Upper and lower cluster headache: clinical and pathogenetic observations in 608 patients

OBJECTIVE, BACKGROUND, AND METHODS: Ever since it was proposed by Ekbom and Kugelberg back in 1968 on the basis of the different location of head pain during attacks, the differentiation of cluster headache into an upper syndrome (US) and a lower syndrome (LS) has been regarded as a purely academic distinction. To evaluate whether this differentiation is indeed well founded and to understand its possible significance in the light of current pathogenetic knowledge, we rigorously applied Ekbom and Kugelberg's classification criteria to a sample of 608 patients with cluster headache (CH; 440 men and 168 women), including 483 with episodic CH, 69 with chronic CH, and 56 with CH periodicity undetermined. RESULTS: Of these patients, 278 could be classified as US sufferers and 330 as LS sufferers. Our data analysis showed statistically significant clinical differences between the two syndromes: pain location was more common in the ocular, temporal, and nuchal regions among LS sufferers; in addition, patients with LS reported not only a higher rate of autonomic symptoms, but also a higher predominance of nasal congestion, ptosis, and forehead and facial sweating among these symptoms. CONCLUSIONS: Based on current anatomofunctional knowledge and on the most recent pathogenetic findings, we believe that changes in hypothalamic activity posteroinferiorly may lead to activation of the caudal part of the spinal trigeminal nucleus by way of the hypothalamus, midbrain, and trigeminal nerve fibers and consequently to activation of the trigeminovascular system with a different location in the two syndromes. More specifically, there seems to be a larger and more extensive involvement of the subnucleus caudalis in LS compared with US, where only its ventrocaudal portions are likely to be affected.     

Trigemino-cervical reflex abnormalities in patients with migraine and cluster headache

BACKGROUND: Head pain arises within the trigeminal nociceptive system. Current theories propose that the trigeminal system is intimately involved in the pathogenesis of migraine. Short-latency responses can be recorded in sternocleidomastoid muscles after stimulation of the trigeminal nerve (trigemino-cervical reflex). This brainstem reflex could be a suitable method to evaluate the trigeminal system in migraine and CH. OBJECTIVE: The aim of the present study was to further elucidate the pathophysiology of migraine and cluster headache (CH) with special reference to the involvement of the central trigeminal system in the different forms of primary headache. METHODS: The trigemino-cervical reflex was investigated in 15 healthy subjects, in 15 patients having migraine with aura, in 15 patients with migraine without aura, and in 10 patients with CH. RESULTS: Significant abnormalities were observed in a great number of patients with both types of migraine and CH during the headache attacks, but only in migraine patients during the interictal period. The alterations are bilateral in migraine, unilateral in CH. CONCLUSIONS: Our results further support the relevance of brainstem mechanisms in the pathogenesis of migraine rather than of CH. These data, taken together with that from experimental head pain and functional imaging studies, demonstrate that primary headache syndromes may be distinguished on a functional basis by areas of activation specific to the clinical syndrome.     

The trigeminal trophic syndrome: an unusual cause of face pain, dysaesthesias, anaesthesia and skin/soft tissue lesions

The trigeminal trophic syndrome is an unusual consequence of trigeminal nerve injury that results in facial anaesthesia, dysaesthesia and skin ulceration. Limited knowledge is available. The aim of this study was to increase the knowledge of this syndrome by performing a retrospective medical record review and case series report. Fourteen cases were identified. The female : male ratio was 6:1. Mean age of onset was 45 years (range 6–82). The cause was iatrogenic in most. Latent period to onset ranged from days to almost one decade. The majority ( n  = 12) had bothersome dysaesthesias. Most ( n  = 9) self-manipulated the face; a third ( n  = 5) did not. Most ulcers affected the second trigeminal division, mainly in the infraorbital nerve distribution. Neuropathic and/or neuralgic facial pain occurred in 50% ( n  = 7). Pain intensity was severe in most ( n  = 6). Gabapentin gave relief in two. To conclude, trigeminal trophic syndrome follows injury to the trigeminal nerve or its nuclei. For unclear reasons, most ulcerations follow infraorbital nerve distribution. Self-manipulation may contribute to ulcer development rather than being required. Gabapentin may help pain.     

Pathophysiology and treatment of trigeminal autonomic cephalalgias

Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders, which are characterized by strictly unilateral pain, together with ipsilateral cranial autonomic symptoms. TACs include cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). These diseases all have one thing in common: an activation of trigeminal nociceptive afferentia with a reflex-like activation of cranial autonomic efferentia via the facial nerve. TACs show differences not only in the length and frequency of attacks but also in the response to drug treatment. It is important to recognize and differentiate between these syndromes because they react very well, but very selectively to therapy.     

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.     

