Subcutaneous Sumatriptan in Cluster Headache: A Time Study of the Effect on Pain and Autonomic Symptoms

SYNOPSIS
A subcutaneous injection of 6 mg sumatriptan rapidly and effectively stopped attacks of cluster headache. After a time lag of 4–14 minutes (mean 7 minutes) pain dramatically dropped to zero within seconds to single minutes (mean 56 seconds). This rapid effect may indicate that mere vasoconstriction is the mechanism behind the beneficial effect of sumatriptan in cluster pain. The findings support a scenario in cluster headache where an inflammation in the cavernous sinus affects the sympathetic fibers traversing the cavernous region. This leads to the miosis, ptosis and forehead anhidrosis but also to a dilated internal carotid arterial tree distal to the lesion. The dilatation, in combination with an obliterated drainage of the cavernous sinus by the inflammatory process, leads to progressive stasis in the sinus, to cause the painful attack. The attack terminates when the enhanced load on the sinus is reduced by constriction of vessels supplying the sinus, as is achieved by administration of sumatriptan. The present observation that other accompanying symptoms during attacks (nasal congestion, rhinorrhea, lacrimation and swelling of eyelids) disappeared in parallel with the pain points to the possibility that these symptoms may be directly related to venous stasis or activation of pain fibers, rather than resulting from a primary parasympathetic activation.     

Activation of Pain Fibers to the Internal Carotid Artery Intracranially May Cause the Pain and Local Signs of Reduced Sympathetic and Enhanced Parasympathetic Activity in Cluster Headache

Several clinical and circulatory physiological observations indicate that the internal carotid artery (ICA) with proximal pial and orbital-periorbital branches, as well as external carotid vessels adjacent to the orbital region, are involved in the autonomic symptoms of an attack of cluster headache. Evidence is presented here that an activation of pain fibers innervating the intracranial segment of ICA may cause not only the retroorbital pain of an attack but also, via the mechanical effect of a neurogenic inflammation in the vessel wall, the local symptoms of a sympathetic defect and, via a reflex are to the parasympathetic pathway along the greater superficial petrosal nerve, the local symptoms from glands and vessels of parasympathetic discharge. Dilation of the intracranial ICA due to activation of this parasympathetic pathway may aggravate pain. Possible mechanisms behind such a local pain fiber activation are discussed.     

Ophthalmologic aspects of headache

Pain around the eye can be caused by local ophthalmic disorders or by disease of other structures sharing trigeminal nerve sensory innervation. In general, most ocular causes for pain also cause the eye to be red, thus alerting the examiner to the focality of the problem. However, conditions like eyestrain, intermittent angleclosure glaucoma or neovascular glaucoma, and low-grade intraocular inflammation can be painful and not be associated with obvious redness. Ocular signs and symptoms also occur with numerous other causes of headache. Double vision in association with periocular pain can result from orbital lesions, isolated cranial neuropathies, and cavernous sinus lesions. Pupillary abnormalities like Horner's syndrome may result from a variety of painful conditions, including cluster headache, parasellar neoplasms or aneurysms, internal carotid dissection or occlusion, and Tolosa-Hunt syndrome. Pain with a dilated and unreactive pupil may reflect a benign condition like Adie's syndrome or ophthalmoplegic migraine, or it may herald the presence of a life-threatening posterior communicating artery aneurysm. Headache and transient visual loss can be manifestations of classic migraine, or be symptoms of ocular hypoperfusion from ipsilateral internal carotid occlusion or increased intracranial pressure from pseudotumor cerebri. In a young patient, head pain with a fixed visual deficit may result from optic neuritis, in an older adult, temporal arteritis may be the culprit. Ophthalmologic aspects of headache thus encompass problems that range from simple and benign to complex and formidable.     

