Grand RoundsGrand Rounds

July 20, 2007July 20, 2007

Marc Moore, MDMarc Moore, MDPGY-3PGY-3

HPIHPI

8 yo WM presents with c/o left eye 8 yo WM presents with c/o left eye crossing in.crossing in.

What else do want to know?What else do want to know?

Med Hx: failure to thriveMed Hx: failure to thriveSurg Hx: tumor removal from hand Surg Hx: tumor removal from hand

and intestines at birthand intestines at birthMeds: Liprum, AdeksMeds: Liprum, AdeksAll: NKDAAll: NKDAFamHx: sister with eye movement FamHx: sister with eye movement

disorder of unclear etiology which disorder of unclear etiology which resolved w/i weeks (5 yrs ago); resolved w/i weeks (5 yrs ago); sister with recent viral resp sister with recent viral resp infectioninfection

ROS: noncontributoryROS: noncontributory

VA: 20/30+2 OD, 20/25 OSVA: 20/30+2 OD, 20/25 OSMot: see picMot: see picPupils: no RAPD, no anisocoriaPupils: no RAPD, no anisocoriaPLE:PLE: Ext/Lids: wnl OUExt/Lids: wnl OU Conj: quiet OUConj: quiet OU K: clear OUK: clear OU A/C: deep OUA/C: deep OU Iris: wnl OUIris: wnl OU Lens: wnl OULens: wnl OU

Differential Dx of CN VI Differential Dx of CN VI palsypalsy

ACUTEACUTE PostviralPostviral Increased ICPIncreased ICP

Idiopathic Intracranial Idiopathic Intracranial HypertensionHypertension

Congenital Congenital hydrocephalushydrocephalus

EncephalitisEncephalitis NeoplasmNeoplasm

Pontine gliomaPontine glioma Posterior fossa Posterior fossa

medulloblastomamedulloblastoma TraumaTrauma Gradenigo syndromeGradenigo syndrome

CHRONICCHRONIC Duane syndromeDuane syndrome Thyroid Eye DiseaseThyroid Eye Disease Myasthenia gravisMyasthenia gravis Mobius syndromeMobius syndrome Congenital esotropiaCongenital esotropia

Dx postviral CN VI palsy. Monitor 1-2 Dx postviral CN VI palsy. Monitor 1-2 weeks.weeks.

Pt RTC 2 weeks later with no Pt RTC 2 weeks later with no improvement in symptoms. Maybe improvement in symptoms. Maybe slightly worse. MRI ordered.slightly worse. MRI ordered.

MRI could not be completed due to MRI could not be completed due to sedation issues. CT shows left sedation issues. CT shows left cavernous sinus fullness.cavernous sinus fullness.

Pt returns to clinic again 1 week later Pt returns to clinic again 1 week later (3 weeks p presentation) again with (3 weeks p presentation) again with no improvement. MRI again ordered.no improvement. MRI again ordered.

MRIMRI

SchwannomaSchwannoma Schwann cell tumor that arises as an Schwann cell tumor that arises as an

outpouching from peripheral or outpouching from peripheral or cranial nervescranial nerves

Neural crest originNeural crest origin Associated with neurofibromatosisAssociated with neurofibromatosis Intracranial schwannomas most often Intracranial schwannomas most often

arise from sensory nerves, seldom arise from sensory nerves, seldom from purely motor nervesfrom purely motor nerves

SchwannomaSchwannoma

All cranial nerves (except I and II) All cranial nerves (except I and II) have myelinated sheaths of Schwann have myelinated sheaths of Schwann cells, thus are potential sites for cells, thus are potential sites for schwannomasschwannomas

Zone of transition from myelination Zone of transition from myelination by oligodendroglia in CNS to by oligodendroglia in CNS to Schwann cells is variableSchwann cells is variable

Transition zone ranges from 1-4 mm Transition zone ranges from 1-4 mm from exiting brainstemfrom exiting brainstem

Cranial Nerve VI Cranial Nerve VI SchwannomaSchwannoma

Very low incidenceVery low incidence 13 cases reported in the literature13 cases reported in the literature 4 of 13 within the cavernous sinus4 of 13 within the cavernous sinus

