Biology Insights

Autoimmune Diseases That Can Cause Seizures

Explore the unexpected link between autoimmune conditions and seizures. Understand how to identify and address these immune-mediated neurological events.

By Carol Ferraro

Several autoimmune diseases can cause seizures, ranging from conditions that directly attack brain tissue to systemic disorders whose immune fallout reaches the central nervous system indirectly. The list is longer than most people expect: anti-NMDA receptor encephalitis, LGI1 antibody encephalitis, systemic lupus erythematosus, Hashimoto’s encephalopathy, multiple sclerosis, Rasmussen encephalitis, and others can all provoke seizures through distinct immune-driven pathways. Recognizing the autoimmune origin matters enormously, because these seizures often resist conventional epilepsy drugs and respond instead to treatments that calm the immune system.

How the Immune System Triggers Seizures

In a healthy brain, neurons fire in tightly regulated patterns, with excitatory and inhibitory signals keeping each other in check. Autoimmune diseases disrupt that balance in several ways. Some produce antibodies that bind directly to receptor proteins on neurons, altering how signals pass between cells. Others drive inflammation that damages the blood-brain barrier, the protective lining that normally keeps immune cells and large molecules out of brain tissue. Once that barrier breaks down, serum proteins like albumin and peripheral immune cells flood in, ramping up the excitability of neuronal networks and lowering the threshold for seizure activity. The specific mechanism matters for treatment: a disease that destroys neurons outright calls for a different strategy than one that reversibly pulls receptors off the cell surface.

Anti-NMDA Receptor Encephalitis

This is the autoimmune brain disease most strongly associated with seizures. In a landmark study of 100 patients, 76 experienced seizures, most commonly generalized tonic-clonic events followed by focal seizures. Six patients developed status epilepticus, a prolonged seizure emergency. The disease is caused by antibodies targeting the NMDA receptor, a protein critical for excitatory signaling in the brain. Rather than destroying neurons, these antibodies cause the receptors to be pulled from the cell surface, leading to a state of NMDA receptor hypofunction.

The illness predominantly strikes young adults and children, and it tends to follow a recognizable course. It begins with a flu-like prodrome lasting up to two weeks, then rapidly escalates into psychiatric symptoms and seizures, often followed by a catatonic or unresponsive phase and involuntary movements before slow recovery begins. In many cases, an ovarian teratoma (a type of benign tumor) is the trigger, producing the rogue antibodies. Removing the tumor, when present, is a critical part of treatment.

One of the more unusual features of anti-NMDA receptor encephalitis shows up on brain wave recordings: a pattern called “extreme delta brush,” named for its resemblance to waveforms seen in premature infants. About 30% of patients in one study showed this pattern, which can help clinicians distinguish the disease from other causes of encephalitis.

LGI1 Antibody Encephalitis

LGI1 encephalitis produces one of the most distinctive seizure types in all of neurology. Patients develop frequent, very brief episodes of involuntary tonic or dystonic posturing, typically affecting one arm and the same side of the face. These “faciobrachial motor seizures” can occur dozens of times per day, each lasting only seconds. They are easy to miss or dismiss as a tic or movement disorder, which is a problem because they are often the earliest warning sign. In one study, about three-quarters of patients experienced these seizures before developing the memory loss and confusion of full-blown limbic encephalitis.

The seizure pattern in LGI1 encephalitis can include tonic, clonic, dystonic, and myoclonic components in various combinations, sometimes with additional features like automatisms or sensory symptoms. Unlike anti-NMDA receptor encephalitis, LGI1-related disease involves antibodies that activate the complement system, leading to actual neuronal destruction rather than reversible receptor changes. That makes early recognition and treatment especially important: the longer the immune attack goes unchecked, the more permanent damage accumulates.

Systemic Lupus Erythematosus

Lupus is a systemic autoimmune disease, meaning it attacks many organ systems rather than focusing exclusively on the brain. Still, it reaches the central nervous system in a significant minority of patients. Seizures occur in roughly 2 to 8% of people with lupus, through a combination of direct neuronal damage, injury to brain blood vessels, and immune complex deposition. Patients who carry certain antibodies, particularly antiphospholipid or anti-β2 glycoprotein antibodies, appear more prone to seizures than those who do not.

