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Chapter 54
Paratrigeminal Oculosympathetic
(Raeder’s) Syndrome
RenanDomingues
54.1 Introduction
Raeder’s syndrome is dened by the triad of unilateral headache (typically periorbital or temporal) and partial Horner’s syndrome (ptosis and miosis without facial
anhidrosis). It is caused by lesions affecting the postganglionic oculosympathetic
bers adjacent to the internal carotid artery (ICA), particularly in the region of the
cavernous sinus or middle cranial fossa. First described in 1924 by Johan Georg
Raeder, the syndrome remains a relevant differential diagnosis in patients with painful Horner’s syndrome [1].
The most common structural etiologies include tumors, inammation, and vascular abnormalities such as dissection or aneurysm of the internal carotid artery
[2–5]. The clinical presentation often mimics trigeminal autonomic cephalalgias
(TACs), such as cluster headaches, but with distinctive neuro-ophthalmologic ndings [6].
54.2 Pathophysiology
Raeder’s syndrome results from injury or compression of postganglionic oculosympathetic bers that travel along the internal carotid artery (ICA), particularly within
its petrous and cavernous segments. These bers originate from preganglionic neurons located in the intermediolateral gray matter of the spinal cord (levels T1–T3).
After synapsing in the superior cervical ganglion, postganglionic bers form a
R. Domingues (*)
Headache Clinic, Neurology Section, Santa Casa de Misericórdia, São Paulo, Brazil
e-mail: contato@renandomingues.med.br
Switzerland AG 2026
D. Uludüz et al. (eds.), Rare Causes of Headache Disorders, Headache,
https://doi.org/10.1007/978-3-032-10242-3_54
513© The Author(s), under exclusive license to Springer Nature
514
R. Domingues
pericarotid plexus and ascend within the carotid canal, closely adherent to the arterial wall [2].
In the petrous portion, these bers are especially vulnerable due to their intimate
contact with the ICA and the surrounding bony canal. After ascending through the
cavernous sinus, they reach ocular structures to innervate the pupillary dilator, and
along this pathway, they maintain close anatomical proximity to the ophthalmic
artery and cranial nerves III, IV, and VI.Lesions in this pathway result in ptosis and
miosis, but not anhidrosis, since sudomotor bers travel with branches of the external carotid artery. Contemporary evidence, particularly from anatomical and immunohistochemical studies, supports the existence of a lateral sellar plexus formed by
sympathetic, parasympathetic, and trigeminal bers around the ICA wall [3, 5, 6].
Raeder’s syndrome is classically subdivided into two types: Type I, in which the
oculosympathetic paresis is accompanied by cranial nerve involvement (typically
III, IV, or VI), indicating a more extensive lesion in the parasellar region; and Type
II, characterized by isolated hemicranial pain and partial Horner’s syndrome without other cranial neuropathies, often reecting more selective involvement of postganglionic sympathetic bers adjacent to the ICA [3, 5]. Mechanical compression
or ischemic injury to this region, regardless of the etiology, can activate nociceptive
trigeminovascular pathways. This leads to pain referred to the orbital, nasal, or deep
facial areas without sensory loss. Neurogenic inammation may contribute to pain
generation through the release of antidromic peptides (e.g., substance P, Calcitonin
gene-related peptide (CGRP)), thereby enhancing pain perception and autonomic
dysfunction [2].
54.3 Case Presentation
A 41-year-old woman presented to the emergency department with the acute onset
of severe left-sided periorbital and temporal headache, associated with drooping of
the left eyelid and photophobia. She denied visual loss, trauma, or systemic symptoms. On neurological examination, she had left-sided ptosis and miosis without
anhidrosis or ophthalmoplegia. Extraocular movements and visual acuity were normal. The rest of the neurological exam was unremarkable.
