Interventional treatment for cluster headache: A review of the options

There is no more severe pain than that sustained by a cluster headache sufferer. Surgical treatment of cluster headache should only be considered after a patient has exhausted all medical options or when a patient’s medical history precludes the use of typical cluster abortive and preventive medications. Once a cluster patient is deemed a medical failure only those who have strictly side-fixed headaches should be considered for surgery. Other criteria for cluster surgery include pain localizing to the ophthalmic division of the trigeminal nerve, a psychologically stable individual, and absence of addictive personality traits. To understand the rationale behind the surgical treatment strategies for cluster, one must have a general understanding of the anatomy of cluster pathogenesis. The most frequently used surgical techniques for cluster are directed toward the sensory trigeminal nerve and the cranial parasympathetic system.     

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.     

Surgical treatment of chronic cluster headache

Chronic cluster headache, also known as chronic migrainous neuralgia, is frequently unresponsive to medical management. Although neuronal factors may be involved in the pathogenesis of this form of recurrent hemicranial pain, vasodilatation within the distribution of the trigeminal nerve is believed to be important. Attempts to provide relief by surgical means have primarily involved interruption of the vasodilator pathways of the greater superficial petrosal nerve and the sphenopalatine ganglion. A more direct approach of interrupting the pain pathways of the trigeminal nerve has been attempted sporadically for more than 50 years. Recent interest in the role of substance P in the production of pain in cluster headache suggests that trigeminal ablative procedures might have a dual role in the relief of medically intractable cases. Among 26 patients who underwent posterior fossa trigeminal sensory rhizotomy or percutaneous radio-frequency trigeminal gangliorhizolysis at our institution, relief of pain was excellent in 14 (54%), fair to good in 4 (15%), and poor in 8 (31%).     

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.     

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.     

A Case‐Control Study on Cortical Thickness in Episodic Cluster Headache

Objective.— This study aims at investigating cortical thickness in cluster headache patients as compared with a healthy control group. Background.— The pathobiology of cluster headache is not yet fully understood, although a dysfunction of the hypothalamus has been suggested to be causal. Previous studies in migraine and trigeminal neuropathic pain have demonstrated changes in cortical thickness using cortex segmentation techniques, but no data have been published on cluster headache. Methods.— We investigated 12 men with episodic cluster headache during a phase without acute headache as well as age and sex‐matched healthy controls using high resolution T1‐weighted magnetic resonance imaging acquired at 3T and performed a categorical whole‐brain surface‐based comparison of cortical thickness between groups. Furthermore, a correlation analysis of disease duration and cortical thickness was conducted. Results.— In comparison with control subjects, we found a reduction of cortical thickness in the angular gyrus and the precentral gyrus in cluster headache patients contralaterally to the headache side. These reductions did not correlate with disease duration. The cortical thickness of an area within the primary sensory cortex correlated with disease duration. Conclusions.— This study demonstrates alterations in cortical thickness in cluster headache patients suggesting a potential role of cortical structures in cluster headache pathogenesis. However, it cannot be determined from this study whether the changes are cause or consequence of the disorder. The correlation of cortical thickness with disease duration in the somatosensory cortex may suggest disease‐related plasticity in the somatosensory system.     

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.     

The trigemino-pupillary response in cluster headache

Central impairment of the integrative neural systems controlling vegetative function and pain perception has been demonstrated in cluster headache (CH). Recently, we described the human pupillary response (trigeminal reflex) to quantified (painless and painful) corneal stimulation with a combined neurophysiological and pharmacological technique. In this study, the trigeminal reflex was evaluated in 26 subjects with episodic cluster headache. During the active phase of the disease, on the side of the pain we observed reduced mydriasis to electrical stimuli with an intensity equal to the corneal reflex threshold, and on both sides to stimuli with intensity that equalled the pain threshold. No difference was found when amplitude of the miotic phase was compared in the different groups. These suggest disordered pupillary activation in response to pain, probably sympathetic in origin, which is bilateral, detectable also during the remission phase and which cannot be explained simply by the antidromic release of pain-related peptides.     

Retro-Gasserian glycerol injection in the treatment of chronic cluster headache

Seven therapy-resistant patients with cluster headache (six of whom were chronic) were treated by percutaneous retro-Gasserian glycerol injections under general anesthesia. In four of the patients immediate and complete relief of attacks was obtained. There was a close correlation between pain relief and the degree of ophthalmic sensory loss. Quantitative estimation of thresholds for thermal perception and pain showed a good correlation to clinically evaluated sensory loss. As the analgesia waned, headaches returned, and the glycerol injections had to be repeated. Two patients were still considerably improved after 5 1/2 and nearly 3 years, respectively. In the other patients the results were less satisfactory at long-term follow-up study. Pure glycerol is highly hypertonic, and the damage of the trigeminal nerve root may be due to this property.     

