Syndromes of Ocular or Retrobulbar Pain with Intracranial Disease
  Raeder’s Paratrigeminal Neuralgia: Ophthalmic Division Pain (Cluster Headache) with Oculosympathetic Palsy

Raeder's syndrome, or Raeder's paratrigeminal neuralgia, is a condition characterized by severe, unilateral headache, facial pain, or dysesthesia that is usually in the distribution of the ophthalmic division of the trigeminal nerve, combined with an ipsilateral oculosympathetic palsy (Horner's syndrome). In many cases, there is associated nasal stuffiness or rhinorrhea. George Raeder, a Norwegian neurologist, first described in 1918 the association of severe facial neuralgia and an incomplete Horner's syndrome (sweating was normal on the side of the lesion) in a patient with a meningioma situated between the internal carotid artery and the Gasserian ganglion. Raeder suggested that the site of the painful oculosympathetic palsy was the point where the oculosympathetic fibers leave the internal carotid artery to join the ophthalmic division of the trigeminal nerve. In 1924, Raeder reported this case and four others. In all cases except one, other cranial nerves were involved. Two of the cases were caused by trauma, but in two cases, no etiology could be determined. Since these initial descriptions, many reports of this syndrome have emphasized various intracranial causes including locally invasive tumors, metastatic tumors to the middle cranial fossa, acquired and congenital abnormalities of the internal carotid artery, and inflammation of adjacent structures (Mokri et al., 1979; see bibliography in Grimson and Thompson, 1980; Harrington and Mayman, 1983). In fact, by 1950, the term ``Raeder's syndrome'' suggested a serious disease in the middle cranial fossa.

During the 1950's and 1960's, a second type of ``Raeder's syndrome'' was identified. Patients with this syndrome had a benign illness without multiple, para-sellar cranial nerve involvement, a description that fits only one of the original five cases described by Raeder. Ford and Walsh (1958) observed 25 cases of the paratrigeminal syndrome in which only pain above the eyes and the oculosympathetic phenomenon were present. Males seemed to be affected almost exclusively. The onset was, as a rule, in middle age or old age. The first symptom was a throbbing headache located behind, within, or above one eye. It was invariably severe and began early in the morning, often awakening the patient from sleep. Frequently, there were associated nausea and vomiting. Often the pain would cease by midday. The pain occurred every morning and usually persisted for a number of weeks or even months. As a rule, the headache was severe for only the first week or two.

Shortly after the headache began, the ipsilateral eyelid began to droop and the pupil became smaller. The pupil did not expand in reduced illumination, so the difference in the size of the pupils was more obvious in a darkened room. In a bright light, the difference in the pupils was often very slight. When cocaine was instilled, the affected pupil did not dilate. The conjunctiva was often somewhat congested for a time. It seemed clear from these findings that the oculosympathetic nerve fibers had been damaged in some way. Ford and Walsh (1958) as well as Toussaint (1959) stressed that this did not represent a complete Horner's syndrome, since there was no loss of sweating on the face. Skin resistance to galvanic current was unaltered on the face. They agreed with Raeder that the lesion must be at the base of the middle fossa. They further noted that the eyelid lifted and the pupil expanded to its normal size after a few months or possibly a year. In a few instances, a second attack occurred.

