Raeder Syndrome

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Original article contributed by: Sunny.B.Patel, Karl C. Golnik, MD, MEd
All contributors: Karl C. Golnik, MD, MEd
Assigned editor:
Review: Assigned status Not reviewed by Sunny.B.Patel, Karl.C.Golnik on August 17, 2017.


Introduction

Disease

Raeder paratrigeminal syndrome (aka Raeder syndrome or paratrigeminal neuralgia) is an uncommon neurological disorder characterized by unilateral oculosympathetic paralysis accompanied by ipsilateral sensory and/or motor abnormalities in the distribution of the trigeminal nerve fibers. It is often described as a painful, postganglionic, incomplete Horner syndrome. The first patient described by Raeder in 1918 demonstrated left sided eye and head pain, ptosis, and miosis, without anhidrosis. It can also include additional cranial nerve (CN) deficits.

History & Subtypes

In 1924, Norwegian Ophthalmologist Johan Georg Raeder reported 5 patients experiencing unilateral oculosympathetic paresis, i.e., an incomplete Horner syndrome, and ipsilateral trigeminal involvement (e.g., neuralgic pain, decreased facial sensation, muscle weakness, etc.). In 4 of 5 of these cases, there was an absence of anhidrosis and involvement of other cranial nerves (e.g., diplopia).1 He had localized the lesion to the limited space in the middle fossa, through which the trigeminal and sympathetic nerve fibers innervating the eye run through. Hence naming the syndrome “paratrigeminal” neuralgia.

The emphasis on unilateral pain led to several subsequent reports of non-neuralgic head pain and ipsliateral oculosympathetic paralysis diagnosed as Raeder paratrigeminal syndrome. These patients did not have other CN involvement.2-6 This description was consistent with only one of the five patients Raeder initially described, which has led to debate about the true definition.7 Since the initial description, there has been further categorization of the disorder.

In 1962 Boniuk and Shelzinger provided their own classification of Raeder syndrome into two types: group I and group II. The group I variant includes patients who experience additional parasellar nerve involvement (e.g., CN III, IV, VI) in addition to the oculosympathetic paresis and trigeminal nerve involvement. The group II subtype occurs without parasellar involvement. They concluded group II Raeder syndrome is a benign entity with a favorable outcome and a self-limited course, although miosis and ptosis may remain.4

Grimson and Thompson modified Boniuk’s classification and introduced 3 subdivisions.8 Group I was identical to Boniuk’s, detailed above. They delineated group II as patients with cluster headache and an isolated oculosympathetic paresis, and group III as a painful postganglionic Horner syndrome with involvement of only the 1st division of the trigeminal nerve.

Mokri argued Raeder Syndrome should only be attributed to cases that were characteristically described as Group I. He also emphasized the need for true trigeminal involvement rather than mere head/face pain to make a diagnosis, claiming many of the subsequent case reports were more simply vascular headaches (e.g., migraine headaches).7

Pathogenesis

Raeder syndrome is a third-order neuron disorder that involves the sympathetic fibers that ultimately innervate Müller and Horner muscles of the eyelids and the dilator muscles of the iris. The third-order sympathetic neurons arise from the superior cervical ganglion and enter the cranial vault with the internal carotid artery (ICA) into the cavernous sinus. Here the oculosympathetic fibers leave the ICA, travel for a short time with the CN VI, and then join the 1st division of the trigeminal nerve to enter the orbit through the superior orbital fissure. Given this anatomy, Raeder syndrome also involves the trigeminal and often oculomotor nerves (CN III, IV, VI), localizing the lesion to the middle cranial fossa. The sympathetic fibers involved in facial sweating diverge from the main branches and follow the external carotid artery, rather than continuing with the ICA, after the carotid artery bifurcation. Therefore, given the preservation of facial sweating in Raeder syndrome, the lesion can be further localized distal to the bifurcation.

Etiology

Many reports are idiopathic. However, a variety of underlying pathologies have been attributed: 8

  • ICA Abnormalities (e.g, aneurysm, dissection, occlusion, inflammation, congenital abnormalities, fibromuscular dysplasia, trauma)9-13
  • Neoplasms of the middle cranial fossa and cavernous sinus (e.g., involving the Gasserian ganglion, local invasion, metastasis, lymphoma)1,14,15
  • Inflammation (e.g., dental abscess, chronic sinusitis, etc.)16,17
  • Trauma (e.g., basilar skull fracture, iatrogenic injury to Gasserian ganglion, gunshot wound)1


Oculosympathetic paralysis with hemicranial pain has been recognized as a clinical manifestation of a spontaneous ICA dissection.8,12,18,19 It is an important diagnosis to recognize early because of the potential for acute ischemic neurologic sequelae.