Endovascular treatment of a direct post-traumatic carotid-cavernous fistula with electrolytically detachable coils

Carotid-cavernous fistulae are abnormal communications between the internal carotid artery and venous compartments of the cavernous sinus. Fistulae are uncommon but well-documented sequelae of craniofacial trauma. The characteristic clinical presentation includes ocular pain, chemosis, exophthalmus and visual disturbances. We report on a 28-year-old man with a history of severe craniocerebral injury, including multiple craniofacial fractures resulting from a fall from a height of approximately 6 meters, who was surgically treated one year ago. Two months before presentation, the patient began to exhibit progressive chemosis, proptosis, eyelid swelling, diplopia and exophthalmus. Computerized tomography and computerized tomographic angiography revealed findings consistent with a carotid-cavernous fistula of the right side of the cavernous sinus with dilatation of the right ocular vein. Digital subtractional angiography of the right internal carotid artery revealed a fistula between the cavernous part of the artery and the right cavernous sinus. There was only minimal blood flow in the supraclinoid part of the internal carotid artery because of the high pressure within the fistula. Our decision was to try to occlude the fistula by means of endovascular embolization. The origin of the fistula in the internal carotid artery was successfully obliterated with seven electolytically detachable coils. Control digital subtractional angiography at the end of the procedure demonstrated minimal residual flow through the fistula. Two months after the treatment, angiographic control revealed complete obliteration of the fistula. Clinical examination showed total resolution of signs and symptoms of a carotid-cavernous fistula. Endovascular transarterial embolization of carotid cavernous fistulae is a widely accepted, safe and successful treatment option. In the case that we describe we occluded the fistula and right cavernous sinus with electrolytically detachable coils that we could place into the sinus. Other endovascular treatment options include the use of detachable balloons, stent placement, transvenous embolization or surgical ligation of the fistula.     

On Pain Mechanisms in Cluster Headache

Various possible pathophysiological mechanisms to explain the pain in cluster headache are reviewed. Several locations for the initiation of pain along the primary afferent pathways in cranial nerves are discussed, together with the local mechanisms that might be responsible. These include neurogenic inflammation of large cranial vessels, irritation of vascular pain fibres by compression of dilated vessels in bony canals, and irritative foci in or around cranial sensory ganglia. In particular, recent neuroanatomical and pharmacological findings on nociceptive innervation of the intracranial segment of the internal carotid artery are commented upon. The possibilities for referred pain to explain the location of pain is illustrated. Evidence for involvement of central pain modulatory systems in the pain production is discussed. Finally a synthesis is made of the probable peripheral and central pain mechanisms in the disease.     

Painful ophthalmoplegia (Tolosa-Hunt variant): autopsy findings in a patient with necrotizing intracavernous carotid vasculitis and inflammatory disease of the orbit

A 79-year-old man with unremitting painful ophthalmoplegia had a necrotizing inflammatory process that involved the intracranial and intracavernous portions of the right internal carotid artery. The condition ultimately resulted in rupture of the carotid vessel and death. At autopsy, thrombophlebitis of the sphenopalatine sinus was also noted. To our knowledge, this is the second reported autopsy study of painful ophthalmoplegia and chronic nongranulomatous inflammation that involved the carotid siphon and the cavernous sinus.     

Effects of increasing the intracranial blood volume in cluster headache patients and controls

Eleven patients with episodic cluster headache in period, five patients out of period and six controls were studied concerning the effects of an increase of the intracranial blood volume by tilting. Common carotid artery (CCA) blood flow was similar in all three groups at baseline and during tilting. CCA diameters were similar at baseline and increased during tilting in all three groups, indicating that tilting caused an increase in the extra- and intracranial blood volume. Unilateral pain or sympathetic dysfunction did not appear during tilting in the patients out of period or in the controls. In four of eight studied patients with cluster headache in period, unilateral miosis and ptosis appeared during tilting. Two of these four patients developed intense unilateral pain, while the other two did not report any pain. Four other patients developed slight unilateral pain but no sympathetic dysfunction during tilting.     

