C32 Neurofibromatosis

1. C32 Neurofibromatosis

2. Thesis Statement • This PowerPoint will discuss the signs, symptoms and complications of Neurofibromatosis, along with imagery methods used to diagnose and monitor the progression of the disease in hopes of finding a cure.

3. Topics of Discussion • Definition of Neurofibromatosis • Different types of NF • Common signs and symptoms • Origins • Associated complications • Radiology aided diagnosis • Treatment options • NF Awareness • Personal Connection

4. What is Neurofibromatosis? • Generally called “NF” • A rare, hereditary neurological disorder resulting in tumors1 • Tumors grow on nerve tissue1 • More specifically the peripheral nerves which originate from the spinal cord and expand to the trunk and extremities2 Nerve cell tissue with neurofibromas Tumor formation on the nerve https://www.pathpedia.com/education/eatlas/histopathology/soft_tissues/neurofibroma_-_plexiform/plexiform-neurofibroma-[1-st024-1].jpeg?Width=600&Height=450&Format=4 http://nerve.wustl.edu/images/ct_tumors_full.jpg

5. What is Neurofibromatosis? • The two main types of tumors:2 • Plexiform tumor – • Grow on the peripheral nerves in the skin, tend to be larger and irregular in shape, have more extensive growth and have a chance of becoming malignant • Dermal tumor – • On the nerves of the skin, can be cutaneous (on the surface), subcutaneous (just below the surface) or deep nodular (under the lowest layer of skin)

6. Types of NF • The term Neurofibromatosis stands for three distinct disorders3 • NF14 • The most common form of Neurofibromatosis • Affects 1 in 3,000 people worldwide • The two less common forms are:4 • NF2, affects 1 in 25,000 people • Schwannomatosis, affects 1 in 40,000 people • Most recently identified form of NF • Each kind of NF has different identifying signs and symptoms3 • As the most frequent disorder, NF1 will be discussed further

7. NF1 • Also referred to as Von Recklinghausen’s Disease1 • It is the most common inherited neurological disorder1 • Mainly affects nerve cell formation and growth5 • Proliferation of tumors, called neurofibromas5 • Ranges fluctuate from hundreds to thousands in adults1 • Tumors are most often benign5 • Tend to have smooth margins • There is a 3-5 percent chance these tumors will become malignant1

8. Basics of NF1 • Indications of NF arise in late childhood to early adulthood3 • Range and severity of symptoms vary1 • Sixty percent affected are described as having a “mild” form of the disorder • According to the National Institute of Health (NIH) Consensus Conference in 1987, NF1 may be diagnosed if a patient demonstrates at least two of the following signs/symptoms:1

9. Signs & Symptoms • Neurofibromas6 • Inside and outside the body • Café au lait spots6 • Light brown spots on the skin • Six or more spots indicate NF • Lisch nodules on the iris of the eyes6 • Abnormal clumps of pigment • Occurs in 97 percent of affected people https://nfcenter.wustl.edu/wp-content/uploads/2010/09/4fd2a76151e1.jpg https://www.reddit.com/r/Pathognomonic/comments/1sz7jl/crowe_signaxillary_freckling_neurofibromatosis/

10. Signs & Symptoms • Freckling in armpits and groin6 • Heavily populated in those specific areas • Bone deformities6 • Leg bowing • Macrocephaly7 • Enlargement of the head • Sphenoid wing dysplasia • Short stature7 http://johnsongen564s17.weebly.com/uploads/9/8/5/8/98580114/published/medical-injuries-and-diseases014.jpg?1485924699

11. Secondary Complications NF does not stop at tumor growth. Further complications include: • Self-images issues3 • Anxiety, depression, and aggressive behavior • Additional bone deformities as a result of decreased Vitamin D3 • Scoliosis • Early onset osteopenia and osteoporosis • Vision problems3 • Due to optic nerve tumors and lisch nodule formation

12. Secondary Complications • Learning disabilities3 • Over 50 percent of affected individuals demonstrate ADHD • Hypertension3 • Suggested to be from renal artery stenosis or tumors on the adrenals of the kidneys • Chronic pain, headaches, epilepsy3 • Due to the development of gliomas on the brain • Greater chance of developing other forms of cancer3 • Women with NF are 3.5 times more likely to develop breast cancer

