Neurofibromatosis Treatment Options

Introduction

Neurofibromatosis (NF) is a genetic condition where tumours grow in both the nervous system (nerve tissues like the brain, spinal cord, and nerves throughout the body) and the skin. There are three types of NF: NF1, NF2 and schwannomatosis (SWN). Each type is caused by different gene mutations. Right now, there's no known way to stop or cure this disease.^1,2

In this article, we'll talk about the different types of NF, treatment options and the importance of multidisciplinary care to help patients cope with the disease.

Types of neurofibromatosis

NF1

Neurofibromatosis type 1, also known as von Recklinghausen disease, is the most common type of neurofibromatosis, making up 96% of cases.¹ While it's inherited in an autosomal dominant pattern, meaning it can be passed from one generation to the next, about half of the cases are due to new mutations in the NF1 gene, which affects a protein called neurofibromin. This leads to the growth of tumours on neurons. 

People with NF1 may have:^1,2,3

• Brown skin patches called café-au-lait spots
• Freckling in skin folds 
• Visible lumps under the skin called neurofibromas
• Small nodules on the iris of the eye.

The symptoms of NF1 can vary widely among individuals. Some may have a mild form of the condition with few complications, while others may experience more severe symptoms. In some cases, the condition may only affect certain parts of the body, known as segmental NF1, due to changes in the NF1 gene happening only in some cells. If the symptoms affect the entire body, it's called generalised NF1.³

NF2

Neurofibromatosis type 2 is rare, occurring in only about 3% of cases. NF2 is caused by a mutation in the NF2 gene, which affects a protein called merlin. Merlin acts as a tumour suppressor, helping to control cell growth in the body. When this gene is mutated, tumours can grow more easily. NF2 is usually inherited from a parent, but sometimes the mutation can happen spontaneously after conception, resulting in a mosaic pattern of symptoms.^1,2

This condition is characterised by the growth of tumours on nerves in the brain and spinal cord. These tumours, called vestibular schwannomas, often develop on both sides of the head. NF2 can also lead to other types of tumours like meningiomas. 

People with NF2 may experience:²

• Hearing loss
• Problems with balance
• Skin growths
• Muscle weakness
• Nerve-related issues like facial paralysis and vision problems

Schwannomatosis

Schwannomatosis (SWN) is the rarest type of neurofibromatosis. It's different from the other types because it doesn't usually involve tumours on both sides of the head. Instead, people with SWN have multiple tumours called schwannomas. About 5% of people with SWN may also develop meningioma. SWN is inherited from parents in about 15-20% of cases.²

Most people with SWN are diagnosed around the age of 40. Usually, symptoms start in early adulthood, including:²

• Chronic pain, can be in one spot or spread out and doesn't always match where the tumours are
• Numbness
• Tingling
• Weakness

Fortunately, people with SWN usually have a normal lifespan and unlike some other forms of neurofibromatosis, SWN doesn't typically cause learning disabilities.²

Treatment options for neurofibromatosis

NF1

Since people with NF1 can present various symptoms, there's no one-size-fits-all treatment. The main goal is managing symptoms as they arise.^1,3

Cafe-au-lait spots and neurofibromas are usually harmless and don't need treatment, but larger ones causing symptoms may be removed surgically. However, there's a chance they could come back.^1,3  Besides, there is a type of neurofibroma called plexiform neurofibromas, which can sometimes become cancerous, with long-lasting pain or a rapid increase in size. In such cases, surgery is the usual treatment, but there's a risk of the cancer coming back. Radiation therapy is generally avoided due to the risk of causing more tumours.^1,2,3

Chemotherapy is used for optic gliomas, which are common brain tumours in NF1 patients. There are also some promising treatments being studied, such as a drug called selumetinib, which has been shown to shrink some types of neurofibromas.^2,3

NF2

So far, there isn't an established treatment for NF2 patients. Surgery is often the first choice for treating tumours, but they often come back after surgery. Doctors usually recommend treatment if the patient's brainstem, hearing, or facial nerves are at risk of getting worse.² Radiation therapy is another option, but it can increase the risk of tumours becoming cancerous.^1,2

A medication called bevacizumab has shown promise in treating NF2 tumours by shrinking them and improving hearing in many cases. However, it needs to be given regularly and can cause side effects like high blood pressure.^2,4

Other treatments being explored include drugs that target specific pathways in tumour cells, as well as vaccines and implants to help with hearing loss. While there's still no cure for NF2, ongoing research offers hope for better management of the condition and improved quality of life for those affected.^2,4

Schwannomatosis

Overall, managing schwannomatosis involves a personalised approach focused on controlling symptoms and preserving quality of life. If a schwannoma isn't causing any problems, doctors typically just monitor it.^2,5

Surgery might be considered if a schwannoma is pressing on the spinal cord or causing pain. However, there's no specific medication or therapy approved for treating schwannomatosis itself.^2,5

Radiation therapy should only be used for schwannomas that are growing very large and putting someone's life at risk, especially if they can't be removed with surgery. It's also considered for the rare cases where a schwannoma is cancerous.⁵

Some medications like gabapentin or pregabalin, along with pain relievers and antidepressants, can help ease discomfort.² Research is ongoing to develop new treatments, including drugs that target specific proteins involved in schwannomas. However, these treatments are still being studied and aren't widely available yet.^2,5

Multidisciplinary approach to treatment

Neurofibromatosis is a condition that needs a team of different specialists to manage it well, including:^1,3

• Primary care physicians
• Dermatologists
• Neurologists 
• Ophthalmologists 
• Paediatricians 
• Psychiatrists 
• Psychologists
• Geneticists and genetic counsellors
• Specialty-trained nurses

The main focus is to keep an eye on any tumours that might grow in the brain, as finding them late can be bad for the patient. It's also important for parents with an affected child to get genetic counselling to help them understand how NF runs in the family. Regular check-ups with various specialists are necessary to make sure no new growths or problems are developing in the body.¹

Annual check-ups for children with NF1 should include measuring their:³

• Height, weight and head size 
• Blood pressure
• Nerve or vision changes, that could indicate tumours are growing
• Development
• Learning or behavioural issues

Women with NF1 should start having mammograms at age 30 instead of 40 because of the link between NF1 and breast cancer.³

For NF2, regular brain scans are essential to watch for tumours. Patients should be educated about the disease and its complications, as well as the fact that it's hard to cure completely. Genetic counselling is also helpful before planning a family.⁴

Summary

NF is a genetic condition where tumours grow in both the nervous system and the skin. There are three types: NF1, NF2, and schwannomatosis, each type caused by different gene mutations. Currently, there's no cure available.^1,2

NF1, the most common type, causes various symptoms like skin spots, lumps, and vision problems. However, the symptoms can vary from person to person.^1,2,3 NF2 affects nerves in the brain and spinal cord, leading to hearing loss, balance problems and other issues.^1,2 Schwannomatosis causes multiple tumours but usually doesn't affect lifespan or cause learning disabilities.²

Treatment for NF focuses on managing symptoms and surgery is often used to remove tumours, although they can come back. Chemotherapy and other drugs may also help in certain cases. Regular check-ups with specialists are crucial to monitor for new tumours and prevent complications.^1,2,3,4,5

A team of specialists, including primary care doctors, dermatologists, neurologists, and others, work together to provide comprehensive care. Genetic counselling is important for families affected by NF to understand how the condition runs in the family.^1,3