Vasoreactivity of the intracranial internal carotid artery

The vasoreactivity of the intracranial segment of the internal carotid artery to transmitters, present in the perivascular sympathetic, parasympathetic and sensory nerves, as well as to other vasoactive agents of relevance for headache, was tested in man and monkey. The total arterial segment from both species is equipped with contractile receptors for noradrenaline, serotonin, prostaglandin F2 alpha, ergotamine and sumatriptan. Further, the total arterial segment dilated upon exposure to calcitonin gene-related peptide in both species. Other vascoactive transmitters, acetylcholine, substance P and neurokinin A, caused only weak dilatation, restricted to the proximal extracavernous segment in the monkey. The findings are discussed in relation to the pathogenesis and treatment of cluster headache.     

Visualization of bilateral carotid cavernous sinus fistulas with duplex sonography

Duplex sonography used as a primary diagnostic tool in the case of a 17-year-old boy with a traumatic head injury revealed bilateral carotid cavernous sinus fistulas, with bilateral dilated venous convolutions next to the carotid siphon and dilated superior ophthalmic veins. A bilateral craniectomy allowed visualization of the entire circle of Willis together with the dilated cavernous sinuses. Doppler spectral analysis of blood flow in the arterialized superior ophthalmic veins revealed an arterialized venous pattern with retrograde and increased blood flow. The same blood flow profile was found in the venous cavernous sinuses. These findings were confirmed by digital subtraction angiography. We planned to perform embolization of the patient's fistulas, but intracranial and subarachnoid hemorrhaging developed, and the patient died the day before the procedure was to have been performed. The entire pathologic state of carotid cavernous sinus fistulas, from their origin beside the carotid siphon to the superior ophthalmic veins, can be visualized with duplex sonography, particularly when patients have undergone craniectomy. We believe that patients with frontal or basilar skull fracture should undergo duplex sonographic examination to detect carotid cavernous sinus fistulas.     

An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones

The aim of this study is to present a rational coherent hypothesis to explain the palpable involuntary movements of the cranium. The arterial and venous anatomy inside and around the skull and spinal column presents a complete vascular system with the capacity to regulate intra-cranial pressure to a level of equilibrium slightly higher than atmospheric pressure. Variations in cerebrospinal fluid (csf) pressure control the volume of blood draining through the cavernous sinus and hence into the inter-vertebral venous plexus in relation to the jugular vein. Stable intra-cranial pressure is maintained by a controlled release of venous blood through the inter-vertebral venous plexus (slow) and the jugular vein (fast) in the cavernous sinus. Any distortion of the skull from its healthy state will lead to reduced intra-cranial volume. The process of release from the state of compression has been interpreted as “cranial rhythm” but may be a mechanical adjustment increasing the internal volume of the skull, aided by the continual maintenance of stable intracranial pressure. This involuntary movement is capable of being assisted manually.     

Swollen and bloodshot eye following headache

A ruptured cavernous carotid aneurysm (CCA) with carotid cavernous fistula can appear as a benign headache but progress to a swollen and bloodshot eye overnight. A 66-year-old woman visited emergency department with sudden onset of pain behind her left forehead and vomiting. She was treated for a migraine-like headache and discharged. She presented again on the next day with a persistent headache and a swollen left eye with blurred vision. An ophthalmologic examination revealed erythema of the left lid and chemosis at the temporal and lower bulbar conjunctiva. A cranial nonenhanced computed tomography (CT) scan had been performed at her previous visit. The scan exhibited a nodular mass lesion involving the left cavernous sinus. CT angiography was subsequently used to determine that the lesion was a giant aneurysm in the left cavernous internal carotid artery, causing enlargement of the left ophthalmic veins. The symptoms of her left eye rapidly progressed to severe chemosis, edematous change over periocular region, and limited movements after 8?h. The patient received emergent lateral canthotomy and inferior cantholysis to avoid acute orbital compartment syndrome and was subsequently treated with stent-assisted coil embolization. A ruptured CCA is an urgent condition that requires rapid assessment of both cranial vascular and ocular lesions. A history of sudden onset headache with a nonpainful acute unilateral red eye may serve as a clue to prompt additional diagnostic studies and ophthalmologist evaluation. Adequate radiological studies and early endovascular intervention can reduce the likelihood of permanent ocular injury and vision impairment.     

