Tolosa-Hunt syndrome is a rare disorder of unknown etiology characterized by periorbital pain and cranial nerve palsies. It may be considered an uncommon form of cavernous sinus syndrome.
THS patients typically present with severe orbital and periorbital pain of acute onset that may exacerbate in episodes. Without appropriate treatment, this pain does not subside and persists for weeks. It coincides with ophthalmoplegia, i.e., cranial nerve palsies indicating lesions of the oculomotor, trochlear and/or abducens nerves (limited eye movement, mydriasis, lacking accomodation and ptosis). A delay of several days between onset of pain and ophthalmoplegia has been observed in some cases. Additionally, patients may report paresthesias in the upper face. The corneal reflex may be disturbed. These symptoms are due to compression of the ophthalmic and maxillary branches of the trigeminal nerve. These symptoms are observed unilaterally and usually, no disturbances can be detected on the contralateral side. Reports about bilateral THS are very rare.
Despite ophthalmoplegia, vision is often not disturbed. Some patients experience diplopia. Vision loss is associated with damage to the optical nerve and thus with extensive inflammation. Visual impairment is not characteristic for THS limited to the cavernous sinus.
Orbital and periorbital pain should resolve within very few days after initiation of corticosteroid therapy. If this is not the case, a thorough re-examination should take place to detect possible alterations that might have been overlooked the first time. Although proof of granulomatous inflammation of the cavernous sinus, either by histopathological analysis of biopsy samples or by magnetic resonance imaging, rises a strong suspicion for THS, there is no pathognomonic symptom for this syndrome. In fact, THS mimics a variety of other, possibly much more severe conditions and its diagnosis is based on ruling out the latter. If any hint as to one of those other diseases is missed, a patient may be erroneously be diagnosed with THS. On the other hand, THS may not be recognized for what it is . In such cases, initiation of the rather simple but effective treatment may unnecessarily be delayed and the risk for further neurological damage increases.
Entire Body System
- Severe Pain
Tolosa-Hunt syndrome (THS) is a condition that includes recurrent attacks of retro-orbital, steady, and severe pain usually as the presenting symptom. [ncbi.nlm.nih.gov]
The history included severe pain on rightward eye movement and parabulbarly on the right, considerable defect in the area supplied by the first division of the trigeminal nerve, right hemicrania, and diplopia on looking to the left, right, upward and [eurekamag.com]
[…] and decreased eye movement; the pain can be severe in nature (stabbing pain is felt) It is common to have nausea and vomiting during severe pain Ptosis (drooping eyelid) Double vision or blurred vision Light sensitivity and neck stiffness The signs and [dovemed.com]
This coupled with steroid responsiveness and long-term asymptomatic follow-up firmly established the diagnosis of THS. [ncbi.nlm.nih.gov]
Follow-up studies while the patients were asymptomatic demonstrated complete resolution of the CT abnormalities in four patients and clinical improvement in all five patients. [ajronline.org]
[…] of ophthalmoplegia • Painful ophthalmoplegia • Proptosis (pulsating exophthalmos suggests a direct C-C fistula) • Ocular and cranial bruits • Conjunctival congestion; arterialization of conjunctival veins • Ocular hypertension • Optic disc edema or pallor [slideshare.net]
Optic nerve disturbance is attributed to lesion extension to the orbital apex which contributes to optic disc swelling or pallor , thickened optic nerve due to edema , and orbital venous congestion  that may cause minimal visual decline though [hindawi.com]
[…] cranial nerve (trigeminal), optic nerve, and facial nerve which suggest an extension of the disease process beyond the cavernous sinus. Rarely, inflammation can involve orbital apex leading to optic nerve damage and consequent optic disc pallor [statpearls.com]