The overlap between lupus and antiphospholipid syndrome complicates matters further. Antiphospholipid syndrome can occur on its own or alongside lupus, and it raises seizure risk through ischemic events: small strokes or blood-flow disruptions in brain tissue caused by clot-promoting antibodies. In these patients, seizures are often a downstream consequence of cerebrovascular damage rather than direct immune-mediated excitability. Managing them involves not just anti-seizure drugs but also anticoagulation and control of the underlying clotting tendency.

Hashimoto’s Encephalopathy

Hashimoto’s encephalopathy, now more formally called steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is one of the more underdiagnosed autoimmune causes of seizures. The name gives away its defining feature: it responds dramatically to steroid treatment, sometimes within 48 hours. But getting to that diagnosis is the hard part, because the symptoms are maddeningly nonspecific: confusion, personality changes, memory problems, speech difficulties, and seizures can mimic almost any brain disease.

In a review of 251 cases from the medical literature, about 47% of patients experienced seizures, making them one of the most common presenting features alongside confusion and memory impairment. Brain wave recordings were abnormal in 82% of patients, though only 14% showed clear-cut epileptic activity; the majority showed diffuse slowing consistent with a more general brain dysfunction. The diagnosis hinges on finding elevated thyroid antibodies in a patient with unexplained encephalopathy, and it is considered in both adults and children. In pediatric cases, seizure and altered mental status are among the most common reasons for presentation.

Multiple Sclerosis

Multiple sclerosis is not typically thought of as a seizure disorder, but people with MS do have seizures more often than the general population. The leading explanation involves cortical and subcortical demyelination: MS strips the insulating myelin sheath from nerve fibers, and when those lesions occur in or near the brain’s outer cortex, they can create focal zones of abnormal electrical activity. Inflammatory cortical demyelination is found in a substantial proportion of MS patients; one biopsy study identified it in about 38% of patients with early MS, with the majority of those lesions showing immune cell infiltration and active inflammation at the tissue margins.

Seizure risk appears to increase in progressive forms of MS, where cortical damage is more widespread and microglia, the brain’s resident immune cells, are chronically activated. For most MS patients, seizures remain a relatively uncommon complication rather than a defining feature, but they can be the first presenting symptom in some cases, adding to the diagnostic confusion.

Rasmussen Encephalitis

Rasmussen encephalitis is rare, but it is among the most devastating autoimmune seizure disorders. It involves chronic, progressive inflammation confined to one hemisphere of the brain, producing drug-resistant epilepsy alongside worsening neurological and cognitive function over time. A hallmark is epilepsia partialis continua, a form of continuous or near-continuous focal seizure activity that can persist for hours, days, or longer.

The disease overwhelmingly affects children, and because the immune attack is relentlessly one-sided, the ultimate treatment in many cases is hemispherectomy: surgical disconnection or removal of the affected hemisphere. It sounds extreme, and it is, but children’s brains have enough plasticity that the remaining hemisphere can take over many functions, particularly when the surgery is performed early. No immunotherapy has been shown to reliably halt the disease’s progression, though some agents can slow it.

Other Autoimmune Conditions Linked to Seizures

Beyond the major players, several other autoimmune or immune-mediated conditions can produce seizures:

GAD65 Antibody-Associated Epilepsy

GAD65 antibodies deserve their own discussion because they produce a clinical picture quite different from the autoimmune encephalitides described above. Rather than causing acute encephalitis with dramatic psychiatric and neurological symptoms, GAD65 antibodies are associated with chronic, drug-resistant epilepsy that looks outwardly like ordinary epilepsy: isolated seizures without striking MRI or spinal-fluid abnormalities. This makes it particularly sneaky. A patient can go years being treated with standard epilepsy drugs that don’t work, without anyone suspecting an autoimmune cause.

Making matters worse, GAD65-associated epilepsy has a very limited response to immunotherapy. Unlike anti-NMDA receptor encephalitis, where steroids and plasma exchange often produce clear improvement, GAD65 patients may show only temporary benefit or none at all. In some cases, antibody levels drop after treatment but rebound within months. Outcomes from epilepsy surgery have also been unsatisfactory for this group, and researchers are exploring whether direct brain-responsive neurostimulation, a device that detects and interrupts seizure activity in real time, might offer a better path.

