Neurosarcoidosis: Sarcoidosis Affecting The Nervous System

Overview

Sarcoidosis is a disease involving inflammation where clusters of white blood cells collect in various regions of the body, known as granulomas. It is a rare condition that is thought to affect 1 in 10,000 individuals in the UK.¹ While granulomas can develop anywhere in the body, 90% of people experience pulmonary sarcoidosis (granulomas which form in the lungs).¹

Granulomas can form in any organ and potential symptoms are varied. In this article, we highlight sarcoidosis affecting nerves, its effect on the body, and the available treatments.

The nervous system 

There are two main branches of the nervous system: central and peripheral (Figure 1). The central nervous system consists of the brain and spinal cord. The peripheral nervous system is formed of nerves elsewhere in the body as well as the cranial nerves that branch out of the central nervous system. 

There are 12 pairs of cranial nerves. Each pair plays its role in allowing us to experience our sensory environment, stimulating muscles to generate movement or a combination of both.²

What is neurosarcoidosis?

Neurosarcoidosis is the clustering of granulomas within the nervous system.³ The cause of neurosarcoidosis is unknown, but problems with the immune system are thought to increase the risk of developing the condition. 

Between 5-15% of individuals with sarcoidosis have granulomas affecting their nervous system, making it much less common than pulmonary sarcoidosis, affecting the lungs.⁴ Sarcoidosis involving only the nervous system is uncommon and 99% of people with neurosarcoidosis have granulomas forming in other organs in the body.⁵

Manifestations of neurosarcoidosis

Since the nervous system is a complex network, with a range of components, there are several ways that neurosarcoidosis can present. The symptoms will depend on where granulomas develop. Neurosarcoidosis tends to occur in people who have active sarcoidosis elsewhere in the body.⁶ 

Cranial neuropathy 

Cranial neuropathy (damage to the cranial nerves) is the most common way neurosarcoidosis presents. The formation of granulomas can disrupt signalling along cranial nerves by applying pressure on them, leading to cranial neuropathy.⁶ Depending on the cranial nerves affected, different symptoms can arise. 

The facial nerve is commonly affected by neurosarcoidosis, resulting in muscle weakness to one side of the face (known as ‘facial palsy’).⁶ Another cranial nerve that tends to be affected by granulomas is the vestibulocochlear nerve, responsible for maintaining balance and hearing in healthy individuals.⁶

When there is disruption to signalling along multiple cranial nerves, as seen with symptoms like facial droop and loss of balance, the possibility of neurosarcoidosis should be raised.⁷

Meningitis 

In more serious cases, neurosarcoidosis could cause the onset of meningitis. This is inflammation involving the inner lining (leptomeningitis) or outer lining (pachymeningitis) of the brain and spinal cord.⁷

Depending on the severity of swelling, meningitis can trigger a whole host of symptoms, including:³

• Headaches 
• Drowsiness
• Slowness of thinking or ‘brain fog’
• Seizures 

Small fibre neuropathy 

Small fibre neuropathy occurs when there is damage to nerves in the periphery. In healthy individuals, these nerves are mainly responsible for detecting pain and temperature.⁸ Some of these nerves have a protective surrounding layer that acts as an insulator, to increase the speed of signalling, known as the myelin sheath. 

When granulomas form in the peripheral nervous system, they can damage the myelin sheath thereby disrupting signalling.⁹ This can lead to symptoms that worsen during the night or when resting, such as:⁸

• Numbness
• Pins and needles 
• Burning sensation

Diagnosis 

Diagnosing neurosarcoidosis is very dependent on your presenting symptoms and diagnosis can be challenging. In theory, a successful biopsy of the growth would decide whether it is a sarcoid granuloma. 

However, biopsies are invasive and can be especially risky in difficult to access areas like the brain. Alternative methods of diagnosis are therefore preferred initially, such as lumbar puncture and brain imaging.

Lumbar puncture 

Lumbar puncture involves inserting a needle between the bones of the lower spine (vertebrae) to take a sample of cerebrospinal fluid (CSF) (Figure 2). This fluid allows the brain and spinal cord to float, thereby reducing their weight.¹⁰ CSF also acts as a shock-absorber to protect the brain and spinal cord from dangerous impacts.¹⁰

In a healthy individual, CSF contains a balance of sugars, proteins, fats and electrolytes.¹⁰ In individuals with neurosarcoidosis, CSF may be abnormal and show, for example, high levels of protein or angiotensin-converting enzyme (ACE).⁷ In up to 50% of cases of neurosarcoidosis, ACE levels in the blood are similarly raised.⁵ 

Abnormal CSF findings can be seen in other conditions so lumbar puncture is usually performed in conjunction with imaging techniques such as MRI. Lumbar puncture can however be a useful tool to monitor the status of neurosarcoidosis over time.⁷

Neuroimaging

Magnetic resonance imaging (MRI) is an imaging technique that is commonly used to help diagnose neurosarcoidosis.⁵ While MRIs are able to detect signs of neurosarcoidosis, they are not specific enough to diagnose the condition alone. Therefore, MRI is used alongside specialist assessment and other diagnostic techniques for a more complete picture.⁵

Treatment

Due to wide variation in the symptoms of neurosarcoidosis, treatment programmes are individualised to suit your specific needs. Medication for neurosarcoidosis aims to target granulomas and help reduce symptoms, ultimately to improve your quality of life.⁷

In some cases, sarcoidosis does not need treatment and goes away on its own.¹ However, not treating granulomas in the nervous system increases the risk of complications. In most cases, therefore, individuals with neurosarcoidosis tend to benefit from treatment. 

Steroids

Glucocorticoids are generally the first-line treatment for neurosarcoidosis. They are a type of steroid that works to rapidly reduce inflammation in the nervous system by changing how the body reacts to abnormal signals.⁷

Prednisolone is a glucocorticoid that is used to treat neurosarcoidosis by targeting the formation of granulomas.⁷ Prednisolone is normally given in a higher dose initially, after which the dose is gradually tapered. This reduces the chances of you withdrawing from steroid treatment.⁶

Immunosuppressive drugs

The goal of using specialised immunosuppressive drugs is to prevent the formation of granulomas that would otherwise develop due to inflammation. When steroid treatments are not working, ‘steroid-sparing’ drugs can be used – for instance, ​​methotrexate.⁷

This acts by slowing the growth of specific cells in the body to lower the sensitivity of the immune system.¹¹ In some cases, methotrexate is used alongside prednisolone for treatment of neurosarcoidosis so that a lower steroid dose can be given.¹²

Summary 

The formation of granulomas in the nervous system can severely impact on quality of life for patients with sarcoidosis. Although rare, sarcoidosis affecting nerves in the body can lead to complications. The majority of people who are diagnosed with neurosarcoidosis respond well to available treatment and, generally, the earlier the condition is diagnosed and treated, the greater the chance of a full recovery.