Neurosarcoidosis

What is Neurosarcoidosis?

Sarcoidosis is a disease that affects the whole body and causes the formation of granulomas, or small areas of inflammation. These granulomas typically do not show signs of tissue destruction and can be found in many parts of the body, including the brain and nervous system. While the exact cause of sarcoidosis is not known, it affects anywhere from 5% to 10% of patients, causing neurological complications.

Even though most people with sarcoidosis do not show symptoms, when it affects the nervous system, a condition known as neurosarcoidosis, it can be potentially life-threatening and is usually seen in patients who have the disease throughout their body.

Diagnosing neurosarcoidosis is challenging and is often only concluded after other potential causes are ruled out. Sometimes, a sample from a nerve or muscle may show a granuloma, which can suggest the presence of the disease. Unfortunately, there is no cure for neurosarcoidosis. Typically, patients need long-term treatment with drugs known as corticosteroids, which help to reduce inflammation.

What Causes Neurosarcoidosis?

Sarcoidosis is a condition that experts believe is caused by an overactive immune system. However, the exact cause is still unknown. This overactivity happens when certain immune cells, known as Th1 cells, trigger the release of substances called IL-2 and IFN-gamma. These substances activate other cells called macrophages.

When these macrophages are activated, they cause an inflammation reaction that results in the formation of small clumps of immune cells, called granulomas. While little lumps like these can be harmless, in sarcoidosis, they can cause problems depending on where they form in the body.

When it comes to the nervous system, sarcoidosis can cause several different issues, including:

• Papilledema, which is swelling of your optic disc, the area where the optic nerve enters the back of your eye. This is often due to increased pressure in or around your brain.
• Cranial neuropathies, which are disorders that affect the cranial nerves. These are 12 pairs of nerves that come directly from your brain.
• Peripheral neuropathy, a condition that affects the nerves in your peripheral nervous system, which includes nerves outside of your brain and spinal cord.
• Myopathy and mononeuropathy, which are diseases that affect your muscles and single nerves, respectively.
• Neuropsychiatric disturbances, which are problems that affect both your mental health and nervous system.
• Ataxia, a lack of muscle control during voluntary movements, such as walking or picking up objects.
• Hydrocephalus, which is a buildup of too much cerebrospinal fluid in the brain.

Risk Factors and Frequency for Neurosarcoidosis

Sarcoidosis is a condition that affects a significant number of people, with an estimated 152 to 215 cases per 100,000 individuals. This condition can lead to neurologic complications in 5 to 10% of patients. Evidence suggests that neurosarcoidosis is more prevalent in individuals from African descent. Interestingly, about half of those diagnosed with sarcoidosis also have systemic disease, with 30% to 70% showing neurological signs at the time of diagnosis. However, this condition is surprisingly rare in children.

• Sarcoidosis affects around 152 to 215 people per 100,000 individuals.
• 5 to 10% of those with sarcoidosis will experience neurologic complications.
• Neurosarcoidosis is more common in Africans and people of African descent.
• About half of those with sarcoidosis have systemic disease.
• 30% to 70% show neurological signs at the first diagnosis.
• The condition is rare in children.

Signs and Symptoms of Neurosarcoidosis

Neurosarcoidosis is a condition that involves the nervous system. It can cause many different symptoms, which can vary depending on which part of the nervous system is affected. The symptoms can also change over time and can be multifocal, meaning they can appear in more than one part of the body at a time.

Common symptoms seen in a patient can be related to the brain and the nerves connected to it, as well as the muscles and other parts of the body.

