SUNCT Syndrome: Trials of Drugs and Anesthetic Blockades

Nine patients with the SUNCT syndrome (Spanish and Norwegian patients) have, over many years, been given several drugs effective in the cluster headache syndrome, trigeminal neuralgia, and other headaches, as well as drugs not previously used in headache. Various cranial nerves were also anesthetized in an endeavor to ameliorate the suffering of those patients.
Although a partial effect was obtained with carbamazepine and corticosteroids in some patients, none of the drugs or anesthetic blockades had consistent, lasting, complete effect on headache paroxysms in SUNCT. The essentially negative outcome of this study aids in further characterizing SUNCT as a separate disorder, and, above all, in distinguishing it from trigeminal neuralgia and the cluster headache syndrome.     

Pharmacotherapy of trigeminal neuralgia.

The efficacy of the anticonvulsant drug carbamazepine in the management of trigeminal neuralgia is evidenced in several controlled trials, and the numbers needed to treat to obtain one patient with at least 50% pain relief (NNT) is 1.7. Single small trials have shown that baclofen alone provides pain relief (NNT = 1.4) and that lamotrigine has an additional effect in patients with insufficient relief using carbamazepine or phenytoin (NNT = 2.1). Uncontrolled observations and clinical practice indicate that phenytoin, clonazepam, sodium valproate, gabapentin, and lidocaine will also relieve trigeminal neuralgia. In case of lacking effect of a single drug, combination of two or more drugs may be used, but with the exception of the lamotrigine-carbamazepine combination, this is not evidence-based medicine. Acute exacerbation has successfully been treated with intravenous loading with phenytoin or lidocaine, but again these procedures have not been tested in controlled trials. In conclusion, carbamazepine is the mainstay of pharmacotherapy of trigeminal neuralgia, and secondary drug choices are baclofen, lamotrigine, oxcarbazepine, phenytoin, gabapentin, and sodium valproate. Controlled trials testing the effect of some of these drugs, new drugs, and drug combinations are needed.     

Cluster headache pain vs. other vascular headache pain: differences revealed with two approaches to the McGill Pain Questionnaire

We compared cluster headache pain and other vascular (migraine and mixed) headache pain on pain intensity ratings and the McGill Pain Questionnaire (MPQ). Cluster headache sufferers reported not only more intense pain and more affective distress, but also different pain qualities than did migraine and mixed headache sufferers. The pain qualities that best distinguished cluster headaches from other vascular headaches were the presence of punctate pressure and thermal sensations and the absence of dull pain. Although cluster headache sufferers and other vascular headache sufferers endorsed different sensory pain qualities, MPQ subscales proved no better than pain intensity ratings at distinguishing these two groups. This finding may have occurred because MPQ subscale scores include an intensity component and do not provide information about specific pain qualities such as that provided by MPQ sensory items. These findings provide evidence that cluster headaches are characterized by distinct pain qualities and are not simply a more intense version of the same vascular headache pain experienced by migraine and mixed headache sufferers. They further suggest than when the MPQ is used to assess specific pain qualities, sensory items and not the sensory subscale are the preferred units for analysis.     

Dental presentations of cluster headaches

Cluster headache has been defined by the International Headache Society (IHS) as one of the primary headaches. A primary headache is a headache that has no other known cause, such as infection or trauma. Cluster headache is also listed as one of the trigeminal autonomic cephalalgias. These headaches are mediated by the trigeminal nerve with accompanying autonomic symptoms that may range from conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, and ptosis to eyelid edema. The IHS has described cluster headache as "attacks of severe, strictly unilateral pain that is orbital, supraorbital, temporal or in any combination of these sites, lasting 15 to 180 minutes." In the author’s practice, as a dentist treating orofacial pain, patients with cluster headache have dental or midfacial complaints as a primary presentation. This paper introduces such presentations based on interviews with cluster headache patients, with the main purpose of having midfacial complaints considered as an important presentation to be added to the IHS diagnostic criteria for cluster headache.     

Cluster-tic syndrome

A case of cluster-tic syndrome is presented. A 51-year-old man developed pain attacks corresponding to the second branch of the trigeminal nerve. After treatment with 1200 mg carbamazepine daily, the attacks disappeared. Full remission was achieved, and carbamazepine therapy was continued. Pain attacks of a quite different character then appeared; their clinical picture corresponded to cluster headache. After treatment with cyproheptadine, the cluster headache attacks ceased, but 2 days later, before the discontinuation of the treatment, the attacks of trigeminal neuralgia reappeared. Treatment with carbamazepine was started again, and there was remission of the trigeminal neuralgia after several weeks.     

Cluster headaches

Cluster headaches are episodes of excruciating unilateral facial pain, typically occurring in young men. Ipsilateral autonomic symptoms of nasal congestion, rhinorrhea, conjunctival injection and lacrimation are commonly present. Characteristic facial features may be found. Migraine and trigeminal neuralgia are two important considerations in the differential diagnosis. Prednisone and lithium are effective prophylactic medications for episodic and chronic forms of cluster headaches. Treatment with oxygen or ergotamines may be useful in aborting attacks.     

