Neurofibromatosis Background Ad hoc management of NF 1

Neurofibromatosis

Background • Ad hoc management of NF 1 pts between a variety of specialties • Sarcoma service sees many NF 1 patients and any ? MPNST • There is no commissioned service for NF 1 in Bristol • There is a commissioned service for NF 2

Aim • To provide a commissioned comprehensive service for the management of NF 1 patients in conjunction with the already established NF 2 service

NF 1 • Neurofibromatosis 1, • previously called von Recklinghausen’s disease • common neurocutaneous condition with an autosomal dominant pattern of inheritance • NF 1 has a birth incidence of 1 in 2, 500 to 1 in 3000 (180)

Diagnostic Criteria for Neurofibromatosis 1 • (NIH consensus development conference 1988) [3] • 6 or more café au lait macules (>0. 5 cm in children or > 1. 5 cm in adults) • 2 or more cutaneous/subcutaneous neurofibromas or one plexiform neurofibroma • Axillary or groin freckling • Optic pathway glioma • 2 or more Lisch nodules (iris hamartomas seen on slit lamp examination) • Bony dysplasia (sphenoid wing dysplasia, bowing of long bone +/- pseudarthrosis) • First degree relative with NF 1

The Skin • • Café au lait patches and skin-fold freckling Hypopigmented macules Juvenile xanthogranulomas Neurofibromas – benign peripheral nerve sheath tumours that are focal cutaneous or subcutaneous or diffuse or nodular plexiform lesions – Risk of malignant change is rare

Malignant peripheral nerve sheath tumours • 8 -13% lifetime risk NF 1 20 -35 y – hard to detect – metastasise widely – poor prognosis • arise in pre-existing plexiform neurofibromas • Diagnostic tool: 18 FDG-PET

• • Glomus tumours Neurological problems Orthopaedic Problems Cardiovascular problems Gastrointestinal problems Psychological problems GENETIC COUNSELLING – 50% risk of passing on the condition to an offspring

SPECIALIST NF 1 CLINICS The multidisciplinary team will consist of a neurologist (adult and paediatric), geneticists (includi • neurosurgery (adult and paediatric) • spinal surgery • plastic surgery • oncology (adult and paediatric) • ophthalmology, neuropsychiatry • respiratory physicians • positron emission tomography (PET) • radiology (musculoskeletal and neuroradiology) • pathology • peripheral nerve surgery • sarcoma units • craniofacial unit • orthopaedic units

• Close collaboration between NF 1 clinicians will facilitate a uniform approach to the diagnosis and management of NF 1 and its complications • Complex NF 1 service has been nationally commissioned since 2009 • The NF 1 -MPNST MDT should discuss the need for referral to a specialist sarcoma unit

• Aims and objectives of Complex NF 1 service • The overall aim of the service is to provide the highest quality of care to people with Complex Neurofibromatosis Type 1 (NF 1). Specifically the Complex NF 1 service aims to provide: • specialist workup of NF 1 patients with suspected complex complications of the disease. Provision of accurate diagnosis of unusual phenotypes and other diseases that can be mistaken for NF 1 by genetic testing and counselling • co-ordinated care from a specialist multidisciplinary team when NF 1 complications behave differently from the general population • monitoring the risk of NF 1 related malignancy and tumour progression • long term monitoring to evaluate need for surgery e. g. the cervical cord • compression group. • Note: Surgery, chemotherapy and radiotherapy are not covered in the designation of this national service.

NF 2 • NF 2 is an autosomal dominant neurocutaneous disease that is clinically and genetically distinct from NF 1 • Occurs in approximately 1 in 25, 000 individuals • It is caused by inactivating mutations on chromosome 22 q 11. 2 • Characterised by bilateral vestibular schwannomas and • Schwannomas on other cranial, spinal, peripheral and cutaneous nerves

• The nationally commissioned service is for coordinated clinical care of all NF 2 patients and for surgery/radiosurgery of NF 2 related vestibular schwannomas.

NF 2 patients are at risk • • of deafness high possibility of facial palsy visual impairment loss of muscle function leading to immobility

• Management of patients through a specialist service minimises the threat of these disabilities and optimises auditory rehabilitation • The national service ensures that all NF 2 patients benefit from a one-stop clinic at which they could see all the necessary specialists in a co-ordinated fashion.

Service description/care pathway NF 2 • four centres to provide multidisciplinary clinics • Cambridge (11. 2 million; 190 patients) • Guys and St Thomas’ (13. 2 million; 224 patients • Manchester (16. 7 million; 284 patients) • Oxford (9. 6 million; 164 patients)

• The national NF 2 centres are commissioned to offer specialist expertise for the main NF 2 tumours (Vestibular schwannoma, meningiomas, spinal tumours) and • advice regarding management of other complications (ophthalmic and peripheral neuropathy),

hub and spoke model • • • neurosurgical units satellite clinics Birmingham Newcastle Liverpool Plymouth Bristol Sheffield Southampton

Multidisciplinary (MDT) NF 2 clinic • • • • consultant neurologist • paediatric neurologist • neurosurgeons • paediatric neurosurgeon • ENT / skull base surgeons • clinical nurse specialist • neuroradiologist • audiologist • consultant clinical geneticist • plastic surgeon • peripheral nerve surgeon • ophthalmologist • All patients are reviewed at least once a year in the MDT monthly clinic.

From england. nhs. uk • Patients must be managed in line with the specification and care standards. Any deviation from these which has not been approved by NHS England is at the trust’s risk both clinically and financially. It is the trust’s responsibility to inform the commissioners of any such nonapproved deviations on an exceptional basis

Questions • Is there a need for a Bristol based NF 1 service? • As a sarcoma service are we de facto a NF spoke unit for NF 1? • Is there a regional service that looks after NF 1 patients? • Should we tie in with the NF 2 service? • Should we be commissioned?

