Disease Burden of NF1 with PNs

Kaleb H. Yohay, MD: How do we identify the symptoms of plexiform neurofibromas? This can happen in a number of ways. First a patient will come to us and tell us what symptoms they’re experiencing. Pain is a common symptom associated with plexiform neurofibromas, or change in neurologic function, such as gait. Patients will also come to attention because of cosmetic issues or disfigurement caused by these tumors. Additionally, upon neurologic examination we can sometimes find evidence of focal neurologic dysfunction, which then leads us to look for a previously undiagnosed plexiform neurofibroma. So a regular and careful neurologic examination for adults and kids with NF1 [neurofibromatosis type 1] is really essential.

Plexiform neurofibromas can have many different symptoms, pain being one of the most important. Pain is important for plexiform neurofibromas for a couple of reasons. One is that the tumors themselves can be painful through direct impact on the associated nerves or nearby organs. But they can also cause impairment of function, which then can lead to a cascade of muscle tightness, gait changes, or functional impairments that then lead to compensation and can lead to musculoskeletal pain as a result. Additionally, pain in plexiform neurofibromas can be a signal of the possibility of malignant transformation. There’s a percentage of these tumors that can become a malignant peripheral nerve sheath tumor, and severe pain that wakes patients up at night can be a red flag that there is a possibility of malignant transformation.

In addition to physical pain, plexiform neurofibromas can cause psychological pain as well. These tumors are often very disfiguring and can be limiting in terms of function, which can be very distressing to the patient.

Herbert B. Newton, MD, FAAN: There’s actually a very high psychological and emotional impact on many patients with NF1. Depending on the severity of their phenotype, they can often have issues including pain, weakness, disfigurement, and other severe symptoms. Some of these can impact the patient quite severely. Many of them are depressed or anxious, feel different from other children or adults, often feel inadequate or inferior, and often have a chronic level of frustration from dealing with their disease.

Especially in children with NF1, there can be quite a few learning and behavioral issues. Neurocognitive deficits are highly prevalent in this group. Learning difficulties can include visual spatial and visual motor deficits, language disorders, as well as fine and gross motor deficiencies. Also attention deficit hyperactivity disorder, autism spectrum disorder, behavioral abnormalities, and psychological issues are very prevalent in this population, especially in the pediatric patients.

In terms of the impact of NF1 and plexiform neurofibromas on quality of life, it depends on how severe a person’s disease is, but in the average patient with a symptomatic plexiform tumor, they have many symptoms that can affect quality of life. In particular, pain is very common. Some patients can have large tumors that disfigure their neck, their face, or their body, which could be a problem. Weakness and other motor deficits can be an issue. Then again, we also see cognitive impairment, depression, and anxiety, which is very common.

The impact on caregivers for patients with NF1, especially for the mothers and parents of children with this disease, can be significant. As with other severe chronic diseases like cancer and Alzheimer disease, the caregiver has a lot on their shoulders, and again, this typically falls on the mother or the parents of a child with NF. They also tend to suffer from anxiety, depression, frustration, and stress due to the impact of the disease on their loved one, as well as frustration with how much of their own time, and energy, and resources are spent taking care of that loved one.

In terms of options for support for caregivers, there are many local and regional chapters related to the Neurofibromatosis Foundation. There’s also the national Neurofibromatosis Network in Chicago, Illinois, which is a national level resource. There are also a lot of social media groups focused on NF and being a caretaker, especially on Facebook and those types of media. Then there are many large tertiary medical centers like our own at AdventHealth that have dedicated NF clinics that also have social workers that could help out with the support for the caregivers.