Noninvasive Investigation of Pericarotid Syndrome: Role of MR Angiography in the Diagnosis of Internal Carotid Dissection

A 52-year-old man presented with unilateral left periorbital and frontotemporal pain associated with a partial ipsilateral Horner's syndrome of the postganglionic type and representing a pericarotid syndrome. MRI demonstrated a perivascular subacute hematoma at the level of the cervical portion of the left internal carotid artery with a markedly reduced flow-void signal. MR angiography confirmed the narrowed lumen of the dissected cervical internal carotid artery. There was also a right-sided precavernous carotid aneurysm. Three months later the left-sided pain had subsided, with complete resolution of the hematoma and incomplete restoration of the left carotid lumen seen on MR angiography. Dissection of the carotid wall may cause the oculosympathetic paralysis by producing a lesion of the superior cervical ganglion, the internal carotid nerve, or the perivascular sympathetic plexus. Whereas in pericarotid syndrome the most common cause is cervical carotid dissection, Raeder's syndrome additionally involving parasellar cranial nerves, may be caused by any paracavernous/cavernous lesion, including neoplasms and intracranial carotid aneurysms. The clinical distinction is useful to determine the appropriate diagnostic investigation, in view of the different pathoanatomical localization and different disease spectrum. As demonstrated in the present case, the combination of MRI and MR angiography is a reliable noninvasive tool to investigate the differential diagnosis of pericarotid syndrome, accurately depicting occlusive, stenotic or aneurysmal lesions of the carotid artery. We suggest that intraarterial angiography is no longer necessary.     

Carotid duplex and transcranial color-coded sonography in evaluation of carotid-cavernous sinus fistulas.

We performed carotid duplex and transcranial color-coded sonography in three patients with traumatic and one patient with spontaneous carotid-cavernous fistulas. High flow and low resistance were detected by carotid Doppler imaging in the extracranial internal carotid artery in three cases and in the external carotid artery in one case. The fistula could be demonstrated directly as heterogenous color flashes with turbulent flow by transcranial color-coded sonography through the orbital or temporal window. The transorbital approach showed that the ophthalmic venous flow was normal or to-and-fro bidirectional in patients without proptosis and was retrograde, away from the cavernous sinus with arteriolization in patients with proptosis. Combination of carotid duplex and transcranial color-coded sonography provides a noninvasive method for more accurate hemodynamic study of cerebral circulation and direct imaging of CCF.     

The Site of Sympathetic Deficit in Cluster Headache

The pattern of autonomic deficit in the face of cluster headache patients resembles the deficit in patients with a postganglionic sympathetic lesion from some other cause; however the presence of abnormal cardiac rhythms and bilateral pupillary reflex deficit in some patients with cluster headache suggests that the lesion might compromise central sympathetic drive. To investigate this possibility, the vasomotor and sudomotor startle reflex was investigated in the hands of sic cluster headache patients with ocular and thermoregulator signs of postganglionic sympathetic deficit in the face; for comparison, responses were also investigated in 15 patients with a lesion in the cervical sympathetic pathway from some other cause. The startle reflex was intact in the hands of the six cluster headache patients, but was diminished ipsilaterally in patients with a central or preganglionic sympathetic lesion and also, surprisingly, in patients with a postganglionic lesion caused by an aneurysm of the internal carotid artery. Ocular sympathetic deficit was greater in patients with an aneurysm of the internal carotid artery than in cluster headache patients or in patients with a postganglionic sympathetic lesion from some other cause; the aneurysm may have compromised neurons with projections to the face and hand, or could have induced transsynaptic degeneration of preganglionic fibers supplying both regions. The findings indicate that central sympathetic drive is not impaired in cluster headache patients; thus, a peripheral lesion probably induces sympathetic deficit on the symptomatic side of the face.     

