Neuroendocrine Tumours and Neurological Symptoms

Neuroendocrine Tumours and Neurological Symptoms

Neuroendocrine tumours (NETs) are a diverse group of malignancies that arise from neuroendocrine cells, which are present throughout the body. These cells have dual functions, acting as both nerve cells and hormone-producing cells. 

Due to their wide distribution, NETs can develop in various organs, including the: 

• Pancreas
• Lungs
• Gastrointestinal tract
• Central nervous system (CNS)

Although NETs are relatively rare, their complexity and varied presentations make them particularly challenging to diagnose and manage. The incidence of NETs has been increasing, with recent statistics indicating that about 18 per 100,000 people are diagnosed with these tumours annually in Australia.

Neuroendocrine Cancer Australia (NECA), is dedicated to assisting individuals with neuroendocrine cancer and their families. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients diagnosed with NETs can engage with NECA’s comprehensive support and information by calling the NET nurse line.

NETs secrete hormones and bioactive substances, leading to a range of systemic symptoms, including those affecting the nervous system. The neurological symptoms associated with NETs can result from:

• Hormonal imbalances
• Paraneoplastic syndromes
• Direct tumour metastasis to the CNS

These symptoms can significantly impact a patient’s quality of life, making early recognition and management crucial.

Causes of neurological symptoms in NET patients

Due to the obscure nature of the condition, the neurological symptoms of NETs can be difficult to pin down. Let’s examine some of the most prevalent and well-understood causes of neurological symptoms.

Hormonal imbalances and neurological impact

Hormonal imbalances are a hallmark of NETs, particularly those classified as functional, meaning they actively produce hormones. Excessive secretion of hormones that are common with NETs include: 

• Serotonin – leading to mood disturbances and other cognitive changes
• Insulin – causing hypoglycemia which can affect the brain’s functionality
• Gastrin – leading to neurotoxic effects in the stomach that can influence the brain.

For example, carcinoid syndrome, caused by the overproduction of serotonin, can lead to flushing, diarrhoea, and in some cases, cognitive changes and mood disturbances. 

Insulinomas, a type of NET, can cause hypoglycemia, leading to confusion, dizziness, and even seizures.

Tumour metastasis to the central nervous system (CNS)

Although NETs primarily metastasise to the liver, bones, and lymph nodes, they can also spread to the CNS. When NETs metastasise to the brain or spinal cord, they can cause a range of neurological symptoms depending on the location and size of the metastasis. 

These may include:

• Headaches
• Seizures
• Cognitive impairments
• Focal neurological deficits
• Weakness or sensory loss in specific areas of the body

Impact on the peripheral nervous system

The peripheral nervous system (PNS) can also be affected by NETs, particularly through the development of neuropathy. Neuropathy in NET patients may be due to direct tumour invasion, or side effects of treatment, such as chemotherapy. 

Symptoms typically include numbness:

• Tingling
• Numbness
• Pain in the extremities

These issues can severely affect a patient’s daily functioning and overall quality of life.

Common neurological symptoms

We’ve briefly discussed how NETs can cause certain neurological symptoms depending on how the tumour affects the body. In a more general sense, let’s discuss the most common neurological symptoms that come with NETs.

Headaches

• Common symptom in patients with NETs, particularly those with CNS involvement
• May result from direct tumour pressure and increased intracranial pressure
• Persistent or severe headaches demand further investigation to rule out serious underlying causes

Dizziness and vertigo

• Dizziness and vertigo can occur due to hormonal imbalances, particularly from insulinomas causing hypoglycemia
• Direct tumour effects can also impact the brainstem or inner ear
• Symptoms can be disorienting and impair a patient’s everyday activities

Seizures

• Serious neurological symptoms that can arise from CNS metastasis or severe metabolic disturbances
• Focal or generalised seizures often require long-term anticonvulsant therapy for management

Neuropathy – numbness and tingling

• Symptoms typically include numbness, tingling, and pain, primarily in the hands and feet
• Neuropathy can lead to significant disability, affecting a patient’s ability to walk and perform fine motor tasks

Cognitive impairment

• Cognitive impairment and memory loss can occur due to direct CNS involvement, metabolic disturbances, or as part of a paraneoplastic syndrome
• These cognitive changes can be subtle, such as difficulty concentrating, or more pronounced, such as confusion and memory lapses
• Both can impact a patient’s ability to manage daily tasks and maintain independence

Mood changes and other psychological problems

• Not uncommon in NET patients, particularly those with hormonal imbalances or CNS involvement. 
• Depression, anxiety, irritability, and can complicate the overall management of the disease. 
• Symptoms require a compassionate approach to care, with attention to both the psychological and physical needs of the patient.

