Brown Syndrome 

Rare Diseases / By

Brown Syndrome – 13 Interesting Facts

  1. Brown syndrome is an uncommon ocular motility disorder characterized by limited ability to gaze upward when the affected eye is in adduction; usually due to abnormalities of the superior oblique muscle/tendon/trochlea complex
  2. some patients may have compensatory head posture (chin up or face turn to contralateral side) when looking up
  3. usually congenital but may be acquired due to a variety of causes such as inflammatory conditions and thyroid dysfunction
  4. diagnosis primarily based on clinical exam and forced duction test
  5. orbital imaging may help demonstrate abnormalities
  6. targeted diagnostic investigations may be important to assess for underlying causes in noncongenital cases
  7. evidence for management limited to small case series and case reports
  8. conservative management usually adequate
  9. for inflammatory acquired Brown syndrome, anti-inflammatory management includes
  10. systemic nonsteroidal anti-inflammatory drugs
  11. oral corticosteroids
  12. local corticosteroid injection for cases refractory to oral medications
  13. surgery aimed at counteracting superior oblique muscle/tendon/trochlea pathology may be considered for severe cases such as severe compensatory head posture or vertical strabismus in primary position

Introduction

  • Brown syndrome is an uncommon ocular motility disorder characterized by limited ability to gaze upward when the affected eye is in adduction(1,3)
    • usually congenital but may be acquired
    • usually due to abnormalities of the superior oblique muscle/tendon/trochlea complex
      • some definitions of Brown syndrome require this as the pathogenic mechanism
      • may be referred to as “true Brown syndrome”
    • some definitions of Brown syndrome allow for other pathogenic mechanisms; these may also be referred to as “simulated” or “pseudo” Brown syndrome

Also Called

  • superior oblique tendon sheath syndrome (term generally no longer used)
  • superior oblique click syndrome (may be used to refer to cases in which eye movement produces an audible or palpable “click”)

Definitions

  • strabismus – any misalignment of the eyes, including
  • terminology for direction of eye rotation
    • adduction – rotation toward midline
    • abduction – rotation away from midline
    • elevation – upward rotation
    • depression – downward rotation
    • Reference – Int Ophthalmol Clin 2018 Spring;58(2):5

Types

  • congenital vs. acquired(3)
    • congenital – constant limited elevation in adduction that is present at birth
    • acquired – limited elevation in adduction with onset occurring after infancy; may be idiopathic or have identified cause
  • classification by severity(1)
    • mild – no vertical deviation in any horizontal position of gaze
    • moderate – disfiguring downshoot in adduction
    • severe – disfiguring downshoot in adduction plus vertical deviation in primary position with or without compensatory head posture

Epidemiology

  • limited evidence for precise epidemiology(1,3)
    • prevalence is low
    • usually presents in childhood
    • slightly higher predilection in girls and women has been reported, but evidence unclear