Raeder syndrome has also been associated attributed towith cluster headache, SUNCT syndrome, trigeminal neuralgia, herpes zoster ophthalmicus, Tolosa-Hunt syndrome, occipital neuralgia, vasculitis, migraine headaches, and Lyme disease.20

Epidemiology

The exact incidence of Raeder syndrome is unknown, but it is an uncommon disorder.9 The disorder most commonly affects middle-aged men.

Clinical Features & Work Up

Signs & Symptoms

Patients classically present with unilateral headache with or without facial pain associated with an ipsilateral ptosis and miosis. The head/facial pain is located in the distribution of the trigeminal nerve, and is often periocular or retroorbital. It may be limited to the ophthalmic division of CN V, but it can also involve the cheek and teeth. The pain is severe and lancinating, often radiating to the face (i.e., tic douloureux-like neuralgia). It may last from hours to weeks to months, and typically remains constant. Pain may occasionally follow a recurrent pattern of “attacks,” similar to cluster headaches.7,8

The trigeminal nerve involvement can also include other sensory or motor abnormalities including decreased sensation of the face, decreased corneal reflex, allodynia, and muscle weakness (e.g., pterygoid and masseter muscles). Patients may complain of symptoms indicating additional cranial nerve involvement such as diplopia, scotoma, and decreased hearing. Other signs and symptoms that may be seen include conjunctival hyperemia, excessive tearing, apparent enophthalmos, and decreased IOP.4,7

Physical Examination

Visual acuity testing, tonometry, and ocular examination should be performed. Examination will demonstrate anisocoria that is more pronounced in the dark, due to impairment of the affected eye to dilate. Mild ptosis of the ipsilateral eye will be present due to the involvement of the sympathetic innervation to Müller’s and Horner’s muscles. Palpation of the head and face should be performed, with any hyperesthesia noted. Careful neurological exam with particular attention to cranial nerve function must be performed. Extraocular movements, corneal reflex, and facial sensation should all be carefully tested when suspicious for Raeder syndrome.

Diagnosis

Paratrigeminal neuralgia, similar to Horner syndrome, is a clinical diagnosis. However, pharmacologic testing is appropriate in confirming the diagnosis.

Cocaine inhibits the reuptake of norepinephrine that allows accumulation of norepinephrine in the synappatic cleft, perpetuating a sympathetic adrenergic response. Thus, 10% topical cocaine will produce dilation in the normal eye but fail to produce the same degree of dilation in the affected eye. A drop should be placed in both eyes, and checked after 15 minutes. If no change in pupillary size is noted, drops should be repeated and pupils rechecked in 15 minutes. As an alternative, either 1% or 0.5% apraclonidine may be used. Apraclonidine causes relative reversal of anisocoria so that the affected pupil will appear larger than the normal pupil.2118

Topical 1% hydroxyamphetamine may be used to distinguish between pre- and post- ganglionic lesions in the oculosympathetic pathway.18 21 Hydroxyamphetamine causes release of epinephrine from the third-order neuron junction with the iris. Therefore, in the case of third-order neuron diseases, such as paratrigeminal neuralgia, the pupil of the affected eye would fail to dilate. Dilation of the pupil would be suggestive of a first or second-order neuron disorder.

Imaging

All patients with Raeder syndrome require MRI/MRA or CT/CTA of the head and neck to exclude compressive or vascular lesions as described above.22,23

Management

Treatment

The treatment of Raeder syndrome depends entirely on the etiology of the case.

Dissections of the ICA require the most urgent treatment to prevent embolic stroke. Prompt anticoagulation and antiplatelet therapy should be started. Rarely surgical intervention is needed if ischemia is refractory to treatment.9,18 21

Without any intracranial etiology, treatment is largely symptomatic. NSAIDs, aspirin, and codeine compounds have been reported helpful in controlling the pain of head and face. Ergotamine, oral and IV steroids, and intensive vitamin-B therapy have been administered with success in helping alleviate pain.10 There have been some reports of patients noting increased severity of pain after ingestion of alcoholic beverages. Therefore, it is recommended patients avoid vasodilating agents, particularly alcohol, during the active stage of the disease.4

Follow-Up

Follow up of Raeder paratrigeminal syndrome depends on the etiology.

Prognosis

Prognosis depends on the etiology of Raeder paratrigeminal syndrome, however, in the absence of other parasellar nerve involvement (group II) the prognosis is quite excellent with a resolution of symptoms typically weeks to months from onset.

