published by nonprofit Johns Hopkins Press
posted in lupus fog on January 10, 2025 by
Updated February 18, 2025
Lupus is an autoimmune disease that can attack the brain, spinal cord, and many other organs. When this occurs, we call it “CNS lupus.” Everyone who has CNS lupus has systemic lupus erythematosus (SLE).
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NOTE: Johns Hopkins University Press, publisher of The Lupus Encyclopedia, is a nonprofit publisher. If you purchase JHUP books, like The Lupus Encyclopedia, you support projects like Project MUSE.
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This article is an adaptation from “The Lupus Encyclopedia,” i.e. it is a shorter, succinct version from the section on CNS lupus. A much more detailed version is found in chapter 13 of The Lupus Encyclopedia.
Anatomically, we divide the nervous system into the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which consists of the nerves leading to and from the CNS. When systemic lupus erythematosus (SLE) affects the nerves, it is referred to as neuropsychiatric systemic lupus erythematosus (NPSLE).
If NPSLE is associated with antiphospholipid antibodies, blood thinners like warfarin and heparin are used to address blood clots from antiphospholipid syndrome. For inflammation-related NPSLE, immunosuppressant drugs are used. In severe cases, cyclophosphamide and high-dose steroids are administered. Other therapies, like plasmapheresis, plasma exchange, and intravenous immunoglobulin (IVIG), may also be considered.
This blog post discusses CNS lupus. For lupus affecting the peripheral nervous system, see my other blog post: lupusencyclopedia.com/lupus-and-the-nervous-system/#pns
When SLE affects the brain (the cerebrum), some doctors refer to it as “lupus cerebritis,” but this term is outdated. “CNS vasculitis” is often used if the inflammation mainly affects blood vessels, though actual blood vessel inflammation is rare. Lupus can also affect the spinal cord. When lupous affects the brain or the spinal cord, it is called CNS lupus.
Meningitis is the inflammation of the meninges, the tissues surrounding the brain and spinal cord. It typically causes headaches, trouble thinking, fever, neck stiffness, and light sensitivity. The most important aspect of meningitis is ensuring it is not due to infection, which can be deadly if not treated immediately with antibiotics. A lumbar puncture (spinal tap) is needed to check for infection or inflammation. If there is no infection, it is called aseptic meningitis. Common causes include viral infections, certain drugs, blood vessel bleeding, and cancer. If these causes are excluded, it is presumed to be due to SLE and treated with immunosuppressants.
This rare SLE problem occurs when the outermost layer of tissue surrounding the brain and spinal cord (called the dura) thickens due to inflammation. Most patients experience headaches, but confusion and cranial neuropathies (damage to the nerves that exit the brain) can also occur. Brain MRI reveals the thickening, and a biopsy is usually done to ensure non-lupus problems are not causing it. SLE pachymeningitis usually responds well to immunosuppressants.
Cerebrovascular disease refers to brain blood vessel problems. CNS lupus due to cerebrovascular disease includes strokes, central venous thrombosis, reversible cerebral vasoconstriction syndrome, and small vessel cerebrovascular disease. All are discussed in this section.
A cerebrovascular accident (CVA), also called a stroke, occurs when blood supply to an area of the brain is lost, causing brain damage. Symptoms include headaches, numbness, weakness, vision loss, difficulty speaking, and incoordination. Strokes cause permanent brain nerve damage, with varying degrees of severity. A transient ischemic attack (TIA), often called a mini-stroke, occurs when stroke symptoms resolve. CVAs and TIAs can result from SLE inflammation, blood clots, bleeding, and hardening of the arteries. Treatment depends on the cause, such as immunosuppressants for inflammation and blood thinners for blood clots.
Cerebral venous thrombosis occurs when blood clots form in the brain’s veins. Symptoms include headaches, nausea, and seizures. Diagnosis is made using brain MRI and a venous angiogram. Treatment usually involves blood thinners and immunosuppressants.
