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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Neurology

Navigating the Diagnosis: Scans, Spinal Fluid, and Criteria

At a Glance

Autoimmune limbic encephalitis (ALE) is diagnosed using the Graus criteria, which evaluate symptoms, MRI scans, spinal fluid analysis, and EEG results. Crucially, doctors do not need to wait for antibody test results to begin potentially brain-saving treatments like steroids.

Diagnosing autoimmune limbic encephalitis (ALE) is like solving a puzzle. Because its symptoms can look like many other conditions—such as infections, psychiatric illness, or dementia—doctors use a standardized set of rules called the Graus Criteria (2016) to determine how likely it is that the immune system is the cause [1][2].

The Graus Criteria: No Need to Wait for Antibodies

A major misconception is that doctors must wait for an antibody test to officially diagnose and treat ALE. In fact, the 2016 Graus criteria were specifically designed so doctors can diagnose Definite Limbic Encephalitis and start treatment immediately if four key conditions are met [1][3]:

  1. Subacute onset: Rapid onset (under 3 months) of memory loss, seizures, or psychiatric symptoms.
  2. Bilateral MRI findings: MRI showing inflammation in both medial temporal lobes.
  3. Positive CSF or EEG: Spinal fluid showing pleocytosis (elevated white blood cells) OR an EEG showing temporal lobe epileptic activity.
  4. Exclusion of alternatives: Ensuring it isn’t an infection or tumor.

If an antibody is found, the diagnosis is also confirmed as Definite, but a negative or pending antibody panel should not delay treatment if the four clinical criteria above are met [1].

Essential Diagnostic Tests

To gather this evidence, your medical team will perform the “Big Three” tests:

1. Brain MRI (The Visual Map)

Doctors look for T2/FLAIR hyperintensities—areas that appear abnormally “bright” on the scan—specifically in the medial temporal lobes [2][4]. This brightness indicates swelling or inflammation. If the MRI is normal but symptoms are severe, doctors may order a more sensitive FDG-PET scan [5][6].

2. Lumbar Puncture / CSF Analysis (The Fluid Test)

A lumbar puncture (often called a “spinal tap”) collects cerebrospinal fluid (CSF) from the lower back.

  • What to expect: The procedure involves numbing the back and using a thin needle to draw fluid. The most common side effect is a “spinal headache,” which can occur when standing up and typically resolves with rest, fluids, or a “blood patch” if severe.
  • What they look for: Pleocytosis (an increased number of white blood cells) signals inflammation [6][7]. It is critical to test BOTH serum (blood) and CSF for antibodies, as some are only detectable in the spinal fluid [8].

3. EEG (The Electrical Test)

An Electroencephalogram (EEG) measures the brain’s electrical activity. In ALE, it often shows “slowing” or “spikes” in the temporal lobes, a sign of seizure activity or brain dysfunction [9][10].

The Completeness Checklist

Before confirming ALE, doctors must rule out “mimickers.” Use this list to ensure your team has considered these alternatives:

  • [ ] Infections: Have they ruled out Herpes Simplex Virus (HSV) and neurosyphilis? [11][12]
  • [ ] Tumors: Have they ruled out brain tumors like gliomas or lymphomas? [13][14]
  • [ ] Nutritional Deficiencies: Have they checked Vitamin B12 and Thiamine levels?
  • [ ] Metabolic Issues: Have they checked thyroid and kidney function?

Because delay can lead to permanent brain damage, starting immunotherapy (like steroids) as soon as the criteria are met is crucial [15][16].

Common questions in this guide

Do I have to wait for antibody test results to start ALE treatment?
No. According to the Graus criteria, if you meet four specific clinical conditions, doctors can diagnose definite limbic encephalitis and begin treatment immediately. Waiting for antibody test results could dangerously delay your care.
What will an MRI show if I have autoimmune limbic encephalitis?
An MRI often shows abnormal brightness in both medial temporal lobes of the brain. These bright spots, known as T2/FLAIR hyperintensities, indicate swelling and inflammation caused by the immune system.
Why do doctors need to do a spinal tap to diagnose ALE?
A lumbar puncture collects cerebrospinal fluid to check for elevated white blood cells, which signal brain inflammation. It is also essential because certain diagnostic antibodies may only appear in the spinal fluid, not in standard blood tests.
What does an EEG look for in limbic encephalitis?
An EEG measures your brain's electrical activity. In patients with ALE, it frequently shows abnormal 'slowing' or 'spikes' in the temporal lobes, which points to brain dysfunction or underlying seizure activity.
What other conditions mimic autoimmune limbic encephalitis?
Because ALE symptoms look similar to many other illnesses, doctors must rule out alternatives before confirming the diagnosis. Common 'mimickers' include viral infections like Herpes Simplex Virus, brain tumors, severe vitamin deficiencies, and metabolic issues.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which level of the Graus criteria do my current findings meet?
  2. 2.Did my MRI show 'T2/FLAIR hyperintensity' on both sides of the medial temporal lobes?
  3. 3.What did the CSF tests show about inflammation in my brain?
  4. 4.Have we tested both my blood (serum) and spinal fluid (CSF) for antibodies?
  5. 5.What other 'mimickers,' like Herpes Simplex Virus (HSV) or neurosyphilis, have we officially ruled out?
  6. 6.Do my clinical and MRI findings meet the criteria to start steroids now, even before antibody results return?