Paroxysmale Hemikranie und SUNCT

Paroxysmal hemicrania is experienced as headache attacks with pain and accompanying symptoms similar to those of cluster headaches. Attacks are, however of shorter duration, occur more frequently, affect predominantly women and respond reliably to indomethacin. Paroxysmal hemicrania can also occur secondary to an identifiable cause. To exclude symptomatic, paroxysmal hemicrania, especially with an atypical clinical picture and poor response to indomethacin, a careful diagnostic approach is necessary. The SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) is characterized by one-sided pain attacks of short duration, much shorter than other trigeminal autonomic cephalgias. Classically, the pain is accompanied by ipsilateral lacrimation and conjunctival injection. Some patients have been described with both cluster headache and trigeminal neuralgia. These patients should receive both diagnoses. It is important to differentiate these headache entities as specific therapy is needed for each to achieve optimal pain relief.     

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.     

Deep brain stimulation for intractable chronic cluster headache: proposals for patient selection

Cluster headache is the most severe of the primary headaches. Positron emission tomography and functional MRI studies have shown that the ipsilateral posterior hypothalamus is activated during cluster headache attacks and is structurally asymmetric in these patients. These changes are highly specific for the condition and suggest that the cluster headache generator may be located in that brain area; they further suggest that electrical stimulation of that region might produce clinical improvement in chronic cluster headache sufferers refractory to medical therapy. In five patients with severe intractable chronic cluster headache, hypothalamic electrical stimulation produced complete and long-term pain relief with no relevant side-effects. We therefore consider it essential to propose criteria for selecting chronic cluster headache patients for hypothalamic deep brain stimulation before this procedure is undertaken at other academic medical centres.     

Failure of Mexiletine to Control Trigeminal Neuralgia

The analgesic effects of lidocaine and tocainide on trigeminal neuralgia have been established. However, both drugs are unpractical: lidocaine can only be used intravenously, and tocainide may exhibit serious haematological side effects. Mexiletine, a structural analogue of lidocaine that can be safely administered by the oral route, was given, as the sole drug, to four patients with active trigeminal neuralgia. After at least seven days on mexiletine they had no clear benefit. The four patients subsequently improved with carbamazepine or phenytoin. Our observations suggest that mexiletine alone is not of value in trigeminal neuralgia.     

Cluster headache pharmacotherapy

Cluster headache is a well-known primary headache syndrome with a prevalence of about 5/10,000 of the adult population, making it much less common than migraine. Diagnostic terms such as histaminic cephalalgia, Horton's headache and ciliary neuralgia have been used for what is now known as cluster headache. This disorder can be differentiated from migraine by clinical and pathophysiologic features. Cluster headache also exhibits a differing therapeutic response to medications when compared with migraine. The pharmacologic treatment of cluster is reviewed in this article. In contrast to migraine, men are 3-4 times more likely to be diagnosed with cluster headache than women, and the cluster headache population is older. Cluster attacks are known for their brief intense unilateral excruciating pain during susceptible periods known as cluster periods, which typically last weeks. Attack-free months generally follow. Pain is experienced in the distribution of the trigeminal nerve, with unilateral autonomic features. Most patients are successfully managed with medical therapy. Medication management can be divided into abortive treatments for an ongoing attack and prophylactic treatment. Prophylaxis aims to induce and maintain a remission. There are a variety of different medications for abortive and prophylactic therapy, accompanied by a variable amount of evidence-based medicine. For patients refractory to medical management, interventional procedures are available as a last resort. Most procedures are directed against the sensory trigeminal nerve and associated ganglia, eg, anesthetizing the sphenopalatine ganglion.     

Relief of cluster-tic syndrome by the combination of lithium and carbamazepine

This paper presents a further case of cluster-tic syndrome. Cluster headache and trigeminal neuralgia have coexisted in our patient for 18 years. Carbamazepine has selectively relieved the tic douloureux, while lithium has completely controlled the cluster headache. Our case shows again that the simultaneous occurrence of cluster headache and trigeminal neuralgia seems to be more than coincidental.     

Relief of cluster headache and cranial neuralgias. Promising prophylactic and symptomatic treatments

When a patient presents with persistently unilateral head or face pain, cluster headache and trigeminal neuralgia should be considered. Diagnosis is based on the patient's history; anatomical studies are performed only to rule out problems other than tumor or stroke. A patient who presents with pain in the pharynx, tonsils, and ear--particularly if it is initiated by swallowing, yawning, or eating--may have glossopharyngeal neuralgia. Treatment with carbamazepine is indicated; if the patient does not respond to this drug, the diagnosis is doubtful. Several effective treatments are available for these conditions. Oxygen, drug therapy, or surgery may be indicated depending on the course of the disease.     

