Lupus and the Brain

It is estimated that up to 75% of individuals with lupus experience symptoms related to the brain. While it is unclear what directly causes these symptoms, researchers agree that this is an area for continued research.

 

 

Introduction

When an individual has lupus, the brain can become just as vulnerable to the disease as any other part of the body. Brain involvement can be due to lupus itself or because of an overlap condition such as antiphospholipid syndromeand its inherent blood clotting issues. Whenever lupus affects the brain or any part of the central nervous system (CNS), it is a condition called neuropsychiatric SLE (NPSLE).

NPSLE can manifest in various ways, some more seriously than others. It is important for individuals with lupus to understand the symptoms and what to look out for in order to promptly communicate changes in health to a healthcare practitioner. A practitioner can properly diagnose these conditions and adjust current treatment plans in order to effectively treat the symptoms as soon as possible.

Anatomy of the Brain and its Role in the Central Nervous System (CNS)

In order to better understand what may be happening in the brain when an individual has lupus, it helps to have a general understanding of the parts of the brain and its role in the central nervous system.

The brain is made up of many parts; here are the most important ones for understanding it while living with lupus:

  • The Cerebrum: The cerebrum is the largest, most complex part of the brain. It is responsible for enabling us to think, emote, perceive our senses, remember and create memories, solve problems and to voluntarily move our skeletal muscles. Each side of the cerebellum also has particular roles, where the right hemisphere tends to help us create and understand in the abstract, while the left side focuses more on thinking logically and on language (hearing and speaking it).
  • The Cerebellum: Lying toward the bottom and back of the brain, the cerebellum helps us coordinate our skeletal muscles so that we don’t have to consciously think about them as we move and maintain balance.
  • The Brain Stem: Resting in front the cerebellum and at the bottom of the cerebrum, the brain stem is the gateway between the spinal column and the rest of the brain and helps us control basic life functions such as breathing, heart rate, blood pressure, sleeping, maintaining body temperature and other autonomic (involuntary) duties.
  • The Hypothalamus: About the size of an almond, the hypothalamus is a primary link between the rest of the brain and the release of important hormones to the blood. Sweating in response to heat and shivering in response to cold means the hypothalamus is doing its job of regulating our body temperature.  It also controls the how the pituitary gland functions.
  • The Pituitary Gland: About the size of a pea, the pituitary gland produces and releases many hormones, including those humans need to grow. It also helps to control the amount of sugar and water in our bodies.

Together, the brain and spinal cord form the CNS. The brain is responsible for interpreting what we see, hear, smell, touch and taste. It is also responsible for regulating how our internal organs respond and react to changes and stimuli in order to maintain homeostasis – though it does not control everything. The brain relies on the spinal cord as the “pathway” for information to flow in order to interpret information when things are not right. If for some reason that pathway is disrupted, the brain cannot do its job.

What are the symptoms of brain involvement in lupus?

The symptoms of brain involvement often coincide with symptoms of a lupus flare. Typically, once the flare is brought under control, NPSLE symptoms will subside.

Some of the most common symptoms of NPSLE include:

  • Headaches and migraines: Though rarely due to lupus itself, many individuals will experience headaches and migraines. Interestingly, researchers have concluded that the incident rate for headaches for individuals with lupus may be the same as the general population. Regardless, the pain associated with a headache may be mild or severe and debilitating, even causing vomiting, which can be an added stressor for someone with lupus. Some individuals report seeing flashing lights and changes in vision as well when they experience headaches and migraines.

A number of things may be to blame for a headache. Changes in eyesight and the need for glasses, sinus infections, tension or conditions such as anxiety and depression may lead to headaches and migraines. Sometimes, the medications used to treat lupus or any other medications may potentially cause headaches as a side effect. Headaches and migraines, therefore, are a gray area of NPSLE – they may or may not be directly caused by lupus itself.

  • Mental health and mood changes: Some individuals may experience issues with their mental health and mood.

Depression is the most reported mood disorder for individuals with lupus – it is estimated that up to 65% of these individuals may experience some degree of depression during their lifetime. Typically younger individuals who experience anxiety are at greater risk for becoming depressed.

Up to 40% of individuals with lupus may experience anxiety.

Between 2% to 11% of individuals may experience psychosis, particularly at lupus onset. Once the lupus is brought under control, the psychosis subsides.

  • Cognitive impairment: Known by individuals with lupus as “brain fog,” cognitive impairment can affect memory, focus, speech and movement. It can also cause fatigue, sleepiness, confusion and depression. It is estimated that approximately 80% of individuals with lupus will experience brain fog. Symptoms typically go away once lupus is better managed.

