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

Sandeep Robert Datta, HMS IVGillian Lieberman, MD

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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.