Dilated fundus exam showed temporal pallor of the disk in the right eye, and slight pallor of the disk in the left eye. Pinprick was mildly impaired in the right V1 and left V3 distributions. The rest of the neurological exam was unremarkable. [journal.frontiersin.org]
- Acute Onset of Symptoms
Usually acute at onset, the patient's symptoms typically last from days to weeks. Before the use of systemic corticosteroids there was clear evidence that spontaneous remissions occurred. [jnnp.bmj.com]
A 19-year-old Dominican woman presented to the emergency department with nausea, vomiting, and a right-sided headache of 1 month’s duration. The nausea and vomiting were associated with anorexia and a 20-lb weight loss since the symptoms began. [consultant360.com]
A 23-year-old woman was admitted with headache, nausea, vomiting and blurred vision on the left side. Neurological examination showed ptosis with a complete internal and external ophthalmoplegia and a red fullness around the left orbita. [ncbi.nlm.nih.gov]
She also had nausea, vomiting, photophobia, phonophobia and blurry vision, which did not respond to nonsteroidal anti-inflammatory drug treatment. She had no weakness or numbness in her limbs. [n.neurology.org]
Nausea and vomiting are reported. Differential diagnosis Several other conditions may present in a similar manner to THS and there is no single feature that is pathognomonic for this disease. Other considerations include: Trauma. [patient.info]
Correspondingly, THS is uncommon etiology of painful diplopia, lesion of the CN IV produces vertical diplopia in the ipsilateral eye intensified by downward gaze, ocular extorsion, downward gaze insufficiency, and head tilting compensatory for extorsion [scirp.org]
Key words: Painful ophthalmoplegia, ptosis, diplopia, Tolosa-Hunt syndrome, cavernous Advertisement Journal of Interdisciplinary Histopathology SUBMIT YOUR ARTICLE NOW [scopemed.org]
She visited the emergency department in October 2011 due to a one-week history of binocular diplopia and headache. Diplopia became worse with right horizontal gaze and did not change with distance. [elsevier.es]
After two months, the patient only complained of diplopia on up-gaze, but the therapy was discontinued two months later on the basis of both clinical signs and MRI findings. [ncbi.nlm.nih.gov]
This is a 55-year-old woman who consulted with a history of variable, intermittent, horizontal diplopia associated with right upper eyelid ptosis and mild pain. [reumatologiaclinica.org]
Nowhere in these cases was anisocoria the sole presenting sign. This case report strives to showcase that anisocoria can manifest as a sole sign of THS with no apparent involvement of the other cranial nerves. [psychiatrist.com]
Anisocoria, Physiologic (Anisocoria) Anisometropia Anisometropic Amblyopia (Amblyopia) Anophthalmia (Anophthalmos) Anophthalmos Anterior Ischemic Optic Neuropathy (Optic Neuropathy, Ischemic) Anterior Uveitides (Uveitis, Anterior) Anton Syndrome (Blindness [provisu.ch]
Presenting After COVID-19 Vaccination. 62 Chuang TY...Athar K 34513398 2021 42 Recurrent Tolosa-Hunt syndrome. 62 Thu PW...Liu WM 34386372 2021 43 Tolosa-Hunt Syndrome: A Case Report. 62 K C S...Dhungana K 34508416 2021 44 Tolosa-Hunt Syndrome With Anisocoria [malacards.org]
A neuro-ophthalmological examination revealed anisocoria (right pupil: 4mm; left pupil: 3mm); changes in illumination did not affect pupil size. Both direct and consensual light reflexes were normal. [elsevier.es]
Help From Wikimedia Commons, the free media repository Jump to navigation Jump to search tolosa-hunt syndrome Human disease Upload media Wikipedia Instance of disease Subclass of ocular motility disease, genetic peripheral neuropathy, rare strabismus [commons.wikimedia.org]
H49.81 Kearns-Sayre syndrome H49.88 Other paralytic strabismus Reimbursement claims with a date of service on or after October 1, 2015 require the use of ICD-10-CM codes. [icd10data.com]
The patients with previously diagnosed paralytic or restrictive strabismus, congenital strabismus, or with previous extraocular muscle surgery were excluded. [bmcophthalmol.biomedcentral.com]