Computed tomography angiography (CTA) and magnetic resonance imaging/
magnetic resonance angiography (MRI/MRA) of the brain and cervical vessels
revealed a dissection with pseudoaneurysm of the left internal carotid artery in its
paraclinoid segment (Figs.54.1 and 54.2). No signs of infarction or subarachnoid
hemorrhage were present. The imaging ndings, together with the clinical features
of unilateral headache and partial Horner’s syndrome without cranial nerve involvement, were consistent with Raeder’s syndrome type II due to an ICA lesion compressing postganglionic oculosympathetic bers traveling along this artery.
The patient was treated conservatively with analgesics and antiplatelet therapy.
Follow-up imaging conrmed stabilization of the vascular lesion. Over the
54 Paratrigeminal Oculosympathetic (Raeder’s) Syndrome
Fig. 54.1 Cranial and
cervical arterial
angiotomography coronal
view. The red circle shows
a left artery carotid artery
pseudoaneurysm
515
following weeks, the ptosis gradually improved, and headache episodes became less
frequent and less intense.
54.4 Case Discussion
Raeder’s syndrome is a painful oculosympathetic paresis due to involvement of
sympathetic bers distal to the bifurcation of the common carotid artery. The rst
case reports were associated with parasellar masses or inammatory lesions [1].
Some of the rst cases did not have an obvious structural etiology when investigated
using the methods available at the time. They were therefore classied as idiopathic
or benign Raeder’s syndrome, but these cases were most likely associated with
some involvement of the ICA [7]. One of the most critical and potentially lifethreatening causes of this syndrome is ICA dissection occurring in the paraclinoid
or cavernous segment [2, 4].
The anatomical proximity of the postganglionic sympathetic bers to this artery
in the cavernous sinus explains how vascular wall disruption can result in partial
Horner’s syndrome and ipsilateral trigeminal pain. The sympathetic bers are
affected by direct compression, perivascular inammation, or ischemia [2, 6].
516
Fig. 54.2 Magnetic
resonance angiography.
The red arrow shows a left
artery carotid artery
pseudoaneurysm
R. Domingues
54.5 Clinical Characteristics
Dissection of the internal carotid artery is an underrecognized cause of painful
Horner’s syndrome and is often missed unless actively investigated with highresolution MRI/MRA or CTA [7]. Importantly, the clinical presentation may resemble cluster headache, leading to initial misdiagnosis. However, unlike primary
headaches, Raeder’s syndrome secondary to vascular lesions often has an acute or
subacute onset, is persistent rather than paroxysmal, and may be associated with
warning signs such as ptosis or focal neurological symptoms [6, 7]. In the present
case, timely imaging investigations enabled the identication of the underlying etiology. The pseudoaneurysm represented a consequence of the spontaneous ICA
dissection [8]. This evolution of the dissection further increases the risk of secondary complications such as embolic stroke or subarachnoid hemorrhage. Therefore,
the recognition of Raeder’s syndrome as a neuro-ophthalmological emergency in
the context of carotid pathology is critical.
54.6 Diagnostic Algorithm
Step 1: Clinical evaluation
54 Paratrigeminal Oculosympathetic (Raeder’s) Syndrome
• Unilateral periorbital or temporal headache
• Ptosis and miosis without anhidrosis
• Cranial nerve palsies investigation
Step 2: Neuroimaging
• MRI/MRA or CTA of intracranial and cervical arteries to evaluate for dissection
or pseudoaneurysm
Step 3: Classication
• Type I: Raeder’s syndrome with cranial nerve involvement
• Type II: Isolated oculosympathetic paresis with hemicranial pain
517
54.7 Management
Treatment is directed by etiology:
• Vascular (e.g., dissection, aneurysm):
– Antiplatelet or anticoagulant therapy
– Neurological monitoring
– In selected cases, endovascular intervention
• Idiopathic/Benign forms:
– Non-steroidal anti-inammatory drugs (NSAIDs), indomethacin, verapamil
• Neoplastic or inammatory causes:
– Immunosuppression or surgery as indicated
Spontaneous resolution is the most common outcome of spontaneous internal
carotid artery dissection, as observed in this patient, who improved clinically over
time without the need for invasive intervention [9].