• Cranial mononeuropathy, especially the facial nerve which may mimic Lyme disease.
• Problems with the pituitary gland leading to conditions like neurogenic diabetes insipidus
• Myelopathy or radiculopathy if the spinal cord is affected, which can, in rare cases, lead to a condition called cauda equina polyradiculopathy
• Hydrocephalus, a condition characterized by an accumulation of cerebrospinal fluid within the brain
• Meningitis, an inflammation of the membranes covering the brain and spinal cord
• Carpal tunnel syndrome, a condition that causes numbness, tingling, or weakness in your hand
• Muscle weakness and wasting
• Heerfordt syndrome which is a rare condition that includes facial nerve palsy, enlargement of the parotid gland (one of the salivary glands), inflammation in the front part of the eye, and fever
• Balance and hearing problems caused by damage to the vestibulocochlear nerve.
• Ataxia, a lack of muscle control during voluntary movements such as walking or picking up and objects, if the cerebellum (part of the brain that controls balance and coordination) is involved

During a physical examination, the doctor may also check for swelling of the optic disk (papilledema) and mental changes as the condition can also lead to psychiatric issues. Chronic inflammation of the membranes that cover the brain is also common in neurosarcoidosis.

In some cases, the first sign of neurosarcoidosis could be seizures. This is a serious symptom and often indicates a poor prognosis. The type of seizure could also affect the prognosis, with simple partial or complex partial seizures having a better prognosis compared to generalized seizures that affect the entire brain.

The condition can also cause other symptoms depending on the location of the disease in the brain. These can include:

• Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), which affects water balance in the body
• Changes in appetite
• Excessive sleepiness
• Problems with the autonomic nervous system that controls involuntary actions like heart rate and digestion
• Weight gain
• Impotence
• Galactorrhea, a condition characterized by the excessive secretion of breast milk
• Dementia
• Cognitive impairment

It’s important to remember that the symptoms of neurosarcoidosis are varied and complex, so a thorough evaluation by a healthcare professional is crucial to provide a satisfactory diagnosis and appropriate treatment plan.

Testing for Neurosarcoidosis

If you have sarcoidosis, a condition that causes small patches of swollen tissue to form in your body, and suddenly start to experience issues related to your nervous system, your doctor may consider that you could have a condition called neurosarcoidosis. However, it tends to be more challenging to make this consideration if a patient who doesn’t know they have sarcoidosis starts having neurological issues. Unfortunately, there are no tests that can definitively diagnose neurosarcoidosis.

If your doctor suspects neurosarcoidosis, they’ll look for signs of diseases in the rest of your body as well, like your skin, lymph nodes, and lungs. They may have you undergo an eye exam, a nasal or sinus exam, a chest x-ray, a blood test for a substance called angiotensin-converting enzyme, and, at times, a special type of scan that highlights inflammation in your body which can be used to pinpoint areas to biopsy.

If you’re experiencing peripheral neuropathy, a condition where the nerves that send signals from your brain and spinal cord to the rest of your body are damaged or not working properly, your doctor will also try to rule out other possible causes like high blood sugar, lack of certain vitamins, kidney failure, or exposure to certain toxins. A test that measures how well your small nerve fibers sense changes in temperature may be used.

Your doctor may also use certain tests to help them rule out other conditions like infections or cancer. The preferred imaging test for neurosarcoidosis is usually an MRI with a contrast dye, which helps to enhance the images. It often reveals inflammation or other abnormalities at the base of the brain, especially around the hypothalamus, pituitary stalk, and nearby tissues. Other MRI techniques may help to identify swelling or other changes in nerves, nerve roots, or nerve clusters. Active inflammation and certain masses or fluid buildup may also be visible on an MRI.

Like other conditions that cause inflammation, neurosarcoidosis may cause your Erythrocyte Sedimentation Rate (ESR) to be higher than normal. Test for muscle damage and liver function may also be abnormal, which could suggest that sarcoidosis is affecting your body in a more widespread way. If the area where the hypothalamus and pituitary gland interact is impacted, your doctor may suggest endocrine studies- tests that look at the hormones in your body. In recent years, a specific type of combined PET and CT scan may be used to help the doctor understand which areas of your body are affected by the disease and to identify the best places to biopsy.