Neoplastic etiology Imaging evidence of mass lesion Restrictive Strabismus CT evidence of muscle entrapment De bulking surgery for NSOI,TAO refractory to medical therapy Confirmation of diagnosis by biopsy 39. [slideshare.net]
- Pupillary Abnormality
[…] ophthalmic branch of trigeminal nerve (approximately 30%), and trochlear nerve (approximately 29%). There can also be sympathetic (third order neuron Horner syndrome, in approximately 20% cases) or parasympathetic (oculomotor) involvement which leads to pupillary [statpearls.com]
There can also be sympathetic (third order neuron Horner syndrome, in approximately 20% cases) or parasympathetic (oculomotor) involvement which leads to pupillary abnormalities 10. [healthjade.net]
- Unilateral Eye Pain
Symptoms include unilateral eye pain, ophthalmoplegia, headache, and facial pain in the distribution of the upper divisions of the trigeminal nerve and are highly responsive to steroid therapy. [ncbi.nlm.nih.gov]
Tolosa–Hunt is a rare condition that presents as an acute unilateral eye pain with motor dysfunction and responds to prolonged treatment with corticosteroids. Presented is a case of Tolosa–Hunt syndrome. [academic.oup.com]
Face, Head & Neck
- Facial Pain
Tolosa- Hunt syndrome is a rare steroid responsive disorder caused by granulation tissue involving the cavernous sinus or superior orbital fissure presenting as painful ophthalmoplegia and facial pain. [ncbi.nlm.nih.gov]
Internationally renowned editors and contributor teamIntegrated approach to the diagnosis and treatment of oral and facial pain syndromes as well as common primary headaches A thorough review of the four majorclinical entities of orofacial pain: acute [books.google.com]
[…] neuropathy 13.11 Burning mouth syndrome (BMS) 13.12 Persistent idiopathic facial pain (PIFP) 13.13 Central neuropathic pain 13.13.1 Central neuropathic pain attributed to multiple sclerosis (MS) 13.13.2 Central post-stroke pain (CPSP) Bibliography 13.8 [ichd-3.org]
A 73-year-old man was admitted to the hospital because of worsening right upper facial pain and decreasing visual acuity in the right eye. [scinapse.io]
J Neurol Neurosurg Psychiatry 1954;17:300-2.doi:10.1136/jnnp.17.4.300 ↑ Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. [eyewiki.aao.org]
Headache, 46 (2006), pp. 336-339  The International Classification of Headache Disorders. 2nd edition. Cephalalgia. 2004;24 Suppl. 1:9–160.  L. La Mantia, M. Curone, A.M. Rapoport, G. Bussone. [elsevier.es]
Headache that preceded the paresis of the III, IV and / or VI nerves for ≤ 2 weeks or developed with it 2. Headache located around the eye and ipsilateral eyebrow D. [nucleodoconhecimento.com.br]
Diagnostic criteria: Unilateral frontal and/or periorbital headache fulfilling criterion C Clinical and imaging evidence confirming an ischaemic ocular motor nerve palsy 1 Evidence of causation demonstrated by both of the following: headache is ipsilateral [ichd-3.org]
We report on a previously healthy 11-year-old boy with unilateral periorbital mild headache and facial nerve palsy, followed during the next 5 months by recurrent unilateral headaches and subsequent extrinsic paresis of the third cranial nerve and paresis [ncbi.nlm.nih.gov]
- Cranial Nerve Involvement
Cranial nerve involvement which may affect any or all of cranial nerves III, IV, V (V1/V2 division) and VI. Cranial nerves III and VI are the most commonly affected. The optic nerve and periarterial sympathetic nerves may also be involved. [patient.info]
In THS patients, the third cranial nerve was most commonly involved (76.3%). The median time interval between pain and cranial nerve palsy was two days, although in five patients (10.9%) the interval ranged from 16 to 30 days. [ncbi.nlm.nih.gov]
Optic nerve function tests were impaired with loss of red desaturation and light brightness. EOM was full and no other cranial nerves involvement. [acquaintpublications.com]