Diagnosis and evaluation

Now that we understand the symptoms and their causes, let’s investigate the proper diagnosis and evaluation process for neurological issues that arise with NETs.

Clinical assessment and neurological examination

Clinical assessment and neurological examination are critical in diagnosing neurological symptoms in NET patients. 

This assessment typically involves a detailed history of symptom onset and progression, a physical examination, and neurological tests to assess cognitive function, motor skills, and sensory perception.

Imaging studies (MRI, CT Scans)

Imaging studies such as MRI and CT scans are essential tools in evaluating neurological symptoms in NET patients. 

These imaging modalities help detect the presence of tumours or metastases in the CNS, assess the extent of disease involvement, and guide treatment planning.

Biomarker testing

Biomarker testing, such as measuring hormone levels and tumour markers in the blood, can provide valuable information about the activity of NETs and the presence of hormonal imbalances contributing to neurological symptoms. 

Specific biomarkers, like chromogranin A (CgA), can help in monitoring disease progression and response to treatment.

Management of neurological symptoms

After testing and confirming a diagnosis, we move on to treatment. Let’s examine how best to manage the neurological symptoms of NETs.

Medical treatments

Medical treatment for neurological symptoms in NET patients often involves a combination of symptomatic management and addressing the underlying cause.

• Anticonvulsant medications are commonly prescribed to control seizures in NET patients, particularly those with CNS involvement.
• Neuropathy symptoms can be managed with medications such as gabapentin or pregabalin, which help reduce nerve pain and discomfort.
• Hormone therapy, including somatostatin analogues, can help control symptoms related to hormonal imbalances and reduce the risk of neurological complications.

Surgical interventions

Surgical options may be necessary in cases where tumours are causing significant neurological symptoms.

• Surgical removal of tumours, particularly those affecting the CNS, can alleviate pressure on neural structures and improve neurological function.
• In cases where curative surgery is not possible, palliative procedures, such as debulking or shunt placement, can help manage symptoms and improve quality of life.

Rehabilitation and supportive care

Rehabilitation and supportive care are essential components of managing neurological symptoms in NET patients.

• Physical therapies help patients regain strength, mobility, and independence, particularly after surgery or during the course of illness.
• Cognitive rehabilitation can assist patients in managing memory loss, attention deficits, and other cognitive challenges, improving their ability to cope with daily tasks.

Impact on quality of life

It almost goes without saying that the neurological effects of NETs have a significant impact on a patient’s quality of life. Understanding these effects is the best way to overcome them.

Physical and emotional effects of neurological symptoms

The physical and emotional effects of neurological symptoms can be profound, affecting not only the patient’s quality of life but also their relationships and ability to function independently. 

Pain, fatigue, and cognitive impairments can lead to social isolation, depression, and anxiety.

Strategies for managing neurological symptoms

Effective management strategies include a combination of medical treatments, rehabilitation, and psychological support. 

Patients are encouraged to engage in activities that promote physical and mental health, such as:

• Regular exercise
• Balanced diet
• Adequate rest
• Psychological support
• Counselling
• Support groups

Support resources for patients and families

Support resources are vital for helping patients and families navigate the complexities of NETs. 

At NeuroEndocrine Cancer Australia, we offer a range of services, including NET Nurse support, patient education, and access to clinical trials. We also provide a specialist NET counsellor, who can provide hope and improve outcomes. 

Research and future directions

Research into the neurological aspects of NETs is ongoing, with advances in imaging, biomarker testing, and treatment modalities helping to improve diagnosis and management. Understanding the molecular mechanisms underlying neurological symptoms is key to developing more targeted therapies.

Emerging therapies, including novel drug treatments and immunotherapies, are being explored in clinical trials, offering hope for improved management of neurological symptoms in NET patients. Participation in clinical trials is encouraged for eligible patients, as these studies provide access to cutting-edge treatments and contribute to the advancement of NET care.

Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.