sodium channel blocking drugs are first choice in treatment of trigeminal neuralgia, operative procedures encompass microvascular decompression,thermocoagulation and percutaneous retrogasserian glycerol rhizotomy. In the acute stage postherpetic neuralgia is treated antivirally and analgesically, in the chronic stage by tricyclic antidepressive substances. Other pain syndromes described encompass the Tolosa-Hunt-syndrome, cervicogenic headache, craniomandibular dysfunction syndrome, atypical facial pain and rarer syndromes. Therapeutic recommendations are based on evidence based medicine criteria (EBM).     

Radiofrequency and Pulsed Radiofrequency Treatment of Chronic Pain Syndromes: The Available Evidence

There are currently 6 reviews on (pulsed) radiofrequency (RF) for the management of spinal pain. Two reviews on interventional pain management techniques in general also discuss RF. The outcomes of those reviews depend on the type of studies included and the opinion of the reviewers, which may result in different evidence levels. Radiofrequency denervation at the cervical and lumbar level has produced the most solid evidence. The differences in treatment outcome registered in the 5 randomized controlled trials (RCTs) regarding lumbar facet denervation can be attributed to differences in patient selection and/or inappropriate technique. There is not sufficient evidence supporting the use of RF facet denervation for the management of cervicogenic headache. The studies examining the management of cervical radicular pain suggest a comparable efficacy for RF and pulsed RF (PRF). The PRF treatment is supposed to be safer and therefore should be preferred. The superiority of RF treatment adjacent to the lumbar dorsal root ganglion for the management of lumbar radicular pain has not been demonstrated in an RCT. Information regarding RF treatment of sacroiliac joint pain is accumulating. No randomized sham‐controlled trials on the value of RF treatment of the Gasserian ganglion for the management of idiopathic trigeminal neuralgia have been published. One RCT indicates superiority of RF over PRF for the management of idiopathic trigeminal neuralgia. Future research to confirm or deny the efficacy of (P)RF should be conducted in carefully selected patient populations. The tests used for patient inclusion in such a trial could potentially help the clinician in selecting patients for this type of treatment. The value of PRF treatment of the peripheral nerves also needs to be confirmed in well‐designed trials.     

Pulsed radiofrequency treatment of the Gasserian ganglion in patients with idiopathic trigeminal neuralgia

Pulsed radiofrequency treatment has been described as a minimal invasive alternative to radiofrequency thermocoagulation for the management of chronic pain syndromes. We present here our first five high-risk patients with idiopathic trigeminal neuralgia who were treated with pulsed radiofrequency after multidisciplinary assessment; with a mean follow-up of 19.2 months (range 10-26). These patients were at high risk due to age, co-morbidities or previous interventional and surgical treatments. An excellent long-term effect was achieved in three of the five patients, a partial effect in one patient and a short-term effect in one patient. No neurological side effects or complications were reported.     

继发性三叉神经痛诊疗策略

目的探讨继发性三叉神经痛的诊断及治疗策略。 方法回顾使分析北京大学人民医院神经外科2017年1月至2022年3月临床收治的继发性三叉神经痛患者，共34例，并参考相关文献。 结果34例继发性三叉神经痛病例均由占位性病变引起，所有患者均接受手术治疗，31例肿瘤完全切除，3例部分切除，其中10例术中发现血管压迫三叉神经，行三叉神经微血管减压术。术后33例患者的疼痛症状消失，1例患者明显减轻。 结论相应CPA区占位性病变是继发性三叉神经痛的首要病因，原发性因素可同时存在，头颅CT及MRI检查必不可少，手术是治疗继发性三叉神经痛的首选治疗手段。术中切除肿瘤后，应注意是否存在血管压迫神经情况，做到三叉神经充分减压。     

A randomized, controlled trial of high-dose dextromethorphan in facial neuralgias. (National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD) Neurology 2000;55:964–971.