The influence of gender and sex steroids on craniofacial nociception

Several pain conditions localized to the craniofacial region show a remarkable sex-related difference in their prevalence. These conditions include temporomandibular disorders and burning mouth syndrome as well as tension-type, migraine, and cluster headaches. The mechanisms that underlie sex-related differences in the prevalence of these craniofacial pain conditions remain obscure and likely involve both physiological and psychosocial factors. In terms of physiological factors relevant to the development of headache, direct evidence of sex-related differences in the properties of dural afferent fibers or durally activated second-order trigeminal sensory neurons has yet to be provided. There is, however, evidence for sex-related differences in the response properties of afferent fibers and second-order trigeminal sensory neurons that convey nociceptive input from other craniofacial tissues associated with sex-related differences in chronic pain conditions, such as those that innervate the masseter muscle and temporomandibular joint. Further, modulation of craniofacial nociceptive input by opioidergic receptor mechanisms appears to be dependent on biological sex. Research into mechanisms that may contribute to sex-related differences in trigeminal nociceptive processing has primarily focused on effect of the female sex hormone estrogen, which appears to alter the excitability of trigeminal afferent fibers and sensory neurons to noxious stimulation of craniofacial tissues. This article discusses current knowledge of potential physiological mechanisms that could contribute to sex-related differences in certain craniofacial pain conditions.     

Trigeminal control of cranio-facial vasomotor response: I. Histamine test in patients with unilateral gasserian ganglion lesions

It has been hypothesized that the trigeminal system may control vasomotor changes and pain in vascular headaches. In this study, headache was induced by an intravenous injection of histamine in 37 patients with trigeminal rhizotomy and in 12 controls. The vasomotor response to histamine was studied with facial telethermography. The headache in patients with trigeminal lesions differed, in a prevalence of unilateral localization contralaterally to the operated side (21 patients), from that in controls. No relationship was found between the hypoesthesia caused by the operation and the prevalence of unilateral headache. A statistically significant correlation (p less than 0.001) was found between unilateral absence of headache and decreased vasomotor response on the operated side. These reactions occurred more in patients who underwent thermocoagulation than in patients who underwent retro-gasserian rhizotomy. Thus the gasserian ganglion seems to control the cranio-facial vasomotor response and the headache through a vascular pathway, acting on cerebral arteries, which differs from the sensory pathway.     

Allodynia in Cluster Headache

Cutaneous allodynia (CA), the perception of pain when a non-noxious stimulus is applied to normal skin, has been described in various pain syndromes. The pathophysiology of CA in headache is thought to be related to central sensitization of brainstem, and possibly thalamic, neurons. The recognition of CA in cluster headache (CH) is recent, and available data are scant. Some studies suggest the occurrence of CA in a significant proportion of CH patients. However, one study that examined sensory thresholds in CH failed to confirm this. CA in CH is characterized by rapid onset and termination, suggesting different mechanisms compared with CA in migraine. CA in CH is common in trigeminal areas but may spread to cervical dermatomes and beyond. The relations between the type of CH (episodic vs chronic) and CA are unknown. Further studies are needed to determine the mechanism of CA in CH, and its clinical implications.     

Cervicogenic headache: Diagnostic evaluation and treatment strategies

Cervicogenic headache is a chronic, hemicranial pain syndrome in which the source of pain is located in the cervical spine or soft tissues of the neck but the sensation of pain is referred to the head. The trigeminocervical nucleus is a region of the upper cervical spinal cord where sensory nerve fibers in the descending tract of the trigeminal nerve converge with sensory fibers from the upper cervical roots. This convergence of upper cervical and trigeminal nociceptive pathways allows the referral of pain signals from the neck to the trigeminal sensory receptive fields of the face and head. The clinical presentation of cervicogenic headache suggests that there is an activation of the trigeminovascular neuroinflammatory cascade, which is thought to be one of the important pathophysiologic mechanisms of migraine. Another convergence of sensorimotor fibers has been described involving intercommunication between the spinal accessory nerve (CN XI), the upper cervical nerve roots, and ultimately the descending tract of the trigeminal nerve. This neural network may be the basis for the wellrecognized patterns of referred pain from the trapezius and sternocleidomastoid muscles to the face and head. Diagnostic criteria have been established for cervicogenic headache but its presenting characteristics may be difficult to distinguish from migraine, tension-type headache, or hemicrania continua. A multidisciplinary treatment program integrating pharmacologic, nonpharmacologic, anesthetic, and rehabilitative interventions is recommended. This article reviews the clinical presentation of cervicogenic headache, its diagnostic evaluation, and treatment strategies.     

Gamma Knife Stereotactic Radiosurgery in the Management of Cluster Headache

Gamma knife stereotactic radiosurgery (SRS) has proven to be an effective management approach for trigeminal neuralgia and as a minimally invasive alternative management option for cluster headache (CH). In CH, patients undergo single-session focused irradiation of the trigeminal nerve root (TN), sometimes coupled with irradiation of the sphenopalatine ganglion (SPG) as well. SRS provides early pain relief in most patients, but is associated with trigeminal sensory dysfunction in some patients. In the future, a prospective trial that compares a single target of TN to dual targets of both the TN and SPG may provide further understanding of the value of SRS for CH.     