If your doctor still isn’t sure whether you have neurosarcoidosis after conducting these tests, they may recommend a biopsy, a procedure where a small tissue sample is taken for further examination. While samples from the meninges (layers of tissue that cover the brain and spinal cord), brain, or spinal cord can be useful, biopsies of the skin, lymph node, and lung are usually preferred because they are lower risk. A biopsy may also be considered if you’re not responding to the treatment for the condition.

Treatment Options for Neurosarcoidosis

Neural sarcoidosis, which is an inflammation in the nerves, is usually treated with medication called corticosteroids. If you have this condition, you could be given a medication like prednisone. Prednisone is used to reduce inflammation and suppress your body’s immune system, which can help manage neural sarcoidosis symptoms like facial nerve palsy or aseptic meningitis. For more severe conditions involving parts of the nervous system (like menigeal which is the membranes that cover the brain and spinal cord, parenchymal mass which is an abnormal tissue growth, or myopathy and neuropathy which are diseases affecting muscles and nerves), you could be treated with prednisone for a longer period.

In cases where your condition is getting worse, medical professionals might administer prednisone intravenously (through a vein) before transitioning you to the oral medication. It’s important that the dosage of this medicine is gradually reduced over time, under the supervision of a medical expert. This is called “tapering”. Generally, you’ll be asked to visit a specialist, a neurologist, frequently every three to six months to ensure the treatment is working effectively.

Immunosuppressants, drugs that reduce the body’s immune response, may also be used to treat neural sarcoidosis. These could include medications like cyclosporine, methotrexate, and cyclophosphamide.

Low dose radiation therapy might be suggested if other treatments aren’t effective. This type of therapy uses radiation to reduce symptoms. Other treatments could involve hormone replacements in case there are hormone deficiencies, antipsychotic drugs for managing behavior control and psychosis, supportive services for dementia, and new methods like treatments that inhibit tumor growth have shown some promise.

What else can Neurosarcoidosis be?

If a person has symptoms of neurosarcoidosis, the doctor would also have to consider other conditions with similar symptoms. These might include:

• Primary brain tumors
• Toxin ingestion
• Neuropathies caused by an excess of specific protein (monoclonal proliferation) or paraproteinemic neuropathy
• Paraneoplastic neuropathy, a nerve disorder related to cancer
• Vitamin deficiency
• Leptomeningeal carcinomatosis, a complication of cancer involving the coverings of the nervous system
• Multiple sclerosis
• Central nervous system (CNS) lymphoma, a type of brain tumor
• Autoimmune conditions like systemic lupus erythematosus, a disease where the body’s immune system attacks its own tissues and organs

To arrive at an accurate diagnosis, the doctor will have to rule out these other possibilities.

What to expect with Neurosarcoidosis

Neurosarcoidosis is a complex condition that can unfold in several ways: it might present as a one-time (monophasic) illness, come and go (relapsing-remitting), or it could progressively worsen over time. It’s unclear what the long-term effects of this disease are.

Usually, patients with weakness or paralysis of the facial nerve (facial nerve palsy) or other single nerve impairments (cranial mononeuropathies) get better over time. However, those with aseptic meningitis (non-infectious inflammation of the brain and spinal cord) or mass lesions in the brain or spinal cord, tend to have a longer recovery period. Symptoms relating to the brain’s control of basic bodily functions (hypothalamic vegetative symptoms), rarely go away fully, although they might improve with treatment.

Conditions involving brain dysfunction or blood vessel disease (encephalopathy/vasculopathy) can have a course where symptoms come and go, typically with worsening over time. Hydrocephalus, a condition where fluid builds up in the brain, might not cause any symptoms, or it can rapidly worsen. Facial paralysis usually improves over 4-6 weeks. Vision issues due to nerve damage (optic neuropathy) might improve over a few weeks, but in some cases, it can lead to blindness.

Peripheral neuropathy (damage to nerves outside the brain and spinal cord) and myopathy (muscle disease) can sometimes improve, but typically, the course is long-term and progressively gets worse.