Autoimmune encephalitis: signs and symptoms, etiology, epidemiology, diagnosis and treatment

Autoimmune encephalitis (AE) is a generic form of encephalitis

1.

1.

The main symptoms include psychobehavioral abnormalities, cognitive impairment, memory loss of recent events, seizures, speech disorders, movement disorders, involuntary movements, decreased level of consciousness and coma, autonomic dysfunction, etc

2.

(1) Sleep disorders

Patients may have various forms of sleep disorders, including insomnia, abnormal behavior during REM sleep, excessive daytime sleep, drowsiness, and disturbances in the sleep-wake cycle

(2) Focal damage to the central nervous system

Less commonly, anti-NMDAR encephalitis can affect the brainstem, cerebellum, etc.

Clinically can be divided into 3 main types:

(1) Anti-NMDAR encephalitis, the most important type of AE, its characteristic clinical manifestations are consistent with diffuse encephalitis

(2) Marginal encephalitis, with psychobehavioral abnormalities, temporal lobe epilepsy and near-memory impairment as the main symptoms, common marginal encephalitis are anti-LGI1 antibody, anti-GABABR antibody and anti-AMPAR antibody-related encephalitis

(3) Other types of AE, including Mowan syndrome, anti-DPPX antibody-related encephalitis, anti-IgLON5 antibody-related encephalopathy, autoimmune cerebellar ataxia, etc

2.

Central nervous system injury is mediated primarily through humoral immunity or cellular immune responses

3.

AE accounts for 10% to 20% of encephalitis cases, with an estimated annual incidence of about

4.

1.

2.
Neuroimaging or electrophysiological examination MRI limbic system T2 or FLAIR abnormal signals, unilateral or bilateral, or other areas of T2 or FLAIR abnormal signals (except for nonspecific white matter changes and stroke); or altered hypermetabolism of the PET limbic system, or multiple hypermetabolism of the cortical and/or basal ganglia; or EEG abnormalities: focal epilepsy or epileptic discharge (located outside the temporal or temporal lobes), or a slow-wave rhythm
of diffuse or multifocal distribution.

3.
AE-related tumor evaluation such as marginal encephalitis complicated with small cell lung cancer, anti-NMDAR encephalitis complicated with teratoma, etc
.

5.
Differential diagnosis

1.
Infectious diseases: Central nervous system infection caused by viral encephalitis, neurosyphilis, bacteria, etc.
, Creutzfeldt-Jakob disease, etc
.

2.
Metabolic and toxic encephalopathy Wernicke encephalopathy, hepatic encephalopathy, pulmonary encephalopathy, renal encephalopathy, etc.
, toxic encephalopathy and radiation encephalopathy caused by antibiotics such as penicillins or quinolones, chemotherapy drugs or immunosuppressants, etc
.

3.
Neoplastic diseases: Primary intracranial tumors, such as cerebral gliomas and primary CNS lymphomas; Intracranial metastases
.

4.
Hereditary or degenerative diseases of the nervous system Mitochondrial encephalopathy or mitochondrial encephalopathy, methylmalonic acidemia, adrenal leukodystrophy, Lewy body dementia, multisystem atrophy, hereditary cerebellar degeneration, etc
.

6.
Diagnosis

According to the recommendations of the "Expert Consensus on the Diagnosis and Treatment of Autoimmune Encephalitis in China", the diagnostic criteria for AE are as follows:

1.
Diagnostic conditions include four aspects: clinical manifestations, auxiliary examinations, confirmatory tests, and exclusion of other causes
.

(1) Clinical manifestations: acute or subacute onset (<3 months), with one or more of the following neurological and psychiatric symptoms or clinical syndromes
.

1) Limbic system symptoms: memory loss of recent events, seizures, mental and behavioral abnormalities, one or more of the 3 symptoms
.

2) Encephalitis syndrome: clinical manifestations
of diffuse or multifocal brain damage.

3) Clinical manifestations
of basal ganglia and/or diencephalic / hypothalamic involvement.

4) Mental disorders, and the psychosocial specialty considers to be non-organic diseases
.

(2) Adjuvant examination: one or more of the following adjuvant examination findings, or associated tumors
.

1) Cerebrospinal fluid abnormalities: CSF leukocytosis (>5×106/L); or cerebrospinal fluid cytology showing lymphocytic inflammation; or CSF oligoclonal band positive
.

2) Neuroimaging or electrophysiological abnormalities: MRI limbic system T2 or FLAIR abnormal signals, unilateral or bilateral, or other areas of T2 or FLAIR abnormal signals (except nonspecific white matter changes and stroke); or altered hypermetabolism of the PET limbic system, or multiple hypermetabolism of the cortical and/or basal ganglia; or EEG abnormalities: focal epilepsy or epileptic discharge (located outside the temporal or temporal lobes), or a slow-wave rhythm
of diffuse or multifocal distribution.

