Radiological Manifestations of...

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

Radiological Manifestations of Neurofibromatosis

Sandeep Robert Datta, Harvard Medical School IVGillian Lieberman, MD

September 2003

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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• What is Neurofibromatosis? • Diagnostic Criteria for NF

• Radiology and NF Management • Natural History / Sequelae of NF

Overview

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Patient L.R

•17 y.o. female•P/W nausea and headache•History of NF-1•NF-1 Dx at 4 months,

asymptomatic until 2002

Courtesy Mustafa Sahin, M. D., Children’s Hospital

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Differential Dx

•Medulloblastoma•Brainstem Glioma•Pilocytic Astrocytoma•Ependymoma•Metastasis

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Phakomatoses (phakos - “mother spot”)

Neurofibromatosis 1 and 2Tuberous Sclerosis Complex

Von Hippel Lindau SyndromeSturge Weber Syndrome

• Hereditary Transmission• Hamartoma Formation• Slowly Progressive• Predisposition towards Malignancy

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Mechanism of Disease

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Neurofibromatosis I

•Von Recklinghausen’s Disease•Loss-of-Fxn BUT Autosomal Dominant• 1:3000, M=F, all races equally affected• 50% inherited, 50% spontaneous• Neurofibromas• 100% Penetrant/ Variable Expressivity

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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• >5 Café-au-Lait Spots •Neurofibromas

2 Cutaneous OR 2 Subcutanous OR 2 Nodular OR 1 Plexiform Neurofibroma

•Axillary/Inguinal Freckling •Optic Glioma •2 Lisch Nodules •Bony Lesions •First-degree relative with NF

Diagnosis of Neurofibromatosis

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Café-au-Lait Spots/

Cutaneous Neurofibroma

Reynolds et al, Lancet 361:1552 (2003)

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Subcutaneous Neurofibroma

Relatively Hypoechoic

Delimited

Collagen Deposition

Beggs, J. Clin. Ultra. 27:363 (1999)

Ultrasound, Transverse Axis, Forearm

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Subcutaneous Neurofibroma

• Fibroblasts cause collagen deposition focally inneurofibromas

• Collagen Deposition is BRIGHT on T2Weighted MRI - assists in diagnosis of NF

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Subcutaneous Neurofibroma

Beggs, J. Clin. Ultra. 27:363 (1999)

Median Nerve

Ultrasound, Longitudinal Axis, Forearm

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Nodular Neurofibroma

•Involve Nerve Rootsand Nerves

•Impinge upon Spine

•DDX limited to NFwith multiple masses

Thakkar et al, Neurorad. 41:625 (1999)

MRI, T2-weighted, Coronal C-spine

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Diffure Plexiform Neurofibroma

MRI, Gad contrast, Coronal, Thoracic spine

Schorry, Am. J. Med. Gen. 74:533 (1997)Ibid.

PA Chest Film

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Diffure Plexiform Neurofibroma

•DPNs consist of tortuous cords of Schwann Cells

•Thought to be Congenital

•Involve Multiple Nerve Roots

•Overlying Hypertrichosis/Hyperpigmentation

•Frequently associated with adjacent scoliosis

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Optic Pathway Glioma

•15% of children < 6 •Anywhere along

visual pathway •Can cause sellar

compression •Can cause visual

acuity loss, proptosis

MRI head, axial inversion recovery

Listernick et al, Am. J. Med. Gen. 89:38 (1999)

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Bony Abnormalities

Leg Film

Courtesy Bruce Korf, M. D.

Courtesy Bruce Korf, M. D.

•Thinning of Cortical Bone •Bowing of Tibia/Forearm •Male Predominance •Pseudoarthrosis

(most common cause) •Sphenoid Dysplasia

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Diagnosis: Bony Abnormalities

DDX of Tibial Bowing •Neurofibromatosis I •Osteogenesis Imperfecta •Pagets Dz •Osteomalacia •Fibrous Dysplasia

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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• Annual MRI/CT used to be standard of care.• Now image per symptoms.

Plains films/CT :Modeling changes in long bones/ribsConcerns re: bony erosion from NFsScoliosisBone Pain

MRI:s in head size, hormones, neuro sx, visual statusConcerns re: deep NFs

Role of Radiology in NF1

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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• Clinical SyndromesMR, Szs, Altered hormonal status

• Spectrum of DiseaseCNS: Dysplasia, Harmartomas, NeoplasmsOcular: BupthalmosOsseus: Kyphoscoliosis, Tibial bowingGI: Carcinoid TumorEndocrine: PheochromocytomaGU: Wilm’s TumorPulmonary: Interstitial Fibrosis

Sequelae of NF1

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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•Dilatation of dural sac•Unknown cause —

possibly congenital•Also in Marfans•Dura erodes adjacent bone

Courtesy Steve Reddy, M. D., BIDMC

Coronal MRI

Sequelae of NF1: Dural Ectasia

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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•On T2, no enhancementno mass effect

• Thought to be Hamartomas• Correlate with MR• Often resolve • Not seen on CT

www.emedicine.com.

Axial MRI

Sequelae of NF1: Unidentified Bright Object

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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MRI head, FLAIR sequence

Listernick et al., Am. J. Med. Gen. 89:38 (1999)

•Astrocytomas when young(p/w hydrocephalus)•Optic glioma increase risk•Also NF gets other cancers:

Brainstem gliomaLeukemiaPheochromocytomaNeurofibrosarcoma

(MPNSTs)

Sequelae of NF1: Astrocytoma

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Patient L.R

• MPNST• Occur in 5% of pts with

Plexiform NFs• Present in adolescence• Aggressive, often fatal

Courtesy Mustafa Sahin, M. D., Children’s Hospital

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Patient L.R

Courtesy Mustafa Sahin, M. D., Children’s Hospital

CT chest

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Patient L.R c/o neck pain 4.5 mos prior.

CT revealed mediastinal mass deviating trachea.

Bx revealed MPNST.

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Quiz

Skolnick, JAMA 277: 367 (1997).

3D CT Reconstruction

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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• Pt is Joseph Merrick, “The Elephant Man”

• Elephant Man Disease - Proteus Syndrome not Neurofibromatosis •Proteus Syndrome - rare (<100 cases ever), bony overgrowth, hemihypertrophy.

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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Acknowledgements

Thanks to:• Steve Reddy, M.D., BIDMC• Mustafa Sahin, M. D., Children’s Hospital• Webmaster Larry Barbaras• Gillian Lieberman, MD• Pamela Lepkowski

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References• Reynolds RM, Browning GGP, Nawroz I, Campbell IW. Von

Recklinghausen’s Neurofibromatosis - Neurofibromatosis I. Lancet 2003; 361:1552-54.

• Beggs I. Sonographic Appearance of Nerve Tumors. J. Clin. Ultrasound 1999; 27: 363-368.

• Thakkar SD, Feigen U, Mautner WF. Spinal Tumors in neurofibromatosis type I: an MRI study of frequency, multiplicity and variety. Neuroradiology 1999; 41: 625-629.

• Schorry EK, Crawford AH, Egelhoff JC, Lovell AM, Saal HM. Thoracic tumors in children with neurofibromatosis-1. Am. J. Med. Gen 1997; 74: 533-537.

• Listernick R, Charrow J, Gutmann DH. Intracranial gliomas in neurofibromatosis type I. Am. J. Med. Gen 1999; 89: 38-44.

• Skolmick AA. Radiologists learn results of new therapy trials, hear latest speculations on cause of old disorder. JAMA 1997; 277: 367-369.