Other symptoms of lupus brain involvement may include:

  • Seizures: Between 10% to 20%% of individuals with lupus may experience seizures. Seizures are more common in teenagers with lupus and often occur in the presence of high fever or as an onset symptom of lupus. Once the fever and/or the lupus symptoms are brought under the control, in most cases, the seizures will stop.
  • Spinal cord disease: Though rare, some individuals may experience weakness and the loss of sensation in their legs for no apparent reason.
  • Neuropathy: Neuropathy or peripheral neuropathy is nerve pain and damage that typically occurs in the hands and feet that many individuals with lupus experience.
  • Stroke: Ischemic strokes – strokes caused by sudden blockage to the arteries leading to the brain – is the most common form of stroke that may occur.
  • Demyelination and transverse myelitis: Sometimes, damage to the myelin sheath which surrounds the nerve fibers of the brain and/or spine may occur, though it is unclear why this happens.
  • Chorea: Chorea is a movement disorder that is common in up to 3% of individuals with SLE. An individual with chorea may appear to be restless, fidget or move parts of their body uncontrollably.
  • Aseptic meningitis: Individuals with lupus may be susceptible to aseptic meningitis. Aseptic meningitis occurs when the thin membranes covering the brain and spinal cord (meninges) become inflamed due to fungi, viruses, certain bacteria, or even medications.

What causes brain impairment in lupus?

It is not exactly clear what causes brain involvement in lupus, though scientists believe it could be due to some of the following risk factors:

  • Antiphospholipid syndrome (APS): Researchers have found that individuals with APS are at greater risk for developing blood clots due to an increased risk for developing conditions such as vasculitis and atherosclerosis. This, in turn, can put these individuals at greater risk for stroke or small blood clots in the brain.
  • Inflammation: Scientists studied lupus in mice and found that the cytokine protein interferon-alpha (IFN-α), which can be present with inflammation, is able to “permeate the blood brain barrier to cause changes to the brain.” They also found this may be a “mechanism that directly links inflammation to mental illness.”

Scientists of another study found that the “default mode network” (DMN) – a system of interacting brain regions that is active when someone is focused internally and not externally – can be impaired in the presence of inflammation. Individuals with lupus who suffer from this impairment may experience a lack of focus and the inability to pay attention for long periods of time.

  • Corticosteroids: Studies have shown that approximately 28% of individuals who take corticosteroids may experience mild-to-moderate brain impairment as a result. The more common conditions from short-term corticosteroid use are euphoria and hypomania (low-level mania) while the most common condition from long-term use is depression. Corticosteroids such as prednisone can also put a person at risk for developing severe infections such as aseptic meningitis as mentioned above as it regulates autoimmune activity.
  • Common health conditions: Mild depression, tension or even sinus problems are just a few of the other conditions that may contribute to brain impairment though they may actually not be due to lupus itself.

 

Antibody Profile of Brain Involvement in Lupus

Scientists have identified the presence of the following autoantibodies that may be implicated in NPSLE:

  • Antiphospholipid antibodies: Antiphospholipid antibodies include anti-cardiolipin, anti-ß2-glycoprotein 1 and lupus anticoagulant antibodies. Individuals with SLE who also have these antibodies are twice as likely to develop NPSLE.
  • Anti-N-methyl-D-aspartate receptor antibodies: These antibodies have also been found in individuals with NPSLE.
  • Anti-aquaporin 4 antibodies: These antibodies are found in individuals with lupus with demyelination.
  • Anti-endothelial cell antibodies: Anti-endothelial cell antibodies are found in a majority of individuals with NPSLE.
  • Anti-MAP2 antibodies: There is a 100% correlation between these antibodies and central nervous system diseases.
  • Anti-suprabasin antibodies: These antibodies appear in high amounts in individuals with NPSLE.

Diagnosing and Treating Brain Involvement in Lupus

A neurologist can work within a lupus healthcare team to diagnose and treat the brain or CNS conditions mentioned in this article. They may use the American College of Rheumatology’s nomenclature and definitions for the 19 common symptoms and conditions of NPSLE, though many clinicians and researchers agree that this tool needs to be improved.

Diagnosis:  A practitioner will also use the following tools to diagnose NPSLE:

  • a complete health history;
  • a physical exam;
  • a psychological exam if necessary;
  • a spinal cord function test to check for impairment or injury;
  • blood tests to determine level of lupus disease activity;
  • magnetic resonance imaging (MRI) in order to identify clots or other neurological issues;
  • an electroencephalography (EEG) that tests for brain activity, especially if an individual is experiencing seizures; and/or
  • a lumbar puncture to rule out infection, or hemorrhage between the brain and the membrane covering the brain (subarachnoid).