Clinically, THS manifested headache and painful ophthalmoplagia with one or more ipsilateral cranial nerve involvement such as oculomotor, trochlear, abducens, and superior and/or maxillary divisions of the trigeminal. [n.neurology.org]
nerve, and, less frequently, the fourth or the sixth cranial nerves. [rbojournal.org]
- Trigeminal Neuralgia
Trigeminal neuralgia attributed to other cause 220.127.116.11 Idiopathic trigeminal neuralgia 18.104.22.168.1 Idiopathic trigeminal neuralgia, purely paroxysmal 22.214.171.124.2 Idiopathic trigeminal neuralgia with concomitant continuous pain 13.1.2 Painful trigeminal [ichd-3.org]
A 59-year-old man presented with left trigeminal neuralgia and right abducens nerve palsy 2 months after the improvement of right oculomotor nerve palsy by corticosteroid therapy. [ncbi.nlm.nih.gov]
He also gave me neurontin for Trigeminal Neuralgia caused by the THS... I had to wait another 2.5 weeks after the spinal tap for the results, which was today. [mdjunction.com]
neuralgia following Tolosa-Hunt syndrome. 62 Durmaz GS...Celebisoy N 33826103 2022 8 Tolosa Hunt Syndrome: A Challenging Diagnosis from Otorhinolaryngologist Perspective-A Case Report. 62 Behera G...Chaurasia JK 36742718 2022 9 Complete ophthalmoplegia [malacards.org]
Trigeminal neuralgia is a chronic condition affecting the trigeminal nerve, and in case of it even a mild stimulation of the face may trigger an attack of shooting pain. [laac.lv]
She had a convulsion with fever and a left facial palsy at 6 years of age and since then complained of headaches. Four years later she had diplopia, left-sided ocular pain and ptosis. [pediatricneurologybriefs.com]
Clinical signs included left ophthalmoplegia, convulsions and right hemiplegia. Etiopathogenesis of this syndrome is unclear but as in our case, response to corticosteroid therapy is spectacular and avoids unnecessary invasive diagnostic procedures. [ncbi.nlm.nih.gov]
Case 6 had in addition to ophthalmic findings history of behavioural abnormalities and one convulsion. So a carotid angiography was done which revealed mass in relation to lesser wing to sphenoid. [ijo.in]
• No H/O nausea, vomitings, giddiness, double vision, LOC, seizures, sweating, lacrimation, flushing, redness of the face and the eye, photophobia, phonophobia. • No h/o similar episodes in the past 4. • with the above complaints approached to local [slideshare.net]
While periorbital pain and ophthalmoplegia may be recognized in anamnesis and clinical examination, respectively, neuroimaging is necessary to detect inflammation of the cavernous sinus. Magnetic resonance imaging is the technique of choice. But although evidence for a granulomatous inflammation is mandatory to diagnose THS, negative findings leave doubts in about 50% of all THS patients. If no signs for inflammation can be observed and the suspicion for THS persists, a biopsy should be taken. If pathohistological analysis of biopsy samples does neither indicate granulomatous inflammation, the patient does not fulfill the diagnostic criteria for THS. Here, further diagnostic imaging, e.g., computed tomography scans and angiography, are recommended to identify the cause of headaches and ophthalmoplegia.
Diagnostic treatment with corticosteroids is reasonable if neuroimaging did not reveal any alterations that require urgent attention. Corticosteroid therapy should significantly improve the patient's condition within a maximum of 72 hours, probably even less.
According to diagnostic criteria published by the International Headache Society in 2004, ruling out differential diagnoses is essential for diagnosing THS. In this context, differential diagnoses to be considered are:
- Cavernous sinus thrombosis
- Carotid-cavernous fistula
- Aneurysm of the internal carotid artery
- Hemorrhage due to trauma or hemorrhagic infarction
- Wegener granulomatosis
Some of these conditions are life-threatening but may nevertheless be missed during first examination. In order to compensate for possible erroneous diagnoses, any patient diagnosed with THS should undergo annual or at least biannual follow-ups. As a part of these exams, magnetic resonance imaging should be repeated.