The Service • • Our service We provide care for children and adults with complex and non complex neurofibromatosis type 1 (NF 1), neurofibromatosis type 2 (NF 2) and schwannomatosis. For information about our children's service, see the Evelina London Children's Hospital website. NF 1, NF 2 and schwannomatosis are inherited conditions that have a major impact on the nervous system and can result in tumour growth. We are the UK's leading centre for complex NF 1, and one of 4 national centres for NF 2. We are an internationally recognised centre for the diagnosis of malignant peripheral nerve sheath tumours in NF 1, using PET/CT with glucose (fluorodeoxyglucose). Our neurofibromatosis specialists work across many areas. See our team page for more information. Our clinical nurse specialists support patients when they come to clinic and are also available to give advice via telephone and email.

Clinical Research • Clinical research • We are committed to the research of neurofibromatosis types 1 and 2, in collaboration with other national and international neurofibromatosis specialists. Current projects include: • improving the diagnosis of malignant peripheral nerve sheath tumours using methionine PET/CT (methionine forms body proteins) • sleep disorders – a significant problem in neurofibromatosis type 1 • optic pathway glioma – we are currently evaluating the best way to diagnose and treat this tumour which can eventually lead to blindness in some patients with neurofibromatosis type 1 • quality of life in neurofibromatosis– we are assessing the impact of complex inherited diseases on quality of life. This will help to evaluate the effect of new treatments.

Support Groups • Support groups • Our clinical nurse specialists and psychologists run neurofibromatosis support groups for our patients and their relatives. The aim of these groups is to inform, educate and promote independence in people with neurofibromatosis.

Useful Websites • The Neuro Foundation website provides patient leaflets about neurofibromatosis types 1 and 2 • The Children's Tumor Foundation • Changing Faces

Referrals • Routine • Emergency • Two week wait

Neurofibromatosis Team Professor Rosalie Ferner Consultant neurologist and national neurofibromatosis lead Dr Shazia Afridi Consultant neurologist and joint lead for NF 2 Simeon Aluko Appointments booking clerk Sarah Cobb Medical secretary Ms Silva Atamian Children's senior orthoptist Dr Sally Barrington Consultant physician Sonia Ciampolini Play specialist Dr Steve Connor Consultant neuroradiologist Shauna Coupar Neurofibromatosis service manager Simon Eccles Consulant craniofacial and plastic surgeon Vanessa Everett Paediatric clinic nurse specialist Vasantha Gowda Consultant children's neurologist Tina Hemblade Matron

Neurofibromatosis Team Professor Christopher Hammond Consultant ophthalmologist Dr Darren Hargrave Consultant children's neuro oncologist Mr Dan Jiang Consultant ENT surgeon Dr Dragana Josifova Consultant clinical geneticist Mr Niall Kirkpatrick Consultant craniofacial and plastic surgeon Dr Karine Lascelles Consultant children's neurologist Dr Guy Leschziner Consultant neurologist Mr Jonathan Lucas Consultant orthopaedic surgeon Mr Anthony Mac. Quillan Consultant peripheral nerve and plastic surgeon Rebecca Mullin Neurofibromatosis physiotherapics Mr Charles Nduka Consultant plastic and reconstructive surgeon Henry Neville Neurofibromatosis coordinator

Neurofibromatosis Team Dr David Pang Consultant in pain medicine Mr Rupert Obholzer Consultant ENT/skull base surgeon Professor Shakeel Saeed Consultant ear, nose and throat (ENT) and skull base surgeon Dr Alistair Santhouse Consultant psychiatrist Dr Angela Swampillai Consultant oncologist Dr Ata Siddiqui Consultant children's neuroradiologist Dr Adam Shaw Consultant clinical geneticist Mary Thomas Deputy clinical nurse specialist (NF 1) Mr Nick Thomas Consultant neurosurgeon Dr Satsuki Thomson Consultant neuroradiologist Jan Tuson Nursing assistant Dr Sanjay Vijayanathan Consultant musculoskeletal radiologist Mr Daniel Walsh Consultant neurosurgeon Dr Victoria Williams Consultant neurologist Sue Wood Clinical nurse specialist (NF 2)

Summary Consultants • • • • Neurologist Physician Neuro-radiologist Craniofacial Surgeon Children’s Neurologist Ophthalmologist Neuro-oncologist Orthopaedic surgeon Peripheral Nerve Surgeon Pain Medicine ENT/Skull Base Psychiatrist Oncologist Children’s Neuroradiologist Clinical Geneticist Neurosurgeon

Specifically the NF 2 service aims • • to improve the quality and quantity of life of NF 2 patients in England • • to increase the number of NF 2 patients with serviceable hearing by appropriate timing of surgery or radiotherapy • • to increase hearing rehabilitation by appropriate implantation of a cochlear or brain stem implant • • to reduce loss of function by avoidance of unnecessary surgery • • to deliver high quality holistic care through a multidisciplinary team including: neurologist, neurosurgeon, clinical geneticist, ENT consultant surgeon, ophthalmologist and specialist nursing care •

• • to provide radiological facilities appropriate to diagnosis and staging of the condition prior to planning treatment • • to provide genetic testing and counselling on mutation types • • to perform appropriate investigations to proceed to surgical treatment options if clinically indicated

• • to provide high quality surgical treatment of patients with NF 2 • • to provide continuous monitoring of risk and governance to ensure that clinical treatment is safe and effective • • to carry out clinical and service audits to ensure highest standards of safety, care and clinical effectiveness.