Brand New Case - July 10/10

[jmj11]

Here’s an interesting case that baffled me at first and it is in my area.

 

It is 1:30 AM Thursday morning and I get a call from the ER. I was in a deep sleep having some strange dream that I was climbing the outside of a very tall (hundreds of floors) building and was being slapped by mermaids as I passed each window (I figured it had something to do with kayaking just before going to bed and following some harbor seas). Anyway . . . that’s beside the point. I didn’t even know I was on call . . .oh, I actually wasn’t on call,but the neurologist who had taken the call first, as soon as the ER doc said “headache” he told them to call me (bad habit of his--but also besides the point).

 

I’m not very bright when I’m awaken from a deep sleep and didn’t figure this one out until the next morning.

 

Hx: A 35 year old man, with no prior history of headache of any sorts, developed over a period of a few hours the worst, by far, headache of his life.

 

The headache was bi-frontal, but may have favored one side more than the other. The pain was boring and a 10/10.

 

Soon, after developing the headache (within an hour) the patient became nauseous and started vomiting. Then he noticed blurred vision and within a few hours, double vision. That is when he decided to come to the ER.

 

By the time the ER doc called and the patient had been there for 6 hours, they had done a CT, labs, LP and of course vitals. All, completely normal. He remained on a morphine drip and his pain had gone down to a 8/10 at best.

 

Exam: Patient appeared to be in a lot of pain. He had a very obvious third nerve palsy (ER doc couldn’t remember if it was bilateral or unilateral). He seemed to have a unilateral ptosis. He was afebrile and no nuchal rigidity.

 

Being still dopey (talking about me now), and a head filled with spider webs and mermaids, I couldn’t make sense of this except to say, "This is not just simple migraine." But I suggested that he be admitted, MRI, MRA in the morning and I would see him in the hospital.

 

Now, unfortunately he was taken by ambulance to a different hospital (where they had a quicker MRI, not a traveling MRI like the first hospital). The second hospital has their own neurologist so I’m sure she got the case and I have no follow up.

 

However, as I was brushing my teeth Thursday morning it dawned on me what he had. I will have to get his records Monday to follow his case.

 

This one is a real brain buster and it is “open book” and open to non-students.

 

Any thoughts? Any discussion?

[meaux]

I know you said bi-frontal, but you also said 1 side may be favored more than the other. Also there was ptosis, was it ipsi-lateral? Anyway, the 1st thing to pop to mind is cluster headache. Just a quick maybe, look forward to hearing the right answer.

[jmj11]

I know you said bi-frontal, but you also said 1 side may be favored more than the other. Also there was ptosis, was it ipsi-lateral? Anyway, the 1st thing to pop to mind is cluster headache. Just a quick maybe, look forward to hearing the right answer.

 

Good guess but wasn't cluster based mostly on duration. It had been going on continuously for over 18 hours. By definition cluster doesn't last more than three hours . . . usually not more than 90 minutes and would not normally cause complete third nerve palsy with strasbismus. Lastly, cluster headache is usually strictly unilateral while this pain is bilateral with one side slightly greater than the other.

[d2305]

Tolosa-Hunt syndrome?

[jmj11]

Tolosa-Hunt syndrome?

 

 

HOLY CRAP BATMAN! How did you get it so quickly? I'm confident it is. I was considering ophthalmologic migraine, but he never has had any type of migraine in the past and that didn't sound right. But, T-H must be the dx. I just wish it had come to me in the middle of the night. I will come back and post some about T-H but I'm on my way out the door.

[meaux]

I had never heard of T-H until now, that was not covered in neuro in my school. I just read about it, so I know, for at least the next 15 minutes.

[jmj11]

I had never heard of T-H until now, that was not covered in neuro in my school. I just read about it, so I know, for at least the next 15 minutes.