The acute painful eye

A number of ocular and nonocular conditions may produce an acutely painful eye or orbit. A careful history and physical examination with special attention to the cornea, sclera, fundus, and cranial nerves will usually delineate the etiology of the pain. In particular, certain life- or vision-threatening conditions such as leaking internal carotid aneurysm, cavernous sinus thrombosis, orbital cellulitis, acute narrow-angle glaucoma, and temporal arteritis must be kept in mind.     

Recurrent Tolosa-Hunt syndrome

Twenty consecutive patients with recurrent Tolosa-Hunt syndrome were studied. One had a parent who suffered from recurrent Tolosa-Hunt syndrome. Thirty-three percent of the patients had also recurrent periods of weeks to months of unilateral periorbital pain without ophthalmoplegia. One patient had cluster headache before the Tolosa-Hunt syndrome started. Some patients had involvement of cranial nerves outside the cavernous sinus region during Tolosa-Hunt syndrome and also between episodes. The same systemic symptoms, i.e. back pain, cold feet, arthralgia, gut problems, varices, vertigo, chronic fatigue, thrombophlebitis, memory deficiency and signs of inflammation in serum, occurred in Tolosa-Hunt syndrome as earlier found in patients with orbital venous vasculitis. Seventy-three percent of the patients had pathologic orbital phlebograms. All patients treated with steroids reacted promptly; four who developed chronic pain syndromes were treated satisfactorily with azathioprine.     

A migraine-like headache induced by carotid-cavernous fistula

Carotid-cavernous fistula (CCF) generally causes periorbital aching with ocular symptoms due to high venous pressure in the cavernous sinus, while migraine is caused by arterial dilatation-stimulating trigeminal nerves around the vessels. The authors present a case of 47-year-old woman with a 4-month history of a temporal throbbing headache. As her symptoms were well controlled by triptans, her headache was considered to be migraine in type. However, a Barrow's type-D CCF was revealed by radiological examinations. Self-compression of common carotid artery method was initially tried for therapy of the CCF, but endovascular embolization was finally necessary due to intractable headache. Although the headache was considered arterial in origin, transvenous embolization of the left cavernous sinus successfully ameliorated the patient's symptoms. CCF should be considered as an unusual etiology of headaches that appear arterial in origin.     

The Cluster Diathesis

We present further evidence for a sympathetic defect of vasomotor control of the anterior cerebral artery (ACA) on the side of the headache during cluster periods. In 119 cluster headache patients, utilizing transcranial Doppler, we measured CO2 reactivity of the major intracranial vessels, in and out of cluster. Reactivity was significantly lower during the cluster period, but only in the ACA on the side of the headache. Nineteen patients followed sequentially for a full cycle (ie/both in and out of a cluster period) showed the same changes. In 3 out of 6 patients in an active cluster period, we describe a lesion on Gallium single-photon emission computerized tomography (SPECT) in the region of the cavernous sinus which fades as the patient moves out of cluster. It is felt that this lesion may represent the cavernous sinus plexus lesion postulated as the central lesion in cluster. Changes in the sympathetic outflow at this point could explain the changes we have described in ACA CO2 reactivity during cluster.     

Carotid-cavernous fistula: a complication of maxillofacial trauma.

Fistulas of the internal carotid-cavernous sinus are an unusual arteriovenous malformation. Two types exist: (1) spontaneous fistulas and (2) traumatic fistulas. This paper deals with the traumatic variety which is seen more commonly in men as a direct result of severe maxillofacial injury. Recent anatomic studies are correlated with the physical findings associated with carotid-cavernous fistula, ie, headache, chemosis, exophthalmos, pulsatile bruit, and multiple cranial nerve paralyses. A case report illustrates these findings. The differential diagnosis which varies from tumors, to cavernous sinus thrombosis, to intraorbital aneurysm is discussed. The role of angiography in diagnosis is described. Present management consists of intracranial ligation of the internal carotid artery with use of a muscle embolus to occlude the fistula and selective ligation of the cervical carotid.