A randomized, double-blinded, crossover trial compared 6 weeks of oral dextromethorphan with active placebo (low-dose lorazepam) in 19 patients, stratified into three groups: 11 with facial pain and possible trigeminal neuropathy, 5 with anesthesia dolorosa, and 3 with idiopathic trigeminal neuralgia. Dosage was titrated in each patient to the highest level reached without disrupting normal activities. Patients completing the trial included 10 with possible trigeminal neuropathy, 4 with anesthesia dolorosa, and 2 with trigeminal neuralgia. In patients with possible trigeminal neuropathy and anesthesia dolorosa, dextromethorphan decreased pain by a mean of only 2% to 4%, and these estimates were not significant. Both patients with trigeminal neuralgia had more pain during dextromethorphan treatment than during placebo treatment. Of the 3 patients who demonstrated an analgesic response to dextromethorphan during the main trial, only 1 repeatedly responded in 4 subsequent confirmatory drug-placebo crossovers. Conclude dextromethorphan shows little or no analgesic efficacy in pain due to possible trigeminal neuropathy and anesthesia dolorosa. Additional trials are necessary to conclusively evaluate the efficacy of NMDA-receptor antagonists in trigeminal neuralgia.     

Trigeminal neuralgia

Trigeminal neuralgia is an uncommon disorder characterized by recurrent attacks of lancinating pain in the trigeminal nerve distribution. Typically, brief attacks are triggered by talking, chewing, teeth brushing, shaving, a light touch, or even a cool breeze. The pain is nearly always unilateral, and it may occur repeatedly throughout the day. The diagnosis is typically determined clinically, although imaging studies or referral for specialized testing may be necessary to rule out other diseases. Accurate and prompt diagnosis is important because the pain of trigeminal neuralgia can be severe. Carbamazepine is the drug of choice for the initial treatment of trigeminal neuralgia; however, baclofen, gabapentin, and other drugs may provide relief in refractory cases. Neurosurgical treatments may help patients in whom medical therapy is unsuccessful or poorly tolerated.     

Long-term pain control in trigeminal neuralgia with local anesthetics using an indwelling catheter in the mandibular nerve

OBJECTIVE: The authors sought to determine the usefulness of long-term continuous trigeminal nerve block with local anesthetics using an indwelling catheter in a patient with trigeminal neuralgia. DESIGN: The study design included pain control in a patient with trigeminal neuralgia until the time of neurosurgical operation. SETTING: The study was conducted in the Dental Hospital of Tokyo Medical and Dental University. PATIENT: The patient was a 78-year-old woman with trigeminal neuralgia in the right maxillary region. Her pain could not be controlled by carbamazepine and was unbearable. INTERVENTION: The authors estimated the patient's pain intensity, quality, and locality using a visual analog scale to determine the effectiveness of continuous nerve block. OUTCOME MEASURES: Visual analog scores were measured during treatment. The treatment term was divided into three periods according to the difference of the catheter location and injection protocol (premandibular nerve block, infuser injection, and patient-controlled analgesia [PCA] pump injection). The authors also examined the patient's general condition and blood concentration of drugs. RESULTS: The visual analog values were 44.8 +/- 3.6, 26.7 +/- 3.5, and 11.9 +/- 3.1 mm in each period, respectively. The value in the PCA pump infusion period was significantly lower than that in the other periods. No side effects of the local anesthetics were observed on the patient's systemic condition. CONCLUSIONS: The authors controlled trigeminal neuralgia pain by blocking the mandibular nerve with local anesthetics administered through an indwelling catheter. Because the continuous nerve block with local anesthetics is reversible and only mildly toxic, this method is beneficial for pain control in patients with trigeminal neuralgia scheduled to undergo microvascular decompression.     

Trigeminal glycerol chemoneurolysis: nursing implications

Patients who have undergone unsuccessful medical treatment of trigeminal neuralgia may require some form of neurosurgical intervention. Injecting glycerol into the trigeminal cistern via the anterior percutaneous route has gained increasing acceptance as a method of relieving the excruciating paroxysmal pain of trigeminal neuralgia. The purpose of this article is to provide neuroscience nurses with an understanding of the rationale for selection of this particular procedure over other methods. The technique and potential complications will be briefly described. Nursing implications for the perioperative period will be discussed.     