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。     

Antidepressants and antiepileptic drugs for chronic non-cancer pain

The development of newer classes of antidepressants and second-generation antiepileptic drugs has created unprecedented opportunities for the treatment of chronic pain. These drugs modulate pain transmission by interacting with specific neurotransmitters and ion channels. The actions of antidepressants and antiepileptic drugs differ in neuropathic and non-neuropathic pain, and agents within each medication class have varying degrees of efficacy. Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, desipramine) and certain novel antidepressants (i.e., bupropion, venlafaxine, duloxetine) are effective in the treatment of neuropathic pain. The analgesic effect of these drugs is independent of their antidepressant effect and appears strongest in agents with mixed-receptor or predominantly noradrenergic activity, rather than serotoninergic activity. First-generation antiepileptic drugs (i.e., carbamazepine, phenytoin) and second-generation antiepileptic drugs (e.g., gabapentin, pregabalin) are effective in the treatment of neuropathic pain. The efficacy of antidepressants and antiepileptic drugs in the treatment of neuropathic pain is comparable; tolerability also is comparable, but safety and side effect profiles differ. Tricyclic antidepressants are the most cost-effective agents, but second-generation antiepileptic drugs are associated with fewer safety concerns in elderly patients. Tricyclic antidepressants have documented (although limited) efficacy in the treatment of fibromyalgia and chronic low back pain. Recent evidence suggests that duloxetine and pregabalin have modest efficacy in patients with fibromyalgia.     

Chronic Cluster Headache Managed by Nervus Intermedius Section

Cluster headache sufferers who become candidates for surgical treatment are those relatively rare patients who are refractory to all attempts at pharmacological relief. Ablative surgical procedures have been directed against either the trigeminal nerve or the nervus intermedius/greater superficial petrosal (NI/GSP) pathway. Both carry nociceptive impulses from the head and face, and the NI also carries parasympathetic fibres which appear to be responsible for the autonomic concomitants of cluster headache. Trigeminal operative procedures are not consistently helpful in chronic cluster headache, while NI section has been shown to give potentially long lasting relief but carries the potential risks of cerebellopontine angle surgery. In eight selected cases of chronic cluster headache we have demonstrated a high early success rate for pain relief, with few complications, in the performance of NI section, combined, when indicated, with microvascular decompression of the trigeminal main sensory root. We believe that cochlear nerve monitoring helps prevent postoperative hearing impairment. An intimate relationship between the NI and arterial loops of the anterior inferior cerebellar artery (AICA) or the internal auditory artery has been frequently observed in our chronic cluster headache patients.     

Endocrinology of cluster headache: Potential for therapeutic manipulation

Cluster headaches have always been among the most intriguing of the commonly recognized primary headache syndromes. This clinical interest is related to a number of factors, including the intense but short-lived nature of the pain, its sexual predilection, associated trigeminal autonomic dysfunction, and the remarkable circadian and circannual periodicity of cluster periods. Recent advances in neuroimaging and neuroendocrinology have shed light on the pivotal role of the hypothalamus in the biology of cluster headache. We discuss these revelations, along with current clinical observations in headache and sleep medicine.     

Hypothalamic involvement and activation in cluster headache

Cluster headache is an episodic form of primary neurovascular headache that is both severe and relatively rare. It is characterized by episodes of headache with cranial parasympathetic activation and sympathetic impairment that come in bouts, or clusters. Its pathophysiology can be divided into understanding the attack phenotype and the biotype of the periodicity. Acute attacks of cluster headache are marked by trigeminal nerve-mediated pain and with cranial autonomic activation, trigeminal-autonomic cephalalgia; an activation that characterizes the phenotype of a group of headaches. The signature feature of cluster headache is its periodicity, the daily cycle of attacks when the patient is in an active bout, or the circumannual, or other period, cycling that distinguishes the on period from the off period. Functional brain imaging with positron emission tomography and structural imaging with voxel-based morphometry have identified an area in the posterior hypothalamic gray as key in understanding cluster headache. This area is subtly enlarged in its gray matter volume, active during an acute cluster headache but inactive when patients are challenged between bouts. Cluster headache is likely to be a form of primary neurovascular pain whose phenotypic expression relies on the trigeminal-autonomic reflex, with a biotype determined by the brain area, the posterior hypothalamus, in which the lesion seems to be located. Understanding both the phenotypic expression and the biotype will, respectively, enable better acute attack treatments and better preventative management of this horrible form of headache.     

Coexistence of TACS and trigeminal neuralgia: pathophysiological conjectures

BACKGROUND: Trigeminal autonomic cephalgias (TACs) and trigeminal neuralgia are short-lasting unilateral primary headaches whose study is providing insights into craniofacial pain mechanisms. We report on 2 patients in whom trigeminal neuralgia coexists with the TACs paroxysmal hemicrania and SUNCT. CONCLUSION: Coexistence of trigeminal neuralgia with various TAC forms suggests a pathophysiological relationship between these short-lasting unilateral headaches.