 

I've worked mostly in headache disorders for 28 years. T-H is something we suppose to know, although it is very rare. I've only read about a few cases over the decades. This is the first time I've come face to face with it in real life. But I feel bad that it didn't grab me as soon as I heard the story. I will cut and post from eMedicine about it below.

 

 

Tolosa-Hunt Syndrome

 

Author: Danette C Taylor, DO, MS, Clinical Assistant Professor, Department of Neurology, Michigan State University College of Osteopathic Medicine; Senior Staff Neurologist, Henry Ford Health Systems

Contributor Information and Disclosures

Updated: Apr 29, 2010

 

Introduction

 

Background

 

Tolosa-Hunt syndrome (THS) is a painful ophthalmoplegia caused by nonspecific inflammation of the cavernous sinus or superior orbital fissure.

 

Pathophysiology

 

Nonspecific inflammation (noncaseating granulomatous or nongranulomatous) within the cavernous sinus or superior orbital fissure is the cause of the constant pain, which characterizes the onset of this disorder. Ophthalmoparesis or disordered eye movements occur when cranial nerves III, IV, and VI are damaged by granulomatous inflammation. Pupillary dysfunction may be present and is related to injury to the sympathetic fibers in the cavernous portion of ICA or parasympathetic fibers that surround the oculomotor nerve. Trigeminal nerve involvement (primarily V1) may cause paresthesias of the forehead. Pathological involvement beyond the cavernous sinus, superior orbital fissure, or apex of the orbit occurs rarely, and the disorder is part of a continuum with idiopathic orbital pseudotumor, with which it shares histopathologic features. Spontaneous remissions can occur; relapses may occur in up to 40% of the patients.

 

Frequency

 

This disorder is uncommon in both the United States and internationally.

 

Mortality/Morbidity

 

Tolosa-Hunt syndrome is not a fatal disorder; patients experience unilateral onset of acute orbital pain and ophthalmoparesis, and the disorder may threaten sight if untreated inflammation extends beyond the cavernous sinus to affect the optic nerve.

 

Sex

 

Males and females are equally affected.

 

Age

 

This disorder is rare during the first 2 decades of life; in people older than 20 years, it appears to have an even distribution. When THS occurs in children, the course of the disorder appears to be similar to that experienced by adults.1

 

Clinical

 

History

 

Patients present with usually severe retro-orbital or periorbital pain of acute onset. This pain may be described as constant and "boring" in nature.

 

Diplopia related to ophthalmoparesis follows the onset of pain (in rare cases, the ophthalmoparesis precedes the pain, sometimes by several days).

 

Patients may report visual loss. This is noted if the inflammation extends into the orbit to affect the optic nerve, and it is not a factor in disease limited to the cavernous sinus.

 

Paresthesias along the forehead may be described if the first division of the trigeminal nerve is involved.

Tolosa-Hunt syndrome is most often unilateral, although bilateral cases have been described.

 

Tolosa-Hunt syndrome frequently mimics other conditions; a single characteristic that is pathognomonic for this process does not exist. As such, realizing that this is a diagnosis of exclusion becomes even more important. Many of the processes that are found within the differential diagnosis of Tolosa-Hunt syndrome can have significant associated morbidity if not diagnosed and treated appropriately.

Physical

 

Painful ophthalmoparesis or ophthalmoplegia is the hallmark of this syndrome.

In addition to the optic and trigeminal nerves (V1, rarely V2 distribution), any of the ocular motor nerves may be involved. The oculomotor and abducens nerves are most commonly affected. Evidence of incomplete third nerve palsy with or without pupillary sparing may be present. Conversely, inflammatory involvement of the sympathetic nerves passing through the interior of the cavernous sinus may produce Horner syndrome with miosis. The combination of unilateral oculomotor palsy and Horner syndrome increases the localization specificity for the cavernous sinus.

 

Ptosis may be observed related to oculomotor palsy. Lid swelling is more likely to occur with orbital disease rather than inflammation limited to the cavernous sinus. These changes have been misdiagnosed as a complication of sinusitis, as reported by Lachanas et al.2

Mild proptosis and/or optic disc edema may be noted if the orbit is involved.