NeuPSIG guidelines on neuropathic pain assessment

This is a revision of guidelines, originally published in 2004, for the assessment of patients with neuropathic pain. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at peripheral or central level.Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes. Clinical examination, including accurate sensory examination, is the basis of neuropathic pain diagnosis. For more accurate sensory profiling, quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes.Measurement of trigeminal reflexes mediated by A-beta fibers can be used to differentiate symptomatic trigeminal neuralgia from classical trigeminal neuralgia. Measurement of laser-evoked potentials is useful for assessing function of the A-delta fiber pathways in patients with neuropathic pain. Functional brain imaging is not currently useful for individual patients in clinical practice, but is an interesting research tool. Skin biopsy to measure the intraepidermal nerve fiber density should be performed in patients with clinical signs of small fiber dysfunction.The intensity of pain and treatment effect (both in clinic and trials) should be assessed with numerical rating scale or visual analog scale. For future neuropathic pain trials, pain relief scales, patient and clinician global impression of change, the proportion of responders (50% and 30% pain relief), validated neuropathic pain quality measures and assessment of sleep, mood, functional capacity and quality of life are recommended.     

SUNCT Syndrome: A Hungarian Case

A Hungarian patient with short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is presented in this paper. This male patient was first diagnosed as having first division trigeminal neuralgia. The location and duration of the attacks and the prominent accompanying autonomic feature on the symptomatic aide, such as conjunctival injection, lacrimation, nasal stuffiness, and the inefficacy of drugs, led to a reconsideration of the diagnosis. The pain paroxysms occurred frequently during a 3-to 4-month period, followed by a longer remission phase. Mechanical precipitating maneuvers were observed during bouts of pain. The clinical picture is reminiscent of the SUNCT syndrome, first described by Sjaastad et al in 1978.
SUNCT and trigeminal neuralgia are in many ways similar, although, some decisive differences have also been noted. Further observations are needed to distinguish the two disorders and to clarify this syndrome as a new headache type or as a trigeminal neuralgia variant.     

阿片类药物在慢性非癌性疼痛中的应用

目的:回顾性分析卡马西平和加巴喷丁治疗原发性三叉神经痛、带状疱疹以及带状疱疹后遗神经痛的疗效、安全性和不良反应。方法:102位患者进入本研究,比较卡马西平或加巴喷丁治疗前后患者疼痛强度的改变和对睡眠影响的改善;依据药物分类,比较两种药物的副作用和不良反应。结果:卡马西平治疗原发性三叉神经痛起效较加巴喷丁快,二者长期疗效相当;加巴喷丁治疗带状疱疹和带状疱疹后神经痛的疗效优于卡马西平;疗效随治疗时间的延长而增加。卡马西平的副作用和不良反应事件发生率较加巴喷丁高。结论:抗癫痫药物卡马西平和加巴喷丁是治疗神经病理性疼痛的有效药物,可以改善患者的睡眠,但副作用和不良反应发生率高。     

Peripheral and gasserian ganglion-level procedures for the treatment of trigeminal neuralgia.

This review discusses the various peripheral and ganglion-level procedures available for treating trigeminal neuralgia and summarizes specific success and complication rates for each technique. METHOD: A review of the available literature. RESULTS: It appears that expertly performed ganglion-level procedures (radiofrequency thermocoagulation, balloon compression, and glycerolysis) are more effective than peripheral procedures but neither approach can be relied on to produce long-term pain relief. All of these procedures are neurodestructive and can cause sensory loss and dysesthesia. Effective drug therapy may not be acceptable to some patients as adverse cognitive side effects are increasingly recognized. CONCLUSIONS: Each patient should receive an informed and impartial account of the available surgical options. There is a need for prospective randomized controlled studies in procedure-na?ve subjects to determine the optimal surgical management of trigeminal neuralgia.     

Middle cranial fossa endoscopy using a rigid endoscope

Trigeminal neuralgia (TN), also known as tic douloureaux, is a craniofacial pain disorder which is typically associated with acute‐onset severe pain on one side of the face usually. The condition is characterized by intermittent unilateral pain affecting the lower face and jaw. Although many potential causes have been implicated, in many patients the etiology remains obscure.

Initially, patients with trigeminal neuralgia should be offered conservative medical management. If surgery is necessary, the simplest and least hazardous procedure should be chosen. The goals of modern surgical therapy are: Long‐term pain control, minimal to no morbidity, and as low a mortality risk as possible.