Etiology and Pathogenesis

Causes

Pathogenesis

Extraocular Musculature
  • eyeball rotates along 3 axes based on actions of 6 extraocular muscles
    • lateral rectus – rotates eyeball away from midline (abduction)
    • medial rectus – rotates eyeball toward midline (adduction)
    • superior rectus – primarily rotates eyeball upward (elevation); secondary actions are incyclotorsion and adduction
    • inferior rectus – primarily rotates eyeball downward (depression); secondary actions are excyclotorsion and adduction
    • superior oblique – primary action is incyclotorsion; secondary actions are depression and abduction
      • originates at the orbital apex (as do the 4 rectus muscles), superior and medial to annulus of Zinn
      • runs anteriorly near superomedial orbital roof and becomes tendinous
      • loops around trochlea, which acts as a pulley, and then changes direction to pass over eyeball posterolaterally (thus, trochlea is effective origin of action)
      • attaches to eyeball under superior rectus
      • vertical action (depression) dominates when eye is in adduction; torsional action (incyclotorsion) dominates when eye is in abduction
    • inferior oblique – primary action is excyclotorsion; secondary actions are elevation and abduction
      • originates at the periosteum of the maxillary bone in the anterior orbit
      • runs posteriorly, temporally, and superiorly to the eyeball
      • remains inferior to inferior rectus
      • attaches to eyeball under lateral rectus
      • vertical action (elevation) dominates when eye is in adduction; torsional action (excyclotorsion) dominates when eye is in abduction
    • Reference – Int Ophthalmol Clin 2018 Spring;58(2):5
Pathogenic Mechanisms
  • potential pathogenic mechanisms involving superior oblique muscle/tendon/trochlea complex(3)
    • tight, short, and/or immobile superior oblique muscle/tendon
      • congenital short length or reduced elasticity
      • mass-displacing tendon, reducing effective length and elasticity
      • acquired fibrosis of superior oblique muscle (rare) such as that following thyroid disease, local intramuscular anesthetic, or Hurler-Scheie syndrome
      • following some procedures such as scleral buckling retinal detachment surgery and superior oblique tendon tuck
    • reduced telescoping elongation of the superior oblique tendon due to
      • congenital abnormality of elastic cross fibers involved with telescoping movement of central tendon fibers
      • vascular dilatation of tendon sheath vessels
      • local edema within trochlea area
    • inflammation-induced nodule on superior oblique tendon posterior to trochlea (superior oblique click syndrome)
      • nodule restricts tendon movement due to difficulties entering trochlea
      • inflammation may be due to congenital anomaly or to systemic inflammatory diseases such as sinusitis, rheumatoid arthritis, and lupus erythematosus
    • stenosing tenosynovitis
      • chronic movement of superior oblique tendon through trochlea, leading to traumatic tenosynovitis with tendon swelling and stenosis surrounding tendon sheath and subsequent restricted tendon movement
      • congenital stenosis of superior oblique tendon sheath and enlarged tendon posterior to trochlea
    • peritrochlear scarring – scarring or fibrosis between trochlea and anterior superior oblique tendon, leading to tethered tendon movement such as with superonasal orbital trauma
  • potential pathogenic mechanisms not caused by superior oblique pathology (may be referred to as “simulated” or “pseudo”-Brown syndrome)(1,3)
    • inferior orbital fibrous adhesions to posterior globe; may follow
      • orbital floor fracture
      • fat adherence syndrome associated with inferior orbital trauma
      • congenital bands
    • anomalous check ligament at insertion of inferior or oblique muscle
    • anomalous bands to inferior rectus muscle
    • anomalous fibrous sheath between superior oblique tendon sheath and upper nasal intermuscular quadrant
    • pulley instability of lateral rectus muscle

History and Physical

Clinical Presentation

  • chief concern is misaligned eyes when gazing upward(1,3)
    • Brown syndrome characterized by limited elevation (upward gaze) when affected eye is in adduction
    • some patients may have compensatory head posture (chin up or face turn to contralateral side) when looking up; such posture allows for binocular fusion
    • in children with suspected Brown syndrome, parents or other family members may be first to notice misaligned eyes and/or compensatory head posture
    • some patients may have symptoms and signs beyond motility abnormalities (less common with congenital Brown syndrome)
      • superonasal orbital pain and tenderness or other inflammatory signs
      • diplopia when forced into gaze that produces hypertropia (occurs if Brown syndrome acquired in late childhood or later; patients with earlier onset may develop suppression)
      • audible and/or palpable superior nasal “click” on ocular rotations up and nasalward
        • may be accompanied by pain
        • may be better heard with a stethoscope
  • additional characteristics in most cases of Brown syndrome(1,3)
    • usually unilateral
    • abnormalities most apparent when suspect eye is in adduction
      • reduced elevation of eye with both monocular (duction) and binocular (version) eye movement
      • may be downshoot as eye moves nasally
      • may be widening of the ipsilateral palpebral fissure
      • forced duction test positive
    • abnormalities less apparent but may not be eliminated when suspect eye is not in adduction
      • elevation improves in straight upgaze; there is either an exotropia producing a “V” pattern or the eyes remain straight
      • may be hypotropia in primary position
      • elevation normal or near normal in abduction
      • smooth progression from reduced to normal/near normal elevation as eye position moves from adduction to abduction
  • eye motility abnormalities may not be constant in patients with acquired Brown syndrome (onset occurring after infancy)(3)
    • may be intermittent
    • may be less or more when eye rotating in specific patterns, depending on the pattern
      • less when eye is rotated in circular pattern that is first down, then temporally, then up, and finally up and nasally
      • more when rotation is first nasally and then up or first from primary position and then going straight up and nasally
    • may be less with digital pressure in area of trochlea
  • signs raising suspicion of other conditions include(3)
    • negative forced duction test
    • superior oblique muscle overaction
    • A-pattern
    • large vertical deviation in primary position
    • fundus torsion in primary or down gaze
  • classification by severity(1)
    • mild – no vertical deviation in any horizontal position of gaze
    • moderate – disfiguring downshoot in adduction
    • severe – disfiguring downshoot in adduction plus vertical deviation in primary position with or without compensatory head posture