 

Evidence of trigeminal nerve involvement is suggested by loss of the ipsilateral corneal reflex.

The International Headache Society criteria for Tolosa-Hunt syndrome3,4 include the following:

Episode(s) of unilateral orbital pain for an average of 8 weeks if left untreated

 

Associated paresis of the third, forth, or sixth cranial nerves, which may coincide with onset of pain or follow it by a period of up to 2 weeks

 

Pain that is relieved within 72 hours of steroid therapy initiation

Exclusion of other conditions by neuroimaging and (not compulsory) angiography

 

Causes

 

The cause of Tolosa-Hunt syndrome is unknown (idiopathic).

 

Differential Diagnoses

 

Anisocoria

Migraine Headache

Arteriovenous Malformations

Migraine Headache: Neuro-Ophthalmic Perspective

Benign Skull Tumors

Neurosarcoidosis

Cavernous Sinus Syndromes

Pituitary Tumors

Cerebral Aneurysms

Polyarteritis Nodosa

Cerebral Venous Thrombosis

Primary CNS Lymphoma

Craniopharyngioma

Primary Malignant Skull Tumors

Diabetic Neuropathy

Systemic Lupus Erythematosus

Epidural Hematoma

Tuberculous Meningitis

Extraocular Muscles, Actions

Varicella Zoster

Extraocular Muscles, Anatomy

Wegener Granulomatosis

Lyme Disease

Whipple Disease

Meningioma

Metastatic Disease to the Brain

 

Other Problems to Be Considered

 

Carotid-cavernous fistula

Cavernous angioma

Fungal infections

Lymphoma

Melanoma

Miller Fisher Syndrome

Orbital myositis

Orbital pseudotumor

Syphilis

Vasculitis

Giant cell arteritis

 

Workup

 

Laboratory Studies

 

The diagnosis of Tolosa-Hunt syndrome is usually one of exclusion.

Laboratory workup: CBC count, erythrocyte sedimentation rate (ESR), electrolytes with glucose, thyroid function tests, fluorescent treponemal antibody (FTA), antinuclear antibody (ANA), lupus erythematosus (LE) preparation, antineutrophil cytoplasmic antibody (ANCA), serum protein electrophoresis, Lyme titre, angiotensin-converting enzyme (ACE) level, and HIV titre are helpful in eliminating other processes. This level of evaluation is required to exclude other conditions, which can have significant morbidity associated.

Cerebrospinal fluid (CSF) studies: Cell count and differential, protein, glucose, fungal and/or bacterial cultures, Gram stain, cytology, and opening pressure of CSF are helpful in eliminating conditions mimicking Tolosa-Hunt syndrome; a mild (lymphocytic) pleocytosis within the spinal fluid may occur in patients with Tolosa-Hunt syndrome.

Anti-GQ1b antibodies may be helpful in distinguishing early, painless Tolosa-Hunt syndrome from Miller Fisher syndrome.

 

Imaging Studies

 

MRI5 of the brain and orbit with and without contrast, magnetic resonance (MR) angiography or digital subtraction angiography (DSA), and CT scan of the brain and orbit with and without contrast may all be useful. Inflammatory changes in the cavernous sinus, superior orbital fissure, and/or orbital apex are typically observed on high-resolution contrast-enhanced imaging. In the authors' experience, thin-slice high–magnetic field MRI of the cavernous sinus region, including coronal sections with and without contrast and fat-suppressed cuts of the orbital regions, is the modality of choice. These changes are not specific for Tolosa-Hunt syndrome and may also be present in neoplastic conditions of the cavernous sinus. Enlargement of the optic nerve or external ocular muscles has been described, emphasizing the continuum with idiopathic orbital inflammatory disorders.

Note that findings on all imaging studies may be normal in some cases of Tolosa-Hunt syndrome.