In this study, we attempted to perform middle cranial fossa endoscopic exploration in four adult phenol‐formalin embalmed cadavers, using a rigid endoscope with 3.8 mm external diameter and two working channels of 1 mm in diameter each (Karl Storz, Tuttlingen, Germany), inserted through a burr‐hole centered at the base of the middle cranial fossa, 1 cm in front and 1 cm upwards of the tragus. Our objective was to determine if this approach provides adequate access to the trigeminal ganglion for possible dissection of V2 and V3 trigeminal roots, the two typically radiating sites of TN. In all four cadavers, middle cranial fossa exploration was possible without difficulties. We offer this approach as a minimally invasive surgical procedure to access the trigeminal ganglion, for potential use as another alternative for the surgical management of medically refractory trigeminal neuralgia.     

Fosphenytoin: an intravenous option for the management of acute trigeminal neuralgia crisis

Timely management of trigeminal neuralgia presenting with severe, sustained, crescendo pain can be difficult with oral medications. More rapid pain control often can be achieved using intravenous phenytoin. Fosphenytoin is a phosphate ester prodrug of phenytoin that is significantly better tolerated parenterally than phenytoin in the treatment of epilepsy. Three patients with trigeminal neuralgia refractory to oral medications and presenting with crisis pain were treated urgently with intravenous fosphenytoin. In each case complete relief of pain was achieved for a duration of two days, affording a window of opportunity to modify oral pharmacotherapeutic strategies or to control pain in preparation for invasive neurosurgical intervention.     

Efficacy of pregabalin in the treatment of trigeminal neuralgia

This prospective, open-label study aimed to evaluate the efficacy of pregabalin treatment in patients suffering from trigeminal neuralgia with and without concomitant facial pain. Fifty-three patients with trigeminal neuralgia (14 with concomitant chronic facial pain) received pregabalin (PGB) 150–600 mg daily and were prospectively followed for 1 year. The primary outcome was number of patients pain free or with reduction of pain intensity by > 50% and of attack frequency by > 50% after 8 weeks. Secondary outcome was sustained pain relief after 1 year. Thirty-nine patients (74%) improved after 8 weeks with a mean dose of 269.8 mg/day (range 150–600 mg/day) PGB: 13 (25%) experienced complete pain relief and 26 (49%) reported pain reduction > 50%, whereas 14 (26%) did not improve. Patients without concomitant facial pain showed better response rates (32 of 39, 82%) compared with patients with concomitant chronic facial pain (7 of 14, 50%, P  = 0.020). Concomitant chronic facial pain appears to be a clinical predictor of poor treatment outcome. PGB appears to be effective in the treatment of trigeminal neuralgia.     

Pathophysiology of trigeminal neuralgia: the ignition hypothesis.

There are no satisfactory animal models of trigeminal neuralgia, and it is difficult to obtain essential data from patients. However, trigeminal neuralgia presents with such idiosyncratic signs and symptoms, and responds to so distinctive a set of therapeutic modalities, that scientific deduction can be used to generate likely hypotheses. The ignition hypothesis of trigeminal neuralgia is based on recent advances in the understanding of abnormal electrical behavior in injured sensory neurons, and new histopathologic observations of biopsy specimens from patients with trigeminal neuralgia who are undergoing microvascular decompression surgery. According to the hypothesis, trigeminal neuralgia results from specific abnormalities of trigeminal afferent neurons in the trigeminal root or ganglion. Injury renders axons and axotomized somata hyperexcitable. The hyperexcitable afferents, in turn, give rise to pain paroxysms as a result of synchronized afterdischarge activity. The ignition hypothesis accounts for the major positive and negative signs and symptoms of trigeminal neuralgia, for its pathogenesis, and for the efficacy of treatment modalities. Proof, however, awaits the availability of key experimental data that can only be obtained from patients with trigeminal neuralgia.     

The Medical Management of Trigeminal Neuralgia

Trigeminal neuralgia results from disturbances in the trigeminal root entry zone which generate repetitive action potentials. Drugs which relieve the pain of trigeminal neuralgia depressed these potentials. Anticonvulsants which exert this or related effects, and which have been demonstrated to be efficacious in trigeminal neuralgia, include carbamazepine, phenytoin, clonazepam, and valproic acid. Baclofen may act by facilitating segmental inhibition of the trigeminal complex. The mechanism of action of pimozide for treating trigeminal neuralgia is not known. Carbamazepine is suggested as the drug of first choice; baclofen or clonazepam could be added if carbamazepine monotherapy is ineffective. When these fail, monotherapy with phenytoin, pimozide, or valproic acid would be a reasonable next step.