3) Specific types of tumors associated with AE: for example, marginal encephalitis complicated with small cell lung cancer, anti-NMDAR encephalitis complicated with teratoma, etc
.

(3) Confirmatory test: positive autoantibodies against neuronal surface antigens
.
Antibody detection is mainly done using indirect immunofluorescence assay (IIF
).
Cell substrate-based experiments (cell based assay, CBA) have high specificity and sensitivity
.
Patients' paired CSF and serum specimens should be tested as much as possible, with initial dilution titers of CSF and serum 1:1 and 1:10
, respectively.

(4) Reasonably exclude other causes

2.
Diagnostic criteria include possible AE versus confirmed AE
.

(1) Possible AE: Meets the 3 conditions
A, B, and D.

(2) Confirmed AE: Meet the 4 conditions
of A, B, C and D.

Adjunctive testing

1.
Cerebrospinal fluid examination The pressure of cerebrospinal fluid through the lumbar puncture is normal or elevated, and it is rare
in patients exceeding 300mmH2O.
The number of white blood cells in the cerebrospinal fluid is mildly elevated or normal, a few exceed 100 × 106/L, and the cSF cytology is lymphocytic inflammation, and plasma cells
are visible.
CSF proteins are mildly elevated, oligoclonal bands of CSF may be positive, and CSF anti-NMDAR antibodies are positive
.

2.
Most patients with head MRI have no obvious abnormalities in head MRI, or only scattered cortical and cortical spot flare flair hyperinflora; Fringe system FLAIR and T2 hyperintensions are visible in some patients, and lesion distribution can extend beyond the
limbic system.

3.
Metabolic abnormalities are seen in head FDG-PET/CT, which is mainly characterized
by a significant decrease in bilateral occipital lobe metabolism.

4.
EEG is mostly diffuse or multifocal slow waves, occasionally epileptic waves can be seen, abnormal d-brush is a more specific EEG change of the disease, more common in severely ill patients
.

5.
Oncology Ovarian teratomas are more common
in young women.
The incidence of ovarian teratomas in Chinese women with anti-NMDAR encephalitis is 14.
3% to 47.
8%.

Ovarian ultrasound and PELVIC CT are helpful in detecting ovarian teratomas, and imaging tests for micro-teratomas of the ovaries may be negative
.
It is rare
in male patients with tumors.

Diagnostic criteria: Confirmed anti-NMDAR encephalitis requires compliance with the following 3 (refer to the 2016 Lancet Neurol criteria):

1.
1 or more of the 6 main symptoms: (1) psychobehavioral abnormalities or cognitive impairments; (2) Speech disorders; (3) Seizures; (4) Movement disorders / involuntary movements; (5) Decreased level of consciousness; (6) Autonomic dysfunction or central hypopnea

2.
Positive anti-NMDAR antibody is recommended to be positive for CBA antibody
in cerebrospinal fluid.
If only serum specimens are available for testing, in addition to a positive CBA result, TBA and culture neurons are required for final confirmation
by IIF.

3.
Reasonably exclude other causes
of illness.

7.
Treatment

Treatment of autoimmune encephalitis includes immunotherapy, symptom treatment of seizures and psychiatric symptoms, supportive care, and rehabilitation
.

Immunotherapy is divided into first-line immunotherapy, second-line immunotherapy, and long-term immunotherapy
.
First-line immunotherapy includes glucocorticoids, intravenous immunoglobulins, and plasmapheresis
.
Second-line immunologies, including rituximab and intravenous cyclophosphamide, are primarily used in patients with
poor first-line immunotherapy.
Long-term immunotherapy drugs, including mycophenolate mofetil and azathioprine, are mainly used in recurrent cases, and can also be used in patients with autoimmune encephalitis with poor first-line immunotherapy and tumor-negative anti-NMDAR encephalitis patients
.
Patients with anti-NMDAR encephalitis should be removed
as soon as an ovarian teratoma is found.
Patients with AE who have malignancy should be treated with a combination of surgery, chemotherapy, and radiation therapy
.

Overall prognosis for AE is good
.
About 80% of patients with anti-NMDAR encephalitis have recovered well, and the case fatality rate is 2.
9% to 9.
5%.

Anti-GABABR antibody-related encephalitis with small cell lung cancer has a poor
prognosis.

author

Department of Neurology, Peking Union Medical College Hospital Guan Hongzhi

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