History

  • ask when misalignment in eyes and/or compensatory head posture were first noticed and if they are constant or intermittent(1,3)
  • ask about symptoms (not present in all patients)(1,3)
    • double vision and gaze direction when double vision maximal
    • presence of audible or palpable “click,” pain, or swelling near the suspect eye
    • systemic symptoms suggesting inflammatory disorders, such as fever, weight change, myalgias
  • ask about medical conditions that may cause Brown syndrome, such as(3)
    • head trauma
    • inflammatory disorders
    • ocular or sinus procedures
    • infections
    • see Etiology and Pathogenesis for detailed list of potential causes

Physical

  • assess for misalignments with eyes in primary and cardinal gaze positions(1,3)
    • Brown syndrome characterized by limited elevation (upward gaze) when suspect eye is in adduction
    • impaired elevation persists even with unaffected eye covered
    • misalignment decreases or is not apparent as gaze position deviates from position producing greatest misalignment
  • positive forced duction test confirms clinical diagnosis(3)
    • may not be necessary in many patients
    • may not be possible in some patients
  • fundus exam findings(3)
    • Brown syndrome due to inelastic muscle tendon complex associated with normal fundus torsion in primary position and intorsion on up gaze
    • other conditions suspected if fundus intorsion increases in downgaze

Diagnosis

Making the Diagnosis

  • suspect Brown syndrome in patients with misaligned eyes when gazing upward(3)
    • Brown syndrome characterized by limited elevation (upward gaze) when suspect eye is in adduction
    • some patients may have symptoms (pain and/or diplopia) and/or compensatory head posture (chin up or face turn to contralateral side) when looking up
  • positive forced duction test confirms clinical diagnosis but may not be necessary or possible(3)
  • if not congenital or if no identified cause, conduct targeted diagnostic investigations to evaluate for associated diseases such as sinusitis, rheumatoid arthritis, systemic lupus erythematosus, or neoplasm (see Etiology and Pathogenesis for detailed list of potential causes)(3)
  • targeted diagnostic investigations may also be useful to(3)
    • determine pathology to inform management (if treatment needed)
    • assess for potentially manageable causes of pain, discomfort, or inflammation
    • assess for other conditions that may be causing signs and symptoms

Differential Diagnosis

  • conditions that may affect eye motility
  • limited elevation due to other ocular abnormalities
    • inferior oblique palsy, paresis, or iatrogenic injury(1,3)
    • double elevator palsy (monocular elevation deficiency)(3)
    • primary superior oblique overaction(3)
    • superior oblique muscle entrapment following orbital fracture (Ophthalmic Plast Reconstr Surg 2014 Mar-Apr;30(2):e26)
    • other acquired nonparalytic disorders of the superior oblique muscle, such as
      • superior oblique myokymia (brief recurrent episodes of diplopia and oscillopsia due to myokymic movements of superior oblique muscle)
      • ocular neuromyotonia (involuntary episodic ocular deviations causing diplopia)
      • Reference – Am Orthopt J 2014;64:89

Testing Overview

  • routine diagnostic testing not needed, but consider(3)
    • targeted testing to evaluate for associated conditions if not congenital or if cause not identified
    • imaging of the orbits and/or rheumatologic studies for some patients who have pain, discomfort, signs of inflammation, or atypical strabismus