13. Origins of NF 50 percent of individuals with NF develop the disease from a parent3 • It is a dominant gene • NF does not skip generations • Males and females are equally affected • Neither race nor ethnicity play a factor https://www.mayoclinic.org/-/media/kcms/gbs/patient-consumer/images/2013/11/15/17/37/r7_autosomaldominantthu_jpg.jpg

14. Origins of NF The other half of all cases occur due to spontaneous gene mutation6 • The NF1 gene is located on chromosome 17 • Produces and regulates formation of neurofibromin • Neurofibromin is thought to regulate cell development • The mutated gene lacks this protein and cells grow out of control http://www.wikiwand.com/en/Chromosome_17

15. Diagnosis • Prenatal genetic counseling is available for fetal diagnosis6 • Radiology is widely used in NF diagnosis and symptom regulation • Neuroradiology • Subspecialty of radiology focusing on diagnosing and characterizing abnormalities of the brain, spine and nervous system1 • MRI • CT • X-RAY • Ultrasound • Nuclear Medicine

16. MRI • Often the physician’s first choice in diagnosing • Looks at any CNS abnormalities in the soft tissue structures, such as tumors, cysts and CSF spaces on the brain and spinal cord8 • T2 weighted scans show a hyperintense (bright) lesion7 MRI showing a neurofibroma in the brain with T2 and T1 weighted scans http://radiologymri.blogspot.com/2012/09/neurofibromatosis-1-recklinghausen.html

17. Computed Tomography • Evaluates bones and most soft tissues structures9 • Used to look for complications within the thoracic, abdominal, and pelvic regions7 • Especially useful in checking kidney function • Renal collecting systems and the bladder function can be inhibited by neurofibromas7 • Neurofibromas on CT have homogenous, smooth, round appearance with distinct outlines and low attenuation values7 Sphenoid Dysplasia NF tumor on the kidney https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcSvhTs7t0_9X-onQmq2M81VqTWAnQMQ52lRtO_3Wq4e8SGwLr0Pug http://www.ajnr.org/content/ajnr/23/4/644/F2.large.jpg

18. X-ray Procedures • Neurofibromas appear as lucent lesions with well-defined margins7 • Lumbar punctures to reduce headaches and hydrocephalus • A needle inserted into the subarachnoid space of the spinal cord where cerebral spinal fluid can be emptied to relieve pressure • Also used to evaluate for joint abnormalities and bowing or S-shaped deformities of the long bones8(eg. Scoliosis) Scoliosis Tibial Bowing https://www.orthobullets.com/pediatrics/4056/anterolateral-bowing-and-congenital-pseudoarthrosis-of-tibia https://radiopaedia.org/cases/scoliosis-7

19. Ultrasound • Non plexiform NF1 masses appear as hypoechoic (dark) masses8 • Biliary obstructions associated with the hepatic vein, along liver, mesentary and retroperitoneal tumors can be detected with Sonography8 • Color doppler ultrasound is also useful to check for vascular complications such as aneurysms and stenosis9 Mesenteric plexiformneurofibromas Peripheral nerve sheath tumor https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcQHX0p9QB2-u64HmSn_ZvoRkWlIh_WPHqBj1Ux0wkNMijiAceynKA https://prod-images.static.radiopaedia.org/images/27457281/83597e611a666e01da2e75fa5d9073_big_gallery.jpeg

20. Nuclear Medicine • Using radionuclides, Nuclear Medicine can detect early signs of cancers9 • PET is used to image malignant transformations of neurofibromas8 • A commonly used radionuclide, Technetium-99m, tends to accumulate in benign, soft tissue tumors8 and shows up as red “hot” spots http://medind.nic.in/iaw/t15/i2/IndianJNuclMed_2015_30_2_148_152979_f1.jpg

21. Treatment • At this time, there is no known cure5 • Close observation and imaging are the main treatments5 • Neurofibromas are always the primary concern5 • Corrective surgeries are done to remove tumors that impede the function of other body parts6 • Radiation and/or chemo therapy may be used to treat certain NF1 tumors6 • Treatment for secondary conditions may vary from person to person • Medications are prescribed to help aid in management of additional signs and symptoms6

22. https://www.ctf.org/images/uploads/resources/CTF_Awareness_Month_Badge4.pnghttps://www.ctf.org/images/uploads/resources/CTF_Awareness_Month_Badge4.png Searching for a Cure… • Children’s Tumor Foundation (CTF) has declared May as NF awareness month4 • This is to educate and raise awareness about NF, help hope grow in the NF community and to create fundraising opportunities for NF research4 • Using a collaborative expert team, CTF is finding new potential pharmaceutical drug targets to help subdue symptoms4 • CTF also uses gene therapy aimed to specifically treat NF1 with in vitro studies to edit the NF1 gene4