This syndrome causes a “thunderclap headache,” a severe headache that comes on abruptly. TIA, stroke, or seizures may occur. Diagnosis is made based on the presence of a thunderclap headache and typical MRI findings of RCVS. Blood pressure medicines are used to relax the arteries, and symptoms usually resolve over days to weeks.
This refers to damage to the brain’s small blood vessels and is the most common finding on SLE brain MRIs. Small vessel disease is expected as people age, but SLE patients tend to develop these changes at a younger age. Most people with mild, early small vessel disease do not have identifiable problems.
Demyelination is the loss of myelin, the tissue covering nerves that increases the speed of electrical impulses. The main demyelinating disorders in SLE are multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD), aquaporin-4-mediated inflammation, Guillain-Barré syndrome, and chronic inflammatory demyelinating polyradiculoneuropathy. These disorders can cause various neurologic symptoms, including numbness, weakness, and vision problems. Diagnosis involves MRI, lumbar puncture, and blood tests. Treatment includes immunosuppressants, IVIG, and plasmapheresis.
Around 70% of SLE patients experience headaches, typically migraines, tension, or fibromyalgia headaches. These are not due to lupus inflammation and are treated similarly to those in people without SLE.
True lupus headaches from lupus inflammation are rare and typically improve with steroids.
Pseudotumor cerebri, also called idiopathic intracranial hypertension (IIH), is another headache-causing condition due to increased fluid pressure around the brain and spinal cord. Diagnosis involves a physical exam, MRI, or CT scan to rule out cancer. Treatment includes draining cerebrospinal fluid (CSF) and using immunosuppressants, acetazolamide, and rarely, surgery.
Several NPSLE movement disorders exist, with tremors being the most common. Substances like mycophenolate, tacrolimus, voclosporin, antidepressants, caffeine, and smoking are more likely to cause tremors than lupus inflammation. Chorea, a rare movement disorder in adults but more common in pediatric SLE patients, causes sudden, uncontrollable movements of the arms, legs, or head. These episodes often resolve without treatment, but sometimes steroids and neurologic medicines are needed.
Spinal cord inflammation is called myelitis. It causes paralysis and numbness below the damaged area. Lupus myelitis is a medical emergency requiring quick diagnosis and treatment to prevent permanent limb paralysis and loss of bladder and bowel function. Treatment includes high-dose steroids, cyclophosphamide, and plasma exchange, followed by maintenance therapy with immunosuppressants.
NMOSD is a myelitis and optic nerve inflammation caused by aquaporin-4 antibodies. Symptoms include vision problems, weakness, numbness, nausea, vomiting, hiccups, confusion, incoordination, and breathing problems. NMOSD is treated with immunosuppressants, plasma exchange, or FDA-approved NMOSD drugs like eculizumab, inebilizumab, or satralizumab.
Seizures, also called epilepsy, are due to repeated episodes of abnormal electrical brain activity. Symptoms vary widely and can include shaking, hallucinations, and loss of consciousness. Diagnosis involves blood tests, lumbar puncture, brain MRI, and EEG. If SLE is the cause, it is treated with anti-seizure drugs, immunosuppressants, or blood thinners.
Acute confusional state, also called delirium or acute encephalopathy, causes difficulty focusing and responding appropriately. It is caused by brain inflammation during severe SLE flares. Diagnosis involves brain MRI, blood tests, and lumbar puncture. Treatment options include immunosuppressants, IVIG, or plasma exchange.
PRESS is characterized by brain tissue swelling in the posterior brain, as seen on MRI. It is usually reversible with treatment. Symptoms include seizures, headaches, blurred vision, and delirium. Blood pressure control is essential, and treatment may involve stopping medications that cause PRES or using immunosuppressants for lupus brain inflammation.
Anxiety disorder involves excessive worrying, nervousness, decreased appetite, difficulty relaxing, insomnia, fatigue, memory problems, pain, and irritability. Also, panic attacks and phobias may occur. Lupus experts do not believe lupus inflammation causes anxiety. Anxiety-causing substances include thyroid medications, steroids, ADHD drugs, albuterol, phenytoin, alcohol, caffeine, and illicit drugs. Treatment involves anti-anxiety medications, exercise, mindfulness, breathing exercises, psychological counseling, and stopping any drugs that may be causing anxiety.