Neues zur Pathophysiologie und Therapie der trigeminoautonomen Kopfschmerzsyndrome

Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders, which are characterized by strictly unilateral pain, together with ipsilateral cranial autonomic symptoms. TACs include cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). These diseases all have one thing in common: an activation of trigeminal nociceptive afferentia with a reflex-like activation of cranial autonomic efferentia via the facial nerve. TACs show differences not only in the length and frequency of attacks but also in the response to drug treatment. It is important to recognize and differentiate between these syndromes because they react very well, but very selectively to therapy.     

Cluster headache syndrome. Ways to abort or ward off attacks.

Cluster headache is a syndrome of severe head and facial pain accompanied by autonomic abnormalities. Men are affected more frequently than women. Headaches occur daily during periods of susceptibility, which may be followed by periods of remission. The etiology of cluster headache is uncertain. Recent work suggests that hypothalamic dysfunction and/or oxyhemoglobin desaturation may be involved in its pathogenesis. Effective medical regimens are available for aborting acute attacks and for preventing attacks. Surgical ablation of the trigeminal ganglion has been effective in some patients when conventional medical therapy has failed.     

Cluster headache--acute and prophylactic therapy

Cluster headache (CH) pain is the most severe of the primary headache syndromes. It is characterized by periodic attacks of strictly unilateral pain associated with ipsilateral cranial autonomic symptoms. The majority of patients have episodic CH, with cluster periods that typically occur in a circannual rhythm, while 10% suffer from the chronic form, with no significant remissions between cluster periods. Sumatriptan injection or oxygen inhalation is the first-line therapy for acute CH attacks, with the majority of patients responding to either treatment. The calcium channel blocker verapamil is the drug of choice for CH prevention. Other drugs that may be used for this purpose include lithium carbonate, topiramate, valproic acid, gabapentin, and baclofen. Transitional prophylaxis, most commonly using corticosteroids, helps to control the attacks at the beginning of a cluster period. Peripheral neural blockade is effective for short-term pain control. Recently, the therapeutic options for refractory CH patients have expanded with the emergence of both peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation. With the emergence of these novel treatments, the role of ablative surgery in CH has declined.     

Atypical Facial Pain, Ectasia of the Basilar Artery, and Baclofen: A Case Report

Atypical facial pain is a clinical syndrome of facial pain that has been related to depression but whose pathogenesis is not known. We describe a 72-year-old woman with a chronic facial pain, and ectasia and left sided deviation of the basilar artery, that responded dramatically to baclofen. This case suggests that vascular compression of the trigeminal nerve may be one of the mechanisms producing this syndrome and in these cases it might respond to baclofen.     

Cutaneous innervation and trigeminal pathway function in a patient with facial pain associated with Parry-Romberg syndrome

Parry-Romberg syndrome (PRS) is a rare condition manifesting with progressive hemifacial atrophy. Although reported PRS clinical disturbances include facial pain and recent studies raised the possibility that PRS-related pain is a neuropathic pain condition due to the trigeminal nerve damage, no studies have directly investigated cutaneous innervation and trigeminal pathway function in patients with this rare condition. In a 50-year-old woman presenting with a 10-year history of slowly progressive hemifacial atrophy and facial pain, we investigated large myelinated fibres with masticatory muscle electromyography and trigeminal reflexes, and tested small myelinated and unmyelinated fibres with laser-evoked potentials. We also investigated cutaneous innervation by measuring the intraepidermal nerve fibre (IENF) density after skin biopsy of the supraorbital regions. We found that neurophysiological data and IENF density came within normal ranges, with no differences between normal and affected side. Our study showing that the standard reference techniques for assessing cutaneous innervation and trigeminal pathway function disclosed no abnormalities in this patient with PRS suggest that this rare and disabling condition is not associated with trigeminal system damage. These findings indicate that in this patient PRS-related pain is not a neuropathic pain condition, rather it probably arises from the musculoskeletal abnormalities.     

Outcome of surgical release among diabetics with carpal tunnel syndrome

OBJECTIVE: To compare the results of surgical decompression of carpal tunnel syndrome (CTS) in patients with diabetes with those of patients with idiopathic CTS. DESIGN: Prospective case series. SETTING: Ambulatory care in Italy. PARTICIPANTS: Twenty-four consecutive patients with diabetes type 1 or 2 and CTS (mean age, 66.7 y) were matched for age and sex with 72 patients (mean age, 66.2 y) with idiopathic CTS. INTERVENTIONS: All patients underwent surgical release of CTS by the mini-incision of palm technique. MAIN OUTCOME MEASURES: Clinical and electrophysiologic evaluation and patient self-administered Boston Questionnaire (BQ) for the assessment of severity of CTS symptoms and hand functional status before and 1 and 6 months after surgery. RESULTS: After surgical release, almost all patients of both groups reported an absence of pain, disappearance or reduction of paresthesia, and improvement in hand function. One month after surgery, there was a significant improvement in clinical status, BQ scores, and distal conduction velocities of the median nerve. A further improvement was evident at 6-month follow-up. There were no differences between the 2 groups in the number of surgical complications, in clinical and electrophysiologic status, or in BQ scores before and after surgery. The improvement in distal conduction velocities of the median nerve, BQ scores, and clinical and electrophysiologic status were similar in the 2 groups after surgery. CONCLUSION: Diabetes is not a risk factor for poor outcome of surgical decompression of CTS. Patients with diabetes have the same probability of positive surgical outcome as patients with idiopathic CTS.     