- Lymphocytic Infiltrate
Histopathological analyses have shown giant-cell granuloma, lymphocyte infiltration and fibroblast proliferation, the latter presumably representing repair processes, in the wall of the dural sinus. [symptoma.com]
Prolonged oral administration of corticosteroids is the treatment of choice. While according to diagnostic criteria, patients should respond within 72 hours to such therapy, most individuals suffering from THS do so within 24 hours. Pain should considerably subside in this time frame, but ophthalmoplegia may persist for several more weeks. In some cases, neuronal damage is partially permanent.
Treatment is initiated with high-dose corticosteroids, but upon response to therapy the patient's dose may be reduced. Success of therapy should be controlled with regular magnetic resonance imaging. Such examinations should be done every one or two months until lesions are no longer detectable .
Failure to respond to therapy strongly suggests an alternative diagnosis. If no hints at any of the above mentioned differential diagnoses can be found and refractory THS is suspected, immunosuppression may be achieved with azathioprine, methotrexate or radiation therapy .
There is no surgical treatment for THS. Any surgical intervention realized in THS patients primarily fulfills diagnostic functions.
THS patients usually respond well to systemic corticosteroid therapy, most likely within 24 hours . If that is not the case, differential diagnoses should be re-considered. Moreover, relapses are common and require prolonged immunosuppressive treatment.
Complications include persisting cranial nerve palsies. These may affect eye movements or, in more severe cases where the inflammation spread, vision.
The precise cause of THS is still unknown. Patients present a granulomatous inflammation of the cavernous sinus, sometimes also of the superior orbital fissure. Due to it being a space-occupying pathological process, it may compress adjacent tissues such as cranial nerves passing through the walls of the above mentioned sinus. The inflammation may also spread to these nerves and thereby impair their function. The granulomatous inflammation may possibly be triggered by an autoimmune response, although this theory requires further corroboration. Indeed, THS has been described in a patient suffering from systemic lupus erythematodes, but this may merely be a coincidence . Vascular alterations are another possible cause of cavernous sinus inflammation.
THS is a rare neurological syndrome. The annual incidence has been estimated to be 1-2 per 1,000,000 individuals .
With regards to age, THS is less frequently diagnosed in children and adolescents. Adults of any age seem to be affected equally. Neither pathophysiological nor clinical differences have been observed regarding disease progress in pediatric, adolescent and adult patients, but this may be due to the restricted case number of younger patients .
No predilections regarding gender or race have been described.
THS-associated morbidity depends on timing of diagnosis and initiation of treatment. If left untreated, the inflammation may spread, compromise additional cranial nerves and cause vision loss. No fatalities have been reported related to THS.
THS is caused by a granulomatous inflammation of the cavernous sinus and possibly of the superior orbital fissure. Histopathological analyses have shown giant-cell granuloma, lymphocyte infiltration and fibroblast proliferation, the latter presumably representing repair processes, in the wall of the dural sinus  . Up to date, no evidence for involvement of infectious agents has been found and granuloma are apparently sterile. Nevertheless, they exert considerable pressure on surrounding tissues, namely those cranial nerves passing through the wall of the cavernous sinus.
Since oculomotor, trochlear and abducens nerves contain the vast majority of motor nerve fibers controlling movements of the ocular globe, pupils and eyelids, damage of these nerves results in ophthalmoplegia. The ophthalmic and maxillary branches of the trigeminal nerve mainly contain somatosensory fibers. If they are affected by cavernous sinus syndromes, sensory loss occurs in the area supplied by these nerves.
If the inflammation spreads any further, other tissues may be compromised .
No preventive measures can be recommended.
