What are Schwannomas?

In order to understand schwannomatosis as a condition, it is important to first establish what schwannomas are, and how they form. Schwannomas are tumours that are composed of Schwann cells and are attached to either peripheral nerves or nerve roots.¹ In most cases these tumours are benign, meaning they are non-cancerous and will not spread beyond the nervous system, but in some cases, cancer can develop from schwannomas.² The tumours are formed by an overproliferation of Schwann cells, which are the cells responsible for peripheral nerve formation and maintaining the myelin sheath.³ The myelin sheath is essential for rapid nerve conduction for motor, sensory and cognitive function.⁴ When the structure of the myelin is compromised, it can lead to loss of motor function in parts of the body, vision problems and numbness or tingling, which is observed in Multiple Sclerosis (MS) patients, due to the demyelination of their nervous system.⁵

What is Schwannomatosis? 

Schwannomas can occur due to a variety of reasons and as such, their very presence is not an automatic diagnosis of schwannomatosis, most commonly schwannoma formation is benign and not indicative of a wider nervous condition.¹ What separates schwannomatosis as a nervous condition from the spontaneous development of schwannomas is that individuals with the former have a genetic predisposition to the development of schwannomas, meaning they have inherited a defective gene which makes them more susceptible to the condition occurring.⁶ This means schwannomatosis is actually classified as a subtype of neurofibromatosis (NF), but it is distinct from the other subtypes in that it lacks the vestibular tumours which are found in individuals with NF type 2 (NF2).⁷

What are the Symptoms of Schwannomatosis?

A clinical review of 87 patients with schwannomatosis at a general hospital between 1995-2011 found that the majority of patients suffered from chronic pain, including migraines due to the condition. Many patients also reported experiencing depression and anxiety, likely attributable to the impact on their quality of life stemming from the chronic pain. Furthermore, after undergoing medical intervention, most patients did not become completely pain-free.⁸ In general, the risk of cancer developing as a result of schwannomatosis is low, but other research has indicated that if individuals with the disorder also exhibit a SWitch/Sucrose Non Fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) gene mutation, they are at increased risk of developing malignant peripheral nerve sheath tumours (MPNST), which is a form of cancer with a poor 5-year survival rate.^9,10 Regardless of whether this occurs or not, schwannomatosis is an extremely painful condition to endure and as such, it is important to discuss what potential treatment options are available to those affected.

What are the Treatment Options for Schwannomatosis? 

Surgery

Firstly it is important to note that treatment for schwannomatosis is symptom-oriented, meaning there is no standard treatment plan applicable to all diagnosed, and instead, intervention should be tailored based on the nature of the condition, and the health and desires of the patient. In the case of surgery, it is opted for in asymptomatic patients who have schwannomas impacting their spinal cord, and it also can be used for patients who exhibit pain due to their schwannomas growing too big.¹¹ In patients with segmental schwannomatosis, which refers to those with multiple schwannomas that occur in only one limb or less than continuous segments of the spine, surgery is an effective option in mitigating the pain related to the condition.¹² 

However, the recurrence or systematic formation of new tumours remains a strong possibility following surgical treatment, as too does the development of a neurological deficit at an increased rate, but this is generally transient and disappears a month after surgery.¹³

Radiotherapy

In instances where tumours grow so large that they are deemed inoperable, or malignant tumours have developed (in cases such as MPNST), radiotherapy can be used to shrink the size of the tumours.¹¹ Research has indicated that for benign spinal schwannomas, stereotactic body radiation therapy (SBRT), which is a high-dose, localised kind of radiotherapy, is effective in controlling the size of the schwannomas and helps manage the symptoms associated with the disease.¹⁴

However, there remains a concern in treating patients with a genetic predisposition for the development of tumours with radiotherapy for benign tumours, and a study of 277 NF2 patients found that there was a 6% increased risk, 20 years post-treatment of developing malignant tumours following radiation therapy, compared to NF2 patients who had not undergone the treatment.¹⁵ As such, it is recommended that radiotherapy should not be used as a first-line treatment of benign schwannomas and that the potential risk of radiotherapy isb made clear to patients. Furthermore, there exist other factors to take into account when deciding on this treatment such as the age of the patient, whether the tumours will impact the patient's hearing and balance and the treatment plan for residual tumours following radiotherapy.

Psychological Intervention

As mentioned previously, the chronic pain and lifestyle changes schwannomatosis can cause patients can be extremely distressing to their mental health, with patients frequently reporting experiences of anxiety and depression.⁸ Therefore, it is important to recognise the holistic needs of the patient that extend beyond the site and size of the tumours, which is why many propose part of their treatment plan also involving a psychological intervention.¹⁶ 

One such intervention that has been trialled to good measure in schwannomatosis patients is an NF-adapted, relaxation response resiliency program (3RP).¹⁷ The 3RP is a patient-focused, 8-week program which was originally envisioned to provide individuals with the tools needed to improve their responses to chronic stress and decrease their behavioural, cognitive, emotional and psychological suffering.¹⁸ When the program was trialled in schwannomatosis and other NF patients, it was found to be effective overall in improving satisfaction with life, resiliency, mindfulness and post-traumatic growth; and it also had significantly positive effects on decreasing depression, worry and stress in patients.¹⁷

Surveillance

Lastly, upon diagnosis with schwannomatosis, one treatment option is to simply wait, survey and decide in the future whether further treatment is needed. This approach is known as surveillance and it is an equally valid option for many patients for a number of reasons. Firstly, as noted in regards to the increased likelihood of malignancy deriving from radiotherapy-treated NF2 patients, sometimes the potential implications of treatment can result in further problems, and while this might not be as severe for all treatments available, they all still come with their unique risk.¹⁵ For example, routinely exposing patients to MRI scans to pinpoint their schwannomas may be more damaging than the schwannomas themselves.¹⁶ Also, given the increase in genetic panel testing, many individuals may be informed that they are predisposed to schwannomatosis, but they may indeed never develop any symptoms, so a wait-and-see approach may be of more value in such cases.¹⁹

Summary

In summary, schwannomatosis is a genetic condition which affects the nervous system due to the development of schwannomas, (often) benign tumours composed of Schwann cells. Schwann cells are essential for nerve formation and maintaining the myelination of the axons, ensuring proper nervous signal conduction. Schwannomatosis is classified as a subtype of the group of genetic disorders known as neurofibromatosis, and it is distinct in that it lacks vestibular tumours. 

These tumours can cause a great deal of pain for patients with the disease, which is often chronic and this can lead to long-term suffering and an astute psychological impact. Differences in the way the disease manifests require different approaches for its treatment, surveillance and management.

One such option is surgery, which can be selected based on the size of the tumour or its proximity to the spinal cord. This option has proven to be effective in managing the pain of the condition, however, schwannomas often recur following it, so a judgement should be made based on the risk associated with the intervention.

Another effective but potentially risky treatment option is radiotherapy. This may be the only option available to individuals who go on to develop malignant peripheral nerve sheath tumours or other such malignancies but for those with strictly benign tumours, it can be effective in shrinking their size; but it also puts individuals at increased risk of malignancy developing in the future.

Due to the chronic pain and difficulties in life, this condition can bring about, it is worth considering the psychological impact the disease can have, and as such, react accordingly with treatment options aimed at helping them deal with stress and negative emotions. The relaxation response resiliency program has shown potential in this regard.

Equally in some cases, the best option may be to wait to see how the condition develops before going forward with a risky intervention, especially in mild cases of the disease.