Oxygen Inhibits Neuronal Activation in the Trigeminocervical Complex After Stimulation of Trigeminal Autonomic Reflex, But Not During Direct Dural Activation of Trigeminal Afferents

Objective.— To understand the mechanism of action of oxygen treatment in cluster headache. Background.— Trigeminal autonomic cephalalgias, including cluster headache, are characterized by unilateral head pain in association with ipsilateral cranial autonomic features. They are believed to involve activation of the trigeminovascular system and the parasympathetic outflow to the cranial vasculature from the superior salivatory nucleus (SuS) projections through the sphenopalatine ganglion, via the greater petrosal nerve of the VIIth (facial) cranial nerve. Cluster headache is remarkably responsive to treatment with oxygen, and yet our understanding of its mode of action is unknown. Methods.— Combining models of trigeminovascular nociception and a novel approach that activates the trigeminal‐autonomic reflex, using SuS/facial nerve stimulation, we explored the effect of oxygen on trigeminal nerve activation as well as on autonomic responses through blood flow observations of the lacrimal duct/sac. Results.— Meningeal vasodilation and neuronal firing in the trigeminocervical complex (TCC), in response to dural electrical stimulation, was unaffected by treatment with 100% oxygen. Stimulation of the SuS via the facial nerve caused only marginal changes in dural blood vessel diameter, but did result in evoked firing in the TCC. Two populations of neurons were characterized, those responsive to 100% oxygen treatment, with a maximal inhibition of 33%, 20 minutes after the start of oxygen treatment (t₁₅ = 4.4, P < .0001). A second population of neurons were not inhibited by oxygen and tended to have shorter latency. Oxygen also inhibited evoked blood flow changes in the lacrimal sac/duct caused by SuS stimulation. Conclusions.— The data provide the first systematic, experimental evidence for a mechanism of action of oxygen in cluster headache. The data show oxygen has no direct effect on trigeminal afferents, acting specifically on the parasympathetic/facial nerve projections to the cranial vasculature to inhibit both evoked trigeminovascular activation and activation of the autonomic pathway during cluster headache attacks. Moreover, the studies begin to characterize a novel laboratory model for the most painful primary headache syndrome known – cluster headache.     

Occipital nerve block is effective in craniofacial neuralgias but not in idiopathic persistent facial pain

Occipital nerve block (ONB) has been used in several primary headache syndromes with good results. Information on its effects in facial pain is sparse. In this chart review, the efficacy of ONB using lidocaine and dexamethasone was evaluated in 20 patients with craniofacial pain syndromes comprising 8 patients with trigeminal neuralgia, 6 with trigeminal neuropathic pain, 5 with persistent idiopathic facial pain and 1 with occipital neuralgia. Response was defined as an at least 50% reduction of original pain. Mean response rate was 55% with greatest efficacy in trigeminal (75%) and occipital neuralgia (100%) and less efficacy in trigeminal neuropathic pain (50%) and persistent idiopathic facial pain (20%). The effects lasted for an average of 27 days with sustained benefits for 69, 77 and 107 days in three patients. Side effects were reported in 50%, albeit transient and mild in nature. ONBs are effective in trigeminal pain involving the second and third branch and seem to be most effective in craniofacial neuralgias. They should be considered in facial pain before more invasive approaches, such as thermocoagulation or vascular decompression, are performed, given that side effects are mild and the procedure is minimally invasive.     

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.     

Impairment of corneal pain perception in cluster headache.

Despite many studies, the mechanisms underlying the pathogenesis of pain in cluster headache (CH) still remain obscure. An involvement of substance P (SP) containing neurons of the Gasserian ganglion and/or of the spinal trigeminal nucleus has recently been suggested, e.g., by impairment of inhibitory descending pathways on trigeminal nociceptive neurons. The electrically elicited corneal reflex was studied in 21 CH patients (15 in active phase, 6 in remission). This method allows simultaneous measurements of the trigemino-facial reflex and corneal pain perception. A significant reduction of pain thresholds (more evident on the pain side) was observed in CH during the active phase, while normal values were recorded during the remission phase. Ten out of 15 patients in the active phase showed a significantly reduced corneal pain threshold on the pain side, while tactile sensibility was normal. Moreover, latency, amplitude and duration of the corneal reflex were normal for both painful and painless stimulations during both phases. The threshold of the nociceptive muscular response in the active phase was significantly reduced, suggesting that the excitability of trigeminal nociceptive neurons or of the motor neurons is increased in CH. The results agree with the hypothesis that a reversible impairment of several integrative functions, including the activity of trigeminal pain control system, exists in CH during the active phase.     