The cavernous sinus is delimited by endothelial-lined dura mater, is located lateral to the sella turcica and borders temporal and sphenoid bones. Of clinical importance is its close proximity to cranial nerves III (oculomotor nerve), IV (trochlear nerve), V (trigeminal nerve) and VI (abducens nerve) as well as the internal carotid artery. These cranial nerves may be affected by space-occupying processes such as aneurysms or neoplasms and may be compressed. This type of disorder is termed cavernous sinus syndrome. According to its respective etiology, different cavernous sinus syndromes may be classified further. Tolosa-Hunt syndrome (THS) is a cavernous sinus syndrome of unknown etiology.
THS has first been described in 1954 by Eduardo Tolosa and William Edward Hunt  . Diagnostic criteria for THS have last been published in 2004, 50 years later  and include a granulomatous inflammation of the cavernous sinus. While such an inflammation may serve as an explanation for symptoms characteristically associated with THS, it is still deemed idiopathic. THS is most frequently unilateral and symptoms are observed ipsilaterally. Typical symptoms comprise headaches, periorbital pain, ophthalmoplegia and sometimes additional neurologic deficits, particularly facial sensory loss. The latter may be caused by damage to the ophthalmic and maxillary branches of the trigeminal nerve. THS patients do not necessarily present the complete spectrum of cranial nerve palsies associated with cavernous sinus syndromes but may rather show any combination thereof.
Patients generally respond well to anti-inflammatory medication in form of corticosteroids. Many THS patients suffer from relapses and require prolonged immunosuppressive treatment. The medical challenge consists in diagnosing THS and effectively distinguishing this syndrome from other, more severe pathologies, e.g. aneurysm, thrombosis, neoplasm and trauma. To date, diagnosis of THS is mainly a diagnosis of exclusion .
Tolosa-Hunt syndrome (THS) is a rare disorder associated with headaches, particularly in close proximity to one of the eyes, and the inability to perform certain eye movements.
Eye movements are controlled by three cranial nerves, namely the oculomotor, trochlear and abducens nerves. They arise from the brain stem and pass through distinct parts of the brain until reaching their target structures. All these nerves pass alongside an enlarged blood bag called the cavernous sinus. In addition to the above mentioned nerves, a sensory cranial nerve named trigeminal nerve and the internal carotid artery also pass the cavernous sinus.
An inflammation or any space-occupying process affecting the cavernous sinus results in compression and subsequent functional impairment of the cranial nerves that cross its wall.
In THS, a granulomatous inflammation of as of yet unknown etiology affects the cavernous sinus. The inflammation itself causes pain that may not subside during weeks if appropriate treatment is not provided. As has been described before, this inflammation results in cranial nerve damage. THS patients do not necessarily present paresis of all cranial nerves crossing the cavernous sinus, but may be unable to move their eye globes and their eyelids. Accommodation, i.e., focusing on near or far objects, and pupillary constriction may be blunted.
If the trigeminal nerve is affected, the patient may experience abnormal sensations in their upper face.
Vision loss is not characteristic for THS. However, the inflammation may spread from the cavernous sinus to adjacent tissues, may damage yet another cranial nerve, the optical nerve, and in these cases, vision loss is possible.
Medical history and clinical examination may prompt a suspicion for THS, but neuroimaging needs to be carried out in order to identify the granulomatous inflammation that affects the cavernous sinus. This is usually done with magnetic resonance imaging. If no alterations can be detected, a small tissue sample will be obtained and histopathologically analyzed. It is of utmost importance to verify if there is a granulomatous inflammation because THS may mimic a variety of other, possibly much more severe conditions that need to be ruled out. If any doubts remain as to the presence of vascular anomalies, thrombosis or a tumor, additional diagnostic imaging will be realized.
Patients diagnosed with THS should undergo regular follow-ups to verify that significant lesions were not missed during first examination.
Therapy aims at relieving pain and reducing the inflammation. Prolonged oral administration of corticosteroids is the method of choice. Most THS patients respond to such treatment within one day, possibly within two or three. Pain should subside shortly after initiation of treatment, but neurologic damage may take weeks or even months to resolve. In rare cases, neurological deficits are partially permanent.
During therapy, patients will undergo regular examinations with magnetic resonance imaging in order to verify if intracranial lesions resolve as well as pain and nerve palsies.
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