Antibody Prevalence in epilepsy and encephalopathy (APE2) score
A guide to predict the likelihood of neural antibody positivity
Determining whether autoimmunity is the cause of a patient’s epilepsy, encephalopathy, or dementia is essential to pinpointing the diagnosis and choosing the appropriate immune-directed therapy. Predicting autoimmunity based on the patient's symptoms can minimize expense and increase the yield of laboratory testing. The antibody prevalence in epilepsy and encephalopathy (APE2) score calculator is a useful tool to predict the likelihood of neural antibody positivity in patients. By combining multiple variables into an aggregate APE2 score, the tool can quickly assess the likelihood of an autoimmune cause.
Advantages
When used as a screening tool, the APE2 score has considerably higher sensitivity (98%) and comparable specificity (85%) to the autoimmune encephalitis diagnostic criteria. An APE2 score that is greater than or equal to 7 demonstrates 100% specificity for an autoimmune etiology.
- Incorporating the APE2 score can significantly increase the yield of lab testing and minimize overutilization of laboratory resources.
- Because some criteria — including behavioral or neuropsychiatric dysfunction and rapid symptom onset — require clinical interpretation, clinical judgment remains essential. More common disorders should be ruled out before the score is used to guide decision-making.
- Due to diminished prevalence of Faciobrachial dystonic seizures (FBDS) and increased frequency of both MOG-IgG and NMDA-R autoantibodies in pediatric patients, caution is advised when using this tool.
Intended use
The APE2 score calculator is intended to be used for patients with suspected immune-mediated encephalopathy, epilepsy, or dementia to reasonably exclude alternate causes, such as genetic, infections, cancerous, neurodegeneration, and metabolic or toxic encephalopathy.
NOTE: An initial workup including thorough clinical evaluation, electroencephalography (EMG), brain MRI, and cerebrospinal fluid analysis is always recommended.
Instructions
- Review variables and check box (assign point value shown) as applicable to your patient’s symptoms. If the listed symptom is not present, do not check the box.
- Results are calculated automatically based on the marked boxes and include recommended laboratory testing.
- A higher score indicates a greater likelihood of an immune-mediated disorder.
A guide to predict the likelihood of neural antibody positivity in patients with encephalopathy and/or seizures1-2
[sustained atrial tachycardia or bradycardia, orthostatic hypotension (≥20 mm Hg fall in systolic pressure or ≥10 mm Hg fall in diastolic pressure within 3 minutes of quiet standing), hyperhidrosis, persistently labile blood pressure, ventricular tachycardia, cardiac asystole, or gastrointestinal dysmotility]
(rhinorrhea, sore throat, low-grade fever) to be scored in the absence of underlying systemic malignancy within 5 years of neurological symptom onset
(elevated CSF protein >50 mg/dL and/or lymphocytic pleocytosis >5 cells/mcL, if the total number of CSF red blood cell count is <1,000 cells/mcL)
Results
- Result >4: Presence of neural specific antibodies clinically validated to have an association with autoimmune encephalopathy or epilepsy is likely.
- Result <4: Presence of neural-specific antibodies clinically validated to have an association with autoimmune encephalopathy or epilepsy is unlikely.
- What to do next? For scores greater than 4, order our autoimmune/paraneoplastic encephalopathy evaluation (Mayo IDs: ENC2 and ENS2).
Highlights
JoAnne Michael’s symptoms started with dizziness and forgetfulness before down spiraling into severe confusion, crying jags, and brain seizures. ER doctors at her local hospital initially thought she was on drugs. JoAnne, terrified, wondered if she was dying. Luckily, she had a guardian angel by her side: her mother, a retired nurse practitioner, who took her to Mayo Clinic, where the clinical experience and expertise of neurologist Andrew McKeon, M.B., B.Ch., M.D., helped give her a diagnosis and hope for a journey back to health.
Anastasia Zekeridou, M.D., Ph.D., explains how Mayo Clinic Laboratories' updated panels and methodology boost the accuracy and efficiency of testing for three autoimmune neurology biomarkers. Early diagnosis is key to managing debilitating conditions associated with these antibodies.
Divyanshu Dubey, M.B.B.S., explains how Mayo Clinic Laboratories' unique PDE10A and TRIM46 tests facilitate the management of central nervous system disorders triggered by cancers. Early diagnosis and treatment are important for managing disabling neurological symptoms and malignancy.
Antibody against the GABA-A receptor is a biomarker of autoimmune encephalopathy that occurs across the lifespan, and disproportionately affects children. In this test-specific episode of the "Answers From the Lab" podcast, Andrew McKeon, M.B., B.Ch., M.D., explains how Mayo Clinic Laboratories' GABA-A receptor antibody assay aids diagnosis of this serious but treatable condition.
Resources
References
- Dubey D, Kothapalli N, McKeon A, et al. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol. 2018;323:62-72.
- Dubey D, Singh J, Britton JW, et al. Predictive models in the diagnosis and treatment of autoimmune epilepsy. Epilepsia. 2017;58(7):1181-1189. doi:10.1111/epi.13797