What are the typical presentation features and first‑line treatment recommendations for LGI‑1 antibody‑associated autoimmune encephalitis in middle‑aged adults?

LGI1 Autoimmune Encephalitis: Clinical Presentation and First-Line Treatment

Typical Clinical Presentation

LGI1 encephalitis characteristically presents with a triad of subacute cognitive impairment, distinctive seizure types (particularly faciobrachial dystonic seizures), and hyponatremia, predominantly affecting older males with a median age of 65 years. 1

Core Neurological Features

• Cognitive impairment is the most prominent feature, occurring in approximately 90% of patients, manifesting as profound anterograde and retrograde amnesia with acute or subacute short-term memory loss 1, 2
• Faciobrachial dystonic seizures (FBDS) are pathognomonic for LGI1 encephalitis, occurring in 38-44% of patients 1, 3
• FBDS often precede cognitive symptoms by weeks to months, providing a critical window for early intervention before widespread cognitive impairment develops 1, 4
• Seizures are generally prominent and may be the presenting symptom in 75% of patients, often refractory to antiepileptic drugs 2, 5
• Disorientation, confusion, and behavioral changes including psychosis, anxiety, and agitation develop early in the disease course 1, 6

Key Diagnostic Clues

• Hyponatremia is present in approximately 55-60% of patients and serves as a critical diagnostic marker 1, 4, 2
• Male predominance with a 2:1 male-to-female ratio 1
• Absence of fever and headache, unlike other forms of autoimmune encephalitis 1

Diagnostic Workup Findings

Brain MRI:

• Abnormalities present in approximately 60% of patients 1, 4
• Bilateral hippocampal high T2/FLAIR signal with associated swelling is the characteristic pattern when present 1
• Normal MRI does not exclude the diagnosis - 38.8% of patients may have no MRI evidence of inflammation 3

Cerebrospinal Fluid:

• CSF abnormalities are uncommon, distinguishing LGI1 from NMDAR encephalitis 1, 4
• Pleocytosis is rare (present in only 16.7% of patients) 2
• Oligoclonal bands are rarely present 1
• Serum antibody testing is more sensitive than CSF (96.8% vs. 48.4%) 3

EEG:

• Frequent subclinical seizures are commonly identified 7
• Patients with classical FBDS may have a normal EEG 7
• Paroxysmal sharp/spike waves and slow waves detected in 50% of patients 2

Malignancy Screening:

• Tumors are rare with LGI1 antibodies, present in less than 10% of cases 1
• When present, associated tumors are typically thymoma or small cell lung cancer 1

First-Line Treatment Recommendations

Begin with high-dose intravenous methylprednisolone (1-2 mg/kg/day) immediately once infection is ruled out by CSF analysis. 4

Treatment Algorithm

Step 1: Initial Immunotherapy

• Initiate intravenous methylprednisolone as first-line treatment once CSF excludes infection 4
• FBDS are particularly steroid-responsive and respond rapidly to immunotherapy 4, 5
• Monitor and manage hyponatremia carefully to prevent complications 4

Step 2: Alternative First-Line Options

• IVIG (0.4 g/kg/day for 5 days) for agitated/combative patients or those with bleeding disorders 4
• Plasma exchange (5-10 sessions every other day) for patients with severe hyponatremia or high thromboembolic risk 4

Step 3: Escalation if No Response

• If no clinical improvement after initial steroid treatment, add IVIG or plasma exchange to enhance treatment efficacy 4
• For patients with no improvement 2-4 weeks after combined first-line therapy, consider second-line agents such as rituximab 4

Treatment Response and Prognosis

• Most patients respond within a few weeks to immunotherapy with good outcomes 4
• Early immunotherapy is crucial for better outcomes and prevention of cognitive dysfunction 4
• LGI1 encephalitis is typically a monophasic illness with good response to immunotherapy 1
• Complete or partial neurological response occurs at median 12-month follow-up 8
• Relapse is uncommon once antibodies become undetectable with treatment 1

Critical Treatment Pitfalls to Avoid

• Do not delay immunotherapy while waiting for antibody test results - treatment should begin once infection is ruled out 4
• Do not rely solely on antiepileptic drugs for FBDS - these seizures show poor response to antiepileptic drugs but are highly steroid-responsive 5, 9
• Do not overlook hyponatremia management - inadequate correction can lead to complications 4
• Do not assume normal MRI and CSF exclude the diagnosis - absence of inflammation in routine CSF analysis and brain MRI does not rule out anti-LGI1 encephalitis 3