Why These Seizures Get Misdiagnosed

Autoimmune encephalitis frequently gets mistaken for a primary psychiatric disorder. When a young adult suddenly develops paranoia, hallucinations, and bizarre behavior, the first assumption is a psychiatric break, not a brain-attacking antibody. Seizures may not appear until days or weeks into the illness, by which point the patient is already in a psychiatric unit. Even when seizures do occur early, they can be written off as panic attacks or conversion disorder. The delay matters: earlier immunotherapy generally leads to better outcomes.

Imaging adds another layer of confusion. Standard MRI is normal in a frustrating number of autoimmune encephalitis cases, particularly in anti-NMDA receptor disease. PET scanning, which measures brain metabolic activity, has proven more sensitive. In one study, PET identified abnormalities in nearly all patients tested during the diagnostic workup, while MRI was abnormal in only about 43%. All five anti-NMDA receptor encephalitis patients in that study had completely normal MRIs but clearly abnormal PET scans, with the most common pattern being reduced metabolism in the parietal and occipital lobes. For clinicians, the takeaway is that a normal MRI should not be taken as reassurance if the clinical picture suggests autoimmune encephalitis.

Treating Autoimmune Seizures

The treatment logic for autoimmune seizures flips the usual epilepsy playbook. In ordinary epilepsy, anti-seizure medications are the backbone, suppressing abnormal electrical activity regardless of its cause. In autoimmune seizures, the immune attack itself is the root problem, so immunotherapy takes center stage and anti-seizure drugs play a supporting role.

First-line immunotherapies include corticosteroids, intravenous immunoglobulin, and plasma exchange. These work reasonably well in many patients, but roughly half or more end up needing second-line treatment with agents like rituximab or cyclophosphamide. Rituximab in particular has shown a meaningful reduction in relapse rates in real-world data from large registries.

Anti-seizure drugs are still used alongside immunotherapy, but their track record in autoimmune epilepsy is uneven. In one study of 50 patients with autoimmune epilepsy, about half achieved seizure freedom, but most of those successes came from immunotherapy rather than anti-seizure drugs alone. Levetiracetam, one of the most commonly prescribed anti-seizure medications, was used in 42 of those patients yet was associated with a 0% seizure-free rate when used without effective immunotherapy. The drugs that did achieve seizure freedom in a small number of patients included carbamazepine, lacosamide, and oxcarbazepine. Anti-NMDA receptor encephalitis appears to respond best to anti-seizure medications among the autoimmune encephalitides, and many patients with that specific diagnosis may not need long-term seizure drugs at all once the immune attack is controlled.

How the Picture Differs in Children

Autoimmune encephalitis affects both children and adults, but the two groups do not look the same. In a multicenter study comparing pediatric and adult presentations, children were significantly more likely to present with psychiatric symptoms, focal seizures or status epilepticus, and sleep disturbances. Anti-NMDA receptor encephalitis was also more common in the pediatric group.

The diagnostic challenge is even steeper in children. Young children cannot articulate psychiatric symptoms the way adults can, so the illness may initially look like a sudden behavioral regression, irritability, or new-onset tantrums. Seizures in a child with rapid behavioral change should always prompt consideration of autoimmune encephalitis, particularly in settings where an infection has been ruled out. The clinical stakes are high: children’s developing brains are vulnerable to prolonged immune-mediated injury, but they also tend to recover more fully than adults when treated early, thanks to greater neural plasticity.

Antibody Testing and What It Can and Cannot Tell You

Testing for the specific antibody is a crucial diagnostic step, but it is not always straightforward. Antibodies against neuronal surface proteins, like NMDA receptors and LGI1, are most reliably detected in cerebrospinal fluid, which requires a lumbar puncture. Blood testing is available and sometimes positive, but false negatives are common, particularly in anti-NMDA receptor encephalitis. A negative blood test does not rule out the disease. Some patients are antibody-negative altogether; in the multicenter study mentioned above, 47 of the 102 patients with autoimmune encephalitis had no identifiable autoantibody. In those cases, clinicians rely on the clinical pattern, brain imaging, EEG findings, and response to immunotherapy to make the diagnosis.

The type of antibody also shapes prognosis and treatment decisions. Antibodies against cell-surface targets (NMDA receptor, LGI1, CASPR2) tend to be more responsive to immunotherapy than antibodies against intracellular targets like GAD65 or the onconeural antibodies seen in paraneoplastic disease. This distinction is not just academic. It directly influences how aggressively clinicians escalate treatment, whether they search for an underlying tumor, and how optimistic the outlook is for seizure control.

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