What are the clinical presentations of Leucine-Rich Glioma-Inactivated 1 (LGI1) encephalitis?

Clinical Presentations of LGI1 Encephalitis

LGI1 encephalitis typically presents with a characteristic triad of subacute cognitive impairment (particularly short-term memory loss), distinctive seizure types (especially faciobrachial dystonic seizures), and hyponatremia, predominantly affecting older males. 1

Core Clinical Features

Cognitive and Psychiatric Manifestations

• Acute or subacute short-term memory loss is the most prominent feature, occurring in approximately 90% of patients, with profound anterograde and retrograde amnesia 1, 2, 3
• Disorientation and confusion develop early in the disease course, often severe enough to prompt initial evaluation 1
• Behavioral changes and psychiatric symptoms including psychosis, anxiety, and agitation are common presenting features 1, 3
• Memory impairment specifically affects recall function most severely, with patients scoring near zero on memory recall testing at presentation 2

Seizure Semiology (Highly Distinctive)

• Faciobrachial dystonic seizures (FBDS) are pathognomonic for LGI1 encephalitis, occurring in 38-44% of patients 1, 4, 5
  • These are brief (seconds), frequent (up to hundreds per day) dystonic postures affecting the arm and ipsilateral face
  • FBDS often precede cognitive symptoms by weeks, providing a critical window for early intervention 1
  • These seizures are frequently unnoticed by clinicians (17% missed in one series) 4
• Mesial temporal lobe epilepsy (MTLE)-like seizures occur in approximately 66% of patients 5
• Focal to bilateral tonic-clonic seizures are seen in 77% of cases 5
• Seizures are generally prominent and may be the presenting symptom 1

Metabolic and Systemic Features

• Hyponatremia is present in approximately 55-60% of patients and is a key diagnostic clue 1, 6, 3
• Unlike other forms of autoimmune encephalitis, fever and headache are uncommon in LGI1 encephalitis 1

Demographic Pattern

• Male predominance with a 2:1 male-to-female ratio 1
• Median age at presentation is 65 years, though younger patients (including those in their 20s) can be affected 1, 2

Neuroimaging Findings

• MRI shows abnormalities in approximately 60% of patients 1, 6
• Bilateral hippocampal high T2/FLAIR signal with associated swelling is the characteristic pattern 1
• Unilateral hippocampal involvement occurs in 15% of cases 1
• Some patients show basal ganglia involvement with high T1/T2 signal 5
• Moderate hippocampal atrophy may be present, particularly in cases with delayed diagnosis 3

Electroencephalography Patterns

• EEG abnormalities occur in 100% of patients 2, 5
• Generalized slowing with or without ictal focus is the most common pattern 1
• Focal slow waves (88%) and interictal epileptic discharges (66%) involving temporal regions are frequent 5
• Epileptiform activity specifically involving the temporal lobes is characteristic 2

Cerebrospinal Fluid Findings

• CSF abnormalities are uncommon in LGI1 encephalitis, distinguishing it from NMDAR encephalitis 1
• Pleocytosis is rare 1
• Oligoclonal bands are rarely present 1
• LGI1 antibodies may be detected in CSF, though serum testing is often sufficient 1, 3, 5

Associated Malignancy

• Tumors are rare with LGI1 antibodies, present in less than 10% of cases 1, 6
• When present, associated tumors are typically thymoma or small cell lung cancer 1
• This contrasts sharply with other autoimmune encephalitides where paraneoplastic associations are more common 1

Sleep and Movement Disorders

• Sleep disorders occur in 58% of patients, including insomnia 4, 5
• REM sleep behavior disorder is present in 50% of cases 4
• Disrupted sleep architecture on polysomnography occurs in 79% of patients 4
• Excessive fragmentary myoclonus (63%) and myokymic discharges (38%) are detectable on videopolysomnography 4
• These features are often clinically unsuspected but treatable 4

Critical Diagnostic Pitfalls

• FBDS are frequently missed (17% unnoticed) and may be misattributed to other movement disorders 4
• Focal onset seizures are underrecognized (21% missed) without careful observation 4
• Patients may be initially misdiagnosed with Alzheimer disease when rapidly progressive dementia is the presenting feature 3
• Ongoing clinical abnormalities persist after initial immunotherapy in most patients, requiring vigilant follow-up 4

Disease Course and Prognosis

• LGI1 encephalitis is typically a monophasic illness with good response to immunotherapy 1
• Spontaneous improvement can occur in some untreated patients, though this is uncommon 1
• Despite good overall response, cognitive deficits persist in 65% of patients at 1 year, particularly affecting short-term memory 2, 4
• 14-29% of patients have significant residual memory impairment despite treatment 2
• Relapse is uncommon once antibodies become undetectable with treatment 1