Ford and Walsh (1958) were impressed with the stereotyped character of the syndrome and suspected that it was usually due to a specific cause. While questioning their patients carefully, they elicited, almost without exception, a clear history of throbbing morning headaches of many years' duration, often associated with nausea and vomiting. They concluded that the syndrome is merely a somewhat unusual result of a series of severe and frequent ``migrainous'' headaches. In 1955, Harold Wolff had shown that in a migrainous attack, the arteries become dilated, and if the attack is prolonged, the wall of the artery becomes edematous and thickened. The oculosympathetic nerve fibers are within the sheath of the internal carotid artery where it lies at the base of the middle fossa adjacent to the trigeminal nerve divisions. Thus, ischemic changes in the internal carotid artery could damage the sympathetic fibers and at the same time produce severe pain. That this appears to be the mechanism in such cases is suggested from the studies by Ekbom and Greitz (1970) who performed carotid angiography on 18 patients with ``cluster headache.'' In one patient, angiography was performed before and during an attack. The patient was a 42-year-old man who was admitted to the hospital with attacks of severe, unilateral headache associated with conjunctival injection, lacrimation, rhinorrhea, and ipsilateral ptosis and miosis. An angiogram performed when the patient was symptom-free showed localized narrowing of the extradural portion of the internal carotid artery distal to its exit from the carotid canal. The ophthalmic artery was markedly dilated. The patient then experienced an attack of eye pain, and an angiogram performed at that time showed extension of narrowing in a proximal direction as far as the superior part of the carotid canal.

Following the report by Ford and Walsh (1958), other investigators described similar patients (Smith, 1958; Boniuk and Schlezinger, 1962; Minton and Bounds, 1964; Grimson and Thompson, 1980--see bibliography). Boniuk and Schlezinger drew similar conclusions to those of Ford and Walsh regarding the vascular cause of the pain. In two of their patients, they noted a mild sweating on the forehead of the affected side. They suggested that in these cases, the oculosympathetic fibers to sweat glands of the forehead may follow the internal carotid artery to the ophthalmic artery and from there to the forehead (Nieden, 1884). Klingon and Smith (1956) made similar observations.

It now seems clear that the terms ``red migraine,'' ``migrainous neuralgia,'' ``ciliary neuralgia,'' ``histamine cephalgia,'' ``Horton's headache,'' and ``cluster headache'' all represent the same syndrome, with most (but not all) cases being accompanied by oculosympathetic paresis (Spierings, 1980; Vijayan and Watson, 1982; Watson and Vijayan, 1982). Data that would appear to support this contention include the clinical use of vasodilators such as nitroglycerine (Ekbom, 1968) or histamine (Horton et al., 1939; Horton, 1956) to induce a headache during cluster periods in patients with the paratrigeminal syndrome, the consistent finding of elevated levels of histamine in the blood and urine of such individuals during headache attacks, and an elevation of plasma serotonin levels in some patients (Anthony and Lance, 1971; Medina et al., 1979). In addition, Medina et al. (1979) reported a reduction in the number of platelets present in blood samples taken from the external jugular vein on the side of the headache as compared to samples taken from the contralateral external jugular vein, and Norris et al. (1976) noted an increased number of mast cells in the skin overlying the painful facial areas. Studies using dynamic brain scanning, Doppler and 133Xe blood flow studies, dynamic tonometry, facial thermography, and carotid arteriography all indicate that specific changes occur in the ipsilateral internal and external carotid artery and that alterations in the vasomotor activity of these vessels may exist between attacks.

Boniuk and Schlezinger (1962) also noted that the conjunctival injection that accompanies an attack of the paratrigeminal syndrome may at first be misdiagnosed as conjunctivitis. In addition, they found that the near point of accommodation on the side of the sympathetic paralysis was slightly closer in some of their patients.

Ford and Walsh (1958), Smith (1958), and others stressed that a case of paratrigeminal neuralgia in which there are no associated cranial nerve palsies is a benign syndrome in which symptoms and signs are so characteristic that extensive neuroradiologic investigations are rarely indicated. In fact, Grimson and Thompson (1980) have defined three major categories of Raeder's paratrigeminal neuralgia. Group I includes patients with either multiple parasellar cranial nerve involvement (cranial nerves II, III, IV, V, VI) or involvement of the second, third, or all three divisions of the trigeminal nerve. Group II includes patients with a ``classic'' history of ``cluster'' headaches (very severe; pain lasts 30---120 minutes and comes in clusters lasting several weeks or months; complete absence of pain between attacks and during months or years separating ``cluster'' periods) and absence of any neurologic signs other than an oculosympathetic paresis. Group III consists of patients with a history of pain that is not typical of cluster headache (frequent variations in severity of pain; lasts for hours or days; may be continuous over several weeks or months), associated with signs of involvement of the ophthalmic division of the trigeminal nerve. In this group, there may be associated systemic conditions including hypertension, atherosclerosis, a past history of vascular headaches, head trauma, and recent local infections, particularly sinusitis.