Questions For You

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References

References (16)
  1. 1

    A clinical approach to diagnosis of autoimmune encephalitis.

    Graus F, Titulaer MJ, Balu R, et al.

    The Lancet. Neurology 2016; (15(4)):391-404.

    PMID: 26906964
  2. 2

    Diagnosing autoimmune limbic encephalitis.

    Budhram A, Leung A, Nicolle MW, Burneo JG

    CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 2019; (191(19)):E529-E534 doi:10.1503/cmaj.181548.

    PMID: 31085562
  3. 3

    Mimics of Autoimmune Encephalitis: Validation of the 2016 Clinical Autoimmune Encephalitis Criteria.

    Van Steenhoven RW, de Vries JM, Bruijstens AL, et al.

    Neurology(R) neuroimmunology & neuroinflammation 2023; (10(6)) doi:10.1212/NXI.0000000000200148.

    PMID: 37582614
  4. 4

    A Case of Febrile Polyphagia With an Underlying Paraneoplastic Limbic Encephalitis.

    João Soares R, Miranda M, Monteiro N, et al.

    Cureus 2023; (15(8)):e42947 doi:10.7759/cureus.42947.

    PMID: 37667691
  5. 5

    Adenylate kinase 5 (AK5) autoimmune encephalitis: Clinical presentations and outcomes in three new patients.

    McKeon-Makki I, McKeon A, Yang B, et al.

    Journal of neuroimmunology 2022; (367()):577861 doi:10.1016/j.jneuroim.2022.577861.

    PMID: 35405429
  6. 6

    Lymphocyte signatures correspond to clinical phenotypes in autoimmune limbic encephalitis.

    Räuber S, Schulte-Mecklenbeck A, Sarink K, et al.

    Brain communications 2025; (7(2)):fcaf156 doi:10.1093/braincomms/fcaf156.

    PMID: 40303600
  7. 7

    Neurosyphilis Presenting as Syndrome of Limbic Encephalitis Mimicking Herpes Simplex Virus Neuro-Infection Diagnosed Using CXCL13 Point-of-Care Assay-Case Report.

    Marešová E, Šutovský S, Štefucová H, et al.

    Brain sciences 2023; (13(3)) doi:10.3390/brainsci13030503.

    PMID: 36979313
  8. 8

    Improving the antibody-based evaluation of autoimmune encephalitis.

    McCracken L, Zhang J, Greene M, et al.

    Neurology(R) neuroimmunology & neuroinflammation 2017; (4(6)):e404 doi:10.1212/NXI.0000000000000404.

    PMID: 29075658
  9. 9

    Temporal lobe epilepsy with GAD antibodies: neurons killed by T cells not by complement membrane attack complex.

    Tröscher AR, Mair KM, Verdú de Juan L, et al.

    Brain : a journal of neurology 2023; (146(4)):1436-1452 doi:10.1093/brain/awac404.

    PMID: 36314080
  10. 10

    Diagnosis and treatment of limbic encephalitis in the cancer patient.

    Kyritsis AP, Markoula S, Alexiou G, et al.

    Future oncology (London, England) 2020; (16(22)):1647-1655 doi:10.2217/fon-2020-0080.

    PMID: 32511017
  11. 11

    Neurosyphilis presenting as autoimmune limbic encephalitis: A case report and literature review.

    Mizoguchi T, Hara M, Nakajima H

    Medicine 2022; (101(33)):e30062 doi:10.1097/MD.0000000000030062.

    PMID: 35984192
  12. 12

    Markedly Elevated IgG Index: A Key to Differentiating Neurosyphilis from Autoimmune Limbic Encephalitis.

    Sanpei Y, Hanazono A, Funasaka M, et al.

    Internal medicine (Tokyo, Japan) 2025; (64(12)):1906-1910 doi:10.2169/internalmedicine.4625-24.

    PMID: 39603625
  13. 13

    Paraneoplastic Limbic Encephalitis Secondary to SCLC on 18F-FDG PET/CT.

    Verçosa AFA, Mota IA, Flamini MEDM, Flamini RC

    Clinical nuclear medicine 2021; (46(6)):494-496 doi:10.1097/RLU.0000000000003628.

    PMID: 33939650
  14. 14

    Ictal piloerection is associated with high-grade glioma and autoimmune encephalitis-Results from a systematic review.

    Tényi D, Bóné B, Horváth R, et al.

    Seizure 2019; (64()):1-5 doi:10.1016/j.seizure.2018.11.009.

    PMID: 30497014
  15. 15

    Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient.

    Cellucci T, Van Mater H, Graus F, et al.

    Neurology(R) neuroimmunology & neuroinflammation 2020; (7(2)) doi:10.1212/NXI.0000000000000663.

    PMID: 31953309
  16. 16

    Autoimmune Encephalitis.

    Jafarpour S, Santoro JD

    Pediatrics in review 2022; (43(4)):198-211 doi:10.1542/pir.2021-005096.

    PMID: 35362030

This page provides educational information on diagnosing autoimmune limbic encephalitis. Always consult your neurologist or healthcare team to interpret your specific MRI scans, spinal fluid tests, and diagnostic results.

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