Tung et al. classified into 2 typesTung et al. classified into 2 types Type 1: arises in cavernous sinus; Type 1: arises in cavernous sinus;

presents with diplopia and CN VI palsypresents with diplopia and CN VI palsy Type 2: arises in prepontine region; Type 2: arises in prepontine region;

presents with hydrocephalus, elevated presents with hydrocephalus, elevated ICP, CN VI palsyICP, CN VI palsy

More historyMore history Pt carries diagnosis of Pt carries diagnosis of Infantile Infantile

MyofibromatosisMyofibromatosis First described by Stout in 1954First described by Stout in 1954 Classified as one of the fibrous Classified as one of the fibrous

proliferations of childhoodproliferations of childhood Multiple fibroblastic tumors involving Multiple fibroblastic tumors involving

skin, striated muscles, bones and skin, striated muscles, bones and visceraviscera

Tumors present at birth or develop Tumors present at birth or develop during the first weeks of lifeduring the first weeks of life

Infantile Myofibromatosis Infantile Myofibromatosis (IM)(IM)

Multiple soft tissue nodules occur as in Multiple soft tissue nodules occur as in neurofibromatosis. These often neurofibromatosis. These often spontaneously regress.spontaneously regress.

Prognosis is poor when several Prognosis is poor when several internal organs are affected; 80% such internal organs are affected; 80% such infants die within first 4 months of lifeinfants die within first 4 months of life

Debate of autosomal recessive vs. Debate of autosomal recessive vs. autosomal dominantautosomal dominant

More Family HistoryMore Family History

Mother, maternal uncle, and 2 Mother, maternal uncle, and 2 cousins with myofibromatosiscousins with myofibromatosis

15 yo brother with 15 yo brother with myofibromatosismyofibromatosis NLP OS from biopsy-proven orbital NLP OS from biopsy-proven orbital

apex myofibromaapex myofibroma Multiple intracranial calvarial Multiple intracranial calvarial

lesions which wax and wanelesions which wax and wane

MRIMRI

More Family HistoryMore Family History

13 yo sister with myofibromatosis13 yo sister with myofibromatosis H/o CN VI palsy of unclear etiologyH/o CN VI palsy of unclear etiology Waxing and waning calvarial lesions Waxing and waning calvarial lesions Latest MRI: new left orbit enhancing roof Latest MRI: new left orbit enhancing roof

lesion anteriorly and laterally which lesion anteriorly and laterally which causes some mild mass effect on the causes some mild mass effect on the adjacent left orbit fat but not the extra-adjacent left orbit fat but not the extra-ocular muscles ocular muscles

MRIMRI

IM with Choroidal IM with Choroidal InvolvementInvolvement

4 mo boy with 3 purple, spherical, 4 mo boy with 3 purple, spherical, non-tender, non-mobile nodules on non-tender, non-mobile nodules on his skull and 1 over left scapulahis skull and 1 over left scapula

Normal physical examination at birthNormal physical examination at birth Biopsy showed plump spindle cells Biopsy showed plump spindle cells

arranged in short fascicles consistent arranged in short fascicles consistent with IMwith IM

Imaging showed cervical spine and Imaging showed cervical spine and liver involvementliver involvement

IM with Choroidal IM with Choroidal InvolvementInvolvement

Pt began chemotherapy at 6 moPt began chemotherapy at 6 mo At 9 mo, noted central vision loss ODAt 9 mo, noted central vision loss OD

Presumed choroidal myofibroma with Presumed choroidal myofibroma with overlying choroid NV and serous RDoverlying choroid NV and serous RD

Small tumor noted OSSmall tumor noted OS Authors recommend careful Authors recommend careful

ophthalmic exam in patients ophthalmic exam in patients diagnosed with IMdiagnosed with IM

Case ReportsCase Reports

4 yo presented with mass of the 4 yo presented with mass of the inferolateral orbital rim. Lesion inferolateral orbital rim. Lesion surgically excised and pathology surgically excised and pathology confirmed myofibroma. Pt did well.confirmed myofibroma. Pt did well.

