How is Hashimoto encephalitis diagnosed in a middle‑aged woman with known or suspected autoimmune thyroid disease?

Diagnosis of Hashimoto Encephalitis

Hashimoto encephalitis (also called steroid-responsive encephalopathy associated with autoimmune thyroiditis, or SREAT) is a diagnosis of exclusion requiring three key elements: elevated anti-thyroid antibodies, encephalopathy without alternative explanation, and dramatic response to corticosteroids. 1

Critical First Step: Rule Out Other Autoimmune Encephalitides

The most important diagnostic pitfall is assuming thyroid antibodies are causative—you must first exclude neuronal surface antibodies, as these may coexist and represent the true pathogenic mechanism. 2, 1 Given that thyroid antibodies are present in up to 10-15% of the general population, their presence alone is insufficient for diagnosis. 3

Essential Antibody Testing

Before diagnosing Hashimoto encephalitis, test both serum and CSF for:

• Anti-NMDAR antibodies 4, 1, 5
• Anti-VGKC complex antibodies (including LGI1 and CASPR2) 4, 1, 5
• Anti-GAD antibodies 2, 1

In a recent 13-year retrospective study of 144 patients referred for suspected Hashimoto encephalitis, 73% ultimately received alternative diagnoses, and thyroid antibody titers did not differ between those with true autoimmune CNS disorders versus those with other conditions. 3

Diagnostic Algorithm

Step 1: Confirm Clinical Presentation

Look for subacute onset (weeks to months, not days) of: 2, 1

• Altered consciousness or confusion 6, 7, 8
• Seizures (common presenting feature) 6, 7, 8
• Cognitive dysfunction or behavioral changes 6, 8, 9
• Stroke-like episodes 6, 7, 9
• Myoclonus or tremor 7, 8, 9
• Cerebellar ataxia 6, 8

Patients with true autoimmune CNS disorders more frequently present with subacute symptom onset, seizures, stroke-like episodes, aphasia, and ataxia compared to those with alternative diagnoses. 3

Step 2: Obtain Brain MRI

Brain MRI with or without contrast is essential to identify characteristic patterns and exclude competing diagnoses. 2, 4 However, brain MRI is often normal or shows only nonspecific findings in Hashimoto encephalitis—this is a key distinguishing feature. 6, 8, 9 When abnormal, you may see:

• Diffuse subcortical white matter lesions 8
• Limbic involvement (less common) 8

Abnormal brain MRI was significantly more frequent in patients with true autoimmune CNS disorders (P=0.003). 3

Step 3: Perform Lumbar Puncture

CSF analysis is crucial to establish inflammatory etiology and exclude infectious causes. 2, 4, 5 Send:

• Cell count with differential 4, 5
• Protein (often elevated without pleocytosis) 7, 9
• Glucose 4, 5
• IgG index and oligoclonal bands 2, 4, 5
• Neuronal autoantibodies in CSF 2, 4, 1
• Infectious studies (HSV PCR, bacterial/fungal cultures) 2

CSF inflammatory findings (elevated protein, lymphocytic pleocytosis, elevated IgG index) were significantly more common in patients with autoimmune CNS disorders (P=0.002) and predicted immunotherapy response (P=0.02). 3

Step 4: Obtain EEG

EEG is commonly abnormal in Hashimoto encephalitis, showing diffuse slowing or nonspecific abnormalities. 7, 8, 9 This helps:

• Exclude subclinical status epilepticus 2
• Provide evidence of brain dysfunction when MRI is normal 2
• Support encephalitis over primary psychiatric disorder 2

Abnormal EEG was significantly more frequent in autoimmune CNS patients (P=0.007). 3

Step 5: Check Thyroid Function and Antibodies

Measure:

• TSH, free T4, free T3 (thyroid function is often normal) 6, 8, 9
• Anti-thyroid peroxidase (anti-TPO) antibodies 6, 8, 9
• Anti-thyroglobulin antibodies 2, 6

Most patients with Hashimoto encephalitis are in euthyroid states despite elevated thyroid antibodies. 8

Step 6: Consider Anti-NAE Antibodies

Serum autoantibodies against the NH2-terminal of α-enolase (NAE) are a highly specific diagnostic biomarker for Hashimoto encephalitis, present in approximately 50% of cases. 8 This test is not widely available but can support the diagnosis when positive.

Step 7: Exclude Alternative Diagnoses

Apply the Graus criteria for autoimmune encephalopathy (sensitivity 92%, specificity 100% in distinguishing true autoimmune CNS disorders from alternatives). 3 Rule out:

• Infectious encephalitis (HSV, VZV, HHV6) 2
• Neuropsychiatric lupus (check anti-dsDNA, complement levels) 1
• Functional neurological disorder 3
• Primary psychiatric disorders 3
• Neurodegenerative conditions 3
• Metabolic/toxic encephalopathies 2

Patients with alternative diagnoses more frequently had depressive symptoms (P=0.008), anxiety (P=0.003), and chronic pain (P=0.002) without objective neurological findings. 3

Diagnostic Confirmation

The diagnosis is ultimately confirmed by dramatic clinical response to corticosteroids—this is a defining feature of the condition. 1, 6, 7, 9 Response typically occurs within weeks of initiating treatment. 1

Key Diagnostic Pitfalls

• Do not diagnose Hashimoto encephalitis based solely on elevated thyroid antibodies in the presence of encephalopathy. Thyroid antibodies are common in the general population and may be incidental. 2, 3
• Always test for neuronal surface antibodies before attributing symptoms to thyroid antibodies alone. 2, 1
• Absence of CSF inflammation should prompt reconsideration of the diagnosis. 3
• Normal brain MRI does not exclude the diagnosis but is actually typical. 8, 9