23. Personal Connection • NF1 runs in my sister-in-law’s family • Great Grandmother  Grandfather Mother  Sister-in-law • Because of the known family history, there has been image monitoring since childhood • She presents: • Neurofibromas, café au lait spots, freckling, lisch nodules, scoliosis, hypertension, and chronic headaches • Her treatment plan includes: • Medication for hypertension • Yearly monitoring with imaging • Tumor removal surgeries http://www.ctf.org/images/uploads/resources/ikaf.png

24. Personal Connection • Coronal and sagittal MRI imaging shows a tumor forming in the thoracic spine at the region of T5 (pictured below) • Monitoring is being done to watch tumor growth and see if it starts to impede function of other body parts Images provided by Children’s Hospital of Wisconsin

25. Personal Connection • Scoliosis has become more dramatic over the years (pictured below) • Most likely caused by tumor growth on the upper thoracic spine previously seen on MRI scan 2013 Images provided by Children’s Hospital of Wisconsin

26. Conclusion • NF is an uncommon, complex disorder with many associated complications • Radiology serves as a main component in diagnosing and monitoring • Treatment is tailored to the specific symptoms an individual presents • Currently there is no known cure, but with continuous research and development, we’re closer to ending NF

27. Let’s see what you remember… Click to move on to the quiz!

28. 1. What are the two main types of Neurofibromatosis tumors? A. Plexiform and Basal B. Basal and Squamous C. Dermal and Plexiform D. Dermal and Basal

29. Correct! Continue Quiz 

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31. 2. What is the most common type of Neurofibromatosis? A. NF1 B. NF2 C. Schwannomatosis

32. Correct! Continue Quiz 

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34. 3. NF1 may be diagnosed if a person has at least how many signs/symptoms? A. Three B. Five C. Two D. Four

35. Correct! Continue Quiz 

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37. 4. Which modality is a Physician’s first choice in aiding with diagnosis? A. Computed Tomography B. Ultrasound C. Diagnostic X ray D. MRI

38. Correct! Continue Quiz 

39. Oops, wrong answer! Try again  Continue on with quiz 

40. 5. There is a cure for NF… A. True B. False

41. Correct! That’s right! Even though there is no cure for NF yet, there is consistent research being done by the Children’s Tumor Foundation! End Quiz 

42. Oops, wrong answer! End Quiz 

43. References • National Organization For Rare Disorders. Rarediseases.org Website. https://rarediseases.org/rare-diseases/neurofibromatosis-type-1-nf1/. Accessed March 9, 2019. • The Limb Preservation Foundation. Limbpreservation.org Website. http://limbpreservation.org/tumor/extremity-tumors/benign-tumors-of-the-extremities/benign-soft-tissue-tumors/neurofibroma-and-neurofibromatosis.html. Accessed March 9, 2019. • Mayo Clinic. Mayoclinic.org Website. https://www.mayoclinic.org/diseases-conditions/neurofibromatosis/symptoms-causes/syc-20350490. Accessed March 9, 2019. • Children’s Tumor Foundation. CTF.orgWebsite. https://www.ctf.org/understanding-nf/nf1/. Accessed March 9, 2019. • U.S. National Library of Medicine. Medlineplus.gov Websites. https://medlineplus.gov/neurofibromatosis.html. Access March 9, 2019. • John Hopkins Medicine. Hopkinsmedicine.org Website. https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/neurofibromatosis/nf1/symptoms-nf1.html. Accessed March 9, 2019. • Brouillette, E. Neurofibromatosis Type 1: Diagnostic and Therapeutic Radiologic Imaging. NSRT.com Website. http://nsrt.net/documents/Essays/Elizabeth_Brouillette.pdf. Accessed March 9, 2019. • Edmedicine. Emedicine.medscapes.com Website. https://emedicine.medscape.com/article/342500-overview. Accessed March 9, 2019. • Kendrick, Leslie E., Lampignano, John P. Bontrager’s Textbook of Radiographic Positioning and Related Anatomy. 9th Ed. St. Louis, MO. Elsevier, Inc.; 2018: 683-730. • Images. https://google.com. Accessed March 16, 2019. • I thank MakensieSeltrecht for granting permission for the use of her images provided by Children’s Hospital of Wisconsin.