autoimmune encephalitis Misdiagnosis is common
Autoimmune encephalitis (AE) patients are frequently misdiagnosed. They tend to present with a constellation of neuropsychiatric symptoms that can lead providers to make a primary psychiatric diagnosis, or to believe that there is a drug or alcohol-related cause.
The accurate diagnosis of AE may be hampered by challenges that include:
The accurate diagnosis of AE may be hampered by challenges that include:
- lack of awareness amongst medical professionals
- limited research—the illness is still in its infancy of understanding
- admission to the psych ward, which may delay the search for a neurological cause
- imperfect lab and imaging tools that may lack sensitivity or specificity
- limited scope of antibody tests currently available—many forms of AE lack an identifiable antibody (seronegative)
Standard diagnostic tests
Patients with suspected AE should receive comprehensive testing that includes:
- Bloodwork, including an autoantibody panel
- Lumbar puncture, including an autoantibody panel
- MRI or FDG-PET scan of the brain
- Electroencephalogram (EEG)
Diagnostics by subtype
LIMBIC ENCEPHALITIS
Three criteria must be met to accurately diagnose
Three criteria must be met to accurately diagnose
- Subacute onset (rapid progression of less than 3 months) of short-term memory loss, altered mental status, or psychiatric symptoms
- At least one of the following:
• MRI or EEG features suggestive of encephalitis
• New focal CNS findings
• Unexplained seizures
• CSF pleocytosis (white blood cell count of more than five cells per mm3) - Reasonable exclusion of alternative causes, such as viruses, tumors, nutritional deficiencies, and acute disseminating encephalomyelitis. This list is not intended to be exhaustive, but representative of other issues the treating physician will likely test for.
ANTI-NMDA RECEPTOR ENCEPHALITIS
Anti-NMDA receptor encephalitis is often found in association with a tumor, which must be removed as part of treatment. Tests used to identify the presence of a tumor include CT and MRI scans of the chest, abdomen, and pelvis; as well as whole body FDG-PET scans. Women should also receive an ultrasound of the ovaries, and men should receive an ultrasound of the testes.
Even after removal, tumors can regrow. Therefore, people with anti-NMDA receptor encephalitis should be checked periodically for the presence (or recurrence) of tumors.
In many people with anti-NMDA receptor encephalitis a tumor is never found. This may be because the tumor is too small to detect with imaging techniques, or because it has been destroyed by the immune system, or there is no tumor.
Anti-NMDA receptor encephalitis is often found in association with a tumor, which must be removed as part of treatment. Tests used to identify the presence of a tumor include CT and MRI scans of the chest, abdomen, and pelvis; as well as whole body FDG-PET scans. Women should also receive an ultrasound of the ovaries, and men should receive an ultrasound of the testes.
Even after removal, tumors can regrow. Therefore, people with anti-NMDA receptor encephalitis should be checked periodically for the presence (or recurrence) of tumors.
In many people with anti-NMDA receptor encephalitis a tumor is never found. This may be because the tumor is too small to detect with imaging techniques, or because it has been destroyed by the immune system, or there is no tumor.
SERONEGATIVE AUTOIMMUNE ENCEPHALITIS
In seronegative encephalitis, the antibodies are not detectable in CSF or serum. There is much research to do to continue to identify antibodies that cause AE and to develop commercially available tests to detect them. This isn't just frustrating for the patient and their family, but the treating physicians as well. Without an identifiable antibody, there is often less certainty over the accuracy of the diagnosis and patients suffer delayed treatment as a result.
In seronegative encephalitis, the antibodies are not detectable in CSF or serum. There is much research to do to continue to identify antibodies that cause AE and to develop commercially available tests to detect them. This isn't just frustrating for the patient and their family, but the treating physicians as well. Without an identifiable antibody, there is often less certainty over the accuracy of the diagnosis and patients suffer delayed treatment as a result.
HASHIMOTO'S ENCEPHALITIS
Patients with Hashimoto's encephalitis often have elevated thyroid antibodies such as thyroid peroxidase (TPO) or thyroglobulin (TgAb). These markers assist in diagnosing HE although research hasn't proven the correlation between TPO or TgAb causing neurological damage. HE patients are often highly responsive to steroids; some clinicians use this as evidence in favour of the diagnosis.
Patients with Hashimoto's encephalitis often have elevated thyroid antibodies such as thyroid peroxidase (TPO) or thyroglobulin (TgAb). These markers assist in diagnosing HE although research hasn't proven the correlation between TPO or TgAb causing neurological damage. HE patients are often highly responsive to steroids; some clinicians use this as evidence in favour of the diagnosis.
ANTI-GABAB RECEPTOR ENCEPHALITIS
Approximately half of anti-GABABR patients are diagnosed with small cell lung cancer (SCLC). In rare cases, thymoma, malignant melanoma, breast carcinoma, rectal carcinoma, multiple myeloma, esophageal carcinoma, sarcomatoid carcinoma (SC), and gastric adenocarcinoma have also been found. Additional autoantibodies can sometimes be found, with studies that have reported the co-occurence of antibodies targeting voltage-gated calcium channel (VGCC), glutamic acid decarboxylase 65 (GAD65), and sex determining region Y-box 1 (SOX1).
Approximately half of anti-GABABR patients are diagnosed with small cell lung cancer (SCLC). In rare cases, thymoma, malignant melanoma, breast carcinoma, rectal carcinoma, multiple myeloma, esophageal carcinoma, sarcomatoid carcinoma (SC), and gastric adenocarcinoma have also been found. Additional autoantibodies can sometimes be found, with studies that have reported the co-occurence of antibodies targeting voltage-gated calcium channel (VGCC), glutamic acid decarboxylase 65 (GAD65), and sex determining region Y-box 1 (SOX1).