Imaging Studies

  • associated orbital imaging findings
    • computed tomography of orbit may demonstrate
      • thickening of reflected portion of superior oblique tendon
      • localized low attenuation representing edema
    • magnetic resonance imaging of orbit in patient with acquired Brown syndrome may demonstrate
      • thickening of superior oblique tendon on T1-weighted imaging
      • high signal intensity on T2-weighted fat-saturated imaging
      • mild enhancement on T1-weighted gadolinium-enhanced imaging
    • Reference – AJNR Am J Neuroradiol 2009 Oct;30(9):1778full-text

Management

Management Overview

  • evidence for management limited to small case series and case reports(1,2)
  • conservative management usually adequate
  • for inflammatory acquired Brown syndrome, anti-inflammatory management includes
    • systemic nonsteroidal anti-inflammatory drugs
    • oral corticosteroids
    • local corticosteroid injection for cases refractory to oral medications
  • surgery aimed at counteracting superior oblique muscle/tendon/trochlea pathology may be considered for severe cases such as severe compensatory head posture or vertical strabismus in primary position

Conservative Management

  • conservative management usually adequate(2,3,4)
    • careful observation
    • reassure patient (or parents of children with Brown syndrome) that
      • management may not be needed if
        • eye position is well-controlled
        • binocular vision is not adversely affected
        • compensatory head posture, if present, is not distressing
      • condition may resolve or improve with time (up to 20 years for congenital cases)

For Inflammatory Acquired Brown Syndrome

  • options include(2,3,4)
    • systemic nonsteroidal anti-inflammatory drugs
    • oral corticosteroids
    • peritrochlear corticosteroid injections such as
      • 1-2 injections of dexamethasone 4 mg in 1-mL solution
      • methylprednisolone
  •  intratrochlear betamethasone injection reported to improve head posture and reduce vertical deviation in 4 of 5 children with severe Brown syndrome of presumed inflammatory etiology refractory to oral prednisolone (level 3 [lacking direct] evidence)
    • based on small case series
    • 5 children (aged 1.5-15 years, 80% girls) with severe acquired Brown syndrome (vertical deviation in primary position) of presumed inflammatory etiology had intratrochlear betamethasone 4-mg injection
      • presentation was diplopia in 2 children and anomalous head posture in 3 children; onset 1-6 weeks before presentation
      • all children had no improvement to 1-2 weeks of oral prednisolone
      • intratrochlear betamethasone administered 2-8 weeks after symptom onset
    • improved head posture and reduced vertical deviation reported in 4 of 5 children at 1-4 months of follow-up
    • median vertical deviation reduced from 11.5 to 3.5 prism diopters (p = 0.094)
    • Reference – J AAPOS 2019 Feb;23(1):23.e1
  • intratrochlear triamcinolone acetonide injection reported to resolve acquired Brown syndrome secondary to trochleitis in 85% of adults (level 3 [lacking direct] evidence)
    • based on small case series
    • 13 patients (median age 30 years, 54% women) with acquired Brown syndrome secondary to trochleitis had 1-mL intratrochlear injections of triamcinolone acetonide 40 mg/mL up to 3 times monthly (median 1.3 injections)
    • first injection given at median 7.8 days after diagnosis
    • complete remission reported in 11 patients (85%) at mean 22.5 days after first injection
    • Reference – Graefes Arch Clin Exp Ophthalmol 2017 Oct;255(10):2045
  • adalimumab reported to resolve inflammatory acquired Brown syndrome refractory to conservative management in 4-year-old boy (J AAPOS 2020 Jun;24(3):167)