References

1. Raeder JG. Paratrigeminal paralysis of the oculopupillary sympathetics. Brain. 1924; 47:149-58.

2. Smith JL. Raeder's paratrigeminal syndrome. Am J Ophthalmol. 1958;46:194-201.

3. Ford FR, Walsh FB. Raeder's paratrigeminal syndrome: a benign disorder, possibly a complication of migraine. Bull Johns Hopkins Hosp. 1958;103:296-298.

4. Bonuik M, Schlezinger NS. Raeder's paratrigeminal syndrome. Am J Ophthalmol. 1962;54:1074-1084.

5. Klingon GH, Smith WM. Raeder's paratrigeminal syndrome. Neurology. 1956;6:750-753.

6. Minton LR, Bounds GW,Jr. Raeder's Paratrigeminal Syndrome. Am J Ophthalmol. 1964;58:271-275.

7. Mokri B. Raeder's paratrigeminal syndrome. Original concept and subsequent deviations. Arch Neurol. 1982;39:395-399.

8. Grimson BS, Thompson HS. Raeder's syndrome. A clinical review. Surv Ophthalmol. 1980;24:199-210.

9. Murnane M, Proano L. Raeder's paratrigeminal syndrome: a case report. Acad Emerg Med. 1996;3:864-867.

10. Jain DC, Ahuja GK, Goulatia RK. Intracranial internal carotid artery aneurysm as a cause of Raeder's paratrigeminal syndrome. Surg Neurol. 1981;16:357-359.

11. Cohen DN, Zakov ZN, Salanga VD, Dohn DF. Raeder's paratrigeminal syndrome. Am J Ophthalmol. 1975;79:1044-1049.

12. Selky AK, Pascuzzi R. Raeder's paratrigeminal syndrome due to spontaneous dissection of the cervical and petrous internal carotid artery. Headache. 1995;35:432-434.

13. Kashihara K, Ito H, Yamamoto S, Yamano K. Raeder's syndrome associated with intracranial internal carotid artery aneurysm. Neurosurgery. 1987;20:49-51.

14. Harrington HJ, Mayman CI. Carotid body tumor associated with partial Horner's syndrome and facial pain ('Raeder's syndrome'). Arch Neurol. 1983;40:564-566.

15. Nogaki H, Nakamura M, Tatsumi S. A case of Raeder's syndrome caused by metastatic malignant lymphoma. No To Shinkei. 1989;41:259-262.

16. Bedrossian EH. Raeder's syndrome. AMA Arch Ophthalmol. 1952;48:620-623.

17. Nolph MB, Dion MW. Raeder's syndrome associated with internal carotid artery dilation and sinusitis. Laryngoscope. 1982;92:1144-1148.

18. Mokri B, Sundt TM,Jr, Houser OW, Piepgras DG. Spontaneous dissection of the cervical internal carotid artery. Ann Neurol. 1986;19:126-138.

19. Kline LB, Vitek JJ, Raymon BC. Painful Horner's syndrome due to spontaneous carotid artery dissection. Ophthalmology. 1987;94:226-230.

1. Murphy MA, Szabados EM, Mitty JA. Lyme disease associated with postganglionic Horner syndrome and Raeder paratrigeminal neuralgia. J Neuroophthalmol. 2007;27:123-124.

20.

21. Bagheri N, Wajda BN, et al. The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease. 7. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2017.

22. Castillo M, Kramer L. Raeder syndrome: MR appearance. AJNR Am J Neuroradiol. 1992;13:1121-1123.

1. Auer D, Karnath HO, Nagele T, Dichgans J. Noninvasive investigation of pericarotid syndrome: role of MR angiography in the diagnosis of internal carotid dissection. Headache. 1995;35:163-168.

23.

1. Thomas JE, Yoss RE. The parasellar syndrome: problems in determining etiology. Mayo Clin Proc. 1970;45:617-623.

Godtfredsen E, Lederman M. Diagnostic and Prognostic Roles of Ophthalmoneurologic Signs and Symptoms in Malignant Nasopharyngeal Tumors. Am J Ophthalmol. 1965;59:1063-1069.

Healy JF, Zyroff J, Rosenkrantz H. Raeder syndrome associated with lesions of the internal carotid artery. Radiology. 1981;141:101-104.

Mokri B, Sundt TM,Jr, Houser OW, Piepgras DG. Spontaneous dissection of the cervical internal carotid artery. Ann Neurol. 1986;19:126-138.Kline LB, Vitek JJ, Raymon BC. Painful Horner's syndrome due to spontaneous carotid artery dissection. Ophthalmology. 1987;94:226-23Murphy MA, Szabados EM, Mitty JA. Lyme disease associated with postganglionic Horner syndrome and Raeder paratrigeminal neuralgia. J Neuroophthalmol. 2007;27:123-124.