Narrowing of the internal carotid artery within the cavernous sinus may be identified on angiography. Note that these changes are not specific to Tolosa-Hunt syndrome.

 

MRI with 3-dimensional constructive interference in steady state (3D CISS) provides an enhanced picture within the cavernous sinus. This type of imaging may assist with future diagnoses of TSH, but it is not yet used routinely.6

 

 

MRI of a 40-year-old man with severe periorbital pain ocular sinister (OS; ie, left eye), complete oculomotor nerve palsy OS, and partial abducens nerve palsy OS (image 1 is axial; image 2 is coronal). Axial imaging without (left) and with (right) enhancement demonstrates nonspecific fullness involving the left cavernous sinus, consistent with Tolosa-Hunt syndrome within the context of the history. Treatment with steroids produced complete resolution of symptoms. Image courtesy of Eric Eggenberger, DO.

 

 

 

 

Coronal T1-weighted MRI with (below) and without (above) enhancement demonstrates left cavernous sinus fullness consistent with Tolosa-Hunt syndrome (THS). The imaging features are nonspecific and must be placed into the context of the history, examination, and clinical course to avoid misdiagnosis of infiltrating, infectious, or neoplastic cavernous sinus processes. Image courtesy of Eric Eggenberger, DO.

 

 

Procedures

 

Biopsy of the lesion may be required to confirm the diagnosis. The technical difficulty of cavernous sinus region biopsies usually mitigates for a trial of steroids; nonetheless, biopsy may be needed to exclude neoplasm or if symptoms are progressing, atypical, or recurrent.

 

Histologic Findings

 

Biopsy reveals nonspecific granulomatous or nongranulomatous inflammation. This is histologically indistinguishable from the pathology of orbital pseudotumor, and these diseases may exist along a continuum.

 

Treatment

 

Medical Care

 

Corticosteroids are the treatment of choice, usually providing significant pain relief within 24-72 hours of therapy initiation. Ophthalmoparesis usually requires weeks to months for resolution; indeed, ophthalmoparesis may not completely resolve in some cases depending on the degree of inflammation and the aggressiveness of therapy. For refractory cases, azathioprine (Imuran), methotrexate, or radiation therapy has been employed.

 

Surgical Care

 

Surgical extirpation is not generally a feasible treatment of Tolosa-Hunt syndrome; the primary value of surgical intervention is a histopathologic diagnosis.

 

Consultations

 

Neuro-ophthalmology evaluation is helpful to confirm the diagnosis and to exclude other etiologies of presenting symptoms. Consultation with a neurosurgeon may be useful in cases requiring biopsy.

 

Medication

 

Steroids are used to treat the inflammation of Tolosa-Hunt syndrome. Pain relief usually occurs rapidly, ie, within 24-72 hours.7 Continue treatment at the initial dose for a short time (ie, 7-10 d) after pain resolves, then taper gradually. If no response to steroid therapy has occurred within 72 hours, the diagnosis of Tolosa-Hunt syndrome should be reevaluated.

 

If a patient is unable to tolerate steroid therapy, other immunosuppressive therapy may be considered.

 

Corticosteroids

 

Reduce pain and inflammation; diminish the size of the inflammatory mass.

 

 

Prednisone (Sterapred)

 

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.

 

Dosing

Interactions

Contraindications

Precautions

Adult

60-120 mg/d PO

 

Pediatric

Not established

 

Immunosuppressive agents

 

Decrease autoimmune reaction.

 

 

Methotrexate (Trexall)

 

Antimetabolite used to treat many autoimmune processes. The mode of action is not known; this drug does interfere with DNA synthesis.

 

Dosing

Interactions

Contraindications

Precautions

Adult

7.5 mg PO weekly (administered as a single dose or as divided doses of 2.5 mg q12h for 3 doses)

 

Pediatric

Not recommended

 

 

Azathioprine (Imuran)

 

Immunosuppressive agent that works primarily on T cells. Works very slowly; may require 6-12 mo of trial prior to effect. Up to 10% of patients may have idiosyncratic reaction disallowing use. Do not allow WBC count to drop below 3000/µL or lymphocyte count to drop below 1000/µL.