Diagnosis and neurosurgical treatment of glossopharyngeal neuralgia: clinical findings and 3-D visualization of neurovascular compression in 19 consecutive patients

Glossopharyngeal neuralgia is a rare condition with neuralgic sharp pain in the pharyngeal and auricular region. Classical glossopharyngeal neuralgia is caused by neurovascular compression at the root entry zone of the nerve. Regarding the rare occurrence of glossopharyngeal neuralgia, we report clinical data and magnetic resonance imaging (MRI) findings in a case series of 19 patients, of whom 18 underwent surgery. Two patients additionally suffered from trigeminal neuralgia and three from additional symptomatic vagal nerve compression. In all patients, ipsilateral neurovascular compression syndrome of the IX cranial nerve could be shown by high-resolution MRI and image processing, which was confirmed intraoperatively. Additional neurovascular compression of the V cranial nerve was shown in patients suffering from trigeminal neuralgia. Vagal nerve neurovascular compression could be seen in all patients during surgery. Sixteen patients were completely pain free after surgery without need of anticonvulsant treatment. As a consequence of the operation, two patients suffered from transient cerebrospinal fluid hypersecretion as a reaction to Teflon implants. One patient suffered postoperatively from deep vein thrombosis and pulmonary embolism. Six patients showed transient cranial nerve dysfunctions (difficulties in swallowing, vocal cord paresis), but all recovered within 1 week. One patient complained of a gnawing and burning pain in the cervical area. Microvascular decompression is a second-line treatment after failure of standard medical treatment with high success in glossopharyngeal neuralgia. High-resolution MRI and 3D visualization of the brainstem and accompanying vessels as well as the cranial nerves is helpful in identifying neurovascular compression before microvascular decompression procedure.     

Dolichoectasia of the cavernous internal carotid artery: another cause for Raeder's syndrome

A 38-year-old man presented with ptosis, miosis, facial pain and hypoesthesia in the ipsilateral ophthalmic division of the trigeminal nerve. Brain magnetic resonance imaging and magnetic resonance antiography showed fusiform dilation of the cavernous portion of the left carotid artery. A diagnosis of Raeder's syndrome (RS) was made. Carbamazepine selectively relieved the facial pain but the partial Horner syndrome persisted. Our case adds dolichoectasia of the intracavernous internal carotid artery to the list of causes of RS. Received: 28 August 2000, Accepted in revised form: 28 September 2000     

Diagnosis and differential diagnosis of trigeminal neuralgia.

Trigeminal neuralgia is a chronic facial pain classified as a neuropathic pain. There is widespread agreement regarding the International Association for the Study of Pain definition of classical idiopathic trigeminal neuralgia as "a sudden, usually unilateral, severe, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve." However, there are variations in presentation that are less easy to diagnose and an erroneous diagnosis of trigeminal neuralgia is occasionally made. In patients with tumors or multiple sclerosis, trigeminal neuralgia is termed secondary. Currently, clinical manifestations are the mainstay for diagnosis because there are no objective tests to validate the diagnosis. The sensitivity and specificity of these clinical manifestations is reviewed. Magnetic resonance imaging (MRI) and three-dimensional fast-in-flow with steady-state precession MRI are performed to determine the presence of tumors or plaques of multiple sclerosis and to assess possible compressions and deformations of the trigeminal nerve. Their specificity and sensitivity regarding compressions found at the time of surgery is reviewed. Other differential diagnoses for chronic unilateral orofacial pain are discussed.     

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.     

微血管减压术治疗三叉神经痛的疗效及其并发症的预防与处理

目的探讨微血管减压术治疗三叉神经痛的疗效及其并发症的预防与处理策略。方法采用微血管减压术治疗93例三叉神经痛患者,对其临床疗效及术后并发症等临床资料进行回顾性分析。结果 93例中89例术后疼痛症状消失,有效率为95.70%。术后并发症的发生情况：皮下积液4例,脑脊液漏1例,听力下降3例,耳鸣3例,面神经功能障碍4例,手术无效4例,死亡1例。结论微血管减压术治疗三叉神经痛是一种十分成熟的技术,规范手术的各种操作和积极应用监测技术能够尽量避免各种并发症的发生,显著提高手术的安全性。