CLINICAL FORMS OF ONSET IN TOLOSA HUNT SYNDROME
Abstract
Tolosa Hunt syndrome (THS) is
considered to be one of the painful cranial
neuropathies according to the International
Headache Society, in its headache
classification. THS is a rare and severe,
unilateral periorbital headache associated
with decreased and painful eye movement,
which is caused by non-specific
inflammation of the cavernous sinus,
superior orbital fissure and the apex of the
orbit. The quick response to corticosteroid
therapy is characteristic for this disease.
Some cases of patients with Tolosa
Hunt syndrome have been studied, following
the onset modalities and the etiology of the
associated diseases. Two patients with
Tolosa Hunt Syndrome were evaluated at
our institution from… to…. We presented a
55 years-old caucasian female patient
diagnosed with THS. The patient had
unilateral periorbital pain, inflammatory
process in the apex of the orbit, Graves
Basedow disease after subtotal
thyroidectomy and osteopenia. The
suspicion of THS was based on the cerebral
MRI which showed tumoral lesion at the left
orbital apex. The second case presents a 51
years-old Caucasian male patient diagnosed
with TSH. The patient presented left ear
tightening and left hemicrania accompanied
by Claude Bernard Horner Syndrom.
Subsequent investigations suspected the
diagnosis of Tolosa-Hunt Syndrom.
Key words : Tolosa-Hunt syndrome,
inflammation, cavernous sinus.
Introduction
Tolosa-Hunt syndrome is a rare
cause of ophthalmoplegia due to a chronic
unspecific inflammation that involves the
cavernous sinus and/or superior orbital
fissure. Clinically, the syndrome is
characterized by strong orbital and
retrobulbar pain, accompanied by
oculomotor (III), trochlear (IV), and/or
abducens (VI) nerve paresis of a varying
degree. Disorders of sensation may also be
present in the area innervated by the ocular
branch of the trigeminal nerve (V1) [1, 2].
Lesions are usually unilateral; so far, only
few bilateral Tolosa-Hunt syndrome cases
have been reported [1, 3, 4].
The syndrome was first described in
1954 by Eduardo Tolosa in a patient with
unilateral, recurrent, painful
ophthalmoplegia involving cranial nerves
III, IV, VI, as well as V1 [5].
The disease affects women and men
equally, with onset around the age of 40, but
early-onset cases have been reported.
The major symptoms of Tolosa-Hunt
syndrome include chronic periorbital
headache, double vision, paralysis (palsy) of
certain cranial nerves, and chronic fatigue.
Affected individuals may also exhibit
protrusion of the eye (proptosis), drooping
of the upper eyelid (ptosis) and diminished
vision. In most cases, symptoms associated
with Tolosa-Hunt syndrome affect only one
side (unilateral). Symptoms will usually
subside without intervention (spontaneous
remission) and may recur without a distinct
pattern (randomly).
The International Headache Society
codified the diagnosis of Tolosa-Hunt
syndrom. For a definitive diagnosis, this are
the criteria to be met:
 Eye pain on one side of the head
that persists for at least eight weeks
if untreated;
 associated irritation or damage to
the third, fourth, or sixth cranial
nerves;
 relief of pain within 48 hours upon
the administration of steroids;
 and specialized testing that rules out
other conditions such as neoplasm,
infection or aneurysm.
The diagnosis may be confirmed by
a thorough clinical evaluation, detailed
patient history, and a variety of specialized
radiologic tests including computed
tomography (CT) scan, and magnetic
resonance imaging (MRI). These
examinations may reveal characteristic
enlargement or inflammation of the areas
behind the eye (cavernous sinus and superior
orbital fissure). Pain is usually reduced in
untreated cases within fifteen to twenty
days. With steroid treatment, pain typically
briskly subsides within twenty-four to
seventy-two hours – and this brisk steroid
response aids in the diagnosis. Affected
individuals may be vulnerable to recurrent
future attacks. [6]
Material and method
A 55 years-old Caucasian female,
with Graves Basedow Disease installed after
subtotal tiroidectomy (1991), without
family history of autoimmune disease,
known with right tonsillar papilloma and
chronic professional laryngitis ( she is a
singer) was admitted in our hospital in
November 2015. She presented unilateral
periorbital and retroocular pain, associated
with left lid ecchymosis , for almost 7 days.
She affirms that she presented same
symptoms twice, in April and June 2015, for
3 days. On physical examination:
conscious, cooperative patient, cranial
nerves urge, sensitivity, motility,
coordination within normal limits,
symmetric osterotensinous reflexes present
bilaterally. The examination of other
systems was normal. Routine biological
analyses were normal with the exception of
an increased ESR (28mm/h) and fibrinogen
(444mg/dL). Patient was HIV negative, the
hormone dosage was also normal (FT4,
TSH) and immunological markers were
negative (double stranded anti-DNA
antibodies, anti- cANCA antibodies, anti-
pANCA antibodies, TPO, ANA). At the
ophthalmologic examination, both eyes
appeared normal. The MRI exam describes a
solid tumor nodule at the level of the left
upper orbital tip as well as several
supratentorial microangiopathy lesions.
Under corticotherapy and symptomatic
treatment, evolution is favorable and the
patient is externalizing.
The patient develops a bilateral
apical pahipleurita, returns after 3 months to
our clinic for clinical biological re-
evaluation, imaging and therapeutic attitude.