11 day old with LLL and medial canthus 11 day old with LLL and medial canthus lesion. Mass grew and was removed at lesion. Mass grew and was removed at 2 months. Myofibroma shown on 2 months. Myofibroma shown on histology. Again, pt had no ocular histology. Again, pt had no ocular sequela.sequela.

Our PatientOur Patient

Exam has remained stableExam has remained stable Will continue to monitorWill continue to monitor Unclear if schwannoma is related to Unclear if schwannoma is related to

myofibromatosis (no other reports in myofibromatosis (no other reports in literature)literature)

Consider neurosurgical evaluationConsider neurosurgical evaluation

Take Home PointsTake Home Points

May monitor CN VI palsy initially, but May monitor CN VI palsy initially, but imaging is warranted if symptoms do imaging is warranted if symptoms do not improvenot improve

Although rare, pt with infantile Although rare, pt with infantile myofibromatosis warrant ophthalmic myofibromatosis warrant ophthalmic evaluationevaluation

ReferencesReferences Acharya R, Husain S, Chhabra SS, Patir R, Bhalla S, Seghal AD. Sixth Acharya R, Husain S, Chhabra SS, Patir R, Bhalla S, Seghal AD. Sixth

nerve schwannoma: a case report with literature review. Neurol Sci. nerve schwannoma: a case report with literature review. Neurol Sci. 2003 Jun;24(2):74-9. 2003 Jun;24(2):74-9.

Day M, Edwards AO, Weinberg A, Leavey PJ. Successful Therapy of a Day M, Edwards AO, Weinberg A, Leavey PJ. Successful Therapy of a Patient With Infantile Generalized Myofibromatosis. Med Pediatr Patient With Infantile Generalized Myofibromatosis. Med Pediatr Oncol. 2002; 38: 371-373Oncol. 2002; 38: 371-373

Duffy MT, Harris M, Hornblass A. Infantile Myofibromatosis of Orbital Duffy MT, Harris M, Hornblass A. Infantile Myofibromatosis of Orbital Bone. Ophthalmology 1997; 104: 1471-74Bone. Ophthalmology 1997; 104: 1471-74

Fibromatosis, Congenital Generalized. Online Mendelian Inheritance Fibromatosis, Congenital Generalized. Online Mendelian Inheritance in Manin Man

Lee MS, Galletta SL, Volpe NJ, Liu GT. Sixth Nerve Palsies in Lee MS, Galletta SL, Volpe NJ, Liu GT. Sixth Nerve Palsies in Children. Pediatr Neurol 1999; 20; 49-52Children. Pediatr Neurol 1999; 20; 49-52

Linder JS, Harris GJ, Segura AD. Periorbital infantile Linder JS, Harris GJ, Segura AD. Periorbital infantile myofibromatosis. Arch Ophthalmol 1996 Feb; 114(2): 219-22myofibromatosis. Arch Ophthalmol 1996 Feb; 114(2): 219-22

Lo PA, Harper CG, Besser M. Intracavernous schwannoma of the Lo PA, Harper CG, Besser M. Intracavernous schwannoma of the abducens nerve: a review of the clinical features, radiology and abducens nerve: a review of the clinical features, radiology and pathology of an unusual case. J Clin Neurosci. 2001 Jul;8(4):357-60 pathology of an unusual case. J Clin Neurosci. 2001 Jul;8(4):357-60

Stout AP. Juvenile fibromatoses. Cancer 1954; 7:953-78Stout AP. Juvenile fibromatoses. Cancer 1954; 7:953-78 Tung H, Chen T, Weiss MH. Sixth nerve schwannomas. Report of Tung H, Chen T, Weiss MH. Sixth nerve schwannomas. Report of

two cases. J Neurosurg 1991 75:638-641two cases. J Neurosurg 1991 75:638-641 Yanoff: Ophthalmology, 2nd ed., Copyright © 2004 Mosby, Inc.Yanoff: Ophthalmology, 2nd ed., Copyright © 2004 Mosby, Inc. 730-730-

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