54.8 Conclusion
Raeder’s syndrome lies at the intersection between trigeminal autonomic cephalalgias and painful cranial neuropathies. While rst associated with parasellar masses
or inammatory lesions in the rst reports, one of the most critical and potentially
life-threatening causes is the ICA dissection, especially when it occurs in the paraclinoid or cavernous segment [1–5].
Raeder’s syndrome is not currently included in the International Classication of
Headache Disorders, third edition (ICHD-3) [10], and this reects the fact that it is
not a headache disorder per se, but rather a topographical and syndromic description
518
R. Domingues
of a lesion affecting the postganglionic oculosympathetic pathway adjacent to the
trigeminal nerve. The term “Raeder’s syndrome” designates a specic anatomical
pattern rather than a single pathophysiological mechanism. As such, it encompasses
different etiologies, including vascular, neoplastic, or infectious, that share the same
neuroanatomical distribution of symptoms. Despite its absence from formal classications, recognizing this pattern remains highly valuable in clinical neurology and
neuro-ophthalmology.
Raeder’s syndrome exemplies the clinical anatomical methodology of early
twentieth-century neurology, in which disease patterns were mapped to anatomical
topographies rather than etiological categories. Raeder’s detailed description of
oculopupillary sympathetic dysfunction due to the middle cranial fossa lesions provided an early framework for understanding painful Horner’s syndromes, long
before the advent of modern neuroimaging. Whether viewed as a historical term or
anatomically grounded description, Raeder’s clinical insight represents a signicant
contribution to the understanding of the pathways connecting cranial pain and autonomic dysfunction.
References
1. Shoja MM, Tubbs RS, Ghabili K, Loukas M, Oakes WJ, Cohen-Gadol AA.Johan Georg Raeder
(1889-1959) and paratrigeminal sympathetic paresis. Childs Nerv Syst. 2010;26(3):373–6.
https://doi.org/10.1007/s00381- 009- 0965- 9.
2. Tatsui CE, Prevedello DM, Koerbel A, Cordeiro JG, Ditzel LF, Araujo JC.Raeder’s syndrome after embolization of a giant intracavernous carotid artery aneurysm: pathophysiological considerations. Arq Neuropsiquiatr. 2005;63(3A):676–80. https://doi.org/10.1590/
s0004- 282x2005000400024.
3. Solomon S. Raeder syndrome. Arch Neurol. 2001;58(4):661–2. https://doi.org/10.1001/
archneur.58.4.661.
4. Higa Lee AA, Montouro Stoarri AC, Domingues R.Internal carotid artery dissection associated with acute dengue virus infection: a case report. Headache Med. 2024;15(1):38–40.
https://doi.org/10.48208/HeadacheMed.2024.10.
5. Salvesen R.Raeder’s syndrome. Cephalalgia. 1999;19(Suppl 25):42–5. https://doi.org/10.117
7/0333102499019s2511.
6. Goadsby PJ. Raeder’s syndrome: paratrigeminal paralysis of the oculopupillary sympathetic system. J Neurol Neurosurg Psychiatry. 2002;72(3):297–9. https://doi.org/10.1136/
jnnp.72.3.297.
7. Solomon S, Lustig JP.Benign Raeder’s syndrome is probably a manifestation of carotid artery
disease. Cephalalgia. 2001;21(1):1–11.
8. Chaves C, Estol C, Esnaola MM, Gorson K, O’Donoghue M, De Witt LD, Caplan
LR.Spontaneous intracranial internal carotid artery dissection: report of 10 patients. Arch
Neurol. 2002;59(6):977–81. https://doi.org/10.1001/archneur.59.6.977.
9. Rao AS, Makaroun MS, Marone LK, Cho JS, Rhee R, Chaer RA.Long-term outcomes of
internal carotid artery dissection. J Vasc Surg. 2011;54(2):370–5. https://doi.org/10.1016/j.
jvs.2011.02.059.
10. Headache Classication Committee of the International Headache Society (IHS) The
International Classication of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.
https://doi.org/10.1177/0333102417738202
https://doi.org/10.1046/j.1468- 2982.2001.00139.x.