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.     

Greater occipital nerve block for migraine and other headaches: Is it useful?

Peripheral nerve blocks have long been used in headache treatment. The most widely used procedure for this purpose has been greater occipital nerve (GON) block. The rationale for using GON block in headache treatment comes from evidence for convergence of sensory input to trigeminal nucleus caudalis neurons from both cervical and trigeminal fibers. Although there is no standardized procedure for GON blockade, the nerve is usually infiltrated with a local anesthetic (lidocaine, bupivacaine, or both). A corticosteroid is sometimes added. Several studies suggested efficacy of GON block in the treatment of migraine, cluster headache, and chronic daily headache. However, few were controlled and blinded. Despite a favorable clinical experience, little evidence exists for the efficacy of GON block in migraine treatment. Controlled studies are needed to better assess the role of GON block in the treatment of migraine and other headaches.     

Cluster headache attacks and multiple sclerosis

We report the case of a patient who developed typical cluster headache attacks and was diagnosed as having multiple sclerosis (MS) at the same time. The headache attacks resolved after i.v. treatment with methylprednisolone. MR imaging showed a pontine demyelinating lesion involving the trigeminal nerve root inlet area, on the same side as the pain. The association between cluster headache and MS has been rarely described before. This case suggests that in patients with cluster headache neuroimaging is often useful in order to exclude structural lesions.     

Quantitative sensory testing in cluster headache: increased sensory thresholds

To determine if recently reported changes in sensory thresholds during migraine attacks can also be seen in cluster headache (CH), we performed quantitative sensory testing (QST) in 10 healthy subjects and in 16 patients with CH. Eight of the patients had an episodic CH and the other eight a chronic CH. The tests were performed on the right and left cheeks and on the right and left side of the back of the hands to determine the subjects' perception and pain thresholds for thermal (use of a thermode) and mechanical (vibration, pressure pain thresholds, pin prick, von Frey hairs) stimuli. Six patients were examined in the attack-free period. Three were also willing to repeat the tests a second time during an acute headache attack, which was elicited with nitroglycerin. The healthy subjects performed the experiments in the morning and evening of the same day to determine if sensory thresholds are independent of the time of day. If they were, this would allow estimation of the influence of the endogenous cortisone concentration on these thresholds. The control group showed no influence of the time of day on the thresholds. There was a significant difference in pain sensitivity between the back of the hands and the cheeks (P<0.05): higher thresholds were found on the back of the hands. The thresholds generally exhibited little intersubject variability, indicating that QST is a reliable method. There was also a significant difference between the test areas in the patient group (P<0.001): the cheeks were also more sensitive than the back of the hands. In comparison with reference data of healthy volunteers, the detection thresholds were increased in the patients on both test areas. These were statistically significant for warmth, thermal sensory limen (TSL), heat and pressure on the back of the hands (P<0.04) and for the warmth and TSL thresholds on the cheeks (P<0.05). There were no differences in the thresholds regardless of whether the patients were examined in or outside of a cluster bout. Furthermore, we found no cutaneous allodynia in the three patients tested during an attack. The increased sensory thresholds on the cheeks as well as on the back of the hands are in agreement with an increased activation of the patients' antinociceptive system. The seasonal variation and the temporal regularity of single attacks as well as the findings in imaging studies indicate that the hypothalamus is involved in the pathophysiology of CH. In view of the strong connectivity between the hypothalamus and areas involved in the antinociceptive system in the brainstem, we hypothesize that this connection is the reason for the increased sensory thresholds in CH patients found in our study.     

Percutaneous Radiofrequency Trigeminal Gangliorhizolysis in Intractable Cluster Headache

SYNOPSIS
Recent interest in the possible role of substance P and other vaso-active polypeptides of the trigeminal vascular system, in the pathogenesis of vascular headache, has lad to a reconsideration of the value of ablative procedures on the trigeminal nerve in the control of chronic, medically intractable cluster headache. Twenty-seven patients with disabling intractable chronic cluster headache underwent radiofrequency trigeminal gangliorhizolysis. Indications included total resistance to prophylactic treatment, narcotic dependency, hypercorticism, and contra-indications to ergotamine and methysergide as a result of severe ischemic heart disease. The procedure had to be repeated in 6 patients, once in 4 and twice in 2. The average follow-up period was 28 months with a range of 6 to 63 months. Excellent results were obtained in 15 patients, very good in 2, good in 3, fair in 1 and poor in 6. Complications were anesthesia dolorosa, stabbing pain over the vertex, ice-pick like pain over the ipsilateral eye, transient corneal infection, transient diplopia, localized dermatosis, and recurrent stye. Complications were mild and transient in the majority of the patients, and the benefits from the surgery far outweighed the discomfort from the complications. The reasons for poor results in some patients were analyzed.
It is concluded that radiofrequency trigeminal gangliorhizolysis is a reasonable alternative in patients with chronic cluster headache 1) who are totally resistant to medical treatment, 2) with a history of strictly unilateral headache, and 3) with stable personality profile and low addiction proneness.