Cognitive dysfunction refers to problems with memory, attention, problem-solving, understanding language, planning, self-control, judgment, abstract thinking, and personality changes. Mild cognitive impairment, commonly called “lupus fog,” is reported by many lupus patients. Severe memory impairment, like dementia, is uncommon. Cognitive impairment can improve over time. Other potential causes include previous brain injury, thyroid disease, low vitamin B12, depression, anxiety disorder, fibromyalgia, steroids, and lack of sleep. Treatment involves addressing any treatable causes and using strategies to help memory problems.
Mood disorders include depression, mania, and bipolar disorder. Depression in SLE is often related to dealing with a chronic disease, low self-body image, multiple medications, and avoiding sunlight. Depression is underdiagnosed and not treated often enough in SLE. Treatment involves exercise, psychotherapy, and medications. Mania and hypomania, the opposite of depression, cause excessive happiness, energy, moodiness, increased sexual desire, aggressive behavior, and religiosity. Steroids are the most common cause of mania and hypomania in SLE patients. Bipolar disorder involves alternating episodes of depression and mania or hypomania and requires regular medication and psychiatric care.
Lupus psychosis causes disordered thinking, delusions, and hallucinations. It can occur with an acute confusional state. NMDA-R or anti-ribosomal-P antibodies may be present in some psychotic patients. Doctors treat lupus psychosis with immunosuppressants and psychiatric medications. Importantly, illicit drugs can also cause psychosis and must be considered as possible causes.
Read more in The Lupus Encyclopedia, edition 2
Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia
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Hello: I am about to begin IVIG treatments for lupus induced peripheral neuropathy. I do not find very much info about how successful this treatment is. My Rheumatologist said neuropathy is hard to target. The burning pain in feet and legs is constant. I’m so hopeful but afraid to be too optimistic. Have you had any of your patients get the IVIG and actually reverse the neuropathy? Thx
Patty: I have used it with great success in several patients with dysautonomia, but it is also used for polyneuropathy as well. Below are some links:
https://pmc.ncbi.nlm.nih.gov/articles/PMC4357394/#b1
https://www.lupusencyclopedia.com/intravenous-immunoglobulin-ivig-for-lupus/
Good luck, I hope it works well for you,
Donald Thomas, MD
In the past, I have been diagnosed with Lupus Cerebritis. (Older definition)
My Immune Neurologist calls it Sjögren’s Disease with MS-like Demyelination. I only have a SS-A (RO) antibody. No Lupus Antibodies. At this time, ANA is negative.
I have had a couple of strokes, not coming from the heart, multiple TIAs.
I am on Rituxan 1000mg. x 2 weeks every six months and IVIG monthly infusion.
My Rheumatologist retired and the new Rheumatologist wants me on Cell Cept. Immune Neurologist wants me on Rituxan.
Do you have a thought on my dilemma?
Thank you so much for your time and consideration.
Judy Terrean
Judy: If you had any new episodes while on rituximab, I can understand your rheumatologist wanting to consider the possibility of mycophenolic acid (CellCept). Also, we rheumatologists are more nervous about rituximab since the COVID-19 epidemic since rituximab greatly reduces response rates to vaccines, and our rituximab patients were repeatedly some of our sickest patients. If you had recurrent episodes on rituximab, another option is rituximab every 4 months instead of every 6 months.
I hope your doctors also considered adding hydroxychloroquine as it reduces stroke risks and increases remission rates in our SLE patients when added to stronger immunosuppressants
Donald Thomas, MD
I have been diagnosed with lupus since 2018 based on blood tests alone – no pain or swelling, rash, or other organ symptoms involved. Just tired, and what I thought was brain fog. However, this “fog” often just feels like my eyes are crossing or like I’m drunk. Is this just fog, or could it be eye related? My field vision tests always come out normal, so it’s not that. I’m sick of feeling this way. I eat healthy, get plenty of sleep, lots of water, exercise, and I’m only on plaquenil for lupus meds…
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