What is the diagnosis and treatment for Hashimoto's (Hashimoto's Thyroiditis) Encephalopathy?

Hashimoto's Encephalopathy: Diagnosis and Treatment

Hashimoto's Encephalopathy (HE), also known as Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT), is a rare but treatable neurological disorder characterized by elevated anti-thyroid antibodies and diverse neurological manifestations that respond well to immunosuppressive therapy.

Diagnostic Criteria

The diagnosis of Hashimoto's Encephalopathy requires:

1. Neurological symptoms affecting cerebrum and/or cerebellum
2. Elevated anti-thyroid antibodies (particularly anti-thyroid peroxidase [TPO] and anti-thyroglobulin [TGA])
3. Positive response to immunotherapy
4. Exclusion of other causes of encephalopathy

Clinical Presentation

HE typically presents with two main clinical patterns:

• Seizure-predominant type (less common):

  • Focal or generalized seizures
  • Verbal memory disturbance
  • Focal MRI lesions

• Diffuse encephalopathy type (more common):

  • Cognitive decline/confusion
  • Neuropsychiatric symptoms
  • Stroke-like episodes
  • Myoclonus
  • Tremor
  • Ataxia

Additional symptoms that may suggest HE include:

• Sensory abnormalities (pain, dysesthesia, paresthesia)
• Motor disturbances (weakness, paresis, dexterity issues)
• Give-way weakness (disruption of continuous muscle contraction)
• Involuntary movements
• Parkinsonism
• Chronic fatigue

Diagnostic Workup

First-Line Investigations

1. Blood tests:

   • Anti-thyroid antibodies (TPO and TGA) 1
   • Thyroid function tests (TSH, free T4)
   • Complete blood count
   • Comprehensive metabolic panel
   • Inflammatory markers (ESR, CRP)

2. Brain MRI (with and without contrast)

   • May show nonspecific abnormalities or be normal
   • Important to exclude other causes of encephalopathy

3. EEG

   • May show nonspecific slowing or epileptiform activity
   • Helps rule out non-convulsive status epilepticus

4. CSF analysis

   • Often shows elevated protein
   • Normal cell count
   • Negative for infectious agents

Differential Diagnosis

Important conditions to exclude:

• Infectious encephalitis
• Metabolic encephalopathies
• Toxic encephalopathies
• Creutzfeldt-Jakob disease
• Paraneoplastic syndromes
• Autoimmune encephalitis (other forms)
• Hepatic encephalopathy
• Cerebrovascular disease
• Primary psychiatric disorders

Treatment

First-Line Treatment

High-dose corticosteroids are the first-line treatment for Hashimoto's Encephalopathy and should be initiated promptly once the diagnosis is established 2, 3.

Initial regimen:

• Methylprednisolone 500-1000 mg IV daily for 3-5 days, followed by
• Oral prednisone 1-2 mg/kg/day with slow taper over months

Second-Line Treatments

For steroid-refractory cases:

1. Rituximab (anti-CD20 monoclonal antibody) 4

   • Particularly effective in steroid-refractory cases
   • Requires monitoring for side effects related to immunoglobulin depletion

2. Other immunomodulatory options:

   • Intravenous immunoglobulin (IVIG)
   • Plasma exchange
   • Azathioprine 5
   • Cyclophosphamide
   • Mycophenolate mofetil

Symptomatic Treatment

• Antiepileptic drugs for seizure control
• Supportive care for other symptoms

Monitoring and Follow-up

1. Clinical response

   • Most patients show significant improvement within days to weeks of starting steroids
   • Regular neurological assessments to monitor symptom improvement

2. Laboratory monitoring

   • Anti-thyroid antibody titers (may correlate with treatment response)
   • Thyroid function tests
   • Metabolic parameters during steroid therapy

3. Long-term management

   • Slow steroid taper to prevent relapse
   • Consider maintenance immunosuppression in relapsing cases
   • Regular follow-up to monitor for recurrence

Prognosis

• Most patients (>90%) respond well to immunotherapy 6, 3
• Some may require long-term immunosuppression
• Relapse can occur, particularly with rapid steroid tapering
• Early diagnosis and treatment are critical to prevent irreversible brain damage 6

Important Considerations

• Thyroid function is often normal despite high antibody titers
• The exact pathogenic role of anti-thyroid antibodies remains unclear
• HE should be considered in all cases of unexplained encephalopathy
• Some experts suggest renaming the condition "Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis" (SREAT) to better reflect current understanding 3

Common Pitfalls

1. Delayed diagnosis due to the rarity of the condition and heterogeneous presentation
2. Misdiagnosis as primary psychiatric disorder or functional neurological disorder
3. Inadequate treatment duration leading to relapse
4. Failure to consider HE in patients with normal thyroid function
5. Overlooking anatomically unexplainable pain and give-way weakness, which are often mistakenly attributed to psychogenic causes but can be manifestations of HE 5