Antibody-mediated autoimmune encephalitis: A practical approach

Article Figures & Data

TABLE 1

Autoantibody biomarkers of autoimmune encephalitis: Intracellular autoantibodies

ANTIBODY TARGET	CENTRAL NERVOUS SYSTEM FEATURES	PERIPHERAL NERVOUS SYSTEM FEATURES	OTHER	ASSOCIATED MALIGNANCY
High-risk paraneoplastic autoantibodies
ANNA-1 (Hu)	Limbic encephalitis Encephalomyelitis Cerebellar ataxia	Sensory neuropathy	Gastrointestinal dysmotility	SCLC Rare: neuroblastoma
ANNA-2 (Ri)	Encephalomyelitis Cerebellar ataxia Rhombencephalitis		Jaw dystonia Laryngospasm	SCLC Breast carcinoma
ANNA-3	Limbic encephalitis Encephalomyelitis Cerebellar degeneration	Sensory and sensorimotor neuropathies		SCLC
Amphiphysin	Stiff-person spectrum disorder			SCLC Breast or ovarian carcinoma
CRMP-5	Limbic encephalitis Cerebellar ataxia Chorea Myelopathy Cranial neuropathies (optic neuritis)	Polyradiculoneuropathy		SCLC Thymoma carcinoma
GAD65	Stiff-person spectrum disorder Limbic encephalitis Cerebellar ataxia			Rare
GFAP	Meningoencephalitis Myelitis Optic neuritis			Ovarian teratoma Adenocarcinomas of various sites
PCA-1 (Yo)	Cerebellar ataxia			Breast or ovarian carcinoma
PCA-2	Limbic encephalitis Cerebellar ataxia	Polyneuropathy		SCLC
PCA-Tr (DNER)	Limbic encephalitis Cerebellar ataxia			Hodgkin lymphoma
Ma 1 and	Diencephalitis			Ma1: Common, diverse
Ma 2 (Ta)	Limbic encephalitis Brain stem encephalitis Cerebellar degeneration			Ma2: Testicular seminoma

ANNA = antineuronal nuclear antibody; CRMP-5 = collapsin response mediator protein 5; DNER = delta/notch-like epidermal growth factor-related receptor; GAD = glutamic acid decarboxylase; GFAP = glial fibrillary acidic protein; PCA = Purkinje cell cytoplasmic antibody; SCLC = small-cell lung cancer

TABLE 2

Autoantibody biomarkers of autoimmune encephalitis: Cell-surface and synaptic antibodies

ANTIBODY	CENTRAL NERVOUS SYSTEM FEATURES	PERIPHERAL NERVOUS SYSTEM FEATURES	OTHER FEATURES	ASSOCIATED MALIGNANCY
AMPAR	Limbic encephalitis			SCLC Breast carcinoma Thymoma
Caspr2	Limbic encephalitis	Peripheral nerve hyperexcitability		Rare, but thymoma carcinoma reported
DPPX	Encephalopathy Myelopathy		GI dysmotility Sleep disorder	Rare, but lymphoma reported
D2R	Parkinsonism Encephalitis
GABA A receptor	Encephalitis Status epilepticus			Thymoma
GABA B receptor	Limbic encephalitis Status epilepticus Opsoclonus myoclonus			SCLC
GQ1b	Bickerstaff brain stem encephalitis	Guillain-Barré-like illness
IgLON5	Sleep disorder Dementia		Dysphagia Respiratory failure	Rare
LGI1	Limbic encephalitis Faciobrachial dystonic seizures			Thymoma
NMDA-R	Limbic encephalitis Status epilepticus Movement disorders Psychosis Catatonia			Ovarian teratoma
mGluR1 mGluR5 Glycine receptor	Cerebellar ataxia Limbic encephalitis Stiff-person spectrum disorder		Dysgeusia	Hodgkin lymphoma Hodgkin lymphoma Rare

AMPAR = 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor; Caspr2 = contactin-associated protein-like 2; D2R = dopamine 2 receptor; DPPX = dipeptidyl-peptidase-like protein 6; GABA = gamma-aminobutyric acid; GI = gastrointestinal; LGI1 = leucine-rich glioma-inactivated 1; mGluR = metabotropic glutamate receptor; NMDA-R = anti-N-methyl-D-aspartate receptor; SCLC = small cell lung cancer

TABLE 3

Clinical, diagnostic, and radiographic clues to autoimmune encephalitis

FINDINGS	COMMENTS
Subacute clinical course	1–3 months of symptoms
Viral-like prodrome	Fever, malaise, headache, gastrointestinal symptoms, etc
Neurocognitive deficits	Agitation, apathy, catatonia, delusions, irritability, mania, psychosis, and paranoia
Neurologic examination abnormalities	Ataxia, brain stem abnormalities, myoclonus, tremor, or myelopathy
New-onset focal seizure disorder or status epilepticus	Often not responsive to antiepileptic medications
New focal electroencephalogram abnormalities	Focal epileptic or slow-wave activity particularly arising from the temporal lobes
Subacute movement disorder	Dyskinesias, dystonia, or choreoathetosis
Subacute sleep disturbance	Central sleep apnea, central neurogenic hypoventilation, or narcolepsy
Subacute autonomic dysfunction	Hyperhidrosis, tachyarrhythmias, labile blood pressure, central hypoventilation, gastrointestinal dysmotility, urinary dysfunction
Brain MRI abnormalities	Bilateral T2-weighted FLAIR hyperintensities in the medial aspect of the temporal lobes, although multifocal changes involving the gray and white matter are also possible
Inflammatory cerebrospinal fluid	Mild to moderate pleocytosis (white blood cell count 5–100/μL)
Previous or current oncologic disorder or risk factors for malignancy such as smoking	Increased risk of a paraneoplastic disorder