Treatment:  Depending on the unique way in which NPSLE may manifest in an individual and the trigger, treatment may include the following:

  • anticoagulants, if the individual has APS;
  • a change in a lupus treatment plan if the symptoms have been triggered by a lupus flare;
  • immunosuppressants, such as cyclophosphamide, mycophenolate mofetil and azathioprine, which can significantly help reduce the symptoms of NPSLE;
  • drugs such as triptans (naratriptan, zolmitriptan, sumatriptan) for chronic migraines;
  • over-the-counter medications (ibuprofen, naproxen, acetaminophen) for headaches and pain;
  • anti-seizure medications;
  • other treatments as prescribed depending on the condition.

Scientists are also looking into the efficacy of drugs that block IFN-α receptors (anti-IFNAR) for treating mental illnesses such as anxiety and depression. There is relatively new anti-IFNAR drug (Anifrolumab) that is currently in Phase 3 and has proven effective at treating inflammation and flares.

Coping with NPSLE along with lupus can be stressful, causing anxiety and depression. It is important to consider treatment plans more holistically that can help manage both the physical and emotional toll that having a chronic illness can take. Mental health professionals are available to help individuals more effectively manage the ups and downs of daily life through therapy. Support groups can link individuals who are dealing with the same illnesses together providing solidarity, compassion and understanding. Support systems that include family and friends can provide love and encouragement when spoons are running low.

In Conclusion

Anything that affects the brain can be scary – the first impulse may be to ignore the symptoms and wish them away. While this initial response is entirely understandable, it does not help treat the symptoms and delays relief in the long run. Paying close attention to new and existing symptoms, being proactive and having the courage to acknowledge and attend to changes in health can help healthcare practitioners quickly address the conditions of neuropsychiatric SLE and provide effective treatment.  While brain science is still in its infancy, more is being done every day to understand the complex mechanism of lupus and how it can affect the nervous system

 

References

 

Barraclough, M., McKie, S., Parker, B., Jackson, A., Pemberton, P., Elliott, R., & Bruce, I. (2019). Altered cognitive function in systemic lupus erythematosus and associations with inflammation and functional and structural brain changes. Annals of Rheumatic Diseases. Doi: 10.1136/annrheumdis-2018-214677. Retrieved August 10, 2020 from   https://ard.bmj.com/content/annrheumdis/78/7/934.full.pdf

Hirsch, L. (2019). Your brain & nervous system. KidsHealth. Retrieved August 10, 2020 from  https://kidshealth.org/en/kids/brain.html

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Kivity, S., Agmon-Levin, N., Zandman-Goddard, Chapman, J., & Shoenfeld, Y. (2015). Neuropsychiatric lupus: A mosaic of clinical presentations. BMC Medicine, 13(43). doi: 10.1186/s12916-015-0269-8. Retrieved August 10, 2020 from  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349748/

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McAlpine, K. (14, June 2017). A surprising new link between inflammation and mental illness – and a potential drug to protect the brain. Boston Children’s Hospital. Retrieved August 10, 2020  from https://vector.childrenshospital.org/2017/06/lupus-inflammation-cns-therapy/

Schwartz, N., Stock, A., & Putterman, C. (2019). Neuropsychiatric lupus: New mechanistic insights and future treatment directions. Nature Reviews Rheumatology. doi: 10.1038/s41584-018-0156-8. Retrieved August 10, 2020 from https://file.zhisci.com/upload_oss%2Fpdf%2F2019%2F0008%2F201900084504-cn.pdf

Shih, Y., Ou, Y., Chang, S., & Lin, C. (2019). A challenging case of neuropsychiatric systematic lupus erythematosus with recurrent antiphospholipid-related stroke: A case report and literature review. Neurology International, 11(3). doi: 10.4081/ni.2019.8182. Retrieved August 10, 2020 from https://europepmc.org/article/pmc/pmc6763748

Warrington, T. & Bostwick, M. (2006). Psychiatric adverse effects of corticosteroids. Mayo Clinic Proceedings, 81(10), 1361-1367. Retrieved August 10, 2020 from  https://www.mayoclinicproceedings.org/article/S0025-6196(11)61160-9/pdf

What is the central nervous system? (n.d.). Christopher & Dana Reeve Foundation. Retrieved August 10, 2020 from https://www.christopherreeve.org/living-with-paralysis/health/how-the-spinal-cord-works#:~:text=The%20central%20nervous%20system%20(CNS,of%20control%20over%20body%20movement.

 

Author: Liz Heintz

Liz Heintz is a medical research writer who received her BA in Communications, Advocacy, and Relational Communications from Marylhurst University in Lake Oswego, Oregon. She most recently worked for several years in the healthcare industry. A native of San Francisco, California, Liz now calls the beautiful Pacific Northwest home.

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