What is the appropriate diagnosis and treatment approach for a middle-aged woman with a history of autoimmune thyroid disease presenting with symptoms suggestive of Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT)?

Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT)

Diagnostic Approach

SREAT is a diagnosis of exclusion requiring elevated anti-thyroid antibodies, encephalopathy without alternative explanation, and dramatic response to corticosteroids. 1

Clinical Presentation to Recognize

• Neurological manifestations: Seizures (47%), confusion (46%), memory impairment (43%), speech disorders (37%), gait disturbance (27%), and myoclonus 2, 3
• Psychiatric features: Psychosis, persecutory delusions (25%), catatonia, or isolated psychiatric symptoms (10%) 2, 4, 5
• Cognitive dysfunction: Progressive memory impairment (11%) or intermittent cognitive lapses 2, 3
• Thyroid status: Usually euthyroid with normal TSH (median 2 IU/mL), though hypothyroidism may coexist 2, 3

Essential Diagnostic Workup

Serum antibody testing:

• Anti-thyroid peroxidase (anti-TPO) antibodies: positive in 34% as sole antibody, 69% in combination 2
• Anti-thyroglobulin (anti-TG) antibodies: positive in 7% as sole antibody, 69% in combination 2
• Both antibodies should be measured as either can be elevated 2, 4

CSF analysis:

• Often unremarkable but may show elevated protein or IgG4 levels 6
• Anti-TPO antibodies detected in CSF in 19% of cases, anti-TG in 4%, both in 53% 2
• Critical to exclude infectious and inflammatory causes 7

Neuroimaging:

• Brain MRI frequently normal but may show cerebral atrophy or medial temporal lobe changes 6, 4
• MRA/MRV to exclude vascular causes 6

EEG findings:

• Abnormal in 82% of cases: diffuse slowing consistent with encephalopathy (70%) or epileptic activity (14%) 2

Critical exclusions:

• Rule out neuronal surface antibodies (NMDAR, VGKC-complex, LGI1, GAD) as these may coexist and represent the true pathogenic mechanism 1
• Exclude neuropsychiatric lupus in patients with SLE (check anti-dsDNA, complement levels) 6
• Rule out infectious encephalitis, metabolic causes, and malignancy-associated encephalopathy 7, 6

Important Diagnostic Caveat

The high prevalence of thyroid antibodies in the general population means they may be incidental findings. Consider testing for neuronal surface antibodies (NMDAR, VGKC-complex) as these may be the actual pathogenic agents, particularly in cases with atypical features. 1 SREAT should only be diagnosed after excluding these more specific antibody-mediated encephalopathies.

Treatment Algorithm

First-Line Treatment

Initiate high-dose corticosteroids immediately once infection is ruled out by CSF analysis:

• Intravenous methylprednisolone 1-2 mg/kg/day OR pulse dosing at 1g daily for 3-5 days 7, 2
• This was the first-line treatment in 193/203 patients (95%) in the largest case series 2
• Dramatic response to steroids is the hallmark diagnostic feature and confirms the diagnosis 2, 3, 5

Steroid taper:

• Slowly taper over weeks to months after clinical improvement 6, 2
• Monitor for relapse during taper (occurs in 16% of patients) 2

Alternative First-Line Options

For patients with contraindications to steroids:

• IVIG (0.4 g/kg/day for 5 days) in agitated/combative patients or those with bleeding disorders 7
• Plasma exchange (5-10 sessions every other day) for severe hyponatremia or high thromboembolic risk 7, 8

Treatment Response and Monitoring

Expected outcomes:

• 91% of patients show complete or partial neurological response at median 12-month follow-up 2
• Response typically occurs within weeks of initiating corticosteroids 8, 3, 5
• Rapid improvement in symptoms confirms the diagnosis retrospectively 3, 5

Relapse risk factors:

• Patients presenting with initial coma have higher relapse rates (26% vs 13%) 2
• 40 patients (16%) experienced at least one relapse during follow-up 2

Second-Line Treatment

For inadequate response to first-line therapy:

• Add IVIG or plasma exchange if no improvement after initial corticosteroid treatment 7, 2
• Consider rituximab for refractory cases or frequent relapses 7
• Other immunosuppressive agents (azathioprine, mycophenolate) may be used 2

Definitive Treatment Consideration

Total thyroidectomy:

• Reported as definitive treatment in some refractory cases 3
• However, SREAT can develop even after partial thyroidectomy 3
• Reserve for cases with multiple relapses despite immunosuppression 3

Critical Pitfalls to Avoid

Do not delay treatment waiting for antibody confirmation - begin corticosteroids once infection is excluded, as delayed treatment worsens outcomes 7, 2

Do not assume normal thyroid function excludes SREAT - most patients are euthyroid at presentation 2, 3

Do not miss coexisting neuronal surface antibodies - thyroid antibodies may be incidental; test for NMDAR, VGKC-complex, and other specific antibodies 1

Do not discontinue steroids abruptly - taper slowly over weeks to months to prevent relapse 6, 2

In patients with SLE, carefully differentiate from neuropsychiatric lupus - check disease activity markers (anti-dsDNA, complement, leukocyte counts) as both conditions respond to steroids but have different long-term management 6