Autoimmune Encephalopathy

What is autoimmune encephalopathy?

Autoimmune encephalopathy refers to cognitive impairment that is thought to be caused by overactivity of the immune system. A variety of conditions may be viewed collectively as instances of autoimmune encephalopathy. These include:

  • paraneoplastic limbic encephalitis
  • Hashimoto’s encephalopathy
  • neuropsychiatric lupus
  • steroid-responsive encephalopathy with antithyroid antibodies

The common theme among these conditions is the presence of cognitive and other neurologic manifestations that scientists believe results from improper function of a person’s immune system.

What are the symptoms of autoimmune encephalopathy?

Given the varied definitions of autoimmune encephalopathy, it is not surprising that clinical symptoms vary significantly between affected patients.

Clinical symptoms may involve nearly any cognitive dysfunction. Unlike the gradual, insidious onset of symptoms that typically characterizes neurodegenerative diseases such as Alzheimer’s disease, the onset of autoimmune encephalopathy more often occurs over the course of several weeks. Often, patients and families will report a waxing and waning clinical course, where deficits vary periodically.

In addition to cognitive impairments, a wide variety of other neurologic manifestations may occur. These include:

  • Parkinsonism – slowness of movement (bradykinesia), increased rigidity in the arms and/or legs, problems with walking (short stride length or a “magnetic”-like gait)
  • Seizures
  • Weakness or sensory changes affecting one side of the body
  • Problems with speech (dysarthria), swallowing (dysphagia), double vision (diplopia), or other “focal” neurologic symptoms
  • Apraxia (loss of ability to perform learned motor movements
  • Neglect – inattention to visual or sensory stimuli on one side (e.g., ignoring these things on the left side of the body)
  • Myoclonus or tremor
  • Headache

What are risk factors for autoimmune encephalopathy?

The risk factors for autoimmune encephalopathy are not completely known. We recognize that a personal history of another autoimmune disease, such as thyroid disease, rheumatoid arthritis, or lupus, increases a person’s risk. Similarly, a strong family history of autoimmune disease may indicate an increased risk that a person may develop an autoimmune disease.

How is autoimmune encephalopathy diagnosed?

Clinicians have not established a widely accepted diagnostic criteria for autoimmune encephalopathy.

Evaluation of patients with cognitive symptoms always begins with a careful medical history,  physical examination and thorough neurologic examination. If autoimmune encephalopathy is suspected, laboratory tests can determine the presence of antibodies known to be associated with autoimmune encephalopathy. Some antibodies, such as the voltage-gated potassium channel (VGKC) antibody, appear to have a direct effect on nerve cells (neurons). Others, such as the thyroid peroxidase (TPO) antibody, appear to serve more as markers of a person’s tendency toward autoimmunity, but have no known direct effect inside the central nervous system.

Cerebrospinal fluid, which can reveal the presence of inflammation, may be collected. Neuroimaging, typically a brain MRI or CT scan, is typically performed and may reveal regions of signal abnormality.

Electroencphalography (EEG) is often utilized to look for evidence of epileptiform discharges (uncontrolled electrical activity in the brain). EEG can also serve a role in documenting clinical response to treatment in some patients. Structural neuroimaging is also important to exclude other possible causes of cognitive function (such as stroke). In some cases, brain FDG-PET or SPECT imaging may provide evidence to support the diagnosis.

What further evaluation is typically recommended?

Laboratory evaluation for patients with autoimmune encephalopathy focuses on medical conditions that have a known association with autoimmunity. Depending on which antibodies are detected, further testing may be recommended.

In people who have antithyroid antibodies, screening for thyroid function should be performed and repeated annually. We also recommend screening for vitamin B12 deficiency.

Some antibodies, referred to as paraneoplastic antibodies, have an association with cancer. Some antibodies have a very strong association with a specific type of cancer (for example, small cell lung cancer), while other antibodies have a weaker association with malignancy and may represent an association with a variety of different types of cancer. If one or more paraneolastic antibodies is detected in the blood, age- and gender-appropriate screening for cancer is performed, generally in collaboration with a person’s primary care physician. When antibodies have a strong association with malignancy, this screening may be repeated periodically.

What treatments exist for autoimmune encephalopathy?

The optimal course of treatment for autoimmune encephalopathy has not been established. Given the central role of the body’s immune system in the condition, most treatments have been directed at modulating the function of the immune system.

Corticosteroids have been one of the most frequently studied interventions for autoimmune encephalopathy. These are typically administered intravenously for a short period of time, although the exact dosing and duration have not been well established. In patients with incomplete response to corticosteroids, intravenous immunoglobulin (IVIg) or plasmapheresis may be considered as a further course of treatment.

As alluded to above, these treatments modulate the function of the immune system. Patients are asked to return to the clinic for an initial follow-up to gauge whether their symptoms have responded in a positive way from such treatments, and for periodic re-assessments thereafter. If symptoms return, re-treatment with immune-modulating medications is instituted. If relapses are common, or if the patient’s response is incomplete, a longer-term course of treatment with medicines that suppress the immune system, such as cyclophosphamide, mycophenolate mofetil, methotrexate or azathioprine, may be considered after careful discussion of potential risks associated with these medicines.

If a malignancy has been identified, a referral is made for a more definitive diagnosis and treatment of the malignancy.