 

Dosing

Interactions

Contraindications

Precautions

Adult

2-3 mg/kg/d (administered as single or divided dose with meals)

Total body weight used, even with obese patients; begin at a tester dose (50 mg/d) because some patients develop an idiosyncratic reaction with flulike symptoms and liver and bone marrow toxicity even at this lower dose; if well tolerated after 1 wk clinically and by laboratory studies, increase to effective dose

 

Pediatric

Not Recommended

[rodan]

I have worked as a neuro PA for only 2 years and I had a patient with Tolosa Hunt after 7 months of practice. 60 y/o female with Rt partial 3rd nerve palsy who first saw opthal locally they said internuclear opthalmoplegia. First MRI normal, I repeated MRI of orbits and nonspecific inflammatory mass was found near the optic nerve. Doing my research I immed suspected TH syndrome . I ended up sending her to a highly regarded neuro opthalmologist who said it "definitetly wasn't TH". Meanwhile a rpt MRI showed the right mass was shrinking and a similar mass on the left which is highly suspicious for TH. In consult with my SP, we had her get high dose IV steroids followed by a very slow taper, which resolved her sxs and the inflammatory mass. She has been asymptomatic for a year.

 

rodan

[shindig]

I was diagnosed with THS a couple months ago. An MRI showed "inflammation" in the cavernous sinus. Spinal tap was clear. Basically he gave me prednisone and said if that didn't shrink the inflammation then it's a tumor. I took 100mg prednisone for 3 days tapered to 60mg for 6 weeks.

 

I just had my follow up MRI a few days ago on Monday after taking the steroids to see if it's gone, I get the results next week.

 

I switched neurologists because the first one only gave me neurontin, and when I complained about the pain he just kept upping the dose. The second guy I went to for a 2nd opinion gave me Trileptal, which helped a million times better, but now after being on it for 6 weeks it's effectiveness is fading as I build a tolerance to it.

 

I've had this agonizing pain for a full year now on the left side of my face, it started last Nov. It took more than 7 months to get to a neurologist as my GP said I had headaches, treated me for "hemicranial continua" with indomethacin and nortriptyline for the nerve pain I was feeling. Eventually I was convinced a tooth had moved up and was poking my sinus with the root. The orthodontist x-ray showed no teeth there, so he referred me to the Neurologist.

 

From this, I have terrible trigeminal neuralgia, both types, as well as pain behind the inside of my eye where it meets the nose, but an inch or more inside. When I move my eye in any direction it hurts, sharp pain. The Trileptal took this pain away for several weeks, so I assume it's nerve pain?

 

From inside my mouth, the source of the main pain is back in the throat where your sinus re-enters your throat, just to the left and slightly forward of that spot, and straight up, there's a constant boring pain, or feels like being cut with a razor blade in there. It feels like a toothpick or tooth root is poking the back of my sinus. It's always there, every moment I'm awake.

 

I'm 28, it happened out of nowhere, 6'4 and 160lbs. Very healthy otherwise but this is complete agony. Steroids didn't relieve the pain at all.

 

I've been to 2 neurologists, should I be going to an ophthalmologist neurologist or something? It's extremely painful.

 

The first MRI showed a lima bean shape of "inflammation" in the cavernous sinus. I have the MRI CD and I cannot find that slide showing the lima bean for the life of me. The new neurologist said he didn't see anything suspicious, so I'm confused. Now I'm wondering if I should go back to the first neurologist who took the first MRI and spinal tap.

 

So far I've been to Swedish Neuroscience and NW Neurology through University of WA.

I didn't reverse the images these are right off the disk, if I understand correctly they're flipped, the right in the picture is the left side of my head right?