Ferri – Antibody-Mediated Autoimmune Encephalitis

Mar 20, 2020 admin THẦN KINH 0

Antibody-Mediated Autoimmune Encephalitis

  • James Earl Corley, M.D.
  • Leonard Jefferson Harris Jr., M.D.

 Basic Information

Definition

Antibody-mediated autoimmune encephalitis is a neurologic disease causing a spectrum of deficits, including subacute memory loss, changes in cognition, and depressed level of consciousness caused by antibodies directed against membrane receptors and ion channel-associated proteins expressed on the surface of neurons in the central nervous system.

Synonyms

  1. Antibody mediated encephalitis

  2. Autoimmune encephalitis

  3. Autoimmune encephalopathy

  4. Anti-NMDAR encephalitis

  5. Voltage-gated potassium channel antibody syndromes

ICD-10CM CODES
G04.81 Other encephalitis and encephalomyelitis

Epidemiology & Demographics

Incidence

  1. •

    It is difficult to estimate incidence as testing for disease is relatively new. The most common form is anti-NMDAR encephalitis. The incidence of anti-NMDAR encephalitis is 0.85 per million children annually. No data about incidence in adults is available.

Peak Incidence

  1. •

    It is difficult to estimate incidence as testing for disease is relatively new.

Prevalence

  1. •

    It is difficult to estimate prevalence as testing for disease is relatively new.

Predominant Age and Sex

  1. •

    Anti-NMDAR predominantly affects young women, with a median age at presentation of 21 to 23 years.

Genetics

  1. •

    There is no known genetic risk factors for developing autoimmune encephalitis.

Risk Factors

  1. •

    Tumors (particularly ovarian) can trigger autoimmune encephalitis.

Physical Findings and Clinical Presentation

  1. •

    Typically presents with subacute (days to a few weeks) deficits of memory and cognition and often followed by suppressed level of consciousness. If untreated, patients can progress to coma.

  2. •

    Psychiatric manifestations are common early in the course of autoimmune encephalitis. These may include psychosis, panic attacks, aggression, inappropriate sexual behaviors, compulsive behaviors, euphoria, or fear.

  3. •

    Physical examination can show neuromyotonia, hyperekplexia, psychosis, or dystonia.

Etiology

  1. •

    One category includes antibodies directed to intracellular antigens, such as anti-Hu. These disorders are strongly associated with cancer and involve T-cell responses targeting neurons. These disorders have a poor prognosis secondary to irreversible neuronal killing. Another category involves autoantibodies to extracellular epitopes of ion channels, receptors, and other associated proteins, such as the NMDA receptor. The cancer associations are variable with the category, and the prognosis tends to be much better because damage is reversible.

     

Diagnosis

Differential Diagnosis

  1. •

    Infectious encephalitis (especially viral)

  2. •

    Metabolic encephalopathy

  3. •

    Wernicke encephalitis

  4. •

    Neuroleptic malignant syndrome

  5. •

    Serotonin syndrome

  6. •

    Lymphoma

  7. •

    Carcinomatous meningitis

Workup

  1. •

    Diagnostic testing to exclude other causes of encephalitis, including infectious and other autoimmune causes, should occur.

Laboratory Tests

  1. •

    Autoantibody testing is important for the diagnosis of autoimmune encephalitis. Tests for autoantibodies to NMDAR, LGI1, Caspr2, AMPAR (GluR1, GluR2 subunits), and GABA-B-R are available. These antibody tests are most sensitive and specific with CSF. Serum may offer a low false-positive rate and a higher false-negative rate.

Imaging Studies

  1. •

    Brain MRI in patients with NMDAR, AMPAR, LGI1, Caspr2, and GABA-B antibodies may be normal or show increased T2 signal, especially in the medial temporal lobes. Testing with MRI and EEG may also be helpful for excluding other causes.

Treatment

Nonpharmacologic Therapy

  1. •

    Supportive care, including nutrition, is crucial in these patients, given changes in mentation.

Acute General Rx

  1. •

    Treatment for suspected autoimmune encephalitis is often given empirically prior to specific antibody test results. This may include IVIG, plasmapheresis, and/or steroids. IVIG may be given early as it is less likely to make infectious encephalitis worse. If patient does not respond in 2 wk or is critically ill, second-line therapies (rituximab or cyclophosphamide) should be considered.

Chronic Rx

  1. •

    No current chronic suppression is recommended for antibody-mediated autoimmune encephalitis, but relapse can occur and tends to follow a similar clinical course to the initial attack.

Complementary and Alternative Medicine

  1. •

    No complementary or alternative medicine is known.

Disposition

  1. •

    Patients require hospitalization during treatment but are often discharged home after resolution of disease process.

Referral

  1. •

    Neurology and rheumatology evaluation may be beneficial to help exclude other causes of encephalitis.

     

Pearls & Considerations

Comments

  1. •

    Autoantibody tests may be used to diagnose or exclude particular causes, but these tests are complex, and not every positive result is definite evidence of an autoimmune disorder.

Prevention

  1. •

    Cancer screening should be completed for high-risk patients, as tumors can be associated with antibody-mediated autoimmune encephalitis. Known associations are HuD proteins in small cell lung cancer and NMDARs in ovarian teratoma.4

Patient/Family Education

  1. •

    The Autoimmune Encephalitis Alliance (https://aealliance.org/) is a resource that can be used by patients and their family for further information and support.

Suggested Readings

  • M.S. Gable, H. Sheriff, J. Dalmau, et al.: The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis. 54 (7):899–904 2012 22281844

  • M. Gastaldi, A. Thouin, A. Vincent: Antibody-mediated autoimmune encephalopathies and immunotherapies. Neurotherapeutics. 13 (1):147–162 2016 26692392

  • H.-Z. Guan, H.-T. Ren, L.-Y. Cui: Autoimmune encephalitis: an expanding frontier of neuroimmunology. Chin Med J. 129 (9):1122–1127 2016 27098800

  • E. Lancaster: The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol. 12 (1):1–13 2016 26754777

 

 

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