Chapter 55
Burning Mouth Syndrome
DanielaAparecidade GodoiGonçalves , JulianaStuginskiBarbosa ,
andMarlonFerreiraDias
55.1 Introduction
Burning mouth syndrome (BMS) is a condition characterized by persistent intraoral
burning or dysesthetic sensation without a medical or dental cause, recurring for
more than two hours per day for more than three months [23]. It is classied as a
neuropathic pain disorder [1], more frequently occurring among women than men,
with studies reporting female-to-male ratio ~7:1 [2]. The prevalence rates range
from 0.7% up to 15%, being higher among postmenopausal women and increasing
with age in both sexes [2, 3].
The symptoms involve the anterior two-thirds of the tongue, lips, and palate [4],
and it is commonly accompanied by xerostomia and taste disturbances. The condition signicantly impacts the patients’ daily activity as speaking and eating [5],
reducing the quality of life and leading to emotional distress and sleep disturbances [6–8].
The diagnosis is primarily clinical, requiring the exclusion of other conditions
that may cause similar discomfort [9]. It is a diagnostic challenge because its symptoms overlap with various systemic and local conditions, including oral candidiasis,
vitamin deciencies, diabetes mellitus, and autoimmune disorders like Sjögren’s
syndrome. Therefore, it is crucial to observe the characteristics of pain (onset, duration, location, exacerbating/ameliorating factors) and psychological and sleep prole [10].
D. A. de GodoiGonçalves (*) · M. F. Dias
São Paulo State University, School of Dentistry, Araraquara, Brazil
e-mail: daniela.g.goncalves@unesp.br
J. S. Barbosa
Bauru Orofacial Pain Group, University of São Paulo, School of Dentistry, Bauru, Brazil
Switzerland AG 2026
D. Uludüz et al. (eds.), Rare Causes of Headache Disorders, Headache,
https://doi.org/10.1007/978-3-032-10242-3_55
519© The Author(s), under exclusive license to Springer Nature
520
D. A. de GodoiGonçalves et al.
55.2 Pathophysiology
The etiology of BMS is multifactorial and may include neuropsychological factors
(nervous system dysfunction and psychological disturbances), local factors (inappropriate dentures, salivary gland diseases), and systemic factors (malnutrition, anemia, thyroid disease, menopause syndrome, diabetes mellitus, and immune system
deciency) [1, 11]. The pathophysiology, in turn, is complex, encompassing neuropathic, endocrinological, and psychoneuroimmunological mechanisms.
A growing body of evidence indicates BMS is, at least in part, a neuropathic pain
condition. Quantitative sensory testing (QST) reveals that many BMS patients have
altered somatosensory function in the oral mucosa as decreased sensitivity to
warmth and cold [12]. Besides, there is evidence of atrophy of the tongue’s epithelium resulting in a reduced number of bers innervating the taste buds and variations in the trigeminal innervation of the fungiform papillae that may contribute to
a decrease in afferent nerve impulses [13–15]. It has also been demonstrated an
increased expression of pain-associated neuroreceptors (TRPV1, P2X3) and sodium
channels (Nav1.7) in mucosal nerves [15, 16]. Such changes indicate damage or
dysfunction in small trigeminal nerve bers and are suggestive of small-ber neuropathy [12]. Additionally, brain function in the processing of nociceptive input is
altered and has patterns like those of patients who had other neuropathic pain conditions [17, 18].
Regarding endocrinological factors, the striking female predominance and typical onset around menopause suggest that hormonal factors contribute to
BMS.Estrogen withdrawal has been hypothesized to play a role in the thickening
and keratinization of the tongue, increased expression of proteins that intensify
pain, as well as dysfunction of salivary glands, resulting in dry mouth and burning
pain [14]. Another hormonal factor that can contribute is related to a dysfunction of
the hypothalamic–pituitary–adrenal axis (HPA axis), also known as the stress axis.