The results of the routine analyzes are
within normal limits with the exception of
basophils and eosinophils which were
slightly low. Compared to the previous
admission, the patient presents normal
values of the inflammatory samples. The
ophthalmologic examination reveals papules
with no changes, retinal arteries with normal
appearance, retinal veins with increased
caliber in the left eye compared to the right
eye. The cerebral MRI exam describes the
same nodular tumor of orbital apex on the
left, dimensionally and morpho-functional
stable compared to the previous
examination, representing most likely a
pseudotumor in the context of Tolosa Hunt
Syndrome.
 A 51-years old Caucasian male with
no significant personal pathological history
is presented for left ear tightening and left
hemicrania accompanied by Sdr. Claude
Bernard Horner (anamnestic after exposure
to cold), installed for about a week. At the
neurological objective examination we
noticed: narrowing of the left palpebral lobe,
miosis, enophthalmia, no oculomotricity
disorders, hypoesthesia in the left
ophthalmic territory. Other investigation
showed the following : normal cerebral CT,
normal MRI, cervical column MRI: C5-C6
intervertebral space narrowing, C5 posterior
osteophyte, C5-C6 disc-osteophyte complex
left left introveredamenal compressing left
nerve root C6. Under corticosteroid therapy
(cortisone 200 mg / day), symptomatology
was resolved within 24 hours. We suspects
to be a Sdr. TOLOSA-HUNT, due to
immediate favorable response to
corticosteroid therapy.
After about a week, after a
concentration effort (a trip to Bucharest and
back), suddenly there are speech disorders
and apraxia.
Neurological objective examination:
cranial nerves: left palpebral ptoza, miosis,
enophthalmia, language examination:
impaired understanding, difficult expression,
preserved repetition, agraphy, ideomotric
apraxia.
Angio MRI with contrast substance:
absence of void flow signal of the right
intracranial ACI of the examination field:
right ACI occlusion
Angio CT extracranial vessels: right
ACI occlusion with right backward artery
compensatory dilatation, approximately 80%
segment C2 stenosis and approximately 95%
C3 segment at left ACI level. Under anti-
agglutination and anticoagulation treatment,
the symptoms return. The patient is
externally on request for further
investigations at a clinic abroad. An Echo
Doppler performed in ambulatory,
highlights left ACI stenosis and right ACI
occlusion. There is suspicion of a congenital
fibromuscular dysplasia (radiologically
refuted by the Doppler exam) or the
presence of some traumatic factors in the
neck vessels. After insisting on the
anamnesis (traumatic factor), the patient
remembers that he stood under an artificial
waterfall, where his throat was exposed to
water pressure.
The radiological images (being
inconclusive) are sent to Turkey, where the
diagnosis of carotid dissection is also
confirmed, and confirmed by the Vascular
Surgery Clinic in Milan, where the chronic
anticoagulant is indicated and the clinical
symptomatology is recovered under the
conditions of recurrence.
After a week, he goes to a
Neurosurgery Clinic in Hungary where a
volumetry is performed that highlights the
presence of bilateral cerebral perfusion.
Currently, the patient has no subjective
accusations. Neurological objective
examination: normal exceptCBH syndrome.
Results and Discussions
We quote a few cases of Tolosa Hunt
syndrome presented in the literature to
highlight the multiple onset methods and the
various associated diseases. A 22-year-old
white man with a 12-year history of Crohn
disease developed bifrontal constant
headache accompanied by nausea, numbness
of the right upper lip, and diplopia on left
lateral and upward gaze 2 weeks before
admission. The pain was more severe over
his right eye.
A healthy 24-year-old white man
developed sudden onset of right retrobulbar
pain relieved by aspirin 3 weeks before
admission. A complete right third nerve
palsy was noted over the next several days.
A CT brain scan and bilateral carotid
angiography at another institution were
reported as normal. Since diabetes,
parasellar tumor, and posterior
communicating artery aneurysms had
apparently been excluded, he was started
empirically on methyl prednisolone, 24 mg/
day to be tapered over a 1-week period. This
relieved the headache almost immediately,
but the diplopia persisted. . When steroids
were restarted, the patient noted marked
improvement of his retrobulbar pain,
pupillary functions, and extraocular
movements. As the steroids were tapered,
there was a mild flare-up of the headache
and the ptosis. The working diagnosis was
leakage from an epidermoid tumor in the
right cavernous sinus with secondary
inflammation.
A 26-year-old previously healthy
black man experienced 2 weeks of
generalized fatigue, fever, and night sweats
8 weeks before admission. By 6 weeks
before admission, the patient experienced
diplopia on left lateral gaze and left
retroorbital pain. Multiple scans and
investigations, a biopsy of a mediastinal
lymph-node showed noncaseating
granulomata compatible with sarcoidosis.
Visual acuity deteriorated. The patient was
subsequently started on methyl
prednisolone, 60 mg every 6 hr, then
changed to oral prednisone, 80 mg every
morning. Visual acuity on the left transiently
improved, headache, facial paresthesias, and
diplopia all resolved within several days.
When the patient prematurely discontinued
the prednisone, visual acuity of the left eye
deteriorated with the development of a
central scotoma. [7]
Conclusions
THS is a disease that occurs rarely,
with unknown etiopathogenesis, clinically
manifested by unilateral orbital pain
associated with simple or multiple
oculomotor paralyses, which resolves
spontaneously but may recur. For making
diagnosis, MRI orbital phlebography and
biopsy are the recommended. In order to
avoid a mistaken Tolosa-Hunt syndrome
diagnosis, magnetic resonance imaging
studies are essential. It is important to note
that this syndrome is misleading, with
different onset and multiple associated
pathologies. The cases presented point out
the importance of building a diagnostic
complex that does not exclude the disease in
a patient with severe retro-orbital or
periorbital pain of acute onset.
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