What are the clinical features and treatment options for Hashimoto encephalitis?

Clinical Features of Hashimoto Encephalitis

Hashimoto encephalitis presents as a subacute encephalopathy with cognitive impairment, psychiatric features (hallucinations, delusions, paranoia), and seizures in patients with elevated anti-thyroid antibodies, typically while euthyroid or mildly hypothyroid. 1, 2

Core Clinical Presentation

Neuropsychiatric Manifestations

• Altered mental status ranging from confusion to profound disorientation occurs in 41-76% of cases 3, 4
• Behavioral changes and personality alterations are hallmark features, including aggressiveness, delusional thinking, and confusion 1, 5, 2
• Psychiatric symptoms such as hallucinations, delusions, and paranoia are required diagnostic components that distinguish HE from other encephalopathies 1, 2
• Cognitive dysfunction presents as progressive dementia-like symptoms with subacute onset over weeks to months 3, 1, 6

Seizure Activity

• Seizures occur in approximately one-third of patients and may be the initial presenting feature 3, 4
• Refractory or intractable seizures are particularly common, often occurring without fever 3, 5
• Status epilepticus has been reported and contributes to mortality risk 1
• Focal seizures with altered mental status are documented presentations 5

Movement Disorders

• Orofacial dyskinesia and choreoathetosis suggest antibody-mediated encephalitis 3
• Faciobrachial dystonia may be present, though this is more characteristic of VGKC-complex antibody encephalitis 3
• Focal neurological deficits including weakness, numbness, and speech disorders occur 5

Other Neurological Features

• Speech disturbances (dysphasia, aphasia) are seen in 59% of cases 3, 4
• Sleep disorders including complete absence of sleep activity on EEG during acute episodes 6
• Dysphagia, nightmares, and nocturnal enuresis have been reported in pediatric cases 5

Distinguishing Clinical Characteristics

Subacute Presentation

• Symptoms evolve over weeks to months rather than the acute onset typical of infectious encephalitis 3, 1
• This subacute timeline is a key diagnostic clue that should trigger consideration of antibody-mediated encephalitis 3

Thyroid Status

• Patients are typically euthyroid or only mildly hypothyroid at presentation, not overtly hypothyroid 5, 2
• The presence of elevated anti-thyroid antibodies (particularly anti-thyroperoxidase) is required for diagnosis 1, 5, 2
• Associated with autoimmune thyroiditis (Hashimoto's thyroiditis) 1, 2

Fever Pattern

• Low-grade pyrexia or absence of fever is more common than high fever, distinguishing it from acute infectious encephalitis 3, 4
• Intractable seizures often occur without fever 3

Laboratory and Imaging Findings

Cerebrospinal Fluid

• Elevated protein is the most consistent CSF abnormality in HE patients 1
• CSF may show lymphomonocytic pleocytosis 7
• CSF analysis is critical for excluding infectious causes 8, 4

Neuroimaging

• Normal brain MRI findings occur in the majority of HE patients, which is an important distinguishing feature 1
• When abnormal, MRI may show discrete hippocampal high signal with associated swelling 3
• MRI should be obtained within 48 hours as the imaging modality of choice 8

Electroencephalography

• EEG abnormalities are present in >80% of encephalitis cases and should be obtained to distinguish organic from psychiatric causes 8
• Complete absence of sleep activity may be recorded during acute episodes 6
• EEG is essential for detecting non-convulsive status epilepticus 3

Differential Diagnosis Considerations

Critical Mimics

• Autoimmune encephalitis (particularly NMDA receptor and VGKC-complex antibody encephalitis) shares overlapping features 1, 2
• Creutzfeldt-Jakob disease can be mimicked by HE at physical examination 6
• Primary psychiatric illness may be mistakenly diagnosed due to behavioral changes and hallucinations 3, 4

Key Distinguishing Features

• Hyponatraemia may suggest antibody-mediated encephalitis but is not specific to HE 3
• The combination of encephalopathy, elevated anti-thyroid antibodies, and steroid-responsiveness confirms HE 1, 2

Treatment Response Pattern

• Most HE patients respond well to corticosteroid therapy, which is both diagnostic and therapeutic 1, 2, 6
• Clinical improvements are observed with IV immunoglobulin and plasmapheresis in steroid-refractory cases 1, 5, 9
• Symptoms may flare after tapering oral steroids, suggesting steroid-dependence 7
• Rituximab can be valuable in steroid-refractory cases, though careful monitoring for immunoglobulin depletion is required 9

Clinical Pitfalls

• Behavioral changes can be mistaken for primary psychiatric illness, leading to dangerous delays in diagnosis and treatment 3, 4
• The disorder can be confused with drug or alcohol-related encephalopathy due to similar presentations 3
• Normal MRI does not exclude HE—this is actually the typical finding 1
• Despite low prevalence, death and status epilepticus have been reported, making early recognition critical 1
• The relatively benign prognosis with aggressive immunosuppressive treatment contrasts sharply with poor outcomes if untreated 3, 2