Cortisol (a glucocorticoid hormone) levels are often elevated in BMS patients under
basal conditions, which might reect chronic stress or altered diurnal rhythm.
Notably, recent ndings point to possible circadian rhythm disruptions in BMS
pathology [2, 14].
Psychological factors, such as chronic stress, anxiety disorder, and depression,
have been widely reported by patients with BMS. They also report poorer overall
health and complain of more illnesses, gastrointestinal (GI) problems, chronic
fatigue, disturbed sleep patterns, headaches, and pain in other locations [19, 20].
The psychological distress closely relates to the activation of the HPA axis, which
consists of the hypothalamic, the anterior pituitary, and the adrenal cortex. In situations of chronic stress, the hypothalamus releases corticotropin- releasing hormone
(CRH), which stimulates the pituitary gland to secrete adrenocorticotropic hormone
(ACTH). This, in turn, prompts the adrenal cortex to release cortisol into the bloodstream. Cortisol is a hormone that regulates growth, development, metabolism, and
immunity [21]. When elevated due to chronic stress, cortisol disrupts the balance of
immune cells, resulting in decreased cellular immunity, increased humoral
55 Burning Mouth Syndrome
521
immunity, and, consequently, immune dysfunction [22]. Together, these ndings
show that BMS is a condition where chronic pain, emotional stress, and immune
dysregulation interact. Pain leads to stress and triggers immune responses, while
pre-existing anxiety or immune changes may reduce the pain threshold. This intricate psychoneuroimmunological interaction likely explains the absence of a single
trigger for BMS and why patients often need a multifaceted treatment approach.
55.3 Case Presentation
A 65-year-old female patient presented with a chief complaint of a persistent oral
burning sensation, predominantly affecting the tongue. The symptoms had begun
six months before consultation and were reminiscent of a similar episode experienced in 2018, which was then attributed to a period of intense emotional stress.
The burning sensation was described as constant in frequency but with intermittent uctuations in intensity, with an average pain score of 8/10 on the Visual Analog
Scale (VAS). The discomfort was aggravated by prolonged speaking, consumption
of hot foods, chewing, and smoking. Relief was noted with cold stimuli, particularly
ice cream, cold water, and sweet foods.
The patient’s medical history was notable for irritable bowel syndrome and dyslipidemia, which were well-managed with pitavastatin 2mg/day. She also reported signicant
anxiety, with a Generalized Anxiety Disorder 7-item scale (GAD-7) score of 14/21, exacerbated by ongoing nancial difculties and the recent cessation of psychological therapy.
Dental history was unremarkable, with regular dental follow-ups and no relevant
oral alterations noted. The patient reported satisfactory sleep quality, with sporadic
use of benzodiazepines, and intense awake and sleep bruxism, which she managed
effectively with the regular use of an occlusal splint. Additionally, she engaged in
regular physical activity, which she felt had a positive impact on her well-being.
Clinical examination revealed no visible lesions in the oral mucosa, buccal
mucosa, or on the tongue. However, hyperalgesia was identied on the left lateral
border of the tongue during qualitative sensory testing (QualST). There was no pain
upon muscular or articular palpation, and sialometry results were normal.
Laboratory investigations, including a complete blood count, fasting glucose,
vitamin panel, lipid prole, thyroid function tests, ferritin, zinc, iron levels, creatinine, C-reactive protein (CRP), antinuclear antibodies (ANA), and erythrocyte sedimentation rate (ESR), were all within normal limits.
A diagnostic anesthetic block of the left lingual nerve resulted in partial symptomatic relief, supporting the diagnosis of burning mouth syndrome (BMS).
Treatment was initiated with a multimodal approach. To manage awake bruxism,
we used Ecological Momentary Intervention (EMI) with random smartphone
prompts to classify real-time jaw states, and aggregated data then guided habitreversal strategies, cue-based reminders, and brief breathing resets to reinforce a
relaxed jaw posture and reduce daytime parafunctional activity. The intervention
also included breathing exercises, mindfulness techniques, yoga, and guided