Tendon-Directed Surgery

  • tendon-directed surgery generally not necessary(1,2,4)
  • potential indications include(1,2,4)
    • severe compensatory head posture
    • vertical strabismus in primary position
    • severe downshoot in adduction
    • exploration and/or foreign body removal for some patients with acquired Brown syndrome due to trauma (such as motor vehicle accident) or other causes
  • goals of tendon-directed surgery are to reduce compensatory head posture, severe eye dysmotility, and symptoms in order to reduce impact on daily activities and function; long-term complete elimination of signs uncommon(1,2,4)
  • risks of surgery include(2)
    • unpredictable outcome
    • iatrogenic superior oblique palsy following superior oblique tenectomy or tenotomy
  • perioperative considerations(1,4)
    • forced duction test before, during, and after surgery can help assess motility restrictions and short-term efficacy
    • exploring all ocular muscles and tendons can help identify pathogenic characteristics and direct management
  • reported procedures on superior oblique tendon include(1,3,4)
    • superior oblique tenotomy (split tendon) or tenectomy to elongate tendon
      • addition of silicone expander may reduce overcorrection
      • separation at tendon ends may be uncontrolled, leading to
        • paresis if ends separate widely
        • undercorrection if ends reunite and scar back together
      • simultaneous inferior oblique recession/weakening has been reported
    • superior oblique silicone tendon expansion – silicone retinal band keeps cut tendon ends apart, producing graded lengthening
    • intraoperative adjustable suture spacer
  • description of trochlea reconstruction for acquired Brown syndrome can be found in J AAPOS 2014 Feb;18(1):56
  • surgery of superior oblique muscle reported to improve abnormal head posture in patients with Brown syndrome (level 3 [lacking direct] evidence)
    •  based on case series
    • 190 patients (mean age 9 years, 58% female) with Brown syndrome had surgery of superior oblique muscle between 2003 and 2011 and were followed for median 21 months
      • right eye affected in 52% and left eye affected in 48%
      • 100% had restriction of elevation in adduction, 49% had abnormal head posture, and 25% had hypotropia
    • common surgical techniques used were superior oblique nasal tenotomy (in 38%), superior oblique suture spacer (in 25%), and superior oblique tenectomy (in 19%)
    • comparing after surgery vs. before surgery
      • abnormal head posture in 23.3% vs. 49% (p < 0.05)
      • mean limitation of elevation in adduction -0.9 vs. -3.58 (p < 0.05)
      • mean hypotropia 4.25 prism diopters vs. 13.15 prism diopters (p < 0.05)
    • consistent results for abnormal head posture and limitation of elevation in adduction in subgroup analysis by surgical technique
    • Reference – Beyoglu Eye J 2021;6(3):223full-text
  • superior oblique split lengthening surgery reported to reduce vertical deviation in patients with severe congenital Brown syndrome (level 3 [lacking direct] evidence)
    • based on small case series
    • 14 patients with severe congenital Brown syndrome had superior oblique split lengthening surgery of 10 mm and followed for 10-16 months
    • mean hyperopia reduced from 16.2 to 5.9 prism diopters (p < 0.001)
    • mean limited elevation in adduction reduced from -7.2 to -1.8 (p < 0.001)
    • no surgical adverse effects reported
    • Reference – Strabismus 2014 Mar;22(1):7
  • silicone spacer partially relieved undercorrection persisting 1 year after superior oblique tendon recession in 8-year-old boy in case report (Strabismus 2016 Sep;24(3):106)

Complications

  • no complications beyond primary symptoms, which, if present, include(1,3)
    • diplopia in certain directions of gaze
    • pain or discomfort, usually from inflammatory causes

Prognosis

  • some cases may improve over time and even resolve without surgery(1,3)
    • estimated to occur in about 6%-7% of all cases, but reported rates vary
    • more likely with acquired Brown syndrome; other factors associated with improvement unclear
    • may occur within months of onset (in cases of acquired Brown syndrome) or take up to 20 years

Prevention and Screening

  • not applicable

Guidelines and Resources

Guidelines

  • no relevant guideline for “Brown Syndrome” found 2020 Dec 14 in systematic search of MEDLINE (using guidelines limiter)

Review Articles

  •  to search MEDLINE for (Brown Syndrome) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis

Patient Information

References

General References Used

  1. Manley DR, Alvi RA. Brown’s syndrome. Curr Opin Ophthalmol. 2011 Sep;22(5):432-40.
  2. Lee J. Management of Brown syndrome. Semin Ophthalmol. 2008 Sep-Oct;23(5):291-93.
  3. Wright KW. Brown’s syndrome: diagnosis and management. Trans Am Ophthalmol Soc. 1999;97:1023-109full-text.
  4. Deutsch JA, Dotan G, Raab EL, Wagner RS. Surgical Management of Brown Syndrome. J Pediatr Ophthalmol Strabismus. 2017 Nov 1;54(6):330-31.

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