Auto-immune encephalitis involves multiple diseases with different pathophysiology, including paraneoplastic syndromes (associated with antibodies to intracellular antigens, such as anti-Hu, discussed elsewhere on this website) and a group of diseases associated with autoantibodies to extracellular epitopes of ion channels, receptors and other associated proteins, such as the NMDA receptor.

Presentation of autoimmune encephalitis:

- Subacute (days to weeks) progressive decrease in consciousness, often with fluctuations and altered cognition.

- Seizures

- Memory, especially retention of new information, may be impaired early in the clinical course.

- Psychiatric symptoms (psychosis, aggression, inappropriate sexual behavior, panic attacks, compulsive behavior, euphoria, or fear)

- Abnormal movements or dystonia may be the presenting symptom

Autoimmune encephalitis mimics/differential diagnosis:

- acute demyelinating encephalomyelitis (ADEM): (characteristic brain lesions, and sometimes involvement of the optic nerves or spinal cord

- Multiple sclerosis: generally easier to distinguish from autoimmune encephalitis due to more focal symptoms and characteristic brain imaging findings

- neuropsychiatric lupus (psychosis, seizures, vasculitis)

- Vasculitis affecting the CNS may rarely present with symptoms resembling encephalitis

- Bickerstaff encephalitis and Miller Fisher syndrome (loss of reflexes, GQ1b antibodies)

- Neuroleptic malignant syndrome

- Wernicke’s encephalopathy/Thiamine deficiency

- Lymphoma or carcinomatous meningitis

- Hashimoto’s encephalopathy

                        Infectious causes of encephalitis:

 - HSV, VZV, CMV, EBV, JE, enterovirus, HHV6 (transplant patients), HHV7

- Neuroborreliosis, Syphilis

- West Nile virus

- Cryptococcus, Aspergillus Fumigatus, Mucor

- Tuberculosis, toxoplasmosis

- Streptococcus, listeria

- Rare causes: leptospirosis, neurotropic astrovirus infection, Balamuthia mandrillaris, and squirrel bornavirus.

Clinical findings associated with autoantibody disorders

Paraneoplastic antibodies

- Anti-Hu (previously called antineuronal nuclear antibody 1 or ANNA-1) is an autoantibody detected in the serum of patients with paraneoplastic subacute sensory neuronopathy and/or encephalomyelitis

- Anti-Ri (previously called antineuronal nuclear antibody 2 or ANNA-2) may be present in patients with opsoclonus/myoclonus syndrome

- Antibodies directed against amphiphysin (a synaptic vesicle protein) have been detected in the serum of patients with the paraneoplastic form of stiff man syndrome ^[47]

- The antineuronal antibodies Ma1 and Ma2 (also called anti-Ta) are members of a novel but expanding family of brain-specific or testis-specific proteins; while Ma1 is not found in association with any one type of tumor, Ma2 seems to be associated strongly with testicular cancer

- The anti-Yo or anti-Purkinje cell antibody 1 (APCA-1) has been detected in patients with paraneoplastic cerebellar degeneration