Grimson and Thompson (1980) believe that patients who fall into Group I clearly require a complete neuroradiologic investigation as well as an otolaryngologic evaluation and possibly a nasopharyngeal biopsy to rule out the various parasellar mass lesions that may be responsible for the syndrome. Patients in Group II do not require investigation but can be treated with medical therapy in anticipation of ultimate resolution of the process. Patients in Group III also usually have a benign, self-limited process; however, the physician should search for and treat any associated systemic or local conditions that may be responsible for the process, particularly paranasal sinusitis, diabetes mellitus, and hypertension. In addition, if the headaches do not resolve within several months or if other neurologic signs develop, a full neuroradiologic investigation that includes carotid angiography is warranted. It is interesting that Grimson and Thompson (1980) have examined six patients with isolated, postganglionic Horner's syndrome who had no associated pain. These six patients were considered to have a ``benign'' syndrome similar to those with associated unilateral headache but without evidence of other cranial nerve involvement. Dr. Miller has seen such a patient at Walter Reed Army Medical Center. The patient, a 23-year-old man, had a history of ``sick headaches'' as a child. At 23 years of age, he had the sudden onset of drooping of his left upper eyelid associated with slight redness of the left eye but without headache, lacrimation, or nasal stuffiness. The ptosis cleared spontaneously after several days, but the patient had several more episodes over the next several weeks, two of which were associated with ipsilateral headache above and behind the left eye. The patient stressed to us, however, that the majority of his episodes were unassociated with any headache or pain. The patient's examination revealed only a left, postganglionic Horner's syndrome. No further investigations were performed.

As might be expected, there are always exceptions to any rule, so that although we would agree in principle with the classification and management proposed by Grimson and Thompson (1980), we would caution the physician who is treating a patient with a ``Group III'' paratrigeminal syndrome to follow the patient carefully and repeat the examination of the cranial nerves at regular intervals to make certain that no new symptoms or signs appear.

The severe pain that occurs in patients with the ``benign'' form of the paratrigeminal syndrome is usually dramatically relieved with vasoconstrictive agents such as ergotamine tartrate (Grimson and Thompson, 1980). In addition, methysergide, systemic corticosteroids, lithium, and the serotonin antagonist BC 105 have all been shown to be useful in some patients (Ekbom, 1969; Jammes, 1975; Ekbom, 1977; Kudrow, 1977; Couch and Ziegler, 1979; Grimson and Thompson, 1980; Ekbom, 1981). Meyer et al. (1970) have recommended sphenopalatine ganglionectomy for those patients who do not respond to medical therapy; however, in our experience, this therapy is rarely, if ever, indicated. The interested reader is urged to consult the excellent monograph by Grimson and Thompson (1980) for a more complete review of this subject. (Further details concerning the differential diagnosis of oculosympathetic palsy are considered elsewhere)

Thalamic division pain as a sign of internal carotid artery dissection has been discussed earlier under section 6.9: Headache associated with other vascular disorder.

According to Dalessio (1993) Raeder’s is summarized as those who had "multiple cranial nerve involvements, primarily parasellar, associated with oculosympathetic paralysis and intact facial sweating. Others have since described almost any lesion in which there is oculosympathetic paralysis associated with head pain as Raeder’s syndrome. Given this confusion, it would probably be best to abandon the eponym and more precisely classify patients with oculosympathetic paralysis and headache, who may or may not have disturbances of sweating as well." In my experience eponymic designation such as "Raeder’s syndrome" or "Tolosa-Hunt syndrome" are often used when a patient has encountered some features of the original description and it is assumed, incorrectly, that a diagnosis has been made.
 

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