Autoimmune encephalitis (AE) is a rare form of reversible brain inflammation that may present with psychosis, seizures, altered consciousness, dystonia, and a diverse spectrum of other neurologic symptoms. Tests for specific antibodies to brain proteins may assist in diagnosis of some of the most common forms of the disease, many of which are associated with specific malignancies (i.e., paraneoplastic disease). Most cases improve substantially with immune therapy.
Certain clinical features may suggest disorders associated with the presence of particular antibodies, although there is considerable overlap in clinical presentation between different forms of AE. NMDAR antibodies strongly predominate in patients under 30 years, and often associate with psychosis, dystonia, catatonia, seizures, respiratory failure, and autonomic instability. AMPAR antibodies may cause similar symptoms but are rarer and affect older adults, often with lung, breast, or thymic tumors. LGI1 antibodies affect mostly older adults and may cause fasciobrachial dystonic seizures, hyponatremia, and insidious memory impairment. GABA-B receptor antibodies are the most common cause of AE in patients with small cell lung cancer and cause particularly severe seizures. GABA-A receptor antibodies associate with characteristic brain lesions and status epilepticus or epilepsy partialis continua. Caspr2 antibodies associate with Morvan syndrome (encephalitis with neuromyotonia). DPPX antibodies associate with central nervous system (CNS) and gastrointestinal hyperexcitability. Ophelia syndrome is a rare form of encephalitis associated with Hodgkin lymphoma and mGluR5 antibodies. Bickerstaff encephalitis is closely related to Miller Fisher syndrome and Gq1b antibodies. Hashimoto encephalitis is a steroid-responsive encephalopathy associated with high-titer thyroid antibodies; however, it should be noted that thyroid antibodies may be found in other forms of AE and also the general population.
The presence of autoantibodies to specific brain antigens together with clinical symptoms can be diagnostic and help guide therapy. Some of the higher-yield tests include autoantibodies to NMDAR, LGI1, AMPAR, Caspr2, GABA-B, and GAD65. GABA-A, glycine, mGluR5, and DPPX antibodies also have value in some cases but may not be commercially available. GQ1b antibodies should sent if Bickerstaff encephalitis is considered. Thyroid antibodies (anti-thyroid peroxidase [TPO], and anti-thyroglobulin, [TG]) may support the diagnosis of Hashimoto encephalopathy but are not specific. In cases with a strong suspicion for AE, consider testing in a research laboratory. Antibody testing should be refined if a tumor is identified, as certain antibodies associate with certain malignancies and this can enhance diagnostic confidence.
Clinical criteria for possible autoimmune encephalitis and definite autoimmune encephalitis are available, and empiric treatment for patients who meet criteria for possible or definite AE can be started while awaiting results of antibody testing. “Possible AE” requires: (1) < 3 months of altered mental status, memory loss, or psychiatric symptoms and (2) new focal CNS findings, CSF pleocytosis or magnetic resonance imaging (MRI) showing features of AE and (3) exclusion of other causes. “Definite AE” requires (1) < 3 months altered mental status, memory loss, or psychiatric symptoms and (2) increased T2 signal in the temporal lobes, electroencephalogram (EEG) with focal temporal abnormalities or CSF pleocytosis and (3) exclusion of alternative causes. Specific criteria for probable and definite anti-NMDAR AE have similarly been proposed and should be considered in children, where anti-NMDAR encephalitis is much more common than the other diseases in this group.
Initial immune therapy typically consists of intravenous steroids plus either intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX). The former may be preferred in patients with agitation in whom maintaining a pheresis access may be difficult. Seizures are common and should be treated with antiepileptic drugs. Autonomic instability, especially in patients with NMDAR antibodies, requires careful management of blood pressure and heart rate during autonomic storms. Respiratory failure may necessitate mechanical ventilation. Psychosis and agitation may be managed with neuroleptics that do not have strong dopamine antagonism, since this can worsen movement disorders. Muscle relaxants and benzodiazepines may be considered for muscle spasms. Focal botulinum toxin may be useful for severe, refractory dystonia, particularly of the jaw. The level of care and possible transfer to a specialized center should be regularly considered.
Close clinical follow-up is necessary to adjust immune therapy based on symptoms. Antibody titers should in general not be used to guide treatment. Additional immunosuppression with rituximab or cyclophosphamide may be necessary in refractory cases. The side effects of immune suppression need to be addressed (e.g., prophylaxis against opportunistic infection, mitigating effects of steroids on bone density, etc.). Relapse is always a risk. Steadily wean symptomatic medications that are no longer needed.
Consider repeat cancer screening at 3, 6, 12, 24, and 36 months, with the specific tests influenced by the precise antibody diagnosis if there is one.
Premium Wordpress